bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide association study reveals novel genetic markers associated with endurance athlete status
Authors: Al-Khelaifi Fatima , Yousri Noha , Albagha Omar , Semenova Ekaterina A. , Kostryukova Elena , Kulemin Nickolay A , Borisov Oleg V , Andryushchenko Liliya B , Larin Andrey K , Generozov Edward V , Donati Francesco , Botrè Francesco , Abraham David , Hingorani Aron , Georgakopoulos Costas , Suhre Karsten , Ahmetov Ildus , Elrayess Mohamed 
Published: September 2019

Abstract
Background: The genetic predisposition to elite athletic performance has been a controversial subject due to the underpowered studies and the small effect size of identified genetic variants. The aims of this study were to investigate the association of common single-nucleotide polymorphisms (SNPs) with endurance athlete status in a large cohort of elite athletes using GWAS approach, followed by a functional validation of significant SNPs by metabolomics analysis.
Results: The association of 476,728 SNPs of Illumina DrugCore Gene chip and endurance athlete status was investigated in 753 European international-level athletes (594 males, 159 females) by comparing allelic frequencies between athletes specialized in sports with high (n=630) and low/moderate (n=123) aerobic component. Validation of results was performed by comparing the frequencies of the most significant SNPs between 176 elite Russian endurance athletes and 173 Russian controls or 43 sprinters. Two novel SNPs showed significant associations with endurance athlete status at Bonferroni level of significance (rs56330321 in ATP2B2, p=1.46E-7) and FDR level of significance (rs2635438 in SYNE1, p=2.54E-7), respectively. Replication study using Russian cohorts and a subsequent meta-analysis have confirmed the association of rs56330321 and rs2635438 SNPs with endurance athlete status at genome-wide significance (P= 5.13E-09 and 1.91E-08, respectively). Metabolomics analysis revealed several amino acids and lipids associated with the identified SNPs with potential roles in performance enhancement.
Conclusions: This is the first report of GWAS significant SNPs and related metabolites associated with elite athlete status. Further investigations of the functional relevance of the identified SNPs and metabolites in relation to enhanced athletic performance are warranted.
Genetic markers-based genome assembly and the reference genome of the selfing fish Kryptolebias hermaphroditus: Identification of 63 cytochrome P450 genes and the interspecific syntenic comparison
Authors: Choi Beom-Soon , Han Jeonghoon , Kim Min-Sub , Sakakura Yoshitaka , Lee Bo-Young , Lee Jae-Seong 
Published: September 2019

Abstract
Background: The selfing fish Kryptolebias hermaphroditus has unique reproductive system for self-fertilization, making genetically homozygous offsprings. Here, we report on high density genetic map-based genome assembly for the K. hermaphroditus Panama line (PanRS).

Results: The numbers of scaffolds were 5,212 and the genome was 683,992,224 bp (N50=27.45 Mb). The length of anchored scaffold onto 24 linkage groups was 652,231,070 bp (95.3% of genome) with the gap 0.01% and GC content 39.33% and complete Benchmarking Universal Single-Copy Orthologs value was 96.6%. The numbers of annotated genes were 36,756 (average gene length 1,368 bp) with the GC content of 54.1%. To examine the difference of two sister species in the genus Kryptolebias, we compared the genomes of K. hermaphroditus PanRS and Kryptolebias marmoratus PAN line on the composition of transposable elements. Also we identified 63 cytochrome P450 (CYP) genes from K. hermaphroditus PanRS with their basal expression levels and compared the syntenies containing loci of CYP genes on five linkage groups.

