bluuebunny/crossref_metadata_2025_split huggingface dataset:
NOTCH signaling pathway is required for bovine early embryonic development
Authors: Li Shuang , Shi Yan , Dang Yanna , Luo Lei , Hu Bingjie , Wang Shaohua , Wang Huanan , Zhang Kun 
Published: March 2021

AbstractThe NOTCH signaling pathway plays an important role in regulating various biological processes, including lineage specification and apoptosis. Multiple components of the NOTCH pathway have been identified in mammalian preimplantation embryos. However, the precise role of the NOTCH pathway in early embryonic development is poorly understood, especially in large animals. Here, we show that the expression of genes encoding key transcripts of the NOTCH pathway is dynamic throughout early embryonic development. We also confirm the presence of active NOTCH1 and RBPJ. By using pharmacological and RNA interference tools, we demonstrate that the NOTCH pathway is required for the proper development of bovine early embryos. This functional consequence could be partly attributed to the major transcriptional mediator, Recombination Signal Binding Protein For Immunoglobulin Kappa J Region (RBPJ), whose deficiency also compromised the embryo quality. Indeed, both NOTCH1 and RBPJ knockdown cause a significant increase of histone H3 serine 10 phosphorylation (pH3S10, a mitosis marker) positive blastomeres, suggesting a cell cycle arrest at mitosis. Importantly, RNA sequencing analyses reveal that either NOTCH1 or RBPJ depletion triggers a reduction in H1FOO that encodes the oocyte-specific linker histone H1 variant. Interestingly, depleting H1FOO results in detrimental effects on the developmental competence of early embryos, similar with NOTCH1 inhibition. Overall, our results reveal a crucial role for NOTCH pathway in regulating bovine preimplantation development, likely by controlling cell proliferation and maintaining H1FOO expression.
Implementation of Two Chromatographic Methods for Simultaneous Quantitation of Thioctic Acid, Benfotiamine and Cyanocobalamin
Authors: Abbas Samah S , Badawey Amr M , Bakr Maryam A , Hegazy Maha A 
Published: March 2021

Abstract
Two accurate and sensitive chromatographic methods have been introduced and validated for the simultaneous determination of thioctic acid, benfotiamine and cyanocobalamin in bulk powders and in their pharmaceutical formulation. Method A is reversed-phase ultra performance liquid chromatographic method with an isocratic elution, where a rapid separation was accomplished on a Zorbax C8 column using a mobile phase of acetonitrile:0.05 M phosphate buffer (pH 6 adjusted by o-phosphoric acid) (23:77, v/v). The retention times (tR) were 0.578, 0.852 and 1.376 for cyanocobalamin, benfotiamine and thioctic acid, respectively. The separated peaks were revealed at 210.0 nm. Method B is a thin-layer densitometric method where the separation of the studied drugs was carried out on silica gel plates using methanol–chloroform–heptane-1-sulphonic acid sodium salt (0.4%) (7:3:0.1, by volume) as a mobile phase, and scanning of the separated bands was done at 240.0 nm. The retardation factor (Rf) values were 0.17, 0.48 and 0.75 for cyanocobalamin, benfotiamine and thioctic acid, respectively. Validation of the methods was achieved following ICH guidelines and the applied methods succeeded to determine the cited drugs in their pure forms and capsules. Results were statistically compared to the manufacturer’s method where no significant difference was observed.
Perianal Fistula-Associated Carcinoma in Crohn’s Disease: A Multicentre Retrospective Case Control Study
Authors: Palmieri Chiara , Müller Gerhard , Kroesen Anton J , Galata Christian , Rink Andreas D , Morgenstern Julia , Kruis Wolfgang 
Published: March 2021

Abstract

Background and Aims
Carcinoma associated with perianal fistula in Crohn’s disease is a pending threat for patients. This study aimed to improve understanding and facilitate development of diagnostic and therapeutic strategies.

Methods
A retrospective case-control study was conducted at four German hospitals. The analysis included 40 patients with proven malignancy associated with perianal Crohn’s fistulas and 40 randomly selected controls with fistulizing perianal Crohn’s disease. Differences between groups were analysed and multivariate calculations were performed to describe risk factors for oncological outcomes.

