bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simultaneous bright‐ and black‐blood whole‐heart MRI for noncontrast enhanced coronary lumen and thrombus visualization
Authors: Ginami Giulia , Neji Radhouene , Phinikaridou Alkystis , Whitaker John , Botnar René M. , Prieto Claudia 
Published: July 2017

PurposeTo develop a 3D whole‐heart Bright‐blood and black‐blOOd phase SensiTive (BOOST) inversion recovery sequence for simultaneous noncontrast enhanced coronary lumen and thrombus/hemorrhage visualization.MethodsThe proposed sequence alternates the acquisition of two bright‐blood datasets preceded by different preparatory pulses to obtain variations in blood/myocardium contrast, which then are combined in a phase‐sensitive inversion recovery (PSIR)‐like reconstruction to obtain a third, coregistered, black‐blood dataset. The bright‐blood datasets are used for both visualization of the coronary lumen and motion estimation, whereas the complementary black‐blood dataset potentially allows for thrombus/hemorrhage visualization. Furthermore, integration with 2D image‐based navigation enables 100% scan efficiency and predictable scan times. The proposed sequence was compared to conventional coronary MR angiography (CMRA) and PSIR sequences in a standardized phantom and in healthy subjects. Feasibility for thrombus depiction was tested ex vivo.ResultsWith BOOST, the coronary lumen is visualized with significantly higher (P < 0.05) contrast‐to‐noise ratio and vessel sharpness when compared to conventional CMRA. Furthermore, BOOST showed effective blood signal suppression as well as feasibility for thrombus visualization ex vivo.ConclusionA new PSIR sequence for noncontrast enhanced simultaneous coronary lumen and thrombus/hemorrhage detection was developed. The sequence provided improved coronary lumen depiction and showed potential for thrombus visualization. Magn Reson Med 79:1460–1472, 2018. © 2017 International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Worth the Wait? The Effect of Early Term Birth on Maternal and Infant Health
Authors: Buckles Kasey , Guldi Melanie 
Published: July 2017

AbstractEarly term birth is defined as birth at 37 or 38 weeks gestation. While infants born early term are not considered premature, the medical literature suggests that they have an increased risk of serious adverse health outcomes compared to infants born at term (39 or 40 weeks). Despite these known harms, we document a rise in early term births in the United States from 1989 to the mid‐2000s, followed by a decline in recent years. We posit that the recent decline in early term births has been driven by changes in medical practice advocated by the American College of Obstetricians and Gynecologists, programs such as the March of Dimes’ “Worth the Wait” campaign, and by Medicaid policy. We first show that this pattern cannot be attributed to changes in the demographic composition of mothers, and provide some evidence that efforts to reduce early term elective deliveries (EEDs) through Medicaid policy were effective. We next exploit county‐level variation in the timing of these changes in medical practice to examine the effect of early term inductions (our proxy for EEDs) on infant and maternal health. We find that early term inductions lower birth weights and increase the risks of precipitous labor, birth injury, and required ventilation. Our results suggest that reductions in early term inductions can explain about one‐third of the overall increase in birth weights between 2010 and 2013 for births at 37 weeks gestation and above.
AT2R deficiency mediated podocyte loss via activation of ectopic hedgehog interacting protein (Hhip) gene expression
Authors: Liao Min‐Chun , Zhao Xin‐Ping , Chang Shiao‐Ying , Lo Chao‐Sheng , Chenier Isabelle , Takano Tomoko , Ingelfinger Julie R , Zhang Shao‐Ling 
Published: July 2017