Conclusions: In this paper, we discussed the potential use of the genome of K. hermaphroditus PanRS with the potential role of duplicated CYP genes, studying in defense mechanism in the view of molecular evolutionary ecotoxicology. This K. hermaphroditus genome information will be helpful for a better understanding on genome-wide mechanistic view of CYP genes over evolution in the view of fish environmental ecotoxicology.
Genomic analysis of a riboflavin-overproducing Ashbya gossypii mutant isolated by disparity mutagenesis
Authors: Kato Tatsuya , Azegami Junya , Yokomori Ami , Dohra Hideo , Enshasy Hesham A. El , Park Enoch Y. 
Published: September 2019

Abstract
Background: Ashbya gossypii naturally overproduces riboflavin and has been utilized for industrial riboflavin production. To improve riboflavin production, various approaches have been developed. In this study, to investigate the change in metabolism of a riboflavin-overproducing mutant, namely, the W122032 strain (MT strain) that was isolated by disparity mutagenesis, genomic analysis was carried out.
Results: In the genomic analysis, 33 homozygous and 1377 heterozygous mutations were detected. Among these heterozygous mutations, the proportion of mutated reads in each gene was different, ranging from 21 to 75%. These results suggest that the MT strain exhibits a mixture of diploidy, triploidy and tetraploidy, or contains multiple nuclei containing different mutations. We tried to isolate haploid spores from the MT strain to prove it ploidy, but these spores were never isolated. This result indicate MT strain does not produce its spores. Homozygous and heterozygous mutations were found in genes encoding enzymes involved in amino acid metabolism, the TCA cycle, purine and pyrimidine nucleotide metabolism and the DNA mismatch repair system. Especially, genes encoding enzymes in mitochondria had many homozygous and heterozygous mutations intensively. These results suggest that the overproduction of riboflavin in the MT strain may be associated with mitochondrial dysfunction.
Conclusion: This study provides new insights into riboflavin production in A. gossypii and the usefulness of disparity mutagenesis for the creation of new types of mutants for metabolic engineering.
Transcriptomic analysis of dead end knockout testis reveals germ cell and gonadal somatic factors in Atlantic salmon
Authors: Kleppe Lene , Edvardsen Rolf Brudvik , Furmanek Tomasz , Andersson Eva , Skaftnesmo Kai Ove , Segafredo Frida Thyri , Wargelius Anna 
Published: September 2019

Abstract
Background
Sustainability challenges are currently hampering an increase in salmon production. Using sterile salmon can solve problems with precocious puberty and genetic introgression from farmed escapees to wild populations. Recently sterile salmon was produced by knocking out the germ cell-specific dead end (dnd). Several approaches may be applied to inhibit Dnd function, including gene knockout, knockdown or immunization. Since it is challenging to develop a successful treatment against a gene product already existing in the body, alternative targets are being explored. Germ cells are surrounded by, and dependent on, gonadal somatic cells. Targeting genes essential for the survival of gonadal somatic cells may be good alternative targets for sterility treatments. Our aim was to identify and characterize novel germ cell and gonadal somatic factors in Atlantic salmon.

Results
We have for the first time analysed RNA-sequencing data from germ cell-free (GCF)/dnd knockout and wild type (WT) salmon testis and searched for genes preferentially expressed in either germ cells or gonadal somatic cells. To exclude genes with extra-gonadal expression, our dataset was merged with available multi-tissue transcriptome data. We identified 389 gonad specific genes, of which 194 were preferentially expressed within germ cells, and 11 were confined to gonadal somatic cells. Interestingly, 5 of the 11 gonadal somatic transcripts represented genes encoding secreted TGF-β factors; gsdf, inha, nodal and two bmp6-like genes, all representative vaccine targets. Of these, gsdf and inha had the highest transcript levels. Expression of gsdf and inha was further confirmed to be gonad specific, and their spatial expression was restricted to granulosa and Sertoli cells of the ovary and testis, respectively. Finally, we show that inha expression increases with puberty in both ovary and testis tissue, while gsdf expression does not change or decreases during puberty in ovary and testis tissue, respectively.