Results
Histology revealed adenocarcinoma in 33/40 patients and squamous cell carcinoma in 7/40 patients. Compared to fistula patients without carcinoma, patients with malignancies associated with fistula had a diagnosis of Crohn’s disease at younger age. Crohn’s disease lasted longer in patients with malignancy [25.8 ± 9.0 vs 19.6 ± 10.4; p = 0.006]. Fistula-related findings differed significantly between the two groups. Signs of complicated and severe fistulation including complex anatomy and chronic activity occurred significantly more often in patients with malignancy associated with fistula. Significant multivariate hazard ratios for overall mortality and progression-free survival were shown for histological type of cancer, metastatic disease and R1 resection. Overall survival was 45.1 ± 28.6 months and the 5-year survival rate was 65%.

Conclusions
In patients with adenocarcinoma or squamous cell carcinoma associated with perianal fistula in Crohn’s disease, fistula characteristics determine the risk of malignancy. Early diagnosis influences outcomes, while treatment of chronic fistula activity may be key to preventing malignancy. Expert multimodal therapy is paramount for successful treatment of perianal fistula-associated malignancies.
The impact of vascularized tissue flap coverage on aortic graft infection with and without infected graft excision
Authors: Shijo Takayuki , Matsuda Hitoshi , Yokawa Koki , Inoue Yosuke , Seike Yoshimasa , Uehara Kyokun , Takahara Mitsuyoshi , Sasaki Hiroaki 
Published: March 2021

Abstract

OBJECTIVES
Aortic graft infection (AGI) is a serious condition associated with a high mortality rate. However, optimal surgical options have not been identified. Therefore, we retrospectively reviewed AGI cases, including those in the thoracic and abdominal regions, with or without fistula formation, to investigate the various options for better outcomes.

METHODS
We reviewed 50 patients who underwent surgical interventions for AGI out of 97 patients with arterial infective disease. The mean patient age was 67 ± 17 years. Fourteen patients (28%) had a fistula with the gastrointestinal tract or lung. A combination of graft excision and vascularized tissue flap coverage was performed in 25 cases (50%). Tissue flap alone, graft excision alone and cleansing alone were performed in 9 (18%), 10 (20%), and 6 cases (12%), respectively.

RESULTS
Total in-hospital mortality rate was 32% (n = 16). In-hospital mortalities in patients with and without fistulas were 43% (6/14) and 28% (10/36), respectively (P = 0.33). Subgroup analysis among patients without fistula demonstrated that the in-hospital mortality rate of the patients with vascularized tissue flap (3/21, 14%) was significantly lower than that of the patients without vascularized tissue flap (7/14, 50%, P = 0.026). Overall 1- and 5-year survival rates were 66% and 46%, respectively. In multivariable analysis, an independent factor associated with in-hospital mortality was vascularized tissue flap (odds ratio 0.20, P = 0.024).

CONCLUSIONS
Vascularized tissue flaps could provide better outcomes for AGI. Graft preservation with vascularized tissue flaps could be a useful option for AGI without fistula.
Detecting sex-linked genes using genotyped individuals sampled in natural populations
Authors: Käfer Jos , Lartillot Nicolas , Marais Gabriel A B , Picard Franck 
Published: March 2021

Abstract
We propose a method, SDpop, able to infer sex-linkage caused by recombination suppression typical of sex chromosomes. The method is based on the modeling of the allele and genotype frequencies of individuals of known sex in natural populations. It is implemented in a hierarchical probabilistic framework, accounting for different sources of error. It allows statistical testing for the presence or absence of sex chromosomes, and detection of sex-linked genes based on the posterior probabilities in the model. Furthermore, for gametologous sequences, the haplotype and level of nucleotide polymorphism of each copy can be inferred, as well as the divergence between them. We test the method using simulated data, as well as data from both a relatively recent and an old sex chromosome system (the plant Silene latifolia and humans) and show that, for most cases, robust predictions are obtained with 5 to 10 individuals per sex.
A chromosome-level genome assembly for the Pacific oyster Crassostrea gigas
Authors: Peñaloza Carolina , Gutierrez Alejandro P , Eöry Lél , Wang Shan , Guo Ximing , Archibald Alan L , Bean Tim P , Houston Ross D 
Published: March 2021

Abstract

Background
The Pacific oyster (Crassostrea gigas) is a bivalve mollusc with vital roles in coastal ecosystems and aquaculture globally. While extensive genomic tools are available for C. gigas, highly contiguous reference genomes are required to support both fundamental and applied research. Herein we report the creation and annotation of a chromosome-level assembly for C. gigas.

