bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sodium tanshinone IIA sulfonate prevents hypoxic trophoblast‐induced endothelial cell dysfunction via targeting HMGB1 release
Authors: Zhao Min , Feng Yaling , Xiao Jianping , Liang Jie , Yin Yongxiang , Chen Daozhen 
Published: February 2017

AbstractPreeclampsia (PE) is a serious blood pressure disorder of pregnancy. Systemic endothelial cell dysfunction, a hallmark of PE, is previously estimated to be induced by hypoxic trophoblast high mobility group box 1 (HMGB1). In the present study, we investigated the protective effect of sodium tanshinone IIA sulfonate (STS), the soluble form of tanshinone IIA isolated from danshen, against hypoxic trophoblast HMGB1‐induced human umbilical vein endothelial cell (HUVEC) dysfunction. Our results showed that HMGB1 expression and release were significantly decreased in STS‐treated hypoxic JEG‐3 cells. A further study revealed hypoxic trophoblast HMGB1‐induced cytotoxicity and leukostasis of HUVEC as well as higher expression of cell adhesion molecules (VCAM‐1 and ICAM‐1) could be reversed by pretreatment with STS. In conclusion, our study suggests that STS is an effective agent against hypoxic trophoblast‐induced cell injury of HUVEC via targeting HMGB1 release and forms the basis of the development of such a compound in treating PE.
Evaluation of smear layer removal and marginal adaptation of root canal sealer after final irrigation using ethylenediaminetetraacetic, peracetic, and etidronic acids with different concentrations
Authors: Ulusoy Özgür İlke , Zeyrek Salev , Çelik Bülent 
Published: February 2017

AbstractThe purpose of this study was to investigate the effects of different irrigation solutions on the smear layer removal and marginal adaptation of a resin‐based sealer to root canal dentine. A total of 152 instrumented roots were irrigated with the following irrigants: 9,18% etidronic acid (HEBP), 0.5, 1,2% peracetic acid (PAA), 17% ethylenediaminetetraacetic acid (EDTA), saline. The amount of smear layer was evaluated using scanning electron microscope (SEM) in seventy root samples. Eighty‐two roots were filled with AH Plus and gutta‐percha. Slices obtained from apical third of each specimen were viewed with SEM to assess marginal adaptation. Use of 9% and 18% HEBP resulted in more efficient smear layer removal in the apical third than the other chelators (p < 0.05). Higher smear layer scores in the coronal and middle thirds were obtained from 0.5%, 1% PAA groups. Regarding marginal adaptation, 18% HEBP group showed the lowest gap size values (p < 0.05), and better marginal adaptation. Etidronic acid is a promising candidate for final irrigation of root canals.
Constructing a Family of 4‐Critical Planar Graphs with High Edge Density
Authors: Yao Tianxing , Zhou Guofei 
Published: February 2017

AbstractA graph is a k‐critical graph if G is not ‐colorable but every proper subgraph of G is ‐colorable. In this article, we construct a family of 4‐critical planar graphs with n vertices and edges. As a consequence, this improves the bound for the maximum edge density attained by Abbott and Zhou. We conjecture that this is the largest edge density for a 4‐critical planar graph.
A Robust Method to Generate Mechanically Anisotropic Vascular Smooth Muscle Cell Sheets for Vascular Tissue Engineering
Authors: Backman Daniel E. , LeSavage Bauer L. , Shah Shivem B. , Wong Joyce Y. 
Published: February 2017

In arterial tissue engineering, mimicking native structure and mechanical properties is essential because compliance mismatch can lead to graft failure and further disease. With bottom‐up tissue engineering approaches, designing tissue components with proper microscale mechanical properties is crucial to achieve the necessary macroscale properties in the final implant. This study develops a thermoresponsive cell culture platform for growing aligned vascular smooth muscle cell (VSMC) sheets by photograftingN‐isopropylacrylamide (NIPAAm) onto micropatterned poly(dimethysiloxane) (PDMS). The grafting process is experimentally and computationally optimized to produce PNIPAAm–PDMS substrates optimal for VSMC attachment. To allow long‐term VSMC sheet culture and increase the rate of VSMC sheet formation, PNIPAAm–PDMS surfaces were further modified with 3‐aminopropyltriethoxysilane yielding a robust, thermoresponsive cell culture platform for culturing VSMC sheets. VSMC cell sheets cultured on patterned thermoresponsive substrates exhibit cellular and collagen alignment in the direction of the micropattern. Mechanical characterization of patterned, single‐layer VSMC sheets reveals increased stiffness in the aligned direction compared to the perpendicular direction whereas nonpatterned cell sheets exhibit no directional dependence. Structural and mechanical anisotropy of aligned, single‐layer VSMC sheets makes this platform an attractive microstructural building block for engineering a vascular graft to match the in vivo mechanical properties of native arterial tissue.image
Frequency of GBA Variants in Autopsy‐proven Multiple System Atrophy
Authors: Sklerov Miriam , Kang Un J. , Liong Christopher , Clark Lorraine , Marder Karen , Pauciulo Michael , Nichols William C. , Chung Wendy K. , Honig Lawrence S. , Cortes Etty , Vonsattel Jean Paul , Alcalay Roy N. 
Published: February 2017

