bluuebunny/crossref_metadata_2025_split huggingface dataset:
Folate Receptor Alpha Upregulates Oct4, Sox2 and Klf4 and Downregulates miR-138 and miR-let-7 in Cranial Neural Crest Cells
Authors: Mohanty Vineet , Shah Amar , Allender Elise , Siddiqui M. Rizwan , Monick Sarah , Ichi Shunsuke , Mania-Farnell Barbara , G. McLone David , Tomita Tadanori , Mayanil Chandra Shekhar 
Published: June 2016

Abstract
Prenatal folic acid (FA) supplementation prevents neural tube defects. Folate receptor alpha (FRα) is critical for embryonic development, including neural crest (NC) development. Previously we showed that FRα translocates to the nucleus in response to FA, where it acts as a transcription factor. In this study, we examined if FA through interaction with FRα regulates stem cell characteristics of cranial neural crest cells (CNCCs)-critical for normal development. We hypothesized that FRα upregulates coding genes and simultaneously downregulates non-coding miRNA which targets coding genes in CNCCs. Quantitative RT-PCR and chromatin immunoprecipitation showed that FRα upregulates Oct4, Sox2, and Klf4 by binding to their cis-regulator elements-5′ enhancer/promoters defined by H3K27Ac and p300 occupancy. FA via FRα downregulates miRNAs, miR-138 and miR-let-7, which target Oct4 and Trim71 (an Oct4 downstream effector), respectively. Co-immunoprecipitation data suggests that FRα interacts with the Drosha-DGCR8 complex to affect pre-miRNA processing. Transfecting anti-miR-138 or anti-miR-let-7 into non-proliferating neural crest cells (NCCs) derived from Splotch (Sp−/−), restored their proliferation potential. In summary, these results suggest a novel pleiotropic role of FRα: (a) direct activation of Oct4, Sox2, and Klf4 genes; and (b) repression of biogenesis of miRNAs that target these genes or their effector molecules.
Histone H3K9 Acetyltransferase PCAF Is Essential for Osteogenic Differentiation Through Bone Morphogenetic Protein Signaling and May Be Involved in Osteoporosis
Authors: Zhang Ping , Liu Yunsong , Jin Chanyuan , Zhang Min , Lv Longwei , Zhang Xiao , Liu Hao , Zhou Yongsheng 
Published: June 2016

Abstract
Human mesenchymal stem cells (MSCs) are multipotent progenitor cells that can differentiate into osteoblasts, chondrocytes, and adipocytes. The importance of epigenetic regulation for osteogenic differentiation of MSCs is widely accepted. However, the molecular mechanisms are poorly understood. Here, we show that histone H3K9 acetyltransferase PCAF plays a critical role in osteogenic differentiation of MSCs. Knockdown of PCAF significantly reduced the bone formation both in vitro and in vivo. Mechanistically, PCAF controls BMP signaling genes expression by increasing H3K9 acetylation. Most importantly, PCAF expression is significantly decreased in bone sections of ovariectomized or aged mice. Histone modification enzyme is chemically modifiable; therefore, PCAF may represent a novel therapeutic target for stem cell-mediated regenerative medicine and the treatment of osteoporosis.
COX-2 Induces Breast Cancer Stem Cells via EP4/PI3K/AKT/NOTCH/WNT Axis
Authors: Majumder Mousumi , Xin Xiping , Liu Ling , Tutunea-Fatan Elena , Rodriguez-Torres Mauricio , Vincent Krista , Postovit Lynne-Marie , Hess David , Lala Peeyush K. 
Published: June 2016

