bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of RICTOR amplification in targeted therapy and drug resistance
Authors: Zhao Deze , Jiang Man , Zhang Xiaochun , Hou Helei 
Published: February 2020

AbstractThe emergence of tyrosine kinase inhibitors (TKIs) has changed the current treatment paradigm and achieved good results in recent decades. However, an increasing number of studies have indicated that the complex network of receptor tyrosine kinase (RTK) co-activation could influence the characteristic phenotypes of cancer and the tumor response to targeted treatments. One of strategies to blocking RTK co-activation is targeting the downstream factors of RTK, such as PI3K-AKT-mTOR pathway. RICTOR, a core component of mTORC2, acts as a key effector molecule of the PI3K-AKT pathway; its amplification is often associated with poor clinical outcomes and resistance to TKIs. Here, we discuss the biology of RICTOR in tumor and the prospects of targeting RICTOR as a complementary therapy to inhibit RTK co-activation.
Position within the hospital and role in the emergency department of emergency physicians in the Netherlands: a national survey
Authors: Coppes Sarah , Veugelers Rebekka , Hessels Roger A. P. A. , van den Brand Crispijn L. , Gaakeer Menno I. 
Published: February 2020

AbstractObjectivesEmergency medicine (EM) in the Netherlands has developed rapidly and initially without central guidance. This has led to heterogeneity in current EM practice. Our aim was to quantify this heterogeneity by answering the following questions: (1) What is the current position of emergency physicians (EPs) within hospital organizations? (2) Which roles and responsibilities do EPs have across emergency departments (EDs)?MethodsDuring 2018, we conducted a survey among all EM consultant bodies (CBs,n = 56) in the Netherlands. Data was analyzed using descriptive statistics.ResultsThe response rate was 91.1%. Presence of EPs has been realized 24/7 in 23.1% of EDs. EPs were the main consultants for all ED patients in 9.8% of CBs, but never had this role in 13.7% of CBs. EPs supervised EM junior doctors in 78.5% of EDs, GPs in training in 80.0% of EDs, and junior doctors of other specialties in 41.5% of EDs. Procedures such as lumbar puncture (LP), procedural sedation and analgesia (PSA), and emergency ultrasound (US) were performed by all EPs in the CB in a range between 5.9 and 78.4%. In 36.9% of EDs, EPs did not analyze patients with presumed cardiac pathology due to a separateFirst Heart Aid.ConclusionWe conclude that there is a high degree of heterogeneity between emergency CBs in regard to the position in the hospital and the role or responsibilities in the ED. Lack of uniformity might inhibit emancipation of the profession.
Influence of seat-belt use on the severity of injury in traffic accidents
Authors: Febres Juan Diego , García-Herrero Susana , Herrera Sixto , Gutiérrez J. M. , López-García J. R. , Mariscal Miguel A. 
Published: February 2020

Abstract
Background
About 1.35 million people died in traffic accidents around the world in 2018, make this type of accidents the 8th cause of death in the world. Particularly, in Spain, there were 204,596 traffic accidents during 2016 and 2017, out of which 349,810 drivers were injured. The objective of this study was to understand to what extent seat belt non-use and human factors contribute to drivers injury severity.

Methodology
The results are based on the information and 2016–17 data provided by the Spain national traffic department “Dirección General de Tráfico” (DGT). The discretization model and Bayesian Networks were developed based on important variables from the literature. These variables were classified as; human factor, demographic factor, conditioning factor and seat belt use.

Results
The results showed that failure to wear the seat belt by drivers are likely to increase the risk of fatal and sever injury significantly. Moreover, distraction and road type road can contribute to the accident severity.
SeqBreed: a python tool to evaluate genomic prediction in complex scenarios
Authors: Pérez-Enciso Miguel , Ramírez-Ayala Lino C. , Zingaretti Laura M. 
Published: February 2020

