bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polyethylenimine: A new differentiation factor to endothelial/cardiac tissue
Authors: Hosseinzadeh Simzar , Nazari Hojjatollah , Sadegzadeh Negar , Babaie Ali , Kabiri Mahboubeh , Tasharrofi Noshin , Soufi Zomorrod Mahsa , Soleimani Masoud 
Published: September 2018

AbstractAmong different tissues, endothelial/cardiac types require specific factors to promote myocardial regeneration after occurred injuries. Herein, cardiac stem cells (CSCs) as the major cell population that involved in cardiovascular repair were selected to study the role of polyethyleneimine (PEI) agent on endothelial differentiation. After preparation of electrospun network of PEI with polyacrylonitrile, the related characterizations were carried out including scanning electron microscope (SEM), field‐emission SEM, water contact angle, Fourier transform infrared spectroscopy and mechanical properties. Also, the release kinetic of the corresponding agent was studied up to 7 days. The cell differentiation studies were done in the following with 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide assay, Real‐time polymerase chain reaction and immunostaining method. The whole obtained results approved the higher differentiation of CSCs into endothelial/cardiac cells. Finally, it is recommended that the PEI delivering increases the healing potency of CSCs and accordingly the regeneration speed of damaged cardiovascular tissue would be improved.
Association between PTCH1 and RAD54B single‐nucleotide polymorphisms and non‐syndromic orofacial clefts in a northern Chinese population
Authors: Liu Xiaotong , Yang Shaoyou , Meng Lingwei , Chen Chunyu , Hui Xiang , Jiang Yuxin , Jiao Xiaohui , Lv Kewen , Song Tao 
Published: September 2018

AbstractBackgroundNon‐syndromic orofacial clefts (NSOC) is one of the most common congenital malformations, and its etiology involves both genetic and environmental factors. The present aimed to investigate the association of six single nucleotide polymorphisms (SNPs) (rs10512248 in PTCH1, rs12681366 and rs958447 in RAD54B, rs13317 in FGFR1, rs1838105 and rs4968247 in WNT9B) with NSOC in a Northern Chinese population.MethodsIn the present study, HI‐SNP technology was used to conduct genotyping of the six SNPs (rs10512248, rs12681366, rs957448, rs13317, rs1838105 and rs4968247) in 596 patients with NSOC and 466 healthy individuals from a Northern Chinese population.ResultsThe results obtained indicated that rs10512248 and rs12681366 minor allele frequencies were statistically significant (p = 0.020 and 0.015, respectively). Statistical analysis confirmed that the CT genotype of RAD54B rs12681366 was associated with a decreased risk of NSOC (odds ratio = 0.62, 95% confidence interval = 0.46–0.82, P = 0.001). After correcting for multiple testing, the associations remained significant. By contrast, nonsignificant differences were found for the rs957448, rs13317, rs1838105 and rs4968247 allele and genotype frequencies between cases and controls.ConclusionsThese results demonstrate that the PTCH1 rs10512248 and RAD54B rs12681366 were significantly associated with NSOC in a Northern Chinese population. Additionally, the RAD54B rs12381366 CT genotype could decrease the risk of NSOC in a Northern Chinese population. We provide novel evidence for the development of NSOC in a Northern Chinese population.
Polyphenolic natural products and natural product–inspired steroidal mimics as aromatase inhibitors
Authors: Nielsen Alexander J. , McNulty James 
Published: September 2018

AbstractThe discovery of biologically active polyphenolic natural products, including chalcones, stilbenes, flavanones, and isoflavones as steroidal mimics has proven to be a subject of considerable importance in medicine. Some of these natural compounds have been shown to modulate key human metabolic processes via steroidal hormone receptors, or to inhibit crucial enzymes involved in the biosynthesis of steroidal hormones themselves. Isoflavone polyphenolics such as genistein are well known for this “phytoestrogenic” biological activity. This review focuses on the ability of select polyphenolics and their synthetic derivatives to function as steroidal mimics in the inhibition of the enzyme aromatase, thereby lowering production of endogenous estrogen growth hormones. The discovery of potent, natural product–based aromatase inhibitors (AIs) as hit compounds has led to the introduction of steroidal‐based irreversible inhibitors, such as exemestane and reversible AIs such as anastrozole and letrozole, now standard therapy in the treatment of estrogen receptor–positive breast cancer and other hormone related indications. Pursuit of this strategy over the last few decades has been largely successful although complications and challenges remain. This review highlights the aromatase activity of natural stilbenes, chalcones, and flavanones and synthetically inspired versions thereof and draws attention to new and under‐investigated areas within each class worthy of pursuit.
Progress in the application of CRISPR: From gene to base editing
Authors: Wu Wenyi , Yang Yanhui , Lei Hetian 
Published: September 2018