Findings
High-coverage long- and short-read sequence data generated on Pacific Biosciences and Illumina platforms were used to generate an initial assembly, which was then scaffolded into 10 pseudo-chromosomes using both Hi-C sequencing and a high-density linkage map. The assembly has a scaffold N50 of 58.4 Mb and a contig N50 of 1.8 Mb, representing a step advance on the previously published C. gigas assembly. Annotation based on Pacific Biosciences Iso-Seq and Illumina RNA-Seq resulted in identification of ∼30,000 putative protein-coding genes. Annotation of putative repeat elements highlighted an enrichment of Helitron rolling-circle transposable elements, suggesting their potential role in shaping the evolution of the C. gigas genome.

Conclusions
This new chromosome-level assembly will be an enabling resource for genetics and genomics studies to support fundamental insight into bivalve biology, as well as for selective breeding of C. gigas in aquaculture.
Discovery and fine-mapping of kidney function loci in first genome-wide association study in Africans
Authors: Fatumo Segun , Chikowore Tinashe , Kalyesubula Robert , Nsubuga Rebecca N , Asiki Gershim , Nashiru Oyekanmi , Seeley Janet , Crampin Amelia C , Nitsch Dorothea , Smeeth Liam , Kaleebu Pontiano , Burgess Stephen , Nyirenda Moffat , Franceschini Nora , Morris Andrew P , Tomlinson Laurie , Newton Robert 
Published: March 2021

Abstract
Genome-wide association studies (GWAS) of kidney function have uncovered hundreds of loci, primarily in populations of European ancestry. We have undertaken the first continental African GWAS of estimated glomerular filtration rate (eGFR), a measure of kidney function used to define chronic kidney disease (CKD). We conducted GWAS of eGFR in 3288 East Africans from the Uganda General Population Cohort (GPC) and replicated in 8224 African Americans from the Women’s Health Initiative. Loci attaining genome-wide significant evidence for association (P &lt; 5 × 10−8) were followed up with Bayesian fine-mapping to localize potential causal variants. The predictive power of a genetic risk score (GRS) constructed from previously reported trans-ancestry eGFR lead single nucleotide polymorphism (SNPs) was evaluated in the Uganda GPC. We identified and validated two eGFR loci. At the glycine amidinotransferase (GATM) locus, the association signal (lead SNP rs2433603, P = 1.0 × 10−8) in the Uganda GPC GWAS was distinct from previously reported signals at this locus. At the haemoglobin beta (HBB) locus, the association signal (lead SNP rs141845179, P = 3.0 × 10−8) has been previously reported. The lead SNP at the HBB locus accounted for 88% of the posterior probability of causality after fine-mapping, but did not colocalise with kidney expression quantitative trait loci. The trans-ancestry GRS of eGFR was not significantly predictive into the Ugandan population. In the first GWAS of eGFR in continental Africa, we validated two previously reported loci at GATM and HBB. At the GATM locus, the association signal was distinct from that previously reported. These results demonstrate the value of performing GWAS in continental Africans, providing a rich genomic resource to larger consortia for further discovery and fine-mapping. The study emphasizes that additional large-scale efforts in Africa are warranted to gain further insight into the genetic architecture of CKD.
Pricing foreign exchange options under a hybrid Heston-Cox-Ingersoll-Ross model with regime switching
Authors: He Xin-Jiang , Chen Wenting 
Published: March 2021

Abstract
In this paper, the pricing of foreign exchange options is considered under a modified Heston–Cox–Ingersoll–Ross hybrid model. This modified model reserves all the characteristics of the Heston–Cox–Ingersoll–Ross model and also additionally assumes regime switching in the key parameters of the volatility as well as the domestic and foreign interest rates. Even though complicated, we have derived a closed-form pricing formula for foreign exchange options after the affinity of this new model is verified. Various properties of the newly derived formula are also shown through numerical experiments. To show the performance of this newly proposed model, an empirical study is also conducted, the result of which suggests that our model is a good alternative to the Heston–Cox–Ingersoll–Ross model for practical purpose.
Numerical analysis of a wave equation for lossy media obeying a frequency power law
Authors: Baker Katherine , Banjai Lehel 
Published: March 2021