AbstractBackgroundGenomic prediction (GP) is a method whereby DNA polymorphism information is used to predict breeding values for complex traits. Although GP can significantly enhance predictive accuracy, it can be expensive and difficult to implement. To help design optimum breeding programs and experiments, including genome-wide association studies and genomic selection experiments, we have developed SeqBreed, a generic and flexible forward simulator programmed in python3.ResultsSeqBreed accommodates sex and mitochondrion chromosomes as well as autopolyploidy. It can simulate any number of complex phenotypes that are determined by any number of causal loci. SeqBreed implements several GP methods, including genomic best linear unbiased prediction (GBLUP), single-step GBLUP, pedigree-based BLUP, and mass selection. We illustrate its functionality with Drosophila genome reference panel (DGRP) sequence data and with tetraploid potato genotype data.ConclusionsSeqBreed is a flexible and easy to use tool that can be used to optimize GP or genome-wide association studies. It incorporates some of the most popular GP methods and includes several visualization tools. Code is open and can be freely modified. Software, documentation, and examples are available athttps://github.com/miguelperezenciso/SeqBreed.
Deep learning improves the ability of sgRNA off-target propensity prediction
Authors: Liu Qiaoyue , Cheng Xiang , Liu Gan , Li Bohao , Liu Xiuqin 
Published: February 2020

Abstract
Background
CRISPR/Cas9 system, as the third-generation genome editing technology, has been widely applied in target gene repair and gene expression regulation. Selection of appropriate sgRNA can improve the on-target knockout efficacy of CRISPR/Cas9 system with high sensitivity and specificity. However, when CRISPR/Cas9 system is operating, unexpected cleavage may occur at some sites, known as off-target. Presently, a number of prediction methods have been developed to predict the off-target propensity of sgRNA at specific DNA fragments. Most of them use artificial feature extraction operations and machine learning techniques to obtain off-target scores. With the rapid expansion of off-target data and the rapid development of deep learning theory, the existing prediction methods can no longer satisfy the prediction accuracy at the clinical level.

Results
Here, we propose a prediction method named CnnCrispr to predict the off-target propensity of sgRNA at specific DNA fragments. CnnCrispr automatically trains the sequence features of sgRNA-DNA pairs with GloVe model, and embeds the trained word vector matrix into the deep learning model including biLSTM and CNN with five hidden layers. We conducted performance verification on the data set provided by DeepCrispr, and found that the auROC and auPRC in the “leave-one-sgRNA-out” cross validation could reach 0.957 and 0.429 respectively (the Pearson value and spearman value could reach 0.495 and 0.151 respectively under the same settings).

Conclusion
Our results show that CnnCrispr has better classification and regression performance than the existing states-of-art models. The code for CnnCrispr can be freely downloaded from https://github.com/LQYoLH/CnnCrispr.
Phylogeographic history of flat periwinkles, Littorina fabalis and L. obtusata
Authors: Sotelo Graciela , Duvetorp Mårten , Costa Diana , Panova Marina , Johannesson Kerstin , Faria Rui 
Published: February 2020

AbstractBackgroundThe flat periwinkles,Littorina fabalisandL. obtusata, are two sister species widely distributed throughout the Northern Atlantic shores with high potential to inform us about the process of ecological speciation in the intertidal. However, whether gene flow has occurred during their divergence is still a matter of debate. A comprehensive assessment of the genetic diversity of these species is also lacking and their main glacial refugia and dispersal barriers remain largely unknown. In order to fill these gaps, we sequenced two mitochondrial genes and two nuclear fragments to perform a phylogeographic analysis of flat periwinkles across their distribution range.ResultsWe identified two main clades largely composed by species-specific haplotypes corresponding toL. obtusataandL. fabalis, with moderate to strong support, respectively. Importantly, a model of divergence with gene flow between the two species (fromL. obtusata to L. fabalis) was better supported, both in Iberia and in northern-central Europe. Three mitochondrial clades were detected withinL. fabalisand two withinL. obtusata, with strong divergence between Iberia and the remaining populations. The largest component of the genetic variance within each species was explained by differences between geographic regions associated with these clades. Our data suggests that overall intraspecific genetic diversity is similar between the two flat periwinkle species and that populations from Iberia tend to be less diverse than populations from northern-central Europe.ConclusionsThe phylogeographic analysis of this sister-species pair supports divergence with gene flow. This system thus provides us with the opportunity to study the contribution of gene flow and natural selection during diversification. The distribution of the different clades suggests the existence of glacial refugia in Iberia and northern-central Europe for both species, with a main phylogeographic break between these regions. Although the genetic diversity results are not fully conclusive, the lower diversity observed in Iberia could reflect marginal conditions at the southern limit of their distribution range during the current interglacial period.
Genomic measures of inbreeding coefficients and genome-wide scan for runs of homozygosity islands in Iranian river buffalo, Bubalus bubalis
Authors: Ghoreishifar Seyed Mohammad , Moradi-Shahrbabak Hossein , Fallahi Mohammad Hossein , Jalil Sarghale Ali , Moradi-Shahrbabak Mohammad , Abdollahi-Arpanahi Rostam , Khansefid Majid 
Published: February 2020