Conclusions
This study contributes with transcriptome data on salmon testis tissue with and without germ cells. We provide a list of novel and known germ cell- and gonad somatic specific transcripts, and show that the expression of two highly active gonadal somatic secreted TGF-β factors, gsdf and inha, are located within granulosa and Sertoli cells.
IPEV: a web server for inferring pathogenic enhancers with variants
Authors: Zhang Guanxiong , Xie Aimin , Bai Jing , Luo Tao , Yuan Huating , Liao Gaoming , Luo Shangyi , Liao Jianlong , Xu Jinyuan , Shi Jian , Zhang Yong , Zhang Xinxin , Zhao Tingting , Xiao Yun , Li Xia 
Published: September 2019

Abstract
Background
Enhancer has been recognized as an important driver whose genetic alterations contribute to disease progression. However, there is still no easy-to-use tools to identify pathogenic enhancers, allowing for deciphering functional influence of genetic variants on enhancer.
Results
We developed a user-friendly one-stop shop platform, named inferring pathogenic enhancer with variant (IPEV), only requiring variants as input, to quickly infer the pathogenic enhancers that harbor variants affecting their activities. Results of IPEV are explored in an interactive, user-friendly web environment, which is designed to highlight the most probable pathogenic enhancers and their target genes. Furthermore, IPEV provides intuitive visualizations of how a variant affects the corresponding enhancer activity by mediating TF binding changes.
Conclusions
IPEV is specially designed to prioritize the potentially pathogenic enhancers with genetic variants, and provides intuitive visualizations how a variant affects the corresponding enhancer activity by mediating which transcription factor binding changes. The use of IPEV does not require any specialized computer skills. We believe that IPEV will be useful in interpreting non-coding variants by the inferring pathogenic enhancers. It is freely available at http://biocc.hrbmu.edu.cn/IPEV/ or http://210.46.80.168/IPEV and supports recent versions of all major browsers.
Unraveling the evolutionary origins of Histone fold motif (HFM) in plants
Authors: Kumar Amish , Yadav Gitanjali 
Published: September 2019

Abstract
Background The three helical Histone Fold Motif (HFM) of core histone proteins provides an evolutionarily favoured site for the protein-DNA interface. Despite significant variation in sequence, the HFM retains a distinctive structural fold that has diversified into several non-histone protein families in. In this work we explore the ancestry of non-histone HFM containing families in the plant kingdom.Results A sequence search algorithm was developed using iterative profile Hidden Markov Models to identify remote homologs of core-histone proteins. The resulting hits were functionally annotated, classified into families, and subjected to comprehensive phylogenetic analyses via Maximum likelihood and Bayesian methods. We have identified over 4000 HFM containing proteins in the plant kingdom that are not histones, mostly existing as diverse transcription factor families, distributed widely within and across taxonomic groups.Conclusion Patterns of homology suggest that core histone subunit H2A has evolved into newer families like NF-YC and DrAp1, whereas the H2B subunit of core histones shares a common ancestry with NF-YB and Dr1 class of TFs. Core histone subunits H3 and H4 were found to have evolved into DPE and TAF proteins, respectively. Taken together these results provide insights into diversification events during the evolution of the histone fold motif, including sub-functionalization and neo-functionalization of the HFM.
Multilocus phylogeny and cryptic diversity of white-toothed shrews (Mammalia, Eulipotyphla, Crocidura) in China
Authors: Chen Shunde , Qing Jiao , Liu Zhu , Liu Yang , Tang Mingkun , Murphy Robert W. , Pu Yingting , Wang Xuming , Guo Keji , Jiang Xuelong , Liu Shaoying 
Published: September 2019

