bluuebunny/crossref_metadata_2025_split huggingface dataset:
Migraine screen questionnaire: further psychometric evidence from categorical data methods
Authors: Manzar Md. Dilshad , Hameed Unaise Abdul , Salahuddin Mohammed , Khan Mohammad Yunus Ali , Nureye Dejen , Wakene Wakuma , Alamri Majed , Albougami Abdulrhman , PandiPerumal Seithikuruppu R. , Bahammam Ahmed S. 
Published: April 2020

AbstractBackgroundPsychometric investigations of tools used in the screening of migraine including the migraine screen questionnaire (MS-Q), using an adequate statistical approach is needed. We assessed the psychometric properties of the migraine screen questionnaire (MS-Q) using categorical data methods.Material and methodsA total of 343 students at Mizan-Tepi University, Ethiopia, age range = 18–35 years were selected by a simple random sampling method to participate in a cross-sectional study. The respondents completed the MS-Q, a semi-structured socio-demographic questionnaire, and a visual analog scale for attention (VAS-A).ResultsThe cumulative variance rule (> 40%), the Kaiser’s criteria (Eigenvalue> 1), the Scree test and, the parallel analysis (minimum rank) identified a 1-factor model for the MS-Q with the factor loadings in the range of 0.78 to 0.84. Fit indices favored a 1-factor model of the MS-Q as indicated by comparative fit index (0.993), weighted root mean square residual (0.048), root mean square error of approximation (0.067), the goodness of fit index (1.00), and non-normed fit index (0.987). The values of the Factor Determinacy Index (0.953), marginal reliability (0.909), H-latent (0.909), H-observed (0.727), explained common variance (0.906) and the mean item residual absolute loadings (0.225) further complimented finding of the 1-Factor model. McDonald’s Omega (0.903) suggested adequate internal consistency. Discriminative validity was supported by significantly higher scores for the total and all the MS-Q items except one among those with complaints of attention.ConclusionThe categorical methods support the psychometric validity of the MS-Q in the study population.
Correction to: LncRNA AFAP1-AS1 promotes tumorigenesis and epithelial-mesenchymal transition of osteosarcoma through RhoC/ROCK1/p38MAPK/Twist1 signaling pathway
Authors: Shi Deyao , Wu Fashuai , Mu Shidai , Hu Binwu , Zhong Binlong , Gao Feng , Qing Xiangcheng , Liu Jianxiang , Zhang Zhicai , Shao Zengwu 
Published: April 2020

In the original publication of this manuscript [1], Fig. 5a needs to be revised, and adjustments have also been made to the captions for Figs. 2, 4, 5 and S1 to improve clarity for the reader.
COVID-19: ICU delirium management during SARS-CoV-2 pandemic
Authors: Kotfis Katarzyna , Williams Roberson Shawniqua , Wilson Jo Ellen , Dabrowski Wojciech , Pun Brenda T. , Ely E. Wesley 
Published: April 2020

AbstractThe novel coronavirus, SARS-CoV-2-causing Coronavirus Disease 19 (COVID-19), emerged as a public health threat in December 2019 and was declared a pandemic by the World Health Organization in March 2020. Delirium, a dangerous untoward prognostic development, serves as a barometer of systemic injury in critical illness. The early reports of 25% encephalopathy from China are likely a gross underestimation, which we know occurs whenever delirium is not monitored with a valid tool. Indeed, patients with COVID-19 are at accelerated risk for delirium due to at least seven factors including (1) direct central nervous system (CNS) invasion, (2) induction of CNS inflammatory mediators, (3) secondary effect of other organ system failure, (4) effect of sedative strategies, (5) prolonged mechanical ventilation time, (6) immobilization, and (7) other needed but unfortunate environmental factors including social isolation and quarantine without family. Given early insights into the pathobiology of the virus, as well as the emerging interventions utilized to treat the critically ill patients, delirium prevention and management will prove exceedingly challenging, especially in the intensive care unit (ICU). The main focus during the COVID-19 pandemic lies within organizational issues, i.e., lack of ventilators, shortage of personal protection equipment, resource allocation, prioritization of limited mechanical ventilation options, and end-of-life care. However, the standard of care for ICU patients, including delirium management, must remain the highest quality possible with an eye towards long-term survival and minimization of issues related to post-intensive care syndrome (PICS). This article discusses how ICU professionals (e.g., physicians, nurses, physiotherapists, pharmacologists) can use our knowledge and resources to limit the burden of delirium on patients by reducing modifiable risk factors despite the imposed heavy workload and difficult clinical challenges posed by the pandemic.
Varlociraptor: enhancing sensitivity and controlling false discovery rate in somatic indel discovery
Authors: Köster Johannes , Dijkstra Louis J. , Marschall Tobias , Schönhuth Alexander 
Published: April 2020