AbstractBackgroundMultiple system atrophy (MSA) is marked by abnormal inclusions of α‐synuclein in oligodendrogliocytes, and its etiology remains unknown. Variants in the glucocerebrosidase (GBA) gene have been associated with the other synucleinopathies, dementia with Lewy bodies, and Parkinson's disease. It is unclear whether glucocerebrosidase variants are associated with MSA. The objective of this study was to analyze the frequency of GBA variants among patients who had autopsy‐proven MSA at a brain bank in New York City.MethodsGBA was fully sequenced in brain tissues from 17 patients with autopsy‐proven MSA for whom there was extractable DNA at the Columbia University New York Brain Bank from 2002 to 2016. To test whether brains from patients with MSA were enriched for GBA variants, the frequency of GBA variants in the MSA brains was compared with that of variants in all brains from patients with pure Alzheimer's disease (AD) at Columbia University for which GBA genotype was available (n = 82).ResultsOf 17 MSA brains, 4 carried GBA variants (23.5%), including 1 that was homozygous for N370S and 1 each that carried heterozygous N370S, T369M, and R496H variants. Among the comparator brains with pure AD, 3 of 82 (3.7%) carried GBA variants (P = 0.0127; Fisher exact test), including 1 each with an N370S homozygous variant, an R496H heterozygous variant, and a T369M heterozygous variant.ConclusionA higher frequency of GBA variants was observed among brains from patients who had pathologically diagnosed MSA compared with the frequency of variants in brains from patients who had AD. The results indicate a need for further investigation into the role of glucocerebrosidase and lysosomal dysfunction in the etiology of MSA.
Comparison between anterolateral thigh, radial forearm, and peroneal artery flap donor site thickness in Asian patients—A sonographic study
Authors: Hsu Kuei‐Chang , Tsai Wei‐Hsuan , Ting Pei‐San , Hsueh Jung‐Hua , Chen Lee‐Wei , Lin Ying‐Sheng 
Published: February 2017

PurposeThis study aimed to determine the thicknesses of the three locations used as donor sites for radial forearm (RF), anterolateral thigh (ALT), and peroneal flaps and to determine probable contributing factors of the thickness.MethodsThis study included 201 healthy participants (mean age: 45.8 ± 17.2 years; male: 114; female: 87; BMI: 24.3 ± 4.3). Sonography was used to measure the thickness of flap donor sites. Forward stepwise regressions were conducted to determine the contributing factors of flap thickness.ResultsThe RF flap (0.28 ± 0.08 cm) was thinner than peroneal flap (0.47 ± 0.17 cm) (P < 0.0001), and peroneal flap was thinner than ALT flap (0.98 ± 0.4 cm) (P < 0.0001). Flap type (P < 0.001, 95%CI: 0.33–0.41), BMI (P < 0.001, 95%CI: 0.02–0.033), gender (P < 0.001, 95%CI: −0.3 to −0.17), and age (P = 0.002, 95%CI: −0.005 to −0.001) were the contributing factors of flap thickness. In the subgroup analysis, BMI was the only contributing factor of RF flap thickness (P < 0.001). For ALT and peroneal flaps, age, gender, and BMI were the contributing factors (P < 0.001). The coefficient of BMI was 0.005 in RF flap, 0.01 in peroneal flap, and 0.04 in ALT flap.ConclusionsThe RF flap was found thinner than peroneal flap, and peroneal flap was found thinner than ALT flap. The BMI effects on RF and peroneal flaps were much less than that on ALT flap. Therefore, the RF and peroneal flaps would be the better choice in obese patients with soft tissue defects where a thin flap is needed.
Geometry calibration method for a cone‐beam CT system
Authors: Yang Hongkai , Kang Kejun , Xing Yuxiang 
Published: February 2017

