bluuebunny/crossref_metadata_2025_split huggingface dataset:
TarPan: an easily adaptable targeted sequencing panel viewer for research and clinical use
Authors: Ashby Cody , Rutherford Michael , Bauer Michael A. , Peterson Erich A. , Wang Yan , Boyle Eileen M. , Wardell Christopher P. , Walker Brian A. 
Published: April 2020

Abstract
Background
The study of cancer genomics continually matures as the number of patient samples sequenced increases. As more data is generated, oncogenic drivers for specific cancer types are discovered along with their associated risks. This in turn leads to potential treatment strategies that pave the way to precision medicine. However, significant financial and analytical barriers make it infeasible to sequence the entire genome of every patient. In contrast, targeted sequencing panels give reliable information on relevant portions of the genome at a fiscally responsible cost. Therefore, we have created the Targeted Panel (TarPan) Viewer, a software tool, to investigate this type of data.

Results
TarPan Viewer helps investigators understand data from targeted sequencing data by displaying the information through a web browser interface. Through this interface, investigators can easily observe copy number changes, mutations, and structural events in cancer samples. The viewer runs in R Shiny with a robust SQLite backend and its input is generated from bioinformatic algorithms reliably described in the literature. Here we show the results from using TarPan Viewer on publicly available follicular lymphoma, breast cancer, and multiple myeloma data. In addition, we have tested and utilized the viewer internally, and this data has been used in high-impact peer-reviewed publications.

Conclusions
We have designed a flexible, simple to setup viewer that is easily adaptable to any type of cancer targeted sequencing, and has already proven its use in a research laboratory environment. Further, we believe with deeper sequencing and/or more targeted application it could be of use in the clinic in conjunction with an appropriate targeted sequencing panel as a cost-effective diagnostic test, especially in cancers such as acute leukemia or diffuse large B-cell lymphoma that require rapid interventions.
Being red, blue and green: the genetic basis of coloration differences in the strawberry poison frog (Oophaga pumilio)
Authors: Rodríguez Ariel , Mundy Nicholas I. , Ibáñez Roberto , Pröhl Heike 
Published: April 2020

Abstract
Background
Animal coloration is usually an adaptive attribute, under strong local selection pressures and often diversified among species or populations. The strawberry poison frog (Oophaga pumilio) shows an impressive array of color morphs across its distribution in Central America. Here we quantify gene expression and genetic variation to identify candidate genes involved in generating divergence in coloration between populations of red, green and blue O. pumilio from the Bocas del Toro archipelago in Panama.

Results
We generated a high quality non-redundant reference transcriptome by mapping the products of genome-guided and de novo transcriptome assemblies onto a re-scaffolded draft genome of O. pumilio. We then measured gene expression in individuals of the three color phenotypes and identified color-associated candidate genes by comparing differential expression results against a list of a priori gene sets for five different functional categories of coloration – pteridine synthesis, carotenoid synthesis, melanin synthesis, iridophore pathways (structural coloration), and chromatophore development. We found 68 candidate coloration loci with significant expression differences among the color phenotypes. Notable upregulated examples include pteridine synthesis genes spr, xdh and pts (in red and green frogs); carotenoid metabolism genes bco2 (in blue frogs), scarb1 (in red frogs), and guanine metabolism gene psat1 (in blue frogs). We detected significantly higher expression of the pteridine synthesis gene set in red and green frogs versus blue frogs. In addition to gene expression differences, we identified 370 outlier SNPs on 162 annotated genes showing signatures of diversifying selection, including eight pigmentation-associated genes.

Conclusions
Gene expression in the skin of the three populations of frogs with differing coloration is highly divergent. The strong signal of differential expression in pteridine genes is consistent with a major role of these genes in generating the coloration differences among the three morphs. However, the finding of differentially expressed genes across pathways and functional categories suggests that multiple mechanisms are responsible for the coloration differences, likely involving both pigmentary and structural coloration. In addition to regulatory differences, we found potential evidence of differential selection acting at the protein sequence level in several color-associated loci, which could contribute to the color polymorphism.
Genomic characterization of an emerging Enterobacteriaceae species: the first case of co-infection with a typical pathogen in a human patient
Authors: Zhang Zhao , Li Daixi , Shi Xing , Zhai Yao , Guo Yatao , Zheng Yali , Zhao Lili , He Yukun , Chen Yusheng , Wang Zhanwei , Su Jianrong , Kang Yu , Gao Zhancheng 
Published: April 2020