AbstractThe system of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR‐associated endonucleases (Cas) has been utilized for genome editing with great accuracy and high efficiency in generating gene knockout, knockin, and point mutations in eukaryotic genomes. However, traditional CRISPR/Cas9 technology introduces double‐stranded DNA breaks (DSBs) at a target locus as the first step to make gene corrections, which easily results in undesired mutations. Thus, it is necessary to develop new methods for correcting the unwanted mutations. In this review, we summarize the recent developments and a new approach to genome and base editing by using CRISPR/Cas9. This methodology renders a conversion of one target base into another, for example, C to T (or G to A), and A to G (or T to C) without producing DSBs, requiring a donor DNA template, or generating excessive insertions and deletions. Furthermore, CRISPR/Cas9‐derived base editing also improves efficiency in repairing point mutations in the genome.
Impact of prenatal diagnosis of complex congenital heart disease on neonatal and infant morbidity and mortality
Authors: Chakraborty Abhishek , Gorla Sudheer R. , Swaminathan Sethuraman 
Published: September 2018

AbstractObjectivesThe objective of this study was to analyze the benefits associated with prenatal diagnosis of complex congenital heart disease (CHD) on preoperative morbidity, 30‐day and 1‐year mortality in this population.MethodThis was a retrospective review of patients with complex CHD born at our tertiary care center over a 10‐year period. Date analysis using Student t test and chi‐square test.ResultsThe overall rate of prenatal detection of complex CHD was 68.1%. A steady increase in the number of complex CHD diagnosed prenatally was noted during the study period. The prenatal diagnosis of complex CHD was associated with significant reduction in the incidence of the following preoperative parameters: antibiotic use, mechanical ventilation, inotropic support, hepatic and renal dysfunction, and acidosis. These beneficial effects were more significant in ductal‐dependent cardiac anomalies. However, there were no neonatal and infant survival benefits in association with prenatal diagnosis.ConclusionPrenatal diagnosis of complex CHD leads to improved preoperative morbidity, especially in patients with ductal‐dependent cardiac anomalies. No survival benefits were noted with prenatal diagnosis of complex CHD.
Ethical and counseling challenges in prenatal exome sequencing
Authors: Harris Sarah , Gilmore Kelly , Hardisty Emily , Lyerly Anne Drapkin , Vora Neeta L. 
Published: September 2018

AbstractObjectiveEthical and counseling challenges are expected with the introduction of prenatal whole exome sequencing. In this study, we describe specific challenges identified through the UNC‐Chapel Hill Prenatal Exome Sequencing Study.MethodsParticipants were a subset of women participating in the fetal exome study, which has enrolled 73 mother‐father‐fetus trios in pregnancies diagnosed with structural anomalies and normal standard genetic testing results. In this descriptive study, cases were reviewed by members of the research team, including a bioethicist, to identify counseling challenges. Illustrative cases were chosen by group consensus.ResultsFour illustrative cases were identified for further analysis. Challenges included need for adequate counseling and informed consent, challenges in prenatal variant interpretation, performing prenatal diagnosis in subsequent pregnancies, inability to identify a genetic etiology, and identifying parental secondary findings.ConclusionOur study illustrates several challenges identified in an ongoing prenatal exome study. While genomic medicine is a powerful tool for prenatal diagnosis, it is important that clinicians understand the ethical implications and parental perceptions of this testing modality.
Barrier Properties and Transcriptome Expression in Human iPSC-Derived Models of the Blood–Brain Barrier
Authors: Delsing Louise , Dönnes Pierre , Sánchez José , Clausen Maryam , Voulgaris Dimitrios , Falk Anna , Herland Anna , Brolén Gabriella , Zetterberg Henrik , Hicks Ryan , Synnergren Jane 
Published: September 2018