AbstractAngiotensin II type 2 receptor (AT2R) deficiency in AT2R knockout (KO) mice has been linked to congenital abnormalities of the kidney and urinary tract; however, the mechanisms by which this occurs are poorly understood. In this study, we examined whether AT2R deficiency impaired glomerulogenesis and mediated podocyte loss/dysfunction in vivo and in vitro. Nephrin‐cyan fluorescent protein (CFP)‐transgenic (Tg) and Nephrin/AT2RKO mice were used to assess glomerulogenesis, while wild‐type and AT2RKO mice were used to evaluate maturation of podocyte morphology/function. Immortalized mouse podocytes (mPODs) were employed for in vitro studies. AT2R deficiency resulted in diminished glomerulogenesis in E15 embryos, but had no impact on actual nephron number in neonates. Pups lacking AT2R displayed features of renal dysplasia with lower glomerular tuft volume and podocyte numbers. In vivo and in vitro studies demonstrated that loss of AT2R was associated with elevated NADPH oxidase 4 levels, which in turn stimulated ectopic hedgehog interacting protein (Hhip) gene expression in podocytes. Consequently, ectopic Hhip expression activation either triggers caspase‐3 and p53‐related apoptotic processes resulting in podocyte loss, or activates TGFβ1–Smad2/3 cascades and α‐SMA expression to transform differentiated podocytes to undifferentiated podocyte‐derived fibrotic cells. We analyzed HHIP expression in the kidney disease database (Nephroseq) and then validated this using HHIP immunohistochemistry staining of human kidney biopsies (controls versus focal segmental glomerulosclerosis). In conclusion, loss of AT2R is associated with podocyte loss/dysfunction and is mediated, at least in part, via augmented ectopic Hhip expression in podocytes. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Temperature stability of proteins: Analysis of irreversible denaturation using isothermal calorimetry
Authors: Schön Arne , Clarkson Benjamin R. , Jaime Maria , Freire Ernesto 
Published: July 2017

AbstractThe structural stability of proteins has been traditionally studied under conditions in which the folding/unfolding reaction is reversible, since thermodynamic parameters can only be determined under these conditions. Achieving reversibility conditions in temperature stability experiments has often required performing the experiments at acidic pH or other nonphysiological solvent conditions. With the rapid development of protein drugs, the fastest growing segment in the pharmaceutical industry, the need to evaluate protein stability under formulation conditions has acquired renewed urgency. Under formulation conditions and the required high protein concentration (∼100 mg/mL), protein denaturation is irreversible and frequently coupled to aggregation and precipitation. In this article, we examine the thermal denaturation of hen egg white lysozyme (HEWL) under irreversible conditions and concentrations up to 100 mg/mL using several techniques, especially isothermal calorimetry which has been used to measure the enthalpy and kinetics of the unfolding and aggregation/precipitation at 12°C below the transition temperature measured by DSC. At those temperatures the rate of irreversible protein denaturation and aggregation of HEWL is measured to be on the order of 1 day−1. Isothermal calorimetry appears a suitable technique to identify buffer formulation conditions that maximize the long term stability of protein drugs.
Prevention against renal damage in rats with subtotal nephrectomy by sacubitril/valsartan (LCZ696), a dual‐acting angiotensin receptor‐neprilysin inhibitor
Authors: Ushijima Kentaro , Ando Hitoshi , Arakawa Yusuke , Aizawa Kenichi , Suzuki Chisato , Shimada Ken , Tsuruoka Shu‐ichi , Fujimura Akio 
Published: July 2017

AbstractAlthough patients with chronic kidney disease (CKD) are at increased risk for end‐stage renal disease and cardiovascular events, adequate drug therapies for preventing the deterioration of these conditions are still not established. This study was undertaken to evaluate a preventive effect of an angiotensin receptor‐neprilysin inhibitor sacubitril/valsartan (LCZ696), which is converted to sacubitril and valsartan in the body, against the progression of renal disease in rats with subtotal nephrectomy, an animal model of human CKD. Mean survival time after subtotal nephrectomy was about 100 days in Wistar rats with vehicle. LCZ696‐(30 mg/kg) and valsartan‐(15 mg/kg) prolonged the survival of these animals, and the effect of LCZ696 on survival was significantly greater than that of valsartan. Renoprotective effects of LCZ696 judged by serum creatinine and urinary protein excretions were larger than those of valsartan. Cardioprotective effects judged by cardiac left ventricular mass, fractional shortening, and fibrosis of LCZ696 and valsartan were not detected under the present condition. Thus, the renoprotective effect of LCZ696 was stronger than that of valsartan in rats with subtotal nephrectomy. This study provides the idea that, compared to valsartan, LCZ696 is more effective for the treatment of human CKD.
Post‐disaster Cooperation Among Aid Agencies
Authors: Heetun Shameem , Phillips Fred , Park Sehee 
Published: July 2017