Abstract
Background: Crocidura, the most speciose mammalian genus, occurs across much of Asia, Europe and Africa. In China, the taxonomy has been primarily based on cursory morphological comparisons and molecular phylogenetic relationships of the genus remain unexplored. In order to understand the phylogeny of this group in China, we estimated the first multi-loci phylogeny and conducted species delimitation, including taxon sampling throughout their distribution range.Results: We obtained one mitochondrial gene (~ 1, 134 bp) and three nuclear genes (~ 2, 170 bp) for 132 samples from 57 localities. Molecular analyses identified at least 14 putative species that occur within two major well-supported groups in China. Polyphyletic C. wuchihensis appears to be composed of two putative species. Two subspecies, C. rapax rapax and C. rapax kurodai should be elevated to full species status. A phylogenetic tree based on mitochondrial gene from Asian Crocidura species showed that C. rapax rapax was found embedded within C. attenuate, making the latter a paraphyletic group. Three strongly supported cryptic species are revealed from Motuo of Xizang, Zada of Xizang, Hunan and Zhejiang. The divergence time estimation suggested that China’s Crocidura species began to diversify during the late Pliocene (3.70 Ma) and the Early Pleistocene (2.33 Ma) periods, followed by a series of diversifications through the Pleistocene period.Conclusions: The cryptic diversity found in this study indicated that the number of species is strongly underestimated under the current taxonomy. We propose that the three cryptic species should be evaluated using extensive taxon sampling and comprehensive morphological and morphometric approaches. Climate change since the late Pliocene periods and the uplift of the Himalayas may have resulted in the diversification and speciation of China’s Crocidura species. In short, the underestimated diversity underlines the need for a taxonomic revision of China’s Crocidura species.
Side Effect Concerns and their Impact on Women’s Uptake of Modern Family Planning Methods in Rural Ghana: A Mixed Methods Study
Authors: Schrumpf Leah A. , Stephens Maya J. , Nsarko Nathaniel E. , Akosah Eric , Baumgartner Joy Noel , Ohemeng-Dapaah Seth , Watt Melissa H. 
Published: September 2019

Abstract
Background: Despite availability of modern family planning methods and a desire for smaller families, many women decide to forgo modern methods due to anticipated side effects. The goal of this study was to examine the use of modern family planning in one district in rural Ghana, and to understand the role that side effects play in women’s decisions to start or continue use. Methods: This exploratory mixed-methods study included 281 surveys and 33 in-depth interviews of women 18-49 years old from the Amansie West District of Ghana. The survey assessed contraceptive use and potential predictors of use. In-depth interviews examined the context around uptake and continuation of contraceptive use, with a particular focus on the role of perceived and experienced side effects. Results: The prevalence of unmet need for modern family planning among sexually active women who wanted to avoid pregnancy (n=135) was 68.9%. No factors were found to be significantly different in comparing those with a met need and unmet for modern family planning. Qualitative interviews revealed significant concerns about side effects stemming from previous method experiences and/or rumors regarding short-term impacts and perceived long-term consequences of family planning use. Conclusion: As programs have improved women’s ability to access modern family planning, it is paramount to address patient-level barriers to uptake, in particular information about side effects and misconceptions about long-term use. Unintended pregnancies can be reduced through comprehensive counseling about contraceptive options including accurate information about side effects, and the development of new contraceptive technologies that meet women’s needs in low-income countries.
Spectrometral and histopathological evaluation of metal ion levels in soft tissue around uncemented implants collected during revision hip replacement.
Authors: Kmieć Krzysztof , Kozłowski Piotr , Synder Marek , Borowski Andrzej 
Published: September 2019

Abstract
Background
The aim of the study was to measure metal ion concentration (Ti, Co, Cr, Mo, Ni, Al) around loosened uncemented hip implants and to compare their levels around the cups and steams.
Methods
Soft tissue samples were collected for analysis in 25 patients (25 hips) during revision hip arthroplasty for aseptic loosening in the years 2007-2009. All tissues collected during the revision arthroplasty were submitted for analysis under a light microscope and ICP –MS analysis. All tissues displayed “foreign body” type chronic inflammatory infiltration with PE and/or metal deposits and metallic inclusions.
Results
The Inductively Coupled Plasma Mass Spectrometry study of cementless hip implants revealed that the metal ions pass from loose elements of the implants to the surrounding tissues in significant concentrations ranging from a few hundred to several thousand μg / kg. Moreover, the tissues surrounding the loosened cups contained significantly higher concentrations of Ti and Ni metal ions than the tissue surrounding the steams.
Conclusions
Of all the metal ions used for construction of hip implants, the highest tissue concentration was noted in the case of Ti ions. In any case, regardless of the type of endoprosthesis, the concentrations of Ti and Ni metal ions were higher in tissues surrounding the cup rather than around the stem.
Relationship Between Postural Stability and Falls Risk in Elderly People with Lumbar Spondylosis During Local Vibratory Stimulation for Proprioception: A Cross-sectional Study
Authors: Ito Tadashi , Sakai Yoshihito , Nishio Reiya , Ito Yohei , Yamazaki Kazunori , Morita Yoshifumi 
Published: September 2019