Abstract
Cell-based models of the blood–brain barrier (BBB) are important for increasing the knowledge of BBB formation, degradation and brain exposure of drug substances. Human models are preferred over animal models because of interspecies differences in BBB structure and function. However, access to human primary BBB tissue is limited and has shown degeneration of BBB functions in vitro. Human induced pluripotent stem cells (iPSCs) can be used to generate relevant cell types to model the BBB with human tissue. We generated a human iPSC-derived model of the BBB that includes endothelial cells in coculture with pericytes, astrocytes and neurons. Evaluation of barrier properties showed that the endothelial cells in our coculture model have high transendothelial electrical resistance, functional efflux and ability to discriminate between CNS permeable and non-permeable substances. Whole genome expression profiling revealed transcriptional changes that occur in coculture, including upregulation of tight junction proteins, such as claudins and neurotransmitter transporters. Pathway analysis implicated changes in the WNT, TNF, and PI3K-Akt pathways upon coculture. Our data suggest that coculture of iPSC-derived endothelial cells promotes barrier formation on a functional and transcriptional level. The information about gene expression changes in coculture can be used to further improve iPSC-derived BBB models through selective pathway manipulation.
Open-string T-duality and applications to non-geometric backgrounds
Authors: Cordonier-Tello Fabrizio , Lüst Dieter , Plauschinn Erik 
Published: September 2018

Abstract

We revisit T-duality transformations for the open string via Buscher’s procedure and work-out technical details which have been missing so far in the literature. We take into account non-trivial topologies of the world-sheet, we consider T-duality along directions with Neumann as well as Dirichlet boundary conditions, and we include collective T-duality along multiple directions.
We illustrate this formalism with the example of the three-torus with H-flux and its T-dual backgrounds, and we discuss global properties of open-string boundary conditions on such spaces.
Inferences of Mantle Viscosity Based on Ice Age Data Sets: The Bias in Radial Viscosity Profiles Due to the Neglect of Laterally Heterogeneous Viscosity Structure
Authors: Lau H. C. P. , Austermann J. , Mitrovica J. X. , Crawford O. , Al‐Attar D. , Latychev K. 
Published: September 2018

AbstractInferences of mantle viscosity using glacial isostatic adjustment (GIA) data are hampered by data sensitivity to the space‐time geometry of ice cover. A subset of GIA data is relatively insensitive to this ice history: the Fennoscandian relaxation spectrum (FRS), postglacial decay times in Canada and Scandinavia, and the rate of change of the degree‐2 zonal harmonic of the geopotential (
). These geographically limited data have been inverted to constrain the radial (one‐dimensional [1D]) mantle viscosity profile. We explore potential biases in these 1D inversions introduced by neglecting a three‐dimensional (3D) viscosity structure. We perform 1D Bayesian inversions of synthetic GIA data generated from Earth models with realistic 3D variations in mantle viscosity and lithospheric thickness and compare results to the 1D viscosity profile associated with the 3D model used to generate the synthetics. Differences between these two 1D profiles reflect GIA data resolution and biasing introduced by neglecting, in the inversions, a 3D viscosity structure. We focus on the second issue, demonstrating that the largest bias occurs within the upper mantle (in particular, the transition zone). This remains consistent when varying inversion parameters (e.g., prior/starting models) and the 1D/3D viscosity fields adopted in generating the synthetics. Inversions of individual data sets show 3D biasing increases for data exhibiting shallower (thus more localized) sensitivity to viscosity. Of the data considered herein, inversions of the FRS are subject to the largest bias followed by decay time data. The bias is minimal for
, as its deeper sensitivity is accompanied by broader averaging of structure in radial and lateral directions.
Agricultural Microcredit for Tenant Farmers: Evidence from a Field Experiment in Bangladesh
Authors: Hossain Marup , Malek Mohammad Abdul , Hossain Md. Amzad , Reza Md. Hasib , Ahmed Md. Shakil 
Published: September 2018