Natural and anthropogenic disasters affect ever‐larger populations. Effective cooperation among aid agencies is key to post‐disaster recovery. Studies in evolutionary game theory suggest two motives for one agency to cooperate with another: the other agency's reputation and the perceived probability of working together again in the future.This mixed method study collected data from decision makers in 30 aid agencies. The quantitative instrument, itself an evolutionary game, showed cooperation heavily influenced both by reputation and by interaction potential, with probable frequency of future interaction being a better predictor. Qualitative interviews affirmed the importance of both and showed learning, directives and reviews are subsidiary determinants of cooperation.This study answers—for the population of disaster aid managers—a controversial question in the evolution of cooperation. It offers guidance for agencies allocating training budget between technical skills (e.g. distributing medicines) and cooperation skills, with the aim of quickly aiding disaster victims. Copyright © 2017 John Wiley & Sons, Ltd.
XIAP inhibitor embelin induces autophagic and apoptotic cell death in human oral squamous cell carcinoma cells
Authors: Lee You‐Jin , Park Bong‐Soo , Park Hae‐Ryoun , Yu Su‐Bin , Kang Hae‐Mi , Kim In‐Ryoung 
Published: July 2017

AbstractEmbelin is an active ingredient of traditional herbal remedies for cancer and other diseases. Recently, it has been suggested that autophagy may play an important role in cancer therapy. However, little data are available regarding the role of autophagy in oral cancers. Therefore, we conducted this study to examine whether Embelin modulates autophagy in Ca9‐22. Our results showed that Embelin had anticancer activity against the Ca9‐22 human tongue squamous cell, and we observed that autophagic vacuoles were formed by MDC and AO. We also analyzed Embelin‐treated Ca9‐22 cells for the presence of biochemical markers and found that it directly affected the conversion of LC3‐II, the degradation of p62/SQSTM1, full‐length cleavage formation of ATG5‐ATG12 complex and Beline‐1, and caspase activation. Rescue experiments using an autophagy inhibitor showed Embelin‐induced cell death in Ca9‐22, confirming that autophagy acts as a pro‐death signal. Furthermore, Embelin exhibited anticancer activity against Ca9‐22 via both autophagy and apoptosis. These findings suggest that Embelin may potentially contribute to oral cancer treatment and provide useful information for the development of a new therapeutic agent.
PacBio assembly of aPlasmodium knowlesigenome sequence with Hi-C correction and manual annotation of theSICAvargene family
Authors: LAPP S. A. , GERALDO J. A. , CHIEN J.-T. , AY F. , PAKALA S. B. , BATUGEDARA G. , HUMPHREY J. ,   the MaHPIC consortium, DeBARRY J. D. , Le ROCH K. G. , GALINSKI M. R. , KISSINGER J. C. 
Published: July 2017

SUMMARYPlasmodium knowlesihas risen in importance as a zoonotic parasite that has been causing regular episodes of malaria throughout South East Asia. TheP. knowlesigenome sequence generated in 2008 highlighted and confirmed many similarities and differences inPlasmodiumspecies, including a global view of several multigene families, such as the largeSICAvarmultigene family encoding the variant antigens known as the schizont-infected cell agglutination proteins. However, repetitive DNA sequences are the bane of any genome project, and this and otherPlasmodiumgenome projects have not been immune to the gaps, rearrangements and other pitfalls created by these genomic features. Today, long-read PacBio and chromatin conformation technologies are overcoming such obstacles. Here, based on the use of these technologies, we present a highly refinedde novo P. knowlesigenome sequence of the Pk1(A+) clone. This sequence and annotation, referred to as the ‘MaHPIC Pk genome sequence’, includes manual annotation of theSICAvargene family with 136 full-length members categorized as type I or II. This sequence provides a framework that will permit a better understanding of theSICAvarrepertoire, selective pressures acting on this gene family and mechanisms of antigenic variation in this species and other pathogens.
Psychological vulnerability of widowhood: financial strain, social engagement and worry about having no care-giver as mediators and moderators
Authors: MIN JOOHONG , LI YAWEN , XU LING , CHI IRIS 
Published: July 2017