Abstract
Cancer stem-like cells (SLC) resist conventional therapies, necessitating searches for SLC-specific targets. We established that cyclo-oxygenase(COX)-2 expression promotes human breast cancer progression by activation of the prostaglandin(PG)E-2 receptor EP4. Present study revealed that COX-2 induces SLCs by EP4-mediated NOTCH/WNT signaling. Ectopic COX-2 over-expression in MCF-7 and SKBR-3 cell lines resulted in: increased migration/invasion/proliferation, epithelial-mesenchymal transition (EMT), elevated SLCs (spheroid formation), increased ALDH activity and colocalization of COX-2 and SLC markers (ALDH1A, CD44, β-Catenin, NANOG, OCT3/4, SOX-2) in spheroids. These changes were reversed with COX-2-inhibitor or EP4-antagonist (EP4A), indicating dependence on COX-2/EP4 activities. COX-2 over-expression or EP4-agonist treatments of COX-2-low cells caused up-regulation of NOTCH/WNT genes, blocked with PI3K/AKT inhibitors. NOTCH/WNT inhibitors also blocked COX-2/EP4 induced SLC induction. Microarray analysis showed up-regulation of numerous SLC-regulatory and EMT-associated genes. MCF-7-COX-2 cells showed increased mammary tumorigenicity and spontaneous multiorgan metastases in NOD/SCID/IL-2Rγ-null mice for successive generations with limiting cell inocula. These tumors showed up-regulation of VEGF-A/C/D, Vimentin and phospho-AKT, down-regulation of E-Cadherin and enrichment of SLC marker positive and spheroid forming cells. MCF-7-COX-2 cells also showed increased lung colonization in NOD/SCID/GUSB-null mice, an effect reversed with EP4-knockdown or EP4A treatment of the MCF-7-COX-2 cells. COX-2/EP4/ALDH1A mRNA expression in human breast cancer tissues were highly correlated with one other, more marked in progressive stage of disease. In situ immunostaining of human breast tumor tissues revealed co-localization of SLC markers with COX-2, supporting COX-2 inducing SLCs. High COX-2/EP4 mRNA expression was linked with reduced survival. Thus, EP4 represents a novel SLC-ablative target in human breast cancer.
Distinct Responses of Stem Cells to Telomere Uncapping—A Potential Strategy to Improve the Safety of Cell Therapy
Authors: Liu Chang Ching , Ma Dong Liang , Yan Ting-Dong , Fan XiuBo , Poon Zhiyong , Poon Lai-Fong , Goh Su-Ann , Rozen Steve G. , Hwang William Ying Khee , Tergaonkar Vinay , Tan Patrick , Ghosh Sujoy , Virshup David M. , Goh Eyleen L. K. , Li Shang 
Published: June 2016

Abstract
In most human somatic cells, the lack of telomerase activity results in progressive telomere shortening during each cell division. Eventually, DNA damage responses triggered by critically short telomeres induce an irreversible cell cycle arrest termed replicative senescence. However, the cellular responses of human pluripotent stem cells to telomere uncapping remain unknown. We generated telomerase knockout human embryonic stem (ES) cells through gene targeting. Telomerase inactivation in ES cells results in progressive telomere shortening. Telomere DNA damage in ES cells and neural progenitor cells induces rapid apoptosis when telomeres are uncapped, in contrast to fibroblast cells that enter a state of replicative senescence. Significantly, telomerase inactivation limits the proliferation capacity of human ES cells without affecting their pluripotency. By targeting telomerase activity, we can functionally separate the two unique properties of human pluripotent stem cells, namely unlimited self-renewal and pluripotency. We show that the potential of ES cells to form teratomas in vivo is dictated by their telomere length. By controlling telomere length of ES cells through telomerase inactivation, we can inhibit teratoma formation and potentially improve the safety of cell therapies involving terminally differentiated cells as well as specific progenitor cells that do not require sustained cellular proliferation in vivo, and thus sustained telomerase activity.
Utility of ultrasound examination at 10–14 weeks prior to cell‐free DNA screening for fetal aneuploidy
Authors: Vora N. L. , Robinson S. , Hardisty E. E. , Stamilio D. M. 
Published: June 2016

ABSTRACTObjectiveTo estimate the frequency of unexpected first‐trimester ultrasound findings that would alter prenatal management in pregnant women eligible for cell‐free (cf) DNA screening because of advanced maternal age (AMA).MethodsThis was a retrospective cohort study of all AMA women at a tertiary care center who had a 10–14‐week ultrasound examination between 1 January 2012 and 27 April 2015. Information on pregnancy dating, obstetric ultrasound examination, prenatal screening and genetic testing were collected from a perinatal database. The primary outcome was an unexpected ultrasound finding in the first trimester that would alter the prenatal screening/testing strategy.ResultsIn total, 2337 women met the inclusion criteria, with a total of 2462 fetuses. Sixty‐eight (2.9%) women had an anomalous fetus, of which 44 (64.7%) had diagnostic testing. In the entire cohort, a non‐viable pregnancy was identified in 153 (6.5%) women. Multiple gestation was identified in 32 (1.4%) women; five had a cotwin demise. Gestational dating was revised for 126 (5.4%) women. Among those who opted for aneuploidy screening (n = 1806), 68.5% had cfDNA screening and 31.5% had first‐trimester screening by analysis of maternal serum biomarkers and nuchal translucency thickness. Among those eligible for cfDNA screening, 16.1% (95% CI, 15.0–18.0%; 377/2337) had an ultrasound finding (anomaly, incorrect dating, multiple gestation, non‐viable pregnancy) at the time of testing that would have altered the provider's counseling regarding the prenatal screening/testing strategy.ConclusionsA substantial proportion of AMA women eligible for cfDNA screening have fetal ultrasound findings that could alter genetic testing strategy and clinical management. This study recommends ultrasound examination prior to cfDNA screening in AMA women. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.
sFlt‐1/PlGF ratio test for pre‐eclampsia: an economic assessment for the UK
Authors: Vatish M. , Strunz‐McKendry T. , Hund M. , Allegranza D. , Wolf C. , Smare C. 
Published: June 2016

