bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associated Risk Factors and Prevalence of Sleep Disorders in Patients With Rheumatoid Arthritis.
Authors: Santos-Moreno Pedro , Castro Carlos Alberto , Villarreal Laura , Sánchez-Vanegas Guillermo 
Published: October 2020

Abstract
Background: Rheumatoid arthritis (RA) is an autoimmune chronic pathology, present in between 0.5% and 1% of adults. This disease is accompanied by comorbidities such as sleep disorders (SD) that occur in between 54% and 70% of the population with RA. The objective of this study was to identify the associated risk factors and the prevalence of sleep disorders in a group of patients with rheumatoid arthritis in a referral center for the management of autoimmune diseases in Bogotá, Colombia.Methods: An analytical cross-sectional study was carried out on a population of patients with Rheumatoid Arthritis (RA) evaluated with the DSM-V. The factors related to sleep disorders and disease activity of were explored. The prevalence of sleep disorders was determined, and a multivariate logistic regression analysis was conducted.Results: the study analyzed a total of 1436 patients, with a median age of 56 years. The prevalence of sleep disorders was 31.1%. There was an association between the presence of sleep disorders and Disease Activity Score 28 (DAS28) (OR: 3.8 CI 95%: 3-5), Health Assessment Questionnaire (HAQ) (OR: 3.2 CI 95%: 2.5-4.1), self-care activities (OR: 0.6 CI 95%: 0.4-0.9), and somatic symptom disorder (OR: 1.8, CI 95%: 1.3-2.6). Conclusions: An association (p-value <0.05) was found between SDs and disease activity (DAS28), functional capacity (HAQ), scholarship level, smoking, sedentary lifestyle, metabolic diseases, and leisure and self-care activities. In one third of patients SD