AbstractAccurate discovery of somatic variants is of central importance in cancer research. However, count statistics on discovered somatic insertions and deletions (indels) indicate that large amounts of discoveries are missed because of the quantification of uncertainties related to gap and alignment ambiguities, twilight zone indels, cancer heterogeneity, sample purity, sampling, and strand bias. We provide a unifying statistical model whose dependency structures enable accurate quantification of all inherent uncertainties in short time. Consequently, false discovery rate (FDR) in somatic indel discovery can now be controlled at utmost accuracy, increasing the amount of true discoveries while safely suppressing the FDR.
CircAtlas: an integrated resource of one million highly accurate circular RNAs from 1070 vertebrate transcriptomes
Authors: Wu Wanying , Ji Peifeng , Zhao Fangqing 
Published: April 2020

AbstractExisting circular RNA (circRNA) databases have become essential for transcriptomics. However, most are unsuitable for mining in-depth information for candidate circRNA prioritization. To address this, we integrate circular transcript collections to develop the circAtlas database based on 1070 RNA-seq samples collected from 19 normal tissues across six vertebrate species. This database contains 1,007,087 highly reliable circRNAs, of which over 81.3% have been assembled into full-length sequences. We profile their expression pattern, conservation, and functional annotation. We describe a novel multiple conservation score, co-expression, and regulatory networks for circRNA annotation and prioritization. CircAtlas can be accessed at http://circatlas.biols.ac.cn/.
Centromeric cohesion failure invokes a conserved choreography of chromosomal mis-segregations in pancreatic neuroendocrine tumor
Authors: Quevedo Rene , Spreafico Anna , Bruce Jeff , Danesh Arnavaz , El Ghamrasni Samah , Giesler Amanda , Hanna Youstina , Have Cherry , Li Tiantian , Yang S. Y. Cindy , Zhang Tong , Asa Sylvia L. , Haibe-Kains Benjamin , Krzyzanowska Monika , Smith Adam C. , Singh Simron , Siu Lillian L. , Pugh Trevor J. 
Published: April 2020

Abstract
Background
Pancreatic neuroendocrine tumors (PANETs) are rare, slow growing cancers that often present with local and distant metastasis upon detection. PANETS contain distinct karyotypes, epigenetic dysregulation, and recurrent mutations in MEN1, ATRX, and DAXX (MAD+); however, the molecular basis of disease progression remains uncharacterized.

Methods
We evaluated associations between aneuploidy and the MAD+ mutational state of 532 PANETs from 11 published genomic studies and 19 new cases using a combination of exome, targeted panel, shallow WGS, or RNA-seq. We mapped the molecular timing of MAD+ PANET progression using cellular fractions corrected for inferred tumor content.

Results
In 287 PANETs with mutational data, MAD+ tumors always exhibited a highly recurrent signature of loss of heterozygosity (LOH) and copy-number alterations affecting 11 chromosomes, typically followed by genome doubling upon metastasis. These LOH chromosomes substantially overlap with those that undergo non-random mis-segregation due to ectopic CENP-A localization to flanking centromeric regions in DAXX-depleted cell lines. Using expression data from 122 PANETs, we found decreased gene expression in the regions immediately adjacent to the centromere in MAD+ PANETs. Using 43 PANETs from AACR GENIE, we inferred this signature to be preceded by mutations in MEN1, ATRX, and DAXX. We conducted a meta-analysis on 226 PANETs from 8 CGH studies to show an association of this signature with metastatic incidence. Our study shows that MAD+ tumors are a genetically diverse and aggressive subtype of PANETs that display extensive chromosomal loss after MAD+ mutation, which is followed by genome doubling.