ABSTRACTObjectivesTo assess the economic impact of introducing into clinical practice in the UK the soluble fms‐like tyrosine kinase (sFlt‐1) to placental growth factor (PlGF) ratio test for guiding the management of pre‐eclampsia.MethodsWe used an economic model estimating the incremental value of information, from a UK National Health Service payer's perspective, generated by the sFlt‐1/PlGF ratio test, compared with current diagnostic procedures, in guiding the management of women with suspected pre‐eclampsia. The economic model estimated costs associated with the diagnosis and management of pre‐eclampsia in pregnant women between 24 + 0 and 36 + 6 weeks' gestation, managed in either a ‘test’ scenario in which the sFlt‐1/PlGF test is used in addition to current diagnostic procedures, or a ‘no‐test’ scenario in which clinical decisions are based on current diagnostic procedures alone. Test characteristics and resource use were derived from PROGNOSIS, a non‐interventional study in women presenting with clinical suspicion of pre‐eclampsia. The main outcome measure from the economic model was the cost per patient per episode of care, from first suspicion of pre‐eclampsia to birth.ResultsIntroduction of the sFlt‐1/PlGF ratio test into clinical practice is expected to result in cost savings of £344 per patient compared with a no‐test scenario. Savings are generated primarily through an improvement in diagnostic accuracy and subsequent reduction in unnecessary hospitalization.ConclusionsIntroducing the sFlt‐1/PlGF ratio test into clinical practice in the UK was shown to be cost‐saving by reducing unnecessary hospitalization of women at low risk of developing pre‐eclampsia. In addition, the test ensures that those women at higher risk are identified and managed appropriately. © 2016 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Perioperative Complications are Associated With Adverse Long‐Term Prognosis and Affect the Cause of Death After General Surgery
Authors: Tjeertes Elke K.M. , Ultee K. H. J. , Stolker R. J. , Verhagen H. J. M. , Bastos Gonçalves F. M. , Hoofwijk A. G. M. , Hoeks S. E. 
Published: June 2016

AbstractBackgroundIt is unclear how mortality and causes of death vary between patients and surgical procedures and how occurrence of postoperative complications is associated with prognosis. This study describes long‐term mortality rates and causes of death in a general surgical population. Furthermore, we explore the effect of postoperative complications on mortality.MethodsA single‐centre analysis of postoperative complications, with mortality as primary endpoint, was conducted in 4479 patients undergoing surgery. We applied univariate and multivariable regression models to analyse the effect of risk factors, including surgical risk and postoperative complications, on mortality. Causes of death were also explored.Results75 patients (1.7 %) died within 30 days after surgery and 730 patients (16.3 %) died during a median follow‐up of 6.3 years (IQR 5.8–6.8). Significant differences in long‐term mortality were observed with worst outcome for patients undergoing high‐risk vascular surgery (HR 1.5; 95 % CI 1.2–1.9). When looking at causes of death, high‐risk surgery was associated with a twofold higher risk of cardiovascular death (HR 1.9; 95 % CI 1.2–3.1), whereas the intermediate‐risk group had a higher risk of dying from cancer‐related causes (HR 1.5; 95 % CI 1.1–2.0). Occurrence of complications—particularly of cardiovascular nature— was associated with worse survival (HR 1.9; 95 % CI 1.3–2.7).ConclusionHigh‐risk vascular surgery and occurrence of postoperative complications are important predictors of late mortality. Further focus on these groups of patients can contribute to reduced morbidity. Improvement in quality of care should be aimed at preventing postoperative complications and thus a better outcome in a general surgical population.
Men's Knowledge About Maternal Serum Screening for Down Syndrome and their Attitude Towards Amniocentesis
Authors: Brajenović‐Milić Bojana , Dorčić Tamara Martinac 
Published: June 2016