PurposeThe positioning accuracy of each component is important to ensure the image quality of cone‐beam CT. However, accurate positioning is not easy and requires experience and time. The option is to calibrate the geometric parameters and then plug them into a reconstruction algorithm which is the preferred solution in practice. In this case, the image quality is determined by the accuracy and precision of the calibration method. This work describes a method to independently calibrate an imaging system in each pose (projection angle) for a cone‐beam CT with a nonideal circular trajectory.MethodsThe calibration method uses a phantom with 12 beads on 2 planes that are observed on the radiographic images. This pose‐independent calibration method (PIC) can decorrelate the relationships among the geometric parameters so that the parameters can be estimated one‐by‐one. This simplifies the calibration process. Besides the pose‐independent calibration method, this paper also describes an extended calibration method with additional constraints on the system geometry. Both methods are validated with numerical simulations and then experimentally on a practical system with a scanning object loosely supported by rotating wheels. The object rotates during the CT data acquisition. The angular and pose information of the CT system are not accurately known a priori in this case.ResultsThe numerical simulations and the experiments both provide satisfactory results. The relative error of the calibrated source‐to‐detector distance in the simulation is less than 0.1%. The errors in the calibrated roll, pitch, and yaw angles are less than 0.04°. A sensitivity study using various bead position uncertainties in random directions shows that the pose‐independent calibration method is robust to measurement errors. Tests were also done with a nonideal circular trajectory for further validation. Images reconstructed using the geometric parameters from both the pose‐independent and the extended calibration methods were free of artifacts and blur from misalignment. All these results demonstrate the effectiveness of these methods.ConclusionsThe PIC method can be used to independently calibrate the geometric parameters of a cone‐beam CT view‐by‐view. Thus, the PIC method can be implemented on commonly used systems such as circular, nonideal circular or C‐arm cone‐beam CTs. The PIC method can also be useful for some irregularly configured CT systems to fulfill special imaging requirements, for example, a CT system when the x ray source or the rotating platform cannot be easily located. The PIC method will reduce the costs of ensuring very precise mechanics and the labor in fine tuning CT systems.
The critical role of the ZNF217 oncogene in promoting breast cancer metastasis to the bone
Authors: Bellanger Aurélie , Donini Caterina F , Vendrell Julie A , Lavaud Jonathan , Machuca‐Gayet Irma , Ruel Maëva , Vollaire Julien , Grisard Evelyne , Győrffy Balázs , Bièche Ivan , Peyruchaud Olivier , Coll Jean‐Luc , Treilleux Isabelle , Maguer‐Satta Véronique , Josserand Véronique , Cohen Pascale A 
Published: February 2017

AbstractBone metastasis affects >70% of patients with advanced breast cancer. However, the molecular mechanisms underlying this process remain unclear. On the basis of analysis of clinical datasets, and in vitro and in vivo experiments, we report that the ZNF217 oncogene is a crucial mediator and indicator of bone metastasis. Patients with high ZNF217 mRNA expression levels in primary breast tumours had a higher risk of developing bone metastases. MDA‐MB‐231 breast cancer cells stably transfected with ZNF217 (MDA‐MB‐231‐ZNF217) showed the dysregulated expression of a set of genes with bone‐homing and metastasis characteristics, which overlapped with two previously described ‘osteolytic bone metastasis’ gene signatures, while also highlighting the bone morphogenetic protein (BMP) pathway. The latter was activated in MDA‐MB‐231‐ZNF217 cells, and its silencing by inhibitors (Noggin and LDN‐193189) was sufficient to rescue ZNF217‐dependent cell migration, invasion or chemotaxis towards the bone environment. Finally, by using non‐invasive multimodal in vivo imaging, we found that ZNF217 increases the metastatic growth rate in the bone and accelerates the development of severe osteolytic lesions. Altogether, the findings of this study highlight ZNF217 as an indicator of the emergence of breast cancer bone metastasis; future therapies targeting ZNF217 and/or the BMP signalling pathway may be beneficial by preventing the development of bone metastases. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Prenatal diagnosis of congenital cytomegalovirus infection in 115 cases: a 5 years' single center experience
Authors: Enders M. , Daiminger A. , Exler S. , Ertan K. , Enders G. , Bald R. 
Published: February 2017