Conclusions
We propose an evolutionary model for a subset of aggressive PANETs that is initiated by mutation of MEN1, ATRX, and DAXX, resulting in defects in centromere cohesion from ectopic CENP-A deposition that leads to selective loss of chromosomes and the LOH phenotype seen in late-stage metastatic PANETs. These insights aid in disease risk stratification and nominate potential therapeutic vulnerabilities to treat this disease.
Exploratory analysis of age and sex dependent DNA methylation patterns on the X-chromosome in whole blood samples
Authors: Li Shuxia , Lund Jesper B. , Christensen Kaare , Baumbach Jan , Mengel-From Jonas , Kruse Torben , Li Weilong , Mohammadnejad Afsaneh , Pattie Alison , Marioni Riccardo E. , Deary Ian J. , Tan Qihua 
Published: April 2020

Abstract
Background
Large numbers of autosomal sites are found differentially methylated in the aging genome. Due to analytical difficulties in dealing with sex differences in X-chromosome content and X-inactivation (XCI) in females, this has not been explored for the X chromosome.

Methods
Using data from middle age to elderly individuals (age 55+ years) from two Danish cohorts of monozygotic twins and the Scottish Lothian Birth Cohort 1921, we conducted an X-chromosome-wide analysis of age-associated DNA methylation patterns with consideration of stably inferred XCI status.

Results
Through analysing and comparing sex-specific X-linked DNA methylation changes over age late in life, we identified 123, 293 and 55 CpG sites significant (FDR < 0.05) only in males, only in females and in both sexes of Danish twins. All findings were significantly replicated in the two Danish twin cohorts. CpG sites escaping XCI are predominantly de-methylated with increasing age across cohorts. In contrast, CpGs highly methylated in both sexes are methylated even further with increasing age. Among the replicated sites in Danish samples, 16 (13%), 24 (8.2%) and 3 (5.5%) CpGs were further validated in LBC1921 (FDR < 0.05).

Conclusions
The X-chromosome of whole blood leukocytes displays age- and sex-dependent DNA methylation patterns in relation to XCI across cohorts.
Self-reactive T cells induce and perpetuate chronic relapsing arthritis
Authors: Tuncel Jonatan , Holmberg Jens , Haag Sabrina , Hopkins Malin Hultqvist , Wester-Rosenlöf Lena , Carlsen Stefan , Olofsson Peter , Holmdahl Rikard 
Published: April 2020

Abstract
Background
CD4+ T cells play a central role during the early stages of rheumatoid arthritis (RA), but to which extent they are required for the perpetuation of the disease is still not fully understood. The aim of the current study was to obtain conclusive evidence that T cells drive chronic relapsing arthritis.

Methods
We used the rat pristane-induced arthritis model, which accurately portrays the chronic relapsing-remitting disease course of RA, to examine the contribution of T cells to chronic arthritis.

Results
Rats subjected to whole-body irradiation and injected with CD4+ T cells from lymph nodes of pristane-injected donors developed chronic arthritis that lasted for more than 4 months, whereas T cells from the spleen only induced acute disease. Thymectomy in combination with irradiation enhanced the severity of arthritis, suggesting that sustained lymphopenia promotes T cell-driven chronic inflammation in this model. The ability of T cells to induce chronic arthritis correlated with their expression of Th17-associated transcripts, and while depletion of T cells in rats with chronic PIA led to transient, albeit significant, reduction in disease, neutralization of IL-17 resulted in almost complete and sustained remission.