AbstractWe study the impact of an agricultural microcredit program on the livelihoods of small, marginal, and landless tenant farmers in Bangladesh based on a Randomized Control Trial (RCT). Twenty percent of eligible households acquire at least one loan from the program within two years of the start of the intervention. Results show that access to credit has positive but imprecisely estimated effects on adoption of modern varieties (MV) of rice as well as rice yield. The microcredit program increases crop farm income but has no significant effect on total income or expenditure. Although the program does not have a significant effect on most economic outcomes, it demonstrates an increase in farm activities among the targeted farmers. Our study suggests that facilitating access to credit without addressing other constraints may not be enough to increase investment and profits of tenant farmers.
Developing and validating the Personal Risk of Oncogenic Human Papillomavirus infection score in US Women
Authors: Thai Thuy N , Bui Thanh C , Ebell Mark H 
Published: September 2018

Abstract

Background
Determining risk scores for genital high-risk human papillomavirus (HRHPV) infection in women will support more efficient cervical cancer screening strategies.

Objective
We developed and validated point scores to predict the likelihood of any genital HRHPV infection in women.

Methods
We conducted the cross-sectional analysis in 2017 and used data from the 2005–14 US National Health and Nutrition Examination Survey (7337 women aged 25–59 years; 6300 women aged 30–59 years). Predictors were reproductive health practices, risk behaviors and demographic variables. The outcome was a positive result for any of the 21 genital HRHPV genotypes. The 2005–12 cohorts were used as training and testing sets to develop scores that best classified women into three risk groups: low risk (<20%), average risk (20–30%) and high risk (>30%). The 2013–14 cohort was used to validate the final scores.

Results
Two-point scores with six self-reported variables were created to predict any HRHPV risks for the two age groups: the Personal Risk of Oncogenic HPV (PRO-HPV25) for women aged 25–59 years old and PRO-HPV30 for women aged 30–59 years old. The scores were successfully prospectively validated, with good calibration with regards to the predicted and observed rates of HRHPV infection. The scores had fair discrimination (c-statistics: 0.67–0.68).

Conclusion
The PRO-HPV risk scores can identify groups at low, average and high risk of genital HRHPV infection. This information can be used to prioritize women for cervical cancer screening in low-resource settings or to personalize screening intervals.
Normative Uncertainty and Social Choice
Authors: Tarsney Christian 
Published: September 2018

AbstractIn ‘Normative Uncertainty as a Voting Problem’, William MacAskill argues that positive credence in ordinal-structured or intertheoretically incomparable normative theories does not prevent an agent from rationally accounting for her normative uncertainties in practical deliberation. Rather, such an agent can aggregate the theories in which she has positive credence by methods borrowed from voting theory—specifically, MacAskill suggests, by a kind of weighted Borda count. The appeal to voting methods opens up a promising new avenue for theories of rational choice under normative uncertainty. The Borda rule, however, is open to at least two serious objections. First, it seems implicitly to ‘cardinalize’ ordinal theories, and so does not fully face up to the problem of merely ordinal theories. Second, the Borda rule faces a problem of option individuation. MacAskill attempts to solve this problem by invoking a measure on the set of practical options. But it is unclear that there is any natural way of defining such a measure that will not make the output of the Borda rule implausibly sensitive to irrelevant empirical features of decision-situations. After developing these objections, I suggest an alternative: the McKelvey uncovered set, a Condorcet method that selects all and only the maximal options under a strong pairwise defeat relation. This decision rule has several advantages over Borda and mostly avoids the force of MacAskill’s objection to Condorcet methods in general.
We Have No Reason to Think There Are No Reasons for Affective Attitudes
Authors: Faraci David 
Published: September 2018

Abstract
Barry Maguire argues that there are no reasons for affective attitudes. ‘There is no reason for your incredulous reaction to’ this thesis, he claims. In this paper, I argue that we have no reason to accept his thesis. I first examine Maguire's purported differences between reasons for action and so-called reasons for affective attitudes. In each case, I argue that the differences are exaggerated and that to the extent they obtain, they are best explained by differences between actions and affective attitudes, not between kinds of normative support. In closing, I argue that even if Maguire were correct, the extent of the threat to one of his central targets—so-called ‘buck-passing’ views—would remain unclear.
Minimum star-forming halo mass in axion cosmology
Authors: Sullivan James M , Hirano Shingo , Bromm Volker 
Published: September 2018

