bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular MRD status and outcome after transplantation in NPM1-mutated AML
Authors: Dillon Richard , Hills Robert , Freeman Sylvie , Potter Nicola , Jovanovic Jelena , Ivey Adam , Kanda Anju Shankar , Runglall Manohursingh , Foot Nicola , Valganon Mikel , Khwaja Asim , Cavenagh Jamie , Smith Matthew , Ommen Hans Beier , Overgaard Ulrik Malthe , Dennis Mike , Knapper Steven , Kaur Harpreet , Taussig David , Mehta Priyanka , Raj Kavita , Novitzky-Basso Igor , Nikolousis Emmanouil , Danby Robert , Krishnamurthy Pramila , Hill Kate , Finnegan Damian , Alimam Samah , Hurst Erin , Johnson Peter , Khan Anjum , Salim Rahuman , Craddock Charles , Spearing Ruth , Gilkes Amanda , Gale Rosemary , Burnett Alan , Russell Nigel H. , Grimwade David 
Published: January 2020

Abstract
Relapse remains the most common cause of treatment failure for patients with acute myeloid leukemia (AML) who undergo allogeneic stem cell transplantation (alloSCT), and carries a grave prognosis. Multiple studies have identified the presence of measurable residual disease (MRD) assessed by flow cytometry before alloSCT as a strong predictor of relapse, but it is not clear how these findings apply to patients who test positive in molecular MRD assays, which have far greater sensitivity. We analyzed pretransplant blood and bone marrow samples by reverse-transcription polymerase chain reaction in 107 patients with NPM1-mutant AML enrolled in the UK National Cancer Research Institute AML17 study. After a median follow-up of 4.9 years, patients with negative, low (&lt;200 copies per 105ABL in the peripheral blood and &lt;1000 copies in the bone marrow aspirate), and high levels of MRD had an estimated 2-year overall survival (2y-OS) of 83%, 63%, and 13%, respectively (P &lt; .0001). Focusing on patients with low-level MRD before alloSCT, those with FLT3 internal tandem duplications(ITDs) had significantly poorer outcome (hazard ratio [HR], 6.14; P = .01). Combining these variables was highly prognostic, dividing patients into 2 groups with 2y-OS of 17% and 82% (HR, 13.2; P &lt; .0001). T-depletion was associated with significantly reduced survival both in the entire cohort (2y-OS, 56% vs 96%; HR, 3.24; P = .0005) and in MRD-positive patients (2y-OS, 34% vs 100%; HR, 3.78; P = .003), but there was no significant effect of either conditioning regimen or donor source on outcome. Registered at ISRCTN (http://www.isrctn.com/ISRCTN55675535).
Large-Area and Patternable Nano-Dot Array from Electrolysis of ITO Film for Surface-Enhanced Raman Spectroscopy
Authors: Lu Han , Han Gengxin , Cao Jieping , Jin Mingliang , Ma Qilin , Akinoglu Eser Metin , Wang Xin , Nian Li , Zhou Guofu , Shui Lingling 
Published: January 2020

AbstractFabrication of large-area devices with patternable nanostructures is important for practical applications in optical or electrical devices. In this work, we describe an easy and environment-friendly method for preparing large-area nano-dot (ND) arrays via the electrolytic reaction of a metal oxide film. NDs with various size and morphology can be obtained by adjusting the applied voltage, electrolysis time, and the film thickness of the indium tin oxide (ITO) layer. High-density NDs with size of 50–60 nm can be obtained by electrolysis of a 25-nm-thick ITO film at 150 V for 1.5 min under a water droplet medium, which have been applied for surface-enhanced Raman spectroscopy (SERS) after depositing a thin layer of silver. The SERS substrate with optimized ND structure exhibits sensitive detection of Rhodamine 6G (R6G) with detection limit down to 5 × 10-12 M. The enhancement factors (EFs) of 1.12 × 106 and 6.79 × 105 have been achieved for characterization of 4-methylbenzenethiol (4-MBT) and R6G, respectively. With an additional photolithographic step, multiple areas of ND arrays can be created on one substrate, enabling simultaneous detection of various samples containing different molecules at once experiment. Such a method is quick, easy, patternable, and environment-friendly, being suitable for on-site quick and synchronous determination of various molecules for applications in point-of-care, environmental monitoring, and airport security fields.
The impact of various seed, accessibility and interaction constraints on sRNA target prediction- a systematic assessment
Authors: Raden Martin , Müller Teresa , Mautner Stefan , Gelhausen Rick , Backofen Rolf 
Published: January 2020