Conclusion
These findings show that, once activated, self-reactive T cells can sustain inflammatory responses for extended periods of time and suggest that such responses are promoted in the presence of IL-17.
Dysregulation of 2-oxoglutarate-dependent dioxygenases by hyperglycaemia: does this link diabetes and vascular disease?
Authors: Green Hannah L. H. , Brewer Alison C. 
Published: April 2020

AbstractThe clinical, social and economic burden of cardiovascular disease (CVD) associated with diabetes underscores an urgency for understanding the disease aetiology. Evidence suggests that the hyperglycaemia associated with diabetes is, of itself, causal in the development of endothelial dysfunction (ED) which is recognised to be the critical determinant in the development of CVD. It is further recognised that epigenetic modifications associated with changes in gene expression are causal in both the initiation of ED and the progression to CVD. Understanding whether and how hyperglycaemia induces epigenetic modifications therefore seems crucial in the development of preventative treatments. A mechanistic link between energy metabolism and epigenetic regulation is increasingly becoming explored as key energy metabolites typically serve as substrates or co-factors for epigenetic modifying enzymes. Intriguing examples are the ten-eleven translocation and Jumonji C proteins which facilitate the demethylation of DNA and histones respectively. These are members of the 2-oxoglutarate-dependent dioxygenase superfamily which require the tricarboxylic acid metabolite, α-ketoglutarate and molecular oxygen (O2) as substrates and Fe (II) as a co-factor. An understanding of precisely how the biochemical effects of high glucose exposure impact upon cellular metabolism, O2 availability and cellular redox in endothelial cells (ECs) may therefore elucidate (in part) the mechanistic link between hyperglycaemia and epigenetic modifications causal in ED and CVD. It would also provide significant proof of concept that dysregulation of the epigenetic landscape may be causal rather than consequential in the development of pathology.
Estimation of inbreeding and identification of regions under heavy selection based on runs of homozygosity in a Large White pig population
Authors: Shi Liangyu , Wang Ligang , Liu Jiaxin , Deng Tianyu , Yan Hua , Zhang Longchao , Liu Xin , Gao Hongmei , Hou Xinhua , Wang Lixian , Zhao Fuping 
Published: April 2020

Abstract
Background
Runs of homozygosity (ROHs) are homozygous segments of the genome where the two haplotypes inherited from the parents are identical. The current availability of genotypes for a very large number of single nucleotide polymorphisms (SNPs) is leading to more accurate characterization of ROHs in the whole genome. Here, we investigated the occurrence and distribution of ROHs in 3,692 Large White pigs and compared estimates of inbreeding coefficients calculated based on ROHs (FROH), homozygosity (FHOM), genomic relationship matrix (FGRM) and pedigree (FPED). Furthermore, we identified genomic regions with high ROH frequencies and annotated their candidate genes.

Results
In total, 176,182 ROHs were identified from 3,569 animals, and all individuals displayed at least one ROH longer than 1 Mb. The ROHs identified were unevenly distributed on the autosomes. The highest and lowest coverages of Sus scrofa chromosomes (SSC) by ROH were on SSC14 and SSC13, respectively. The highest pairwise correlation among the different inbreeding coefficient estimates was 0.95 between FROH_total and FHOM, while the lowest was − 0.083 between FGRM and FPED. The correlations between FPED and FROH using four classes of ROH lengths ranged from 0.18 to 0.37 and increased with increasing ROH length, except for ROH > 10 Mb. Twelve ROH islands were located on four chromosomes (SSC1, 4, 6 and 14). These ROH islands harboured genes associated with reproduction, muscular development, fat deposition and adaptation, such as SIRT1, MYPN, SETDB1 and PSMD4.

Conclusion
FROH can be used to accurately assess individual inbreeding levels compared to other inbreeding coefficient estimators. In the absence of pedigree records, FROH can provide an alternative to inbreeding estimates. Our findings can be used not only to effectively increase the response to selection by appropriately managing the rate of inbreeding and minimizing the negative effects of inbreeding depression but also to help detect genomic regions with an effect on traits under selection.
Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues
Authors: Li Meng-Yuan , Li Lin , Zhang Yue , Wang Xiao-Sheng 
Published: April 2020