AbstractThe present study aimed to assess (i) the impact of screening consultation on male partner's knowledge about second trimester maternal serum screening for Down syndrome and on their attitudes toward amniocentesis, and (ii) the concomitant effect of men's involvement in pregnancy on both knowledge and attitudes. The study included 164 men who accompanied their partners to the screening appointment. Knowledge Questionnaire and Partner's Involvement in Pregnancy Scale with two dimensions, support and distance, were administered. Involvement in pregnancy was determined using two factors; support and distance. Findings revealed a significant post‐consultation improvement in men's knowledge about the test, but less‐educated men and those who were more distanced from partner and pregnancy were less knowledgeable even post‐consultation. Compared to before the consultation, most men had a positive attitude toward amniocentesis and were willing to suggest it to their partners in case of positive test results (77 % and 42 %, respectively). The remainder would either leave the decision to their partners (20 %) or were undecided (3 %). Higher perception of distance was associated with men's unwillingness to be involved in amniocentesis decisions, particularly before consultation. However, the consultation had considerable potential to engage men with this attitude in the decision‐making process. The study highlights the need to change woman‐oriented prenatal screening practices for Down syndrome to involve their male partners in the consultation.
Effect of Inorganic Salts on the Aggregation Behavior of AOT at the Air/Water Interface
Authors: Pang Jinyu , Zhao Taotao , Xin Xia , Chen Yijian , Tan Yebang , Xu Guiying 
Published: June 2016

AbstractThe aggregation behavior of sodium bis‐(2‐ethylhexyl)‐sulfosuccinate (AOT) at the air/water interface in the absence and presence of inorganic salts was investigated by molecular dynamics simulation. Both monovalent and divalent ions were studied, such as LiCl, NaCl, KCl, MgCl2 and CaCl2. It has been proved that these inorganic ions have great influence on the structure of the AOT monolayer and water molecules around its headgroup. In the presence of inorganic salts, AOT molecules are relatively ordered at the interface and water around the headgroups of AOT shows a lower diffusion coefficient compared with the situation without inorganic salts. All the counterions are prone to move toward the headgroups and locate at the interface. Divalent ions have a strong interaction with AOT, thus they affect the aggregation behavior of AOT remarkably.
Drag reduction characteristics and flow field analysis of textured surface
Authors: Bai Qingshun , Bai Jinxuan , Meng Xiangpan , Ji Chengcheng , Liang Yingchun 
Published: June 2016

Abstract
A textured surface with a micro-groove structure exerts a distinct characteristic on drag reduction behavior. The fluid dynamic models of four textured surfaces are constructed in various profile geometries. Computational fluid dynamics is used to study the friction factors and drag reduction properties with various flow speeds on the textured surfaces. The friction coefficient varieties in the interface between the fluid and the textured surface are examined according to the simulation of the four geometries with V-shaped, saw tooth, rectangular, and semi-circular sections. The drag reduction efficiencies decrease with the increase in water velocity while it is less than a certain value. Moreover, the simulation results of the velocity, shear stress, energy, and turbulence effect on the V-shaped groove surface are presented in comparison with those of the smooth surface to illustrate the drag reduction mechanism. The results indicate that the peaks of the V-shaped grooves inhibit the lateral movement of the turbulent flow and generate the secondary vortex, which plays a key role in the impeding momentum exchange, thereby decreasing turbulent bursting intensity and reducing shear stress in the near-wall flow field. The kinetic energy and turbulence analysis shows that the vortex in the near-wall flow field on the textured surface is more stable compared to that on the smooth surface.
Selection of micro-fabrication techniques on stainless steel sheet for skin friction
Authors: Zhang S. , Zeng X. , Matthews D. T. A. , Igartua A. , Rodriguez-Vidal E. , Contreras Fortes J. , Saenz de Viteri V. , Pagano F. , Wadman B. , Wiklund E. D. , van der Heide E. 
Published: June 2016

AbstractThis review gives a concise introduction to the state-of-art techniques used for surface texturing, e.g., wet etching, plasma etching, laser surface texturing (LST), 3D printing, etc. In order to fabricate deterministic textures with the desired geometric structures and scales, the innovative texturing technologies are developed and extended. Such texturing technology is an emerging frontier with revolutionary impact in industrial and scientific fields. With the help of the latest fabrication technologies, surface textures are scaling down and more complex deterministic patterns may be fabricated with desired functions, e.g., lotus effect (hydrophobic), gecko feet (adhesive), haptic tactile, etc. The objective of this review is to explore the surface texturing technology and its contributions to the applications.
Early-life metal exposure and schizophrenia: A proof-of-concept study using novel tooth-matrix biomarkers
Authors: Modabbernia A. , Velthorst E. , Gennings C. , De Haan L. , Austin C. , Sutterland A. , Mollon J. , Frangou S. , Wright R. , Arora M. , Reichenberg A. 
Published: June 2016