Abstract
Background
Opportunistic pathogens are important for clinical practice as they often cause antibiotic-resistant infections. However, little is documented for many emerging opportunistic pathogens and their biological characteristics. Here, we isolated a strain of extended-spectrum β-lactamase-producing Enterobacteriaceae from a patient with a biliary tract infection. We explored the biological and genomic characteristics of this strain to provide new evidence and detailed information for opportunistic pathogens about the co-infection they may cause.

Results
The isolate grew very slowly but conferred strong protection for the co-infected cephalosporin-sensitive Klebsiella pneumoniae. As the initial laboratory testing failed to identify the taxonomy of the strain, great perplexity was caused in the etiological diagnosis and anti-infection treatment for the patient. Rigorous sequencing efforts achieved the complete genome sequence of the isolate which we designated as AF18. AF18 is phylogenetically close to a few strains isolated from soil, clinical sewage, and patients, forming a novel species together, while the taxonomic nomenclature of which is still under discussion. And this is the first report of human infection of this novel species. Like its relatives, AF18 harbors many genes related to cell mobility, various genes adaptive to both the natural environment and animal host, over 30 mobile genetic elements, and a plasmid bearing blaCTX-M-3 gene, indicating its ability to disseminate antimicrobial-resistant genes from the natural environment to patients. Transcriptome sequencing identified two sRNAs that critically regulate the growth rate of AF18, which could serve as targets for novel antimicrobial strategies.

Conclusions
Our findings imply that AF18 and its species are not only infection-relevant but also potential disseminators of antibiotic resistance genes, which highlights the need for continuous monitoring for this novel species and efforts to develop treatment strategies.
Difference in virulence between Neisseria meningitidis serogroups W and Y in transgenic mice
Authors: Eriksson Lorraine , Stenmark Bianca , Deghmane Ala-Eddine , Thulin Hedberg Sara , Säll Olof , Fredlund Hans , Mölling Paula , Taha Muhamed-Kheir 
Published: April 2020

Abstract
Background
Neisseria meningitidis serogroups W and Y are the most common serogroups causing invasive meningococcal disease in Sweden. The majority of cases are caused by the serogroup W UK 2013 strain of clonal complex (cc) 11, and subtype 1 of the serogroup Y, YI strain of cc23. In this study, virulence factors of several lineages within cc11 and cc23 were investigated in transgenic BALB/c mice expressing human transferrin.
Transgenic mice were infected intraperitoneally with serogroup W and Y isolates. Levels of bacteria and the proinflammatory cytokine CXCL1 were determined in blood collected 3 h and 24 h post-infection. Apoptosis was investigated in immune cells from peritoneal washes of infected mice. Adhesion and induction of apoptosis in human epithelial cells were also scored.

Results
The levels of bacteraemia, CXCL1, and apoptosis were higher in serogroup W infected mice than in serogroup Y infected mice. Serogroup W isolates also induced higher levels of apoptosis and adhesion in human epithelial cells. No significant differences were observed between different lineages within cc11 and cc23.

Conclusions
N. meningitidis Serogroup W displayed a higher virulence in vivo in transgenic mice, compared to serogroup Y. This was reflected by higher bacteremia, proinflammatory activity, and ability to induce apoptosis in mouse immune cells and human epithelial cells.
The organ-specific differential roles of rice DXS and DXR, the first two enzymes of the MEP pathway, in carotenoid metabolism in Oryza sativa leaves and seeds
Authors: You MK , Lee YJ , Kim JK , Baek SA , Jeon YA , Lim SH , Ha SH 
Published: April 2020