Abstract
Background
Seed and accessibility constraints are core features to enable highly accurate sRNA target screens based on RNA-RNA interaction prediction. Currently, available tools provide different (sets of) constraints and default parameter sets. Thus, it is hard to impossible for users to estimate the influence of individual restrictions on the prediction results.

Results
Here, we present a systematic assessment of the impact of established and new constraints on sRNA target prediction both on a qualitative as well as computational level. This is done exemplarily based on the performance of IntaRNA, one of the most exact sRNA target prediction tools. IntaRNA provides various ways to constrain considered seed interactions, e.g. based on seed length, its accessibility, minimal unpaired probabilities, or energy thresholds, beside analogous constraints for the overall interaction. Thus, our results reveal the impact of individual constraints and their combinations.

Conclusions
This provides both a guide for users what is important and recommendations for existing and upcoming sRNA target prediction approaches.We show on a large sRNA target screen benchmark data set that only by altering the parameter set, IntaRNA recovers 30% more verified interactions while becoming 5-times faster. This exemplifies the potential of seed, accessibility and interaction constraints for sRNA target prediction.
Deep neural networks for human microRNA precursor detection
Authors: Zheng Xueming , Fu Xingli , Wang Kaicheng , Wang Meng 
Published: January 2020

Abstract
Background
MicroRNAs (miRNAs) play important roles in a variety of biological processes by regulating gene expression at the post-transcriptional level. So, the discovery of new miRNAs has become a popular task in biological research. Since the experimental identification of miRNAs is time-consuming, many computational tools have been developed to identify miRNA precursor (pre-miRNA). Most of these computation methods are based on traditional machine learning methods and their performance depends heavily on the selected features which are usually determined by domain experts. To develop easily implemented methods with better performance, we investigated different deep learning architectures for the pre-miRNAs identification.

Results
In this work, we applied convolution neural networks (CNN) and recurrent neural networks (RNN) to predict human pre-miRNAs. We combined the sequences with the predicted secondary structures of pre-miRNAs as input features of our models, avoiding the feature extraction and selection process by hand. The models were easily trained on the training dataset with low generalization error, and therefore had satisfactory performance on the test dataset. The prediction results on the same benchmark dataset showed that our models outperformed or were highly comparable to other state-of-the-art methods in this area. Furthermore, our CNN model trained on human dataset had high prediction accuracy on data from other species.

Conclusions
Deep neural networks (DNN) could be utilized for the human pre-miRNAs detection with high performance. Complex features of RNA sequences could be automatically extracted by CNN and RNN, which were used for the pre-miRNAs prediction. Through proper regularization, our deep learning models, although trained on comparatively small dataset, had strong generalization ability.
Fruit syndromes in Viburnum: correlated evolution of color, nutritional content, and morphology in bird-dispersed fleshy fruits
Authors: Sinnott-Armstrong Miranda A. , Lee Chong , Clement Wendy L. , Donoghue Michael J. 
Published: January 2020