Abstract
We study a wave equation with a nonlocal time fractional damping term that models the effects of acoustic attenuation characterized by a frequency-dependent power law. First we prove the existence of a unique solution to this equation with particular attention paid to the handling of the fractional derivative. Then we derive an explicit time-stepping scheme based on the finite element method in space and a combination of convolution quadrature and second-order central differences in time. We conduct a full error analysis of the mixed time discretization and in turn the fully space-time discretized scheme. Error estimates are given for both smooth solutions and solutions with a singularity at $t = 0$ of a type that is typical for equations involving fractional time derivatives. A number of numerical results are presented to support the error analysis.
Uniform Hölder-norm bounds for finite element approximations of second-order elliptic equations
Authors: Diening Lars , Scharle Toni , Süli Endre 
Published: March 2021

Abstract
We develop a discrete counterpart of the De Giorgi–Nash–Moser theory, which provides uniform Hölder-norm bounds on continuous piecewise affine finite element approximations of second-order linear elliptic problems of the form $-\nabla \cdot (A\nabla u)=f-\nabla \cdot F$ with $A\in L^\infty (\varOmega ; {{\mathbb{R}}}^{n\times n})$ a uniformly elliptic matrix-valued function, $f\in L^{q}(\varOmega )$, $F\in L^p(\varOmega ; {{\mathbb{R}}}^n)$, with $p&gt; n$ and $q&gt; n/2$, on $A$-nonobtuse shape-regular triangulations, which are not required to be quasi-uniform, of a bounded polyhedral Lipschitz domain $\varOmega \subset {{\mathbb{R}}}^n$.
Isolated Singularities of Solutions to the Yamabe Equation in Dimension 6
Authors: Xiong J , Zhang L 
Published: March 2021

AbstractWe study the asymptotic behavior of local solutions to the Yamabe equation near an isolated singularity, when the metric is not conformally flat. We prove that, in dimension 6, any solution is asymptotically close to a Fowler solution, which is an extension of the same result for lower dimensions by F.C. Marques in 2008.
Determination of Tetracycline Using Ultrasound-Assisted Dispersive Liquid–Liquid Microextraction Based on Solidification of Floating Organic Droplet Followed by HPLC–UV System
Authors: Rahimi Moghadam Mojtaba , Zargar Behrooz , Rastegarzadeh Saadat 
Published: March 2021

Abstract

Background
Tetracyclines (TCs) are a group of broad-spectrum antibiotics that may be used to control bacterial diseases in humans or are applied as feed additives to enhance growth in farm animals. TCs are released into the aquatic environment via different pathways. Many analytical methods combined with a preconcentration step have been introduced for the determination of TC in various environmental samples.

Objective
The objective this paper is developing reliable analytical methods for determination of TC trace in various environmental samples.

Method
In the present work, combined ultrasound-assisted and dispersive liquid–liquid microextraction according to the solidification of floating organic drop as a sample preconcentration procedure for determining TC hydrochloride HPLC in water and serum samples was used.

Results
A series of parameters, including the type and volume of disperser and extraction solvents, salt effect, extraction time, and pH of solution influencing the extraction efficiency of UA-DLLME-SFO was examined. Enrichment factors were in the range of 125–137 for TC hydrochloride under optimum conditions. The linear range was calculated from 0.005 to 3 mg/L and LOD at 0.002 mg/L. RSDs were in the range of 2.7 to 3.2 (n = 5). The UA-DLLME-SFO method used in water and serum samples revealed good extraction recoveries with RSD of 2.7–4.3%.

Conclusions
This method significantly decreased the organic solvent volume from 3 mL to 90 µL, also LOD and linear ranges were lower than or almost close to levels obtained in other research studies. In this procedure, an ultrasound bath enhanced the mixing and contact between the sample solution and the extraction solvent.
Online Advertising Suppresses Visual Competition during Planned Purchases
Authors: van der Lans Ralf , Pieters Rik , Wedel Michel 
Published: March 2021