ABSTRACT
Elucidating the particle physics nature of dark matter (DM) is one of the great challenges in modern science. The current lack of any direct DM detections in the laboratory heightens the need for astrophysical constraints, extending the search to DM models beyond the popular weakly interacting massive particle scenario. We here apply the classical Rees–Ostriker–Silk cooling criterion for galaxy formation to models with ultralight axion DM, also known as fuzzy dark matter (FDM). The resulting constraints provide a heuristic framework for upcoming observations, and our approximate analysis motivates the need for future self-consistent simulations of FDM structure formation. We use observational constraints for the DM hosts of ultra-faint dwarf (UFD) galaxies in the Local Group, together with the redshift constraints for the onset of primordial star formation from the recent EDGES 21-cm cosmology measurement, to illustrate this approach. We find that the existing constraints are straightforward to reconcile with standard ΛCDM, but disfavour FDM axion masses below ${\sim } 10^{-21}\, {\rm eV}/c^2$. The future potential for harnessing astrophysical probes of DM particle physics is compelling.
Synergy with TGFß ligands switches WNT pathway dynamics from transient to sustained during human pluripotent cell differentiation
Authors: Masseya Joseph , Liua Yida , Alvarengaa Omar , Saeza Teresa , Schmerera Matthew , Warmflasha Aryeh 
Published: September 2018

AbstractWNT/ß-catenin signaling is crucial to all stages of life. It controls early morphogenetic events in embryos, maintains stem-cell niches in adults, and is disregulated in many types of cancer. Despite its ubiquity, little is known about the dynamics of signal transduction or whether it varies across contexts. Here we probe the dynamics of signaling by monitoring nuclear accumulation of ß-catenin, the primary transducer of canonical WNT signals, using quantitative live-cell imaging. We show that ß-catenin signaling responds adaptively to constant WNT signaling in pluripotent stem cells, and that these dynamics become sustained upon differentiation. Varying dynamics were also observed in the response to WNT in commonly used mammalian cell-lines. Signal attenuation in pluripotent cells is controlled by both intra- and extra-cellular negative regulation of WNT signaling. TGFß-superfamily ligands Activin and BMP, which coordinate with WNT signaling to pattern the gastrula, increase the ß-catenin response in a manner independent of their ability to induce new WNT-ligand production. Our results reveal how variables external to the pathway, including differentiation status and crosstalk with other pathways, dramatically alter WNT/ß-catenin dynamics.
Polyploid plants have faster rates of multivariate climatic niche evolution than their diploid relatives
Authors: Baniaga Anthony E. , Marx Hannah E. , Arrigo Nils , Barker Michael S. 
Published: September 2018

AbstractWhole genome duplication is an important evolutionary process in plants. In contrast to other speciation mechanisms, polyploid species begin with substantial postzygotic reproductive isolation from progenitors while being sympatric with one or both. These nascent polyploid species often go extinct due to ecological and evolutionary genetic obstacles. Interestingly, polyploid species appear to quickly occupy different geographic distributions and ecological niches than their diploid progenitors. Using biogeographic data from polyploid and diploid species representing 49 genera of vascular plants, we tested whether climatic niches of polyploid species evolve faster than their diploid relatives. We found polyploid species often have less climatic overlap than expected with diploid progenitors. Consistent with this pattern, we estimated that the climatic niches of polyploid plants consistently evolved faster than the niches of diploid relatives. Our results indicate ecological niche differentiation is important for polyploid establishment, and suggest ecological differentiation is important for speciation processes more widely.Statement of AuthorshipAB and MS conceived of project, AB and NA generated the dataset, AB and HM performed analyses, AB and MS cowrote manuscript.Data Accessibility StatementUpon acceptance all necessary R scripts, data, and files supporting the results will be archived on FigShare with the data DOI included at the end of the article.