AbstractBackgroundDeoxyxylulose 5-phosphate synthase (DXS) and deoxyxylulose 5-phosphate reductoisomerase (DXR) are the enzymes that catalyze the first two enzyme steps of the methylerythritol 4-phosphate (MEP) pathway to supply the isoprene building-blocks of carotenoids. Plant DXR and DXS enzymes have been reported to function differently depending on the plant species. In this study, the differential roles of riceDXSandDXRgenes in carotenoid metabolism were investigated.ResultsThe accumulation of carotenoids in rice seeds co-expressingOsDXS2andstPACwas largely enhanced by 3.4-fold relative to thestPACseeds and 315.3-fold relative to non-transgenic (NT) seeds, while the overexpression of eachOsDXS2orOsDXRcaused no positive effect on the accumulation of either carotenoids or chlorophylls in leaves and seeds, suggesting that OsDXS2 functions as a rate-limiting enzyme supplying IPP/DMAPPs to seed carotenoid metabolism, but OsDXR doesn’t in either leaves or seeds. The expressions ofOsDXS1,OsPSY1,OsPSY2, andOsBCH2genes were upregulated regardless of the reductions of chlorophylls and carotenoids in leaves; however, there was no significant change in the expression of most carotenogenic genes, even though there was a 315.3-fold increase in the amount of carotenoid in rice seeds. These non-proportional expression patterns in leaves and seeds suggest that those metabolic changes of carotenoids were associated with overexpression of theOsDXS2,OsDXRandstPACtransgenes, and the capacities of the intermediate biosynthetic enzymes might be much more important for those metabolic alterations than the transcript levels of intermediate biosynthetic genes are. Taken together, we propose a ‘Three Faucets and Cisterns Model’ about the relationship among the rate-limiting enzymes OsDXSs, OsPSYs, and OsBCHs as a “Faucet”, the biosynthetic capacity of intermediate metabolites as a “Cistern”, and the carotenoid accumulations as the content of “Cistern”.ConclusionOur study suggests that OsDXS2 plays an important role as a rate-limiting enzyme supplying IPP/DMAPPs to the seed-carotenoid accumulation, and rice seed carotenoid metabolism could be largely enhanced without any significant transcriptional alteration of carotenogenic genes. Finally, the “Three Faucets and Cisterns model” presents the extenuating circumstance to elucidate rice seed carotenoid metabolism.
High abundance of Ralstonia solanacearum changed tomato rhizosphere microbiome and metabolome
Authors: Wen Tao , Zhao Mengli , Liu Ting , Huang Qiwei , Yuan Jun , Shen Qirong 
Published: April 2020

Abstract
Background
Rhizosphere microbiome is dynamic and influenced by environment factors surrounded including pathogen invasion. We studied the effects of Ralstonia solanacearum pathogen abundance on rhizosphere microbiome and metabolome by using high throughput sequencing and GC-MS technology.

Results
There is significant difference between two rhizosphere bacterial communities of higher or lower pathogen abundance, and this difference of microbiomes was significant even ignoring the existence of pathogen. Higher pathogen abundance decreased the alpha diversity of rhizosphere bacterial community as well as connections in co-occurrence networks. Several bacterial groups such as Bacillus and Chitinophaga were negatively related to the pathogen abundance. The GC-MS analysis revealed significantly different metabolomes in two groups of rhizosphere soils, i.e., the rhizosphere soil of lower harbored more sugars such as fructose, sucrose and melibiose than that in high pathogen abundance.

Conclusions
The dissimilar metabolomes in two rhizosphere soils likely explained the difference of bacterial communities with Mantel test. Bacillus and Chitinophaga as well as sugar compounds negatively correlated with high abundance of pathogen indicated their potential biocontrol ability.
Molecular cytogenetic characterization of a novel wheat–Psathyrostachys huashanica Keng T3DS-5NsL•5NsS and T5DL-3DS•3DL dual translocation line with powdery mildew resistance
Authors: Li Jiachuang , Zhao Li , Cheng Xueni , Bai Guihua , Li Mao , Wu Jun , Yang Qunhui , Chen Xinhong , Yang Zujun , Zhao Jixin 
Published: April 2020

Abstract
Background
Psathyrostachys huashanica Keng (2n = 2x = 14, NsNs) carries many outstanding agronomic traits, therefore is a valuable resource for wheat genetic improvement. Wheat–P. huashanica translocation lines are important intermediate materials for wheat breeding and studying the functions of alien chromosomes. However, powdery mildew resistance in these translocation lines has not been reported previously.