AbstractBackgroundConsecutive homozygous fragments of a genome inherited by offspring from a common ancestor are known as runs of homozygosity (ROH). ROH can be used to calculate genomic inbreeding and to identify genomic regions that are potentially under historical selection pressure. The dataset of our study consisted of 254 Azeri (AZ) and 115 Khuzestani (KHZ) river buffalo genotyped for ~ 65,000 SNPs for the following two purposes: 1) to estimate and compare inbreeding calculated using ROH (FROH), excess of homozygosity (FHOM), correlation between uniting gametes (FUNI), and diagonal elements of the genomic relationship matrix (FGRM); 2) to identify frequently occurring ROH (i.e. ROH islands) for our selection signature and gene enrichment studies.ResultsIn this study, 9102 ROH were identified, with an average number of 21.2 ± 13.1 and 33.2 ± 15.9 segments per animal in AZ and KHZ breeds, respectively. On average in AZ, 4.35% (108.8 ± 120.3 Mb), and in KHZ, 5.96% (149.1 ± 107.7 Mb) of the genome was autozygous. The estimated inbreeding values based on FHOM, FUNIand FGRMwere higher in AZ than they were in KHZ, which was in contrast to the FROHestimates. We identified 11 ROH islands (four in AZ and seven in KHZ). In the KHZ breed, the genes located in ROH islands were enriched for multiple Gene Ontology (GO) terms (P ≤ 0.05). The genes located in ROH islands were associated with diverse biological functions and traits such as body size and muscle development (BMP2), immune response (CYP27B1), milk production and components (MARS, ADRA1A, and KCTD16), coat colour and pigmentation (PMEL and MYO1A), reproductive traits (INHBC, INHBE, STAT6 and PCNA), and bone development (SUOX).ConclusionThe calculated FROHwas in line with expected higher inbreeding in KHZ than in AZ because of the smaller effective population size of KHZ. Thus, we find that FROHcan be used as a robust estimate of genomic inbreeding. Further, the majority of ROH peaks were overlapped with or in close proximity to the previously reported genomic regions with signatures of selection. This tells us that it is likely that the genes in the ROH islands have been subject to artificial or natural selection.
Transcriptional profiling and physiological roles of Aedes aegypti spermathecal-related genes
Authors: Pascini Tales Vicari , Ramalho-Ortigão Marcelo , Ribeiro José Marcos , Jacobs-Lorena Marcelo , Martins Gustavo Ferreira 
Published: February 2020

AbstractBackgroundSuccessful mating of female mosquitoes typically occurs once, with the male sperm being stored in the female spermatheca for every subsequent oviposition event. The female spermatheca is responsible for the maintenance, nourishment, and protection of the male sperm against damage during storage.Aedes aegyptiis a major vector of arboviruses, including Yellow Fever, Dengue, Chikungunya, and Zika. Vector control is difficult due to this mosquito high reproductive capacity.ResultsFollowing comparative RNA-seq analyses of spermathecae obtained from virgin and inseminated females, eight transcripts were selected based on their putative roles in sperm maintenance and survival, including energy metabolism, chitin components, transcriptional regulation, hormonal signaling, enzymatic activity, antimicrobial activity, and ionic homeostasis. In situ RNA hybridization confirmed tissue-specific expression of the eight transcripts. Following RNA interference (RNAi), observed outcomes varied between targeted transcripts, affecting mosquito survival, egg morphology, fecundity, and sperm motility within the spermathecae.ConclusionsThis study identified spermatheca-specific transcripts associated with sperm storage inAe. aegypti. Using RNAi we characterized the role of eight spermathecal transcripts on various aspects of female fecundity and offspring survival. RNAi-induced knockdown of transcriptAeSigP-66,427,coding for a Na+/Ca2+protein exchanger, specifically interfered with egg production and reduced sperm motility. Our results bring new insights into the molecular basis of sperm storage and identify potential targets forAe. aegypticontrol.
A combined microRNA and transcriptome analyses illuminates the resistance response of rice against brown planthopper
Authors: Tan Jiaoyan , Wu Yan , Guo Jianping , Li Huimin , Zhu Lili , Chen Rongzhi , He Guangcun , Du Bo 
Published: February 2020