Abstract
Background: The proprioceptive postural strategy for elderly people with lumbar spondylosis who are at risk for falls has not been extensively investigated.
Aims : We aimed to investigate the relationship between proprioceptive postural stability and falls risk in elderly people with lumbar spondylosis.
Methods : In this cross-sectional study, centre-of-pressure displacement was determined in elderly people with lumbar spondylosis during upright stance while standing on a Wii Balance Board with their eyes closed (falls risk group, n = 27; non-fall risk group, n = 88). Vibratory stimulations at 30 Hz were applied to the lumbar multifidus and gastrocnemius to evaluate the relative contribution of different proprioceptive signals used in postural control (relative proprioceptive weighting ratio [RPW]).
Results: Compared with the non-fall risk group, the falls risk group showed a high RPW at 30 Hz (P = 0.002) and high falls score (P < 0.001). Logistic regression analysis revealed that RPW at 30 Hz (odds ratio, 1.2; 95% confidence interval: 1.044–1.194) was independently associated with falls risk after controlling for confounding factors. Among variables of falls risk, RPW at 30 Hz was found to be a significant factor (P < 0.001).
Discussion: The falls risk group of elderly people with lumbar spondylosis was at a higher risk for falls, which was exacerbated by RPW at 30 Hz depending on the ankle strategy. A decrease in the input of the muscle spindles in the lumbar multifidus could be a possible mechanism underlying the decreased reliance on lumbar muscle proprioception in these individuals.
Managing clustering effects and learning effects in the design and analysis of multicentre randomised trials: A survey to establish current practice
Authors: Conroy Elizabeth J. , Blazeby Jane M. , Burnside Girvan , Cook Jonathan A , Gamble Carrol 
Published: September 2019

Abstract
Background

Patient outcomes can depend on the treating centre, or health professional, delivering the intervention. Skills of health professionals improve with experience in delivery, meaning that outcomes may also be associated with changes in skill, or learning. Considering any potential difference in intervention delivery at trial design will ensure that any adjustments can be made, as appropriate, at the analysis. The objective of this work was to establish current practice for the allowance of clustering and learning effects in the design and analysis of randomised multicentre trials.

Methods

A ten-question survey was developed comprising open and closed questions that drew upon quotes from existing guidelines, references to relevant publications, and example trial scenarios. It was piloted and checked for face validity within the research team. All registered UK Clinical Research Collaborative registered Clinical Trials Units were invited to participate.

Results

Completed surveys were obtained from 44 of 50 Units. Clustering was managed through design by stratification, commonly by centre and less commonly by treatment provider. Most Units had allowed for learning by design through defining a minimum level of expertise for treatment provider (89%). One third of Units reported experience of expertise-based designs. The majority of Units indicated experience in adjusting for clustering during analysis, by centre or treatment provider, although approaches to doing so varied. Analysis of learning was rarely performed for the main analysis (n=1), although many Units reported approaches to consider such effects, such as sensitivity analyses. Responders provided insight behind the approaches used within their Unit and reasons for, or against, alternative approaches.

Conclusion

This survey identifies widespread awareness of the potential methodological challenges associated with the design and analysis of multicentre trials, although approaches used and opinions on these vary. These results suggest that variation in approaches used exists both across Units and within, suggesting that this decision can depend on the type of trial being conducted. Reasons for approaches were provided and approaches justified by responders. These results highlight the need for more agreement between triallists about how to best design and analyse trials of different types and/or further research to establish optimal methods.