Abstract
Online advertising can help consumers to implement their purchase intentions on shopping websites. This research tests the hypothesis that online advertising can speed-up product search by visually suppressing competing products rather than by enhancing the target product on websites that lack a systematic visual organization. First, a survey shows that searching for products on a shopping website after having clicked on an online ad is a common experience. Second, a lay-theory experiment shows that the majority of participants incorrectly predict that online ads do not affect product search, but if these ads do, product search would be independent of shopping website design. Third, three eye-tracking and two search-time experiments reveal that online ads with an image of the target product improved search speed by about 25%, for websites without a systematic visual organization of products. Improved search speed was primarily due to faster rejection of competing products because the ads helped to perceptually suppress their color features. These results provide new insights into online advertising effects, the fundamental search processes through which these accrue, and how ads can support consumers in making their planned purchases.
Why Ideal Epistemology?
Authors: Carr Jennifer Rose 
Published: March 2021

Abstract
Ideal epistemologists investigate the nature of pure epistemic rationality, abstracting away from human cognitive limitations. Non-ideal epistemologists investigate epistemic norms that are satisfiable by most humans, most of the time. Ideal epistemology faces a number of challenges, aimed at both its substantive commitments and its philosophical worth. This paper explains the relation between ideal and non-ideal epistemology, with the aim of justifying ideal epistemology. Its approach is meta-epistemological, focusing on the meaning and purpose of epistemic evaluations. I provide an account on which the fundamental difference between ideal and non-ideal epistemic evaluations is that only the non-ideal epistemic ‘ought’ implies any substantive ‘can’. I argue that only ideal epistemic evaluations are ‘normatively robust’: they are neither conventional nor seriously context-sensitive. Non-ideal epistemic evaluations are normatively non-robust, exhibiting both conventionality and serious context-sensitivity from an interesting variety of distinct sources. For this reason, non-ideal epistemic evaluations won’t characterize the fundamental nature of epistemic rationality. Non-ideal epistemic rationality depends, not merely on what’s epistemically valuable, but also on modally contingent epistemic conventions and contextually contingent constraints on epistemic options. If we want a normatively robust theory of epistemic rationality, ideal epistemology is the only game in town.
BIMG-04. MAPPING HETEROGENEITY OF HIGH-GRADE GLIOMA METABOLISM USING HIGH RESOLUTION 7T MRSI
Authors: Hangel Gilbert , Cadrien Cornelius , Lazen Philipp , Sharma Sukrit , Furtner Julia , Lipka Alexandra , Heckova Eva , Hingerl Lukas , Motyka Stanislav , Gruber Stephan , Strasser Bernhard , Kiesel Barbara , Mischkulnig Mario , Preusser Matthias , Roetzer Thomas , Wöhrer Adelheid , Widhalm Georg , Rössler Karl , Trattnig Siegfried , Bogner Wolfgang 
Published: March 2021

Abstract

OBJECTIVES
Neurosurgical resection in gliomas depends on the precise preoperative definition of the tumor and its margins to realize a safe maximum resection that translates into a better patient outcome. New metabolic imaging techniques could improve this delineation as well as designate targets for biopsies. We validated the performance of our fast high-resolution whole-brain 3D-magnetic resonance spectroscopic imaging (MRSI) method at 7T in high-grade gliomas (HGGs) as first step to this regard.

METHODS
We measured 23 patients with HGGs at 7T with MRSI covering the whole cerebrum with 3.4mm isotropic resolution in 15 min. Quantification used a basis-set of 17 neurochemical components. They were evaluated for their reliability/quality and compared to neuroradiologically segmented tumor regions-of-interest (necrosis, contrast-enhanced, non-contrast-enhanced+edema, peritumoral) and histopathology (e.g., grade, IDH-status).

RESULTS
We found 18/23 measurements to be usable and ten neurochemicals quantified with acceptable quality. The most common denominators were increases of glutamine, glycine, and total choline as well as decreases of N-acetyl-aspartate and total creatine over most tumor regions. Other metabolites like taurine and serine showed mixed behavior. We further found that heterogeneity in the metabolic images often continued into the peritumoral region. While 2-hydroxy-glutarate could not be satisfyingly quantified, we found a tendency for a decrease of glutamate in IDH1-mutant HGGs.

DISCUSSION
Our findings corresponded well to clinical tumor segmentation but were more heterogeneous and often extended into the peritumoral region. Our results corresponded to previous knowledge, but with previously not feasible resolution. Apart from glycine/glutamine and their role in glioma progression, more research on the connection of glutamate and others to specific mutations is necessary. The addition of low-grade gliomas and statistical ROI analysis in a larger cohort will be the next important steps to define the benefits of our 7T MRSI approach for the definition of spatial metabolic tumor profiles.