AbstractPremiseA key question in plant dispersal via animal vectors is where and why fruit colors vary between species and how color relates to other fruit traits. To better understand the factors shaping the evolution of fruit color diversity, we tested for the existence of syndromes of traits (color, morphology, and nutrition) in the fruits ofViburnum. We placed these results in a larger phylogenetic context and reconstructed ancestral states to assess howViburnumfruit traits have evolved across the clade.ResultsWe find that blueViburnumfruits are not very juicy, and have high lipid content and large, round endocarps surrounded by a small quantity of pulp. Red fruits display the opposite suite of traits: they are very juicy with low lipid content and smaller, flatter endocarps. The ancestralViburnumfruit may have gone through a sequence of color changes before maturation (green to yellow to red to black), though our reconstructions are equivocal. In one major clade ofViburnum(Nectarotinus), fruits mature synchronously with reduced intermediate color stages. Most transitions between fruit colors occurred in this synchronously fruiting clade.ConclusionsIt is widely accepted that fruit trait diversity has primarily been driven by the differing perceptual abilities of bird versus mammal frugivores. Yet within a clade of largely bird-dispersed fruits, we find clear correlations between color, morphology, and nutrition. These correlations are likely driven by a shift from sequential to synchronous development, followed by diversification in color, nutrition, and morphology. A deeper understanding of fruit evolution within clades will elucidate the degree to which such syndromes structure extant fruit diversity.
Differential expression of microRNAs in tomato leaves treated with different light qualities
Authors: Dong Fei , Wang Chuanzeng , Dong Yuhui , Hao Shuqin , Wang Lixia , Sun Xiudong , Liu Shiqi 
Published: January 2020

AbstractBackgroundLight is the main source of energy and, as such, is one of the most important environmental factors for plant growth, morphogenesis, and other physiological responses. MicroRNAs (miRNAs) are endogenous non-coding RNAs that contain 21–24 nucleotides (nt) and play important roles in plant growth and development as well as stress responses. However, the role of miRNAs in the light response is less studied. We used tomato seedlings that were cultured in red light then transferred to blue light for 2 min to identify miRNAs related to light response by high-throughput sequencing.ResultsA total of 108 known miRNAs and 141 predicted novel miRNAs were identified in leaf samples from tomato leaves treated with the different light qualities. Among them, 15 known and 5 predicted novel miRNAs were differentially expressed after blue light treatment compared with the control (red light treatment). KEGG enrichment analysis showed that significantly enriched pathways included zeatin biosynthesis (ko00908), homologous recombination (ko03440), and plant hormone signal transduction (ko04075). Zeatin biosynthesis and plant hormone signal transduction are related to plant hormones, indicating that plant hormones play important roles in the light response.ConclusionOur results provide a theoretical basis for further understanding the role of miRNAs in the light response of plants.
Comparative transcriptomics of stem bark reveals genes associated with bast fiber development in Boehmeria nivea L. gaud (ramie)
Authors: Xie Jiyong , Li Jiaqi , Jie Yucheng , Xie Deyu , Yang Di , Shi Huazhong , Zhong Yingli 
Published: January 2020

Abstract
Background
Boehmeria nivea L. Gaud (Ramie) produces one of the longest natural fibers in nature. The bark of ramie mainly comprises of the phloem tissue of stem and is the raw material for fiber. Therefore, identifying the molecular regulation of phloem development is important for understanding of bast fiber biosynthesis and improvement of fiber quality in ramie.

Results
In this study, we collected top bud (TB), bark from internode elongating region (ER) and bark from internode fully elongated region (FER) from the ramie variety Zhongzhu No. 1. Histological study indicated that these samples contain phloem tissues at different developmental and maturation stages, with a higher degree of maturation of phloem tissue in FER. RNA sequencing (RNA-seq) was performed and de novo transcriptome was assembled. Unigenes and differentially expressed genes (DEGs) in these three samples were identified. The analysis of DEGs by using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed clear differences in gene expression between ER and FER. Some unigenes involved in secondary cell wall biosynthesis were up-regulated in both ER and FER, while unigenes for some cell wall components or cell wall modifications showed differential expression between ER and FER. In addition, the ethylene respond factors (ERFs) in the ethylene signaling pathway were up-regulated in FER, and ent-kaurenoic acid oxidase (KAO) and GA 20-oxidase (GA20ox) for gibberellins biosynthesis were up-regulated while GA 2-oxidase (GA2ox) for gibberellin inactivation was down-regulated in FER.

