bluuebunny/crossref_metadata_2025_split huggingface dataset:
Canonical Wnt/β-Catenin Regulation of Liver Receptor Homolog-1 Mediates Pluripotency Gene Expression
Authors: Wagner Ryan T. , Xu Xueping , Yi Fei , Merrill Bradley J. , Cooney Austin J. 
Published: August 2010

Abstract
Delineating the signaling pathways that underlie ESC pluripotency is paramount for development of ESC applications in both the research and clinical settings. In culture pluripotency is maintained by leukemia inhibitory factor (LIF) stimulation of two separate signaling axes: Stat3/Klf4/Sox2 and PI3K/Tbx3/Nanog, which converge in the regulation of Oct4 expression. However, LIF signaling is not required in vivo for self-renewal, thus alternate signaling axes likely mediate these pathways. Additional factors that promote pluripotency gene expression have been identified, including the direct regulation of Oct4 by liver receptor homolog-1 (Lrh-1) and β-catenin regulation of Nanog. Here, we present genetic, molecular, and pharmacological studies identifying a signaling axis in which β-catenin promotes pluripotency gene expression in an Lrh-1-dependent manner. Furthermore, Lrh-1 was identified as a novel β-catenin target gene, and Lrh-1 regulation is required for maintaining proper levels of Oct4, Nanog, and Tbx3. Elucidation of this pathway provides an alternate mechanism by which the primary pluripotency axis may be regulated in vivo and may pave the way for small molecule applications to manipulate pluripotency or improve the efficiency of somatic cell reprogramming.
Human Gingiva-Derived Mesenchymal Stem Cells Elicit Polarization of M2 Macrophages and Enhance Cutaneous Wound Healing
Authors: Zhang Qun-Zhou , Su Wen-Ru , Shi Shi-Hong , Wilder-Smith Petra , Xiang Andy Peng , Wong Alex , Nguyen Andrew L. , Kwon Chan Wook , Le Anh D. 
Published: August 2010

Abstract
Increasing evidence has supported the important role of mesenchymal stem cells (MSCs) in wound healing, however, the underlying mechanism remains unclear. Recently, we have isolated a unique population of MSCs from human gingiva (GMSCs) with similar stem cell-like properties, immunosuppressive, and anti-inflammatory functions as human bone marrow-derived MSCs (BMSCs). We describe here the interplay between GMSCs and macrophages and the potential relevance in skin wound healing. When cocultured with GMSCs, macrophages acquired an anti-inflammatory M2 phenotype characterized by an increased expression of mannose receptor (MR; CD206) and secretory cytokines interleukin (IL)-10 and IL-6, a suppressed production of tumor necrosis factor (TNF)-α, and decreased ability to induce Th-17 cell expansion. In vivo, we demonstrated that systemically infused GMSCs could home to the wound site in a tight spatial interaction with host macrophages, promoted them toward M2 polarization, and significantly enhanced wound repair. Mechanistically, GMSC treatment mitigated local inflammation mediated by a suppressed infiltration of inflammatory cells and production of IL-6 and TNF-α, and an increased expression of IL-10. The GMSC-induced suppression of TNF-α secretion by macrophages appears to correlate with impaired activation of NFκB p50. These findings provide first evidence that GMSCs are capable to elicit M2 polarization of macrophages, which might contribute to a marked acceleration of wound healing.
High-Efficiency Induction of Neural Conversion in Human ESCs and Human Induced Pluripotent Stem Cells with a Single Chemical Inhibitor of Transforming Growth Factor Beta Superfamily Receptors
Authors: Zhou Jiaxi , Su Pei , Li Dong , Tsang Stephanie , Duan Enkui , Wang Fei 
Published: August 2010

Abstract
Chemical compounds have emerged as powerful tools for modulating ESC functions and deriving induced pluripotent stem cells (iPSCs), but documentation of compound-induced efficient directed differentiation in human ESCs (hESCs) and human iPSC (hiPSCs) is limited. By screening a collection of chemical compounds, we identified compound C (also denoted as dorsomorphin), a protein kinase inhibitor, as a potent regulator of hESC and hiPSC fate decisions. Compound C suppresses mesoderm, endoderm, and trophoectoderm differentiation and induces rapid and high-efficiency neural conversion in both hESCs and hiPSCs, 88.7% and 70.4%, respectively. Interestingly, compound C is ineffective in inducing neural conversion in mouse ESCs (mESCs). Large-scale kinase assay revealed that compound C targets at least seven transforming growth factor beta (TGF-β) superfamily receptors, including both type I and type II receptors, and thereby blocks both the Activin and bone morphogenesis protein (BMP) signaling pathways in hESCs. Dual inhibition of Activin and BMP signaling accounts for the effects of compound C on hESC differentiation and neural conversion. We also identified muscle segment homeobox gene 2 (MSX2) as a downstream target gene of compound C and a key signaling intermediate of the BMP pathway in hESCs. Our findings provide a single-step cost-effective method for efficient derivation of neural progenitor cells in adherent culture from human pluripotent stem cells. Therefore, it will be uniquely suitable for the production of neural progenitor cells in large scale and should facilitate the use of stem cells in drug screening and regenerative medicine and study of early human neural development.
A Role for Regulatory T Cells in Acceptance of ESC-Derived Tissues Transplanted Across an Major Histocompatibility Complex Barrier
Authors: Lui Kathy O. , Boyd Ashleigh S. , Cobbold Stephen P. , Waldmann Herman , Fairchild Paul J. 
Published: August 2010