ABSTRACTThis study examined how financial strain, worry about having no care-giver and social engagement modify the association between widowhood and depressive symptoms among older adults in China. Using national representative data from older adults in China in 2006, we ran structural equation models and ordinary least square regressions to investigate the mediating and moderating effects of financial strain, worry about having no care-giver and social engagement on the association between widowhood and depressive symptoms. All three variables significantly mediated the association between widowhood and depressive symptoms. Compared to their married counterparts, widowed older adults showed more worry about having no care-giver, increased financial strain and lower social engagement, which were significantly associated with depressive symptoms. Higher level of worry about having no care-giver and lower social engagement significantly exacerbated the adverse effects of widowhood on depressive symptoms in the moderation analyses. Our finding of mediating effects suggests that widowhood is negatively related to psychological wellbeing via financial strain, social engagement and care resources. The results regarding moderating effects suggest that alleviating worry about having no care-giver and increasing social engagement may buffer the deleterious effect of widowhood on psychological wellbeing in later life.
A DECADE OF HEALTH TECHNOLOGY ASSESSMENT IN POLAND
Authors: Lipska Iga , McAuslane Neil , Leufkens Hubert , Hövels Anke 
Published: July 2017

Objectives: The objective of this study is to illustrate and provide a better understanding of the role of health technology assessment (HTA) processes in decision making for drug reimbursement in Poland and how this approach could be considered by other countries of limited resources.Methods: We analyzed the evolution of the HTA system and processes in Poland over the past decade and current developments based on publicly available information.Results: The role of HTA in drug-reimbursement process in Poland has increased substantially over the recent decade, starting in 2005 with the formation the Agency for Health Technology Assessment and Tariff System (AOTMiT). The key success factors in this development were effective capacity building based on the use of international expertise, the implementation of transparent criteria into the drug reimbursement processes, and the selective approach to the adoption of innovative medicines based on the cost-effectiveness threshold among other criteria.Conclusions: While Poland is regarded as a leader in Central and Eastern Europe, there is room for improvement, especially with regard to the quality of HTA processes and the consistency of HTA guidelines with reimbursement law. In the “pragmatic” HTA model use by AOTMiT, the pharmaceutical company is responsible for the preparation of a reimbursement dossier of good quality in line with HTA guidelines while the assessment team in AOTMiT is responsible for critical review of that dossier. Adoption of this model may be considered by other countries with limited resources to balance differing priorities and ensure transparent and objective access to medicines for patients who need them.
Physical properties of the HIV-1 capsid from all-atom molecular dynamics simulations
Authors: Perilla Juan R. , Schulten Klaus 
Published: July 2017

AbstractHuman immunodeficiency virus type 1 (HIV-1) infection is highly dependent on its capsid. The capsid is a large container, made of ∼1,300 proteins with altogether 4 million atoms. Although the capsid proteins are all identical, they nevertheless arrange themselves into a largely asymmetric structure made of hexamers and pentamers. The large number of degrees of freedom and lack of symmetry pose a challenge to studying the chemical details of the HIV capsid. Simulations of over 64 million atoms for over 1 μs allow us to conduct a comprehensive study of the chemical–physical properties of an empty HIV-1 capsid, including its electrostatics, vibrational and acoustic properties, and the effects of solvent (ions and water) on the capsid. The simulations reveal critical details about the capsid with implications to biological function.
Anterior cingulate is a source of valence-specific information about value and uncertainty
Authors: Monosov Ilya E. 
Published: July 2017

AbstractAnterior cingulate cortex (ACC) is thought to control a wide range of reward, punishment, and uncertainty-related behaviors. However, how it does so is unclear. Here, in a Pavlovian procedure in which monkeys displayed a diverse repertoire of reward-related, punishment-related, and uncertainty-related behaviors, we show that many ACC-neurons represent expected value and uncertainty in a valence-specific manner, signaling value or uncertainty predictions about either rewards or punishments. Other ACC-neurons signal prediction information about rewards and punishments by displaying excitation to both (rather than excitation to one and inhibition to the other). This diversity in valence representations may support the role of ACC in many behavioral states that are either enhanced by reward and punishment (e.g., vigilance) or specific to either reward or punishment (e.g., approach and avoidance). Also, this first demonstration of punishment-uncertainty signals in the brain suggests that ACC could be a target for the treatment of uncertainty-related disorders of mood.
Various effects of magnetite on international simple glass (ISG) dissolution: implications for the long-term durability of nuclear glasses
Authors: Neill Lindsey , Gin Stéphane , Ducasse Thomas , De Echave Trilce , Fournier Maxime , Jollivet Patrick , Gourgiotis Alkiviadis , Wall Nathalie A. 
Published: July 2017