Results
This study developed a novel wheat–P. huashanica translocation line TR77 by selecting a F7 progeny from the cross between heptaploid hybrid H8911 (2n = 7x = 49, AABBDDNs) and durum wheat line Trs-372. Chromosome karyotype of 2n = 42 = 21II was observed in both mitotic and meiotic stages of TR77. Genomic in situ hybridization analysis identified two translocated chromosomes that paired normally at meiosis stage in TR77. Molecular marker analysis showed that part of chromosome 5D was replaced by part of alien chromosome fragment 5Ns. It meant replacement made part 5DL and part 5NsL·5NsS existed in wheat background, and then translocation happened between these chromosomes and wheat 3D chromosome. Fluorescence in situ hybridization demonstrated that TR77 carries dual translocations: T3DS-5NsL·5NsS and T5DL-3DS·3DL. Analysis using a 15 K-wheat-SNP chip confirmed that SNP genotypes on the 5D chromosome of TR77 matched well with these of P. huashanica, but poorly with common wheat line 7182. The translocation was physically located between 202.3 and 213.1 Mb in 5D. TR77 showed longer spikes, more kernels per spike, and much better powdery mildew resistance than its wheat parents: common wheat line 7182 and durum wheat line Trs-372.

Conclusions
TR77 is a novel stable wheat–P. huashanica T3DS-5NsL·5NsS and T5DL-3DS·3DL dual translocation line and showed significant improved spike traits and resistance to powdery mildew compared to its parents, thus, it can be an useful germplasm for breeding disease resistance and studying the genetic mechanism of dual translocations.
Modelling seizure rates rather than time to an event within clinical trials of antiepileptic drugs
Authors: Bonnett Laura J. , Hutton Jane L. , Marson Anthony G. 
Published: April 2020

AbstractBackgroundPredictive models within epilepsy are frequently developed via Cox’s proportional hazards models. These models estimate risk of a specified event such as 12-month remission. They are relatively simple to produce, have familiar output, and are useful to answer questions about short-term prognosis. However, the Cox model only considers time to first event rather than all seizures after starting treatment for example. This makes assessing change in seizure rates over time difficult. Variants to the Cox model exist enabling recurrent events to be modelled. One such variant is the Prentice, Williams and Peterson – Total Time (PWP-TT) model. An alternative is the negative binomial model for event counts. This study aims to demonstrate the differences between the three approaches, and to consider the benefits of the PWP-TT approach for assessing change in seizure rates over time.MethodsTime to 12-month remission and time to first seizure after randomisation were modelled using the Cox model. Risk of seizure recurrence was modelled using the PWP-TT model, including all seizures across the whole follow-up period. Seizure counts were modelled using negative binomial regression. Differences between the approaches were demonstrated using participants recruited to the UK-based multi-centre Standard versus New Antiepileptic Drug (SANAD) study.ResultsResults from the PWP-TT model were similar to those from the conventional Cox and negative binomial models. In general, the direction of effect was consistent although the variables included in the models and the significance of the predictors varied. The confidence intervals obtained via the PWP-TT model tended to be narrower due to the increase in statistical power of the model.ConclusionsThe Cox model is useful for determining the initial response to treatment and potentially informing when the next intervention may be required. The negative binomial model is useful for modelling event counts. The PWP-TT model extends the Cox model to all included events. This is useful in determining the longer-term effects of treatment policy. Such a model should be considered when designing future clinical trials in medical conditions typified by recurrent events to improve efficiency and statistical power as well as providing evidence regarding changes in event rates over time.
The Enhanced Liver Fibrosis test is associated with liver-related outcomes in postmenopausal women with risk factors for liver disease
Authors: Trembling Paul M. , Apostolidou Sophia , Gentry-Maharaj Aleksandra , Parkes Julie , Ryan Andy , Tanwar Sudeep , Burnell Matthew , Harris Scott , Menon Usha , Rosenberg William M. 
Published: April 2020

Abstract
Background
Chronic liver disease (CLD) is usually asymptomatic but earlier detection is critical to permit life-saving interventions for those at risk due to high alcohol consumption and increased body mass index (BMI). The aim of this study was to estimate the association between the Enhanced Liver Fibrosis (ELF) test and liver-related events (LRE) and its performance in predicting LRE in postmenopausal women with risk factors in a nested case-control study within the United Kingdom Trial of Ovarian Cancer Screening (UKCTOCS).