Conclusions
Both morphological study and gene expression analysis supported a burst of phloem and vascular developmental processes during the fiber maturation in the ramie stem, and ethylene and gibberellin are likely to be involved in this process. Our findings provide novel insights into the phloem development and fiber maturation in ramie, which could be useful for fiber improvement in ramie and other fiber crops.
GWAS and fine-mapping of livability and six disease traits in Holstein cattle
Authors: Freebern Ellen , Santos Daniel J. A. , Fang Lingzhao , Jiang Jicai , Parker Gaddis Kristen L. , Liu George E. , VanRaden Paul M. , Maltecca Christian , Cole John B. , Ma Li 
Published: January 2020

Abstract
Background
Health traits are of significant economic importance to the dairy industry due to their effects on milk production and associated treatment costs. Genome-wide association studies (GWAS) provide a means to identify associated genomic variants and thus reveal insights into the genetic architecture of complex traits and diseases. The objective of this study is to investigate the genetic basis of seven health traits in dairy cattle and to identify potential candidate genes associated with cattle health using GWAS, fine mapping, and analyses of multi-tissue transcriptome data.

Results
We studied cow livability and six direct disease traits, mastitis, ketosis, hypocalcemia, displaced abomasum, metritis, and retained placenta, using de-regressed breeding values and more than three million imputed DNA sequence variants. After data edits and filtering on reliability, the number of bulls included in the analyses ranged from 11,880 (hypocalcemia) to 24,699 (livability). GWAS was performed using a mixed-model association test, and a Bayesian fine-mapping procedure was conducted to calculate a posterior probability of causality to each variant and gene in the candidate regions. The GWAS detected a total of eight genome-wide significant associations for three traits, cow livability, ketosis, and hypocalcemia, including the bovine Major Histocompatibility Complex (MHC) region associated with livability. Our fine-mapping of associated regions reported 20 candidate genes with the highest posterior probabilities of causality for cattle health. Combined with transcriptome data across multiple tissues in cattle, we further exploited these candidate genes to identify specific expression patterns in disease-related tissues and relevant biological explanations such as the expression of Group-specific Component (GC) in the liver and association with mastitis as well as the Coiled-Coil Domain Containing 88C (CCDC88C) expression in CD8 cells and association with cow livability.

Conclusions
Collectively, our analyses report six significant associations and 20 candidate genes of cattle health. With the integration of multi-tissue transcriptome data, our results provide useful information for future functional studies and better understanding of the biological relationship between genetics and disease susceptibility in cattle.
Transcriptome-wide map of m6A circRNAs identified in a rat model of hypoxia mediated pulmonary hypertension
Authors: Su Hua , Wang Guowen , Wu Lingfang , Ma Xiuqing , Ying Kejing , Zhang Ruifeng 
Published: January 2020

Abstract
Background
Hypoxia mediated pulmonary hypertension (HPH) is a lethal disease and lacks effective therapy. CircRNAs play significant roles in physiological process. Recently, circRNAs are found to be m6A-modified. The abundance of circRNAs was influenced by m6A. Furthermore, the significance of m6A circRNAs has not been elucidated in HPH yet. Here we aim to investigate the transcriptome-wide map of m6A circRNAs in HPH.

Results
Differentially expressed m6A abundance was detected in lungs of HPH rats. M6A abundance in circRNAs was significantly reduced in hypoxia in vitro. M6A circRNAs were mainly from protein-coding genes spanned single exons in control and HPH groups. Moreover, m6A influenced the circRNA–miRNA–mRNA co-expression network in hypoxia. M6A circXpo6 and m6A circTmtc3 were firstly identified to be downregulated in HPH.

Conclusion
Our study firstly identified the transcriptome-wide map of m6A circRNAs in HPH.
M6A can influence circRNA–miRNA–mRNA network. Furthermore, we firstly identified two HPH-associated m6A circRNAs: circXpo6 and circTmtc3. However, the clinical significance of m6A circRNAs for HPH should be further validated.
Gene regulatory response to hyposalinity in the brown seaweed Fucus vesiculosus
Authors: Rugiu Luca , Panova Marina , Pereyra Ricardo Tomás , Jormalainen Veijo 
Published: January 2020