AbstractObjectiveThe objective of this study is to investigate the diagnostic value of invasive prenatal diagnosis (PD) of congenital cytomegalovirus (CMV) infection from amniotic fluid (AF) and fetal blood (FB).MethodsA retrospective study was conducted on 115 pregnancies with CMV primary infection. A total of 111 AF and 106 FB samples were investigated for various virological and non‐virological markers. Detailed ultrasound examinations were performed at time of PD.ResultsOverall sensitivity of CMV PCR in FB (75.6%; 95%CI 60–87) and AF (72.7%; 95%CI 57–85) was comparable. In women with amniocentesis >8 weeks between seroconversion and PD, we did not observe significant differences between amniocentesis performed ≥17 + 0 (sensitivity 90.9%; 95%CI 71–99) and ≥20 + 0 gestational weeks (sensitivity 90.0%; 95%CI 68–99). Virological markers in FB were higher in symptomatic compared with asymptomatic fetuses (p < 0.05). No significant differences were observed for non‐virological markers. However, platelet counts <120 × 10e9/L and beta‐2 microglobulin values >14 mg/L were more frequently found in fetuses with severe ultrasound abnormalities compared with fetuses with no or mild abnormalities (p < 0.001).ConclusionOptimal timing of amniocentesis in women with primary infection in early gestation should be reevaluated in a prospective study. Analysis of FB markers may be beneficial in the individual management of pregnant women with confirmed congenital CMV infection. © 2017 John Wiley & Sons, Ltd.
Molecular dynamics simulation study of the “stay or leave” problem for two magnesium ions in gene transcription
Authors: Wu Shaogui 
Published: February 2017

ABSTRACTTwo magnesium ions play important roles in nucleotide addition cycle (NAC) of gene transcription. However, at the end of each NAC, why does one ion stay in the active site while the other ion leaves with product pyrophosphate (PPi)? This problem still remains obscure. In this work, we studied the problem using all‐atom molecular dynamics simulation combined with steered molecular dynamics and umbrella sampling simulation methods. Our simulations reveal that although both ions are located in the active site after chemistry, their detailed positions are not symmetrical, leading to their different forces from surrounding groups. One ion makes weaker contacts with PPi than the whole protein. Hence, PPi release is less likely to take it away. The other one forms tighter contacts with PPi relative to the protein. The formed (Mg2+‐PPi)2− complex is found to break the contacts with surrounding protein residues one by one so as to dissociate from the active site. This effectively avoids the coexistence of two ions in the active site after PPi release and guarantees a reasonable Mg2+ ion number in the active site for the next NAC. The observations from this work can provide valuable information for comprehensively understanding the molecular mechanism of transcription. Proteins 2017; 85:1002–1007. © 2017 Wiley Periodicals, Inc.
Statistical issues in first‐in‐human studies on BIA 10‐2474: Neglected comparison of protocol against practice
Authors: Bird Sheila M. , Bailey Rosemary A. , Grieve Andrew P. , Senn Stephen 
Published: February 2017

By setting the regulatory‐approved protocol for a suite of first‐in‐human studies on BIA 10‐2474 against the subsequent French investigations, we highlight 6 key design and statistical issues, which reinforce recommendations by a Royal Statistical Society Working Party, which were made in the aftermath of cytokine release storm in 6 healthy volunteers in the United Kingdom in 2006.The 6 issues are dose determination, availability of pharmacokinetic results, dosing interval, stopping rules, appraisal by safety committee, and clear algorithm required if combining approvals for single and multiple ascending dose studies.
Potency of Human Cardiosphere-Derived Cells from Patients with Ischemic Heart Disease Is Associated with Robust Vascular Supportive Ability
Authors: Harvey Emma , Zhang Huajun , Sepúlveda Pilar , Garcia Sara P. , Sweeney Dominic , Choudry Fizzah A. , Castellano Delia , Thomas George N. , Kattach Hassan , Petersen Romina , Blake Derek J. , Taggart David P. , Frontini Mattia , Watt Suzanne M. , Martin-Rendon Enca 
Published: February 2017