Abstract
Background
The brown planthopper (BPH, Nilaparvata lugens Stål) is a kind of phloem-feeding pest that adversely affects rice yield. Recently, the BPH-resistance gene, BPH6, was cloned and applied in rice breeding to effectively control BPH. However, the molecular mechanisms underlying BPH6 are poorly understood.

Results
Here, an integrated miRNA and mRNA expression profiling analysis was performed on BPH6-transgenic (BPH6G) and Nipponbare (wild type, WT) plants after BPH infestation, and a total of 217 differentially expressed miRNAs (DEMs) and 7874 differentially expressed mRNAs (DEGs) were identified. 29 miRNAs, including members of miR160, miR166 and miR169 family were opposite expressed during early or late feeding stages between the two varieties, whilst 9 miRNAs were specifically expressed in BPH6G plants, suggesting involvement of these miRNAs in BPH6-mediated resistance to BPH. In the transcriptome analysis, 949 DEGs were opposite expressed during early or late feeding stages of the two genotypes, which were enriched in metabolic processes, cellular development, cell wall organization, cellular component movement and hormone transport, and certain primary and secondary metabolite synthesis. 24 genes were further selected as candidates for BPH resistance. Integrated analysis of the DEMs and DEGs showed that 34 miRNAs corresponding to 42 target genes were candidate miRNA-mRNA pairs for BPH resistance, 18 pairs were verified by qRT-PCR, and two pairs were confirmed by in vivo analysis.

Conclusions
For the first time, we reported integrated small RNA and transcriptome sequencing to illustrate resistance mechanisms against BPH in rice. Our results provide a valuable resource to ascertain changes in BPH-induced miRNA and mRNA expression profiles and enable to comprehend plant-insect interactions and find a way for efficient insect control.
Transcriptomic study of pedicels from GA3-treated table grape genotypes with different susceptibility to berry drop reveals responses elicited in cell wall yield, primary growth and phenylpropanoids synthesis
Authors: Meneses Marco , García-Rojas Miguel , Muñoz-Espinoza Claudia , Carrasco-Valenzuela Tomás , Defilippi Bruno , González-Agüero Mauricio , Meneses Claudio , Infante Rodrigo , Hinrichsen Patricio 
Published: February 2020

AbstractBackgroundGibberellins (GA3) are the most sprayed growth regulator for table grape production worldwide, increasing berry size of seedless varieties through pericarp cell expansion. However, these treatments also exacerbate berry drop, which has a detrimental effect on the postharvest quality of commercialized clusters. Several studies have suggested that pedicel stiffening caused by GA3would have a role in this disorder. Nevertheless, transcriptional and phenotypic information regarding pedicel responses to GA3is minimal.ResultsCharacterization of responses to GA3treatments using the lines L23 and Thompson Seedless showed that the former was up to six times more susceptible to berry drop than the latter. GA3also increased the diameter and dry matter percentage of the pedicel on both genotypes. Induction of lignin biosynthesis-related genes by GA3has been reported, so the quantity of this polymer was measured. The acetyl bromide method detected a decreased concentration of lignin 7 days after GA3treatment, due to a higher cell wall yield of the isolated fractions of GA3-treated pedicel samples which caused a dilution effect. Thus, an initial enrichment of primary cell wall components in response to GA3was suggested, particularly in the L23 background. A transcriptomic profiling was performed to identify which genes were associated with these phenotypic changes. This analysis identified 1281 and 1787 genes differentially upregulated by GA3in L23 and cv. Thompson Seedless, respectively. Concomitantly, 1202 and 1317 downregulated genes were detected in L23 and cv. Thompson Seedless (FDR < 0.05). Gene ontology analysis of upregulated genes showed enrichment in pathways including phenylpropanoids, cell wall metabolism, xylem development, photosynthesis and the cell cycle at 7 days post GA3application. Twelve genes were characterized by qPCR and striking differences were observed between genotypes, mainly in genes related to cell wall synthesis.ConclusionsHigh levels of berry drop are related to an early strong response of primary cell wall synthesis in the pedicel promoted by GA3treatment. Genetic backgrounds can produce similar phenotypic responses to GA3, although there is considerable variation in the regulation of genes in terms of which are expressed, and the extent of transcript levels achieved within the same time frame.
Identification of two recessive etiolation genes (py1, py2) in pakchoi (Brassica rapa L. ssp. chinensis)
Authors: Zhang Kun , Mu Yu , Li Weijia , Shan Xiaofei , Wang Nan , Feng Hui 
Published: February 2020