AbstractUnderstanding the effect of near-field materials, such as iron corrosion products, on the alteration of vitreous nuclear waste is essential for modeling long-term stability of these waste forms in a geological repository. This work presents experimental results for which monoliths of International Simple Glass—a six oxide borosilicate glass–, with polished and unpolished cut sides, were aged for 70 days under oxic conditions at 90 °C in a solution initially saturated in 29SiO2 at pH 7; then magnetite was added to the leaching environment. Solution and solid analyses were performed to correlate the changes in the surface features and dissolution kinetics. It was found that magnetite primarily influences the mechanically constrained surface of the non-polished sides of the monoliths, with little to no effect on the polished surfaces. This work highlights the importance of the unique chemistry within surface cracks that invokes a drastic change in alteration of glass in environments containing iron corrosion products.
Knockdown of anion exchanger 2 suppressed the growth of ovarian cancer cells via mTOR/p70S6K1 signaling
Authors: Zhang Li-Jun , Lu Renquan , Song Ya-Nan , Zhu Jian-Yong , Xia Wei , Zhang Miao , Shao Zhi-Yi , Huang Yan , Zhou Yuqi , Zhang Hongqin , Guo Lin , Zhang Meiqin , Zhang Hong 
Published: July 2017

AbstractAnion exchanger 2 (AE2, encoded by SLC4A2) is a sodium-independent chloride/bicarbonate transporter and implicated in the regulation of intracellular pH and membrane potential. Previous studies have linked AE2 to the tumorigenesis of various cancers. Here, AE2 was identified as an up-regulated protein in ovarian cancer tissues compared to adjacent non-tumor lesions based on quantitative proteomics analysis. AE2 mRNA was also overexpressed in human ovarian cancer samples, and that AE2 overexpression correlated with the shortened survival time of ovarian cancer patients. Short-hairpin RNA-mediated knockdown of AE2 in A2780 and SK-OV-R3 cells inhibited cell growth and induced cell cycle G1 phase arrest. In nude mice, its stable knockdown inhibited the tumorigenicity of A2780 cells. Gene set enrichment analysis on The Cancer Genome Atlas dataset identified that the cell cycle process and mTOR pathway were correlatively with the AE2 expression. Expression of key regulators of G1/S transition (Cyclin D1 and CDK4), and phosphorylation levels of p70S6K were notably reduced in AE2 knockdown cells. Moreover, experiments with mTOR inhibitor suggested that AE2 may promote cell cycle progression through mTOR/p70S6K1 pathway. Together, our results suggest up-regulated AE2 promotes ovarian cancer tumorigenesis by activating mTOR/p70S6K1 pathway and implicate the potential application of AE2 in cancer therapy.
The healing of alveolar bone defects with novel bio-implants composed of Ad-BMP9-transfected rDFCs and CHA scaffolds
Authors: Nie Li , Yang Xia , Duan Liang , Huang Enyi , Pengfei Zhou , Luo Wenping , Zhang Yan , Zeng Xingqi , Qiu Ye , Cai Ting , Li Conghua 
Published: July 2017

AbstractCells, scaffolds, and growth factors play important roles in bone regeneration. Bone morphogenetic protein 9 (BMP9), a member of BMP family, could facilitate osteogenesis by regulating growth factors and promoting angiogenesis. Similar to other stem cells, rat dental follicle stem cells (rDFCs), the precursor cells of cementoblasts, osteoblasts and periodontal ligament cells, can self-renew and exhibit multipotential capacity. Coralline hydroxyapatite (CHA) has good biocompatibility and conductivity required for bone tissue engineering. Here, we reported that BMP9 could enhance the osteogenic differentiation of rDFCs in cell culture. Moreover, our results suggested that BMP9 acted through the Smad1/5/8 signaling pathway. We also produced a novel scaffold that encompasses bio-degradable CHA seeded with recombinant adenoviruses expressing BMP9-transfected rDFCs (Ad-BMP9-transfected rDFCs). With this implant, we achieved more alveolar bone regeneration in the alveolar bone defect compared to blank group, CHA group and rDFCs group. Our results provided a novel bio-implants composed of Ad-BMP9-transfected rDFCs and CHA scaffolds and its mechanism is regarding the activation of Smad1/5/8 signaling pathway in BMP9-induced rDFCs osteogenesis.