Abstract
Cardiosphere-derived cell (CDC) infusion into damaged myocardium has shown some reparative effect; this could be improved by better selection of patients and cell subtype. CDCs isolated from patients with ischemic heart disease are able to support vessel formation in vitro but this ability varies between patients. The primary aim of our study was to investigate whether the vascular supportive function of CDCs impacts on their therapeutic potential, with the goal of improving patient stratification. A subgroup of patients produced CDCs which did not efficiently support vessel formation (poor supporter CDCs), had reduced levels of proliferation and increased senescence, despite them being isolated in the same manner and having a similar immunophenotype to CDCs able to support vessel formation. In a rodent model of myocardial infarction, poor supporter CDCs had a limited reparative effect when compared to CDCs which had efficiently supported vessel formation in vitro. This work suggests that not all patients provide cells which are suitable for cell therapy. Assessing the vascular supportive function of cells could be used to stratify which patients will truly benefit from cell therapy and those who would be better suited to an allogeneic transplant or regenerative preconditioning of their cells in a precision medicine fashion. This could reduce costs, culture times and improve clinical outcomes and patient prognosis.
Authenticated encryption: how reordering can impact performance
Authors: Alomair Basel 
Published: February 2017

AbstractIn this work, we look at authenticated encryption schemes from a new perspective. As opposed to focusing solely on the “security” implications of the different methods for constructing authenticated encryption schemes, we investigate the effect of the method used to construct an authenticated encryption scheme on the “performance” of the construction. We show that, as opposed to the current National Institute of Standards and Technology standard, by performing the authentication operation before the encryption operation, the computational efficiency of the construction can be increased, without affecting the security of the overall construction. In fact, we show that the proposed construction is even more secure than standard authentication based on universal hashing in the sense that the hashing key is resilient to key recovery attacks. Copyright © 2017 John Wiley & Sons, Ltd.
Concise Review: An (Im)Penetrable Shield: How the Tumor Microenvironment Protects Cancer Stem Cells
Authors: Relation Theresa , Dominici Massimo , Horwitz Edwin M. 
Published: February 2017

AbstractCancer stem cells (CSCs) are defined by their unlimited self-renewal ability and their capacity to initiate and maintain malignancy, traits that are not found in most cells that comprise the tumor. Although current cancer treatments successfully reduce tumor burden, the tumor will likely recur unless CSCs are effectively eradicated. This challenge is made greater by the protective impact of the tumor microenvironment (TME), consisting of infiltrating immune cells, endothelial cells, extracellular matrix, and signaling molecules. The TME acts as a therapeutic barrier through immunosuppressive, and thereby tumor-promoting, actions. These factors, outside of the cancer cell lineage, work in concert to shelter CSCs from both the body's intrinsic anticancer immunity and pharmaceutical interventions to maintain cancer growth. Emerging therapies aimed at the TME offer a promising new tool in breaking through this shield to target the CSCs, yet definitive treatments remain unrealized. In this review, we summarize the mechanisms by which CSCs are protected by the TME and current efforts to overcome these barriers.
Temporal-Spatial Establishment of Initial Niche for the Primary Spermatogonial Stem Cell Formation Is Determined by an ARID4B Regulatory Network
Authors: Wu Ray-Chang , Zeng Yang , Chen Yu-Fang , Lanz Rainer B. , Wu Mei-Yi 
Published: February 2017

Abstract
During neonatal testis development, centrally located gonocytes migrate to basement membrane of the seminiferous cords, where physical contact with a niche established by Sertoli cells is essential for transition of gonocytes into spermatogonial stem cells (SSCs). To provide structural support and signaling stimuli for the gonocyte-to-SSC transition that occurs at a specific location during a finite phase, temporal-spatial establishment of the niche is critical. To date, the factors that guide Sertoli cells to establish the initial stem cell niche remain largely unknown. Using the Sertoli cell-specific Arid4b knockout (Arid4bSCKO) mice, we demonstrated that ablation of AT-rich interaction domain 4B (ARID4B) resulted in abnormal detachment of Sertoli cells from the basement membrane of seminiferous cords during the gonocyte-to-SSC transition phase, suggesting failure to establish a niche for the SSC formation. Without support by a niche environment, gonocytes showed disarranged cell distribution in the Arid4bSCKO testes and underwent apoptosis. The commitment of gonocytes to differentiate into the spermatogonial lineage was broken and the capability of SSCs to self-renew and differentiate was also impaired. Gene expression profiling revealed the molecular mechanisms responsible for the phenotypic changes in the Arid4bSCKO testes, by identifying genes important for stem cell niche function as downstream effectors of ARID4B, including genes that encode gap junction protein alpha-1, KIT ligand, anti-Müllerian hormone, Glial cell-line derived neurotrophic factor, inhibin alpha, inhibin beta, and cytochrome P450 family 26 subfamily b polypeptide 1. Our results identified ARID4B as a master regulator of a signaling network that governs the establishment of a niche during the critical gonocyte-to-SSC transition phase to control the fate of gonocytes and SSCs.