AbstractBackgroundSince its discovery in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 2 180 000 people worldwide and has caused more than 150 000 deaths as of April 16, 2020. SARS-CoV-2, which is the virus causing coronavirus disease 2019 (COVID-19), uses the angiotensin-converting enzyme 2 (ACE2) as a cell receptor to invade human cells. Thus, ACE2 is the key to understanding the mechanism of SARS-CoV-2 infection. This study is to investigate the ACE2 expression in various human tissues in order to provide insights into the mechanism of SARS-CoV-2 infection.MethodsWe comparedACE2expression levels across 31 normal human tissues between males and females and between younger (ages ≤ 49 years) and older (ages > 49 years) persons using two-sided Student’sttest. We also investigated the correlations betweenACE2expression and immune signatures in various tissues using Pearson’s correlation test.ResultsACE2expression levels were the highest in the small intestine, testis, kidneys, heart, thyroid, and adipose tissue, and were the lowest in the blood, spleen, bone marrow, brain, blood vessels, and muscle.ACE2showed medium expression levels in the lungs, colon, liver, bladder, and adrenal gland.ACE2was not differentially expressed between males and females or between younger and older persons in any tissue. In the skin, digestive system, brain, and blood vessels,ACE2expression levels were positively associated with immune signatures in both males and females. In the thyroid and lungs,ACE2expression levels were positively and negatively associated with immune signatures in males and females, respectively, and in the lungs they had a positive and a negative correlation in the older and younger groups, respectively.ConclusionsOur data indicate that SARS-CoV-2 may infect other tissues aside from the lungs and infect persons with different sexes, ages, and races equally. The different host immune responses to SARS-CoV-2 infection may partially explain why males and females, young and old persons infected with this virus have markedly distinct disease severity. This study provides new insights into the role of ACE2 in the SARS-CoV-2 pandemic.
Multiobjective clustering algorithm for complex data in learning management systems
Authors: Ramadan Rabie A. , Alhaisoni Majed Mohaia , Khedr Ahmed Y. 
Published: April 2020

AbstractLearning Management Systems (LMS) is now an emergent technology where massive data are collected and requires handling. This data comes from different sources with multiple features which represents another complex paradigm. However, as part of business intelligence and decision support, this data needs to be classified and analyzed for the management, teachers, as well as students to make the appropriate decisions. Thus, one of the effective data analysis methods is clustering. However, LMS data encompasses multi-features, which are not sufficient to make appropriate decisions. Therefore, single feature clustering algorithms would not help LMS decision-makers. Consequently, multifeatured/multiobjective clustering algorithms could be one of the proposed solutions. Thus, looking at different multiobjective clustering algorithms as compared to the LMS nature of data, those algorithms do not satisfy the clustering purpose. In addition, the LMS data could be huge, complex, and sequential algorithms would not help as well. Thus, this paper is a step forward towards clustering LMS data for better decision making. The paper proposes a new clustering framework based upon distributed systems and a new multiobjective algorithm for the purpose of LMS clustering. The algorithm has been examined experimentally in order to answer some of the questions that help taking decision based upon LMS collected data.
Association of Aβ with ceramide-enriched astrosomes mediates Aβ neurotoxicity
Authors: Elsherbini Ahmed , Kirov Alexander S. , Dinkins Michael B. , Wang Guanghu , Qin Haiyan , Zhu Zhihui , Tripathi Priyanka , Crivelli Simone M. , Bieberich Erhard 
Published: April 2020

AbstractAmyloid-β (Aβ) associates with extracellular vesicles termed exosomes. It is not clear whether and how exosomes modulate Aβ neurotoxicity in Alzheimer’s disease (AD). We show here that brain tissue and serum from the transgenic mouse model of familial AD (5xFAD) and serum from AD patients contains ceramide-enriched and astrocyte-derived exosomes (termed astrosomes) that are associated with Aβ. In Neuro-2a cells, primary cultured neurons, and human induced pluripotent stem cell-derived neurons, Aβ-associated astrosomes from 5xFAD mice and AD patient serum were specifically transported to mitochondria, induced mitochondrial clustering, and upregulated the fission protein Drp-1 at a concentration corresponding to 5 femtomoles Aβ/L of medium. Aβ-associated astrosomes, but not wild type or control human serum exosomes, mediated binding of Aβ to voltage-dependent anion channel 1 (VDAC1) and subsequently, activated caspases. Aβ-associated astrosomes induced neurite fragmentation and neuronal cell death, suggesting that association with astrosomes substantially enhances Aβ neurotoxicity in AD and may comprise a novel target for therapy.