AbstractBackgroundLeaf color is a major agronomic trait, which has a strong influence on crop yields. Isolating leaf color mutants can represent valuable materials for research in chlorophyll (Chl) biosynthesis and metabolism regulation.ResultsIn this study, we identified a stably inherited yellow leaf mutant derived from ‘Huaguan’ pakchoi variety via isolated microspore culture and designated aspylm. This mutant displayed yellow leaves after germination. Its etiolated phenotype was nonlethal and stable during the whole growth period. Its growth was weak and its hypocotyls were markedly elongated. Genetic analysis revealed that two recessive nuclear genes, namedpy1andpy2, are responsible for the etiolation phenotype. Bulked segregant RNA sequencing (BSR-Seq) showed thatpy1andpy2were mapped on chromosomes A09 and A07, respectively. The genes were single Mendelian factors in F3:4populations based on a 3:1 phenotypic segregation ratio. Thepy1was localized to a 258.3-kb interval on a 34-gene genome. The differentially expressed geneBraA09004189was detected in thepy1mapping region and regulated heme catabolism. One single-nucleotide polymorphism (SNP) ofBraA09004189occurred inpylm.A candidate gene-specific SNP marker in 1520 F3:4yellow-colored individuals co-segregated withpy1. Forpy2, 1860 recessive homozygous F3:4individuals were investigated and localizedpy2to a 4.4-kb interval. Of the five genes in this region,BraA07001774was predicted as a candidate forpy2.It encoded anembryo defective 1187and a phosphotransferase related to chlorophyll deficiency and hypocotyl elongation. One SNP ofBraA07001774occurred inpylm.It caused a single amino acid mutation from Asp to Asn. According to quantitative real-time polymerase chain reaction (qRT-PCR),BraA07001774was downregulated inpylm.ConclusionsOur study identified a Chl deficiency mutantpylmin pakchoi. Two recessive nuclear genes namedpy1andpy2had a significant effect on etiolation. Candidate genes regulating etiolation were identified asBraA09004189andBraA07001774, respectively. These findings will elucidate chlorophyll metabolism and the molecular mechanisms of the gene interactions controlling pakchoi etiolation.
Simultaneous pacing from two branches of coronary sinus in a patient with prosthetic tricuspid valve and complete heart block
Authors: Yolcu Mustafa 
Published: February 2020

AbstractBackgroundComplete heart blocks underwent to permanent pacemaker placement are a common complication of tricuspid valve replacement (TVR). If indicated, endocardial placement of a right ventricular (RV) lead is precluded in the presence of mechanical TVR.Case presentationA 20-year-old female patient firstly underwent metallic prosthetic valve operation with tricuspid valve endocarditis in 2014. Three years after the operation, echocardiography revealed dysfunction of the prosthetic valve thus reoperation was decided. In the second operation, the patient underwent a bioprosthesis valve and AV complete block developed in the postoperative period. Left ventricular ejection fraction (EF) was 45% was found on echocardiography. Pacemaker dependence of the patient, it was aimed to place two electrodes into the left ventricle. Electrodes were placed the target two branches in coronary sinus (CS) and right atrium. Univentricular bifocal pacing was enabled to work.ConclusionElectrode placement in the CS is a very good alternative to epicardial surgical lead placement in cases where endocardial lead placement from the right atrium to the RV is contraindicated. In patients with lower left ventricular EF who will be pacemaker dependent, the insertion of two electrodes into the CS to prevent pacemaker is a safe and effective treatment.