Abstract
We have previously reported that ESC-derived tissues are subject to some level of immune privilege, which might facilitate induction of immune tolerance. Herein, we further demonstrate that fully allogeneic ESC-derived tissues are accepted with a regimen of coreceptor blockade even in recipients known to be relatively resistant to such a tolerizing protocol. Moreover, ESC-derived tissues could be spontaneously accepted across a class I major histocompatibility complex disparity. We further show that CD4+FoxP3+ regulatory T cells (Treg) appear to be essential for this natural “privileged” state as their ablation with an anti-CD25 mAb results in rejection of ESC-derived tissue. This same treatment exposes activation of macrophages and effector CD8+ T cells, suggesting that these cells are subject to regulatory T cell control. Thus, spontaneous acceptance of ESC-derived tissues mimics the acquired immune privilege induced by coreceptor blockade and is determined by Treg-mediated suppression.
Test data regeneration: generating new test data from existing test data
Authors: Yoo S. , Harman M. 
Published: August 2010

SUMMARYExisting automated test data generation techniques tend to start from scratch, implicitly assuming that no pre‐existing test data are available. However, this assumption may not always hold, and where it does not, there may be a missed opportunity; perhaps the pre‐existing test cases could be used to assist the automated generation of additional test cases. This paper introduces search‐based test data regeneration, a technique that can generate additional test data from existing test data using a meta‐heuristic search algorithm. The proposed technique is compared to a widely studied test data generation approach in terms of both efficiency and effectiveness. The empirical evaluation shows that test data regeneration can be up to 2 orders of magnitude more efficient than existing test data generation techniques, while achieving comparable effectiveness in terms of structural coverage and mutation score. Copyright © 2010 John Wiley & Sons, Ltd.
Automated functional testing of online search services
Authors: Zhou Zhi Quan , Zhang ShuJia , Hagenbuchner Markus , Tse T. H. , Kuo Fei‐Ching , Chen T. Y. 
Published: August 2010

SUMMARYSearch services are the main interface through which people discover information on the Internet. A fundamental challenge in testing search services is the lack of oracles. The sheer volume of data on the Internet prohibits testers from verifying the results. Furthermore, it is difficult to objectively assess the ranking quality because different assessors can have very different opinions on the relevance of a Web page to a query. This paper presents a novel method for automatically testing search services without the need of a human oracle. The experimental findings reveal that some commonly used search engines, including Google, Yahoo!, and Live Search, are not as reliable as what most users would expect. For example, they may fail to find pages that exist in their own repositories, or rank pages in a way that is logically inconsistent. Suggestions are made for search service providers to improve their service quality. Copyright © 2010 John Wiley & Sons, Ltd.
Automated verification and testing of user‐interactive undo features in database applications
Authors: Ngo Minh Ngoc , Tan Hee Beng Kuan 
Published: August 2010

SUMMARYUser‐interactive undo is a recovery facility that enables users to correct mistakes easily by canceling or re‐executing operations that have already been executed. This paper presents an interesting common structural property that has been discovered in programs that implementing user‐interactive undo features. The property shows that there is a one‐to‐one correspondence between program statements that raise erroneous effects and those statements that can undo these effects. Statistical validation has been conducted which gives evidences to show that this property holds for 99 per cent of all the cases. An approach for automated verification of user‐interactive undo features in database applications through the use of this empirical property is further proposed. Based on the verification results, test cases are automatically generated to confirm the correctness of these features. A case study has been conducted to evaluate the performance of the proposed verification and testing approach in terms of fault detection capability. Copyright © 2010 John Wiley & Sons, Ltd.
Subchronic effects of perfluorooctanesulfonate exposure on inflammation in adult male C57BL/6 mice
Authors: Dong Guang‐Hui , Zhang Ying‐Hua , Zheng Li , Liang Zai‐Fu , Jin Yi‐He , He Qin‐Cheng 
Published: August 2010

AbstractPrevious studies indicate that exposure to perfluorooctanesulfonate (PFOS), a ubiquitous and highly persistent environmental contaminant, induces immunotoxicity in mice. However, few studies have specifically assessed the effects of PFOS on inflammation. This study utilized a standard 60‐day oral exposure period to assess the effects of PFOS on the response of inflammatory cytokines [tumor necrosis factor α (TNF‐α), interleukin‐1 β (IL‐1β), and interleukin‐6 (IL‐6)]. Adult male C57BL/6 mice were dosed daily by oral gavage with PFOS at 0, 0.0083, 0.0167, 0.0833, 0.4167, 0.8333 or 2.0833 mg/kg/day to yield a targeted Total Administered Dose (TAD) over 60 days of 0, 0.5, 1, 5, 25, 50, or 125 mg PFOS/kg, respectively. The percentage of peritoneal macrophages (CD11b+ cells) was significantly increased at concentrations ≥1 mg PFOS/kg TAD in a dose‐dependent manner. Ex vivo IL‐1β production by peritoneal macrophages was elevated substantially at concentrations of ≥5 mg PFOS/kg TAD. Moreover, PFOS exposure markedly enhanced the ex vivo production of TNF‐α, IL‐1β and IL‐6 by peritoneal and splenic macrophages when stimulated either in vitro or in vivo with lipopolysaccharide (LPS). The serum levels of these inflammatory cytokines observed in response to in vivo stimulation with LPS were elevated substantially by exposure to PFOS. PFOS exposure elevated the expression of pro‐inflammatory cytokines TNF‐α, IL‐1β, IL‐6, and proto‐oncogene, c‐myc, in the spleen. These data suggest that exposure to PFOS modulates the inflammatory response, and further research is needed to determine the mechanism of action. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2012.
Environmental nitration processes enhance the mutagenic potency of aromatic compounds
Authors: Bonnefoy Aurélie , Chiron Serge , Botta Alain 
Published: August 2010

AbstractThis work is an attempt to establish if aromatic nitration processes are always associated with an increase of genotoxicity. We determined the mutagenic and genotoxic effects of Benzene (B), Nitrobenzene (NB), Phenol (P), 2‐Nitrophenol (2‐NP), 2,4‐Dinitrophenol (2,4‐DNP), Pyrene (Py), 1‐Nitropyrene (1‐NPy), 1,3‐Dinitropyrene (1,3‐DNPy), 1,6‐Dinitropyrene (1,6‐DNPy), and 1,8‐Dinitropyrene (1,8‐DNPy). The mutagenic activities were evaluated with umuC test in presence and in absence of metabolic activation with S9 mix. Then, we used both cytokinesis‐blocked micronucleus (CBMN) assay, in combination with fluorescent in situ hybridization (FISH) of human pan‐centromeric DNA probes on human lymphocytes in order to evaluate the genotoxic effects. Analysis of all results shows that nitro polycyclic aromatic hydrocarbons (PAHs) are definitely environmental genotoxic/mutagenic hazards and confirms that environmental aromatic nitration reactions lead to an increase in genotoxicity and mutagenicity properties. Particularly 1‐NPy and 1,8‐DNPy can be considered as human potential carcinogens. They seem to be significant markers of the genotoxicity, mutagenicity, and potential carcinogenicity of complex PAHs mixtures present in traffic emission and industrial environment. In prevention of environmental carcinogenic risk 1‐NPy and 1,8‐DNPy must therefore be systematically analyzed in environmental complex mixtures in association with combined umuC test, CBMN assay, and FISH on cultured human lymphocytes. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2012.
Can syndromic macrocephaly be diagnosed in utero?
Authors: Malinger G. , Lev D. , Ben‐Sira L. , Hoffmann C. , Herrera M. , Viñals F. , Vinkler H. , Ginath S. , Biran‐Gol Y. , Kidron D. , Lerman‐Sagie T. 
Published: August 2010

AbstractObjectivesTo compare the outcomes of fetuses with apparently isolated macrocephaly and those with associated findings, and to compare prenatal findings with postnatal diagnoses in children with syndromic macrocephaly.MethodsWe reviewed the files of all patients referred for suspected fetal macrocephaly, during a 10‐year period from 2000, to a large prenatal diagnosis unit with expertise in fetal neurology counseling. Macrocephaly was defined as head circumference (HC) > 2 SDs of the norm. Patients with confirmed HC > 2 SD were identified and contacted, and their development was evaluated.ResultsAdequate data for analysis were available for 98 patients, in 82 of whom the fetal macrocephaly was considered isolated (Group A), and in 16 of whom associated fetal anomalies were identified (Group B). Macrocephaly was diagnosed earlier in Group B patients (28.4 vs. 32.3 weeks, P = 0.069), and the HC in Group B patients was larger (Z‐score 2.95 vs. 2.3, P < 0.001). From Group A there were 81 liveborn; one of whom was diagnosed as having infantile autism. From Group B, there were nine liveborn. The associated central nervous system findings, as demonstrated by ultrasound and magnetic resonance imaging, included mild ventriculomegaly, malformations of cortical development, callosal abnormalities, overdeveloped sulcation, large cavum septi pellucidi, large subarachnoid spaces, mega cisterna magna, periventricular pseudocyst, open operculum and vermian dysgenesis. Syndromic diagnosis was made in utero in five fetuses and after birth in three. In eight patients, associated malformations were confirmed after birth but a specific diagnosis was not reached.ConclusionsWhen fetal macrocephaly is associated with other brain or systemic anomalies, syndromic macrocephaly can be diagnosed in utero. Fetuses with syndromic macrocephaly have a significantly larger HC, usually > 2.5 SD above the mean. Isolated macrocephaly, particularly when the HC is < 2.5 SD above the norm, may be clinically benign. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.
Inhibin A, activin A, placental growth factor and uterine artery Doppler pulsatility index in the prediction of pre‐eclampsia
Authors: Yu J. , Shixia C. Z. , Wu Y. , Duan T. 
Published: August 2010

AbstractObjectivesTo evaluate whether the measurement of maternal serum inhibin A, activin A and placental growth factor (PlGF) at 12 + 0 to 16 + 0 weeks of gestation alone or in combination with second‐trimester uterine artery Doppler pulsatility index (PI) is useful in predicting pre‐eclampsia.MethodsThis was a case–control study of pre‐eclampsia. From pregnant women attending their first antenatal examination at 12–16 weeks we collected serum samples and stored them at − 80 °C. All patients also underwent uterine artery Doppler examination to measure the PI at 22–24 weeks' gestation. We retrieved for analysis frozen samples from women who then developed pre‐eclampsia, as well as three control samples per woman, matched for gestational age and storage time. Inhibin A, activin A and PlGF were measured using an enzyme‐linked immunosorbent assay (ELISA) by an examiner who was blinded to the pregnancy outcome.ResultsThere were 31 cases with pre‐eclampsia and 93 controls. Second‐trimester uterine artery PI and marker levels were expressed as multiples of the median (MoM). The uterine artery PI was increased in pregnancies with pre‐eclampsia compared with controls (mean ± SD, 1.45 ± 0.31 MoM vs. 1.02 ± 0.25 MoM, P < 0.001), as were the level of inhibin A (mean ± SD, 1.57 ± 0.34 MoM vs. 1.08 ± 0.43 MoM, P < 0.001) and the level of activin A (mean ± SD, 1.68 ± 0.38 MoM vs. 1.06 ± 0.42 MoM, P < 0.001). The level of PlGF was decreased in pre‐eclampsia compared with controls (mean ± SD, 0.69 ± 0.23 MoM vs. 1.00 ± 0.26 MoM, P < 0.001). Receiver–operating characteristics curves were analyzed for controls and cases and areas under the curve (AUC) were 0.796 (95% CI, 0.712–0.880, P < 0.001) for inhibin A, 0.823 (95% CI, 0.746–0.899, P < 0.001) for activin A, 0.831 (95% CI, 0.752–0.910, P < 0.001) for PlGF and 0.851 (95% CI, 0.783–0.920, P < 0.001) for uterine artery PI. The combination of activin A, inhibin A and PI using logistic regression analysis yielded an AUC of 0.907 (95% CI, 0.830–0.938, P < 0.001) with a sensitivity of 87% and a specificity of 80%. The combination of activin A, PlGF and PI gave an AUC of 0.925 (95% CI, 0.852–0.978, P < 0.001) with a sensitivity of 90% and a specificity of 80%. Combining all four markers gave an AUC of 0.941 (95% CI, 0.891–0.990, P < 0.001) with a sensitivity of 93% and a specificity of 80%.ConclusionEarly second‐trimester serum inhibin A, activin A, PlGF and second‐trimester uterine artery Doppler PI may add further information for the prediction of pre‐eclampsia. The combination of the three serum markers and uterine artery Doppler PI has the highest prediction value for pre‐eclampsia. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.
Gastrointestinal stromal tumors presenting as gynecological masses: usefulness of multidetector computed tomography
Authors: Teoh W. C. , Teo S. Y. , Ong C. L. 
Published: August 2010

AbstractLarge extraluminal gastrointestinal tumors (GISTs) may present as pelvic masses and thus mimic gynecological neoplasms in female patients. On clinical examination and pelvic ultrasound, these tumors resemble pedunculated fibroids or ovarian tumors. Multidetector computed tomography (CT), with its ability to perform isotropic multiplanar reconstruction, is useful in differentiating GISTs from true gynecological masses by demonstrating the pedicle sign connecting a pelvic GIST to its organ of origin. This allows a preoperative diagnosis to be made, which may be helpful in guiding therapeutic options and management. We present two cases of GISTs presenting as pelvic masses in which ultrasound findings suggested a gynecological cause, but multidetector CT with multiplanar reconstruction was able to determine their true organ of origin. Copyright © 2010 ISUOG. Published by John Wiley & Sons, Ltd.
Outcome prediction in monochorionic diamniotic twin pregnancies with moderately discordant amniotic fluid
Authors: Van Mieghem T. , Eixarch E. , Gucciardo L. , Done E. , Gonzales I. , Van Schoubroeck D. , Lewi L. , Gratacos E. , Deprest J. 
Published: August 2010

AbstractObjectiveThe aim of this study was to identify predictors of twin‐to‐twin transfusion syndrome (TTTS) and selective intrauterine growth restriction (sIUGR) in monochorionic diamniotic (MCDA) twin pregnancies with moderate amniotic fluid discordance (mAFD).MethodsMonochorionic twins with mAFD (n = 45; gestational age, 15–29 weeks) were assessed for extent of fluid discordance, fetal growth discordance and fetal cardiac dysfunction, and were followed longitudinally. A prediction algorithm was constructed for TTTS and sIUGR and validated in an unrelated cohort (n = 52).ResultsCardiac dysfunction could not predict TTTS or sIUGR. Twins below 20 weeks of gestation with a fluid discordance of ≥ 3.1 cm had a risk of TTTS of 85.7%. Sensitivity for TTTS was nevertheless only 55%. An intertwin weight discordance of ≥ 25% had 63% sensitivity and 76% specificity for sIUGR without TTTS.ConclusionThe outcome of MCDA twins with mAFD remains unpredictable, yet high‐risk and low‐risk subgroups for TTTS can be identified based on severity of fluid discordance and gestational age. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.
Ultrasound‐guided tru‐cut biopsy of abdominal and pelvic tumors in gynecology
Authors: Zikan M. , Fischerova D. , Pinkavova I. , Dundr P. , Cibula D. 
Published: August 2010

AbstractObjectiveTo analyze the safety, adequacy and accuracy of tru‐cut biopsy and to evaluate factors potentially affecting adequacy.MethodsWe analyzed retrospectively a group of patients who had undergone tru‐cut biopsy for either primary suboptimally operable tumors, recurrence or suspected non‐genital or secondary tumor. Tru‐cut biopsy was performed either transvaginally or transabdominally, using an automatic biopsy gun with disposable needle and needle guide attached to the probe. The adequacy, i.e. obtaining a sample sufficient for identification of the origin of the tumor and performance of immunohistochemistry; accuracy, i.e. agreement between biopsy and final postoperative histology; and safety, as determined by complication rate, were assessed. Variables potentially influencing adequacy were analyzed using the orthogonal projections to latent structure method.ResultsA total of 195 biopsies were performed on 190 patients. An adequate sample was obtained in 178 (91.3%) biopsies. The final histology was not in agreement with the result from tru‐cut biopsy in two out of 118 patients who underwent subsequent surgery (accuracy 98.3%). There were complications in two cases out of the 195 biopsies performed (1.0%). Ascites, elevated CA 125, primary suboptimal operable tumor, serous epithelial ovarian cancer histology, carcinomatosis and vaginal approach were significant positive predictors for the achievement of an adequate sample, while recurrence as an indication, non‐serous and non‐ovarian histotypes and transabdominal approach were negative predictors.ConclusionUltrasound‐guided tru‐cut biopsy is an efficient, minimally invasive, accurate and safe diagnostic method in the management of advanced, recurrent or atypical abdominal and pelvic tumors of probable non‐genital origin, where unnecessary laparotomy or laparoscopy can be avoided. The adequacy of tru‐cut biopsy is mainly influenced by indication group, histology, site of biopsy and approach. Our analysis can help in counseling the patient before the procedure and helps to explain the possible causes of failure of the procedure. Copyright © 2010 ISUOG. Published by John Wiley & Sons, Ltd.