Methods
In a cohort of 95,126 we performed a case-control study measuring ELF in blinded samples from 173 participants with self-reported high alcohol use and / or BMI ≥25 kg/m2 comprising all 58 cases who developed LRE and 115 controls matched for age, alcohol and BMI who did not develop LRE during median follow-up of 8.5 years.

Results
Using Cox regression at an ELF threshold of 10.51 hazard ratios (HR) for LRE were 4.88 (95% confidence interval (CI) 2.37–10.03) (unadjusted model) and 4.62 (95% CI 2.12–10.08) (adjusted for deprivation and self-reported hypertension, heart disease, hypercholesterolaemia and diabetes). At a threshold of 9.8 HR for LRE were 2.21 (95% CI 1.22–3.97) (unadjusted model) and 2.18 (95% CI 1.19–4.01) (adjusted). ELF was evaluated as a time dependent variable by generating time-dependent Cox models; HRs at an ELF threshold of 10.51 were 1.94 (95% CI 1.10–3.39) (unadjusted) and 2.05 (95% CI 1.16–3.64) (adjusted) and at a threshold of 9.8 HRs were 1.85 (95% CI 1.09–3.15) (unadjusted) and 1.80 (95% CI 1.04–3.13) (adjusted). Area under the receiver operating characteristic curve for recruitment ELF predicting LRE was 0.58 (95% CI 0.49–0.68), and for second subsequent ELF 0.61 (95% CI 0.52–0.71).

Conclusion
This study demonstrates the association between ELF and CLD in postmenopausal women with risk factors for liver disease, creating the opportunity to intervene to reduce liver-related mortality and morbidity. Although larger studies are required, these results demonstrate the potential of ELF as a prognostic tool in health checks in primary care.

Trial registration
This study is nested in UKCTOCS. UKCTOCS is registered as an International Standard Randomised Controlled Trial, number ISRCTN22488978. Registered 06/04/2000.
Gastroesophageal reflux disease in a typical African population: a symptom-based multicenter study
Authors: Nwokediuko Sylvester Chuks , Adekanle Olusegun , Akere Adegboyega , Olokoba Abdulfatai , Anyanechi Chiedozie , Umar Sabo Mustapha , Maiyaki Abubakar , Ijoma Uchenna , Obienu Olive , Uhunmwangho Augustine , Ndububa Dennis 
Published: April 2020

Abstract
Background
The prevalence of gastroesophageal reflux disease (GERD) in Africa is not known but is believed to be increasing because of demographic and epidemiologic transition. The main objectives of this study were to determine the prevalence and risk factors of GERD, and its degree of overlap with dyspepsia and irritable bowel syndrome (IBS) in Nigeria, a typical African population.

Methods
This was an observational, cross-sectional and descriptive study of adult Nigerians. Diagnosis of GERD was by means of the gastroesophageal reflux disease questionnaire (GERDQ) while the diagnosis of dyspepsia and IBS was based on the Rome III criteria for the diagnosis of functional gastrointestinal disorders. The GERDQ and Rome III questionnaires for dyspepsia and IBS were merged into a composite questionnaire and administered to the study participants who were recruited with a multi-stage sampling technique.

Results
Out of 3520 subjects who participated in the study across the country, 269 (7.6%) satisfied the diagnostic criteria for GERD, while 107 (3.0%) had GERD associated with significant impairment of quality of life. Risk factors of GERD (represented by odds ratios) were age 1.014(95% CI: 1.006–1.022), use of analgesics 1.461 (95% CI: 1.060–2.025), and use of herbs 1.318 (95% CI: 1.020–1.704). Overlap of GERD with dyspepsia and/or IBS was observed in over 50% of cases.

Conclusions
The prevalence of GERD in this study is 7.6%. Age, use of analgesics and use of herbs increase the risk, albeit minimally. A high degree of overlap with dyspepsia and IBS exists in Nigerian patients with GERD.