AbstractBackgroundDespite evidence for the effects of metals on neurodevelopment, the long-term effects on mental health remain unclear due to methodological limitations. Our objective was to determine the feasibility of studying metal exposure during critical neurodevelopmental periods and to explore the association between early-life metal exposure and adult schizophrenia.MethodsWe analyzed childhood-shed teeth from nine individuals with schizophrenia and five healthy controls. We investigated the association between exposure to lead (Pb2+), manganese (Mn2+), cadmium (Cd2+), copper (Cu2+), magnesium (Mg2+), and zinc (Zn2+), and schizophrenia, psychotic experiences, and intelligence quotient (IQ). We reconstructed the dose and timing of early-life metal exposures using laser ablation inductively coupled plasma mass spectrometry.ResultsWe found higher early-life Pb2+exposure among patients with schizophrenia than controls. The differences in log Mn2+and log Cu2+changed relatively linearly over time to postnatal negative values. There was a positive correlation between early-life Pb2+levels and psychotic experiences in adulthood. Moreover, we found a negative correlation between Pb2+levels and adult IQ.ConclusionsIn our proof-of-concept study, using tooth-matrix biomarker that provides direct measurement of exposure in the fetus and newborn, we provide support for the role of metal exposure during critical neurodevelopmental periods in psychosis.
Comparison of Diaphragm Thickness Measurements Among Postures Via Ultrasound Imaging
Authors: Hellyer Nathan J. , Andreas Nicholas M. , Bernstetter Andrew S. , Cieslak Kathryn R. , Donahue Gerad F. , Steiner Elizabeth A. , Hollman John H. , Boon Andrea J. 
Published: June 2016

AbstractBackgroundAssessment of diaphragm contraction may be useful for identifying impairments in patients with movement dysfunction involving trunk stabilization, respiration, or both. Real‐time ultrasound imaging is a readily available technology that can be used to quickly assess this aspect of diaphragm activity. Although previous studies have examined diaphragm contraction in the supine posture, a comparison of measurements between supine and upright postures has not been made.ObjectiveTo examine whether diaphragm thickness measurements differ among 3 different body postures in healthy subjects.DesignDescriptive repeated measures.SettingClinical laboratory.Patients (or Participants)Twenty‐four healthy subjects (12 male and 12 female) aged 22‐35 years old were recruited and completed the study.MethodDiaphragm thickness was assessed in via B‐mode ultrasound imaging in supine, seated, and standing postures. Measurements of diaphragm thickness were taken in the zone of apposition during maximal inspiration to total lung capacity (TLC) and end‐tidal expiratory lung volume (EELV). A thickness ratio (inspiration thickness/expiration thickness) was calculated to compare relative diaphragm contraction during each condition.Main Outcome MeasurementsThe primary dependent variable was diaphragm thickness (mm).ResultsAverage diaphragm thickness at EELV and maximum TLC were more than 20% greater in the seated and standing postures than in supine (P < .05). Moreover, the diaphragm was approximately 205% thicker at TLC than at EELV (P < .05). Relative inspiratory to expiratory thickness ratios (TLC/EELV) did not differ among postures (P = .24).ConclusionsThe diaphragm is thicker when the body is in more upright postures (standing and sitting versus supine) perhaps due to greater vertical gravitational load on the muscle and associated change in the resting length of the muscle fibers. Thus it appears that ultrasound imaging may be a sensitive tool to examine changes in diaphragm contraction during varying postural tasks.Level of EvidenceIV
What is Bayesian statistics?
Authors: Marrero Osvaldo 
Published: June 2016

Bayesian statistics is included in few elementary statistics courses, and many mathematicians have heard of it, perhaps through collateral readings from popular literature or [1], selected as an Editor's Choice in the New York Times Book Review. ‘Bayesian statistics’ provides for a way to incorporate prior beliefs, experience, or information into the analysis of data. Bayesian thinking is natural, and that is an advantage. For example, on a summer morning, if we see dark rain clouds up in the sky, we leave home for work with an umbrella because prior experience tells us that doing so is beneficial. In general, the idea is simple; schematically, it looks like this:(prior belief) + (data: new information) ⇒ (posterior belief).Thus, we begin with a prior belief that we allow to be modified or informed by new data to produce a posterior belief, which then becomes our new prior, and this process is never-ending. We are always willing to update our beliefs according to new information.