AbstractBackgroundRockweeds are among the most important foundation species of temperate rocky littoral shores. In the Baltic Sea, the rockweedFucus vesiculosusis distributed along a decreasing salinity gradient from the North Atlantic entrance to the low-salinity regions in the north-eastern margins, thus, demonstrating a remarkable tolerance to hyposalinity. The underlying mechanisms for this tolerance are still poorly understood. Here, we exposedF. vesiculosusfrom two range-margin populations to the hyposaline (2.5 PSU - practical salinity unit) conditions that are projected to occur in the region by the end of this century as a result of climate change. We used transcriptome analysis (RNA-seq) to determine the gene expression patterns associated with hyposalinity acclimation, and examined the variation in these patterns between the sampled populations.ResultsHyposalinity induced different responses in the two populations: in one, only 26 genes were differentially expressed between salinity treatments, while the other population demonstrated up- or downregulation in 3072 genes. In the latter population, the projected future hyposalinity induced an acute response in terms of antioxidant production. Genes associated with membrane composition and structure were also heavily involved, with the upregulation of fatty acid and actin production, and the downregulation of ion channels and alginate pathways. Changes in gene expression patterns clearly indicated an inhibition of the photosynthetic machinery, with a consequent downregulation of carbohydrate production. Simultaneously, energy consumption increased, as revealed by the upregulation of genes associated with respiration and ATP synthesis. Overall, the genes that demonstrated the largest increase in expression were ribosomal proteins involved in translation pathways. The fixation rate of SNP:s was higher within genes responding to hyposalinity than elsewhere in the transcriptome.ConclusionsThe high fixation rate in the genes coding for salinity acclimation mechanisms implies strong selection for them. The among-population differentiation that we observed in the transcriptomic response to hyposalinity stress suggests that populations ofF. vesiculosusmay differ in their tolerance to future desalination, possibly as a result of local adaptation to salinity conditions within the Baltic Sea. These results emphasise the importance of considering interspecific genetic variation when evaluating the consequences of environmental change.
Comparative transcriptomic and metabolic analysis of wild and domesticated wheat genotypes reveals differences in chemical and physical defense responses against aphids
Authors: Batyrshina Zhaniya S. , Yaakov Beery , Shavit Reut , Singh Anuradha , Tzin Vered 
Published: January 2020

AbstractBackgroundYoung wheat plants are continuously exposed to herbivorous insect attack. To reduce insect damage and maintain their growth, plants evolved different defense mechanisms, including the biosynthesis of deterrent compounds named benzoxazinoids, and/or trichome formation that provides physical barriers. It is unclear whether both of these mechanisms are equally critical in providing an efficient defense for wheat seedlings against aphids—an economically costly pest in cereal production.ResultsIn this study, we compared the transcriptome, metabolome, benzoxazinoids, and trichome density of three selected wheat genotypes, with a focus on differences related to defense mechanisms. We chose diverse wheat genotypes: two tetraploid wheat genotypes, domesticated durum ‘Svevo’ and wild emmer ‘Zavitan,’ and one hexaploid bread wheat, ‘Chinese Spring.’ The full transcriptomic analysis revealed a major difference between the three genotypes, while the clustering of significantly different genes suggested a higher similarity between the two domesticated wheats than between either and the wild wheat. A pathway enrichment analysis indicated that the genes associated with primary metabolism, as well as the pathways associated with defense such as phytohormones and specialized metabolites, were different between the three genotypes. Measurement of benzoxazinoid levels at the three time points (11, 15, and 18 days after germination) revealed high levels in the two domesticated genotypes, while in wild emmer wheat, they were below detection level. In contrast to the benzoxazinoid levels, the trichome density was dramatically higher in the wild emmer than in the domesticated wheat. Lastly, we tested the bird cherry-oat aphid’s (Rhopalosiphum padi) performance and found that Chinese Spring is more resistant than the tetraploid genotypes.ConclusionsOur results show that benzoxazinoids play a more significant defensive role than trichomes. Differences between the abundance of defense mechanisms in the wild and domesticated plants were observed in which wild emmer possesses high physical defenses while the domesticated wheat genotypes have high chemical defenses. These findings provide new insights into the defense adaptations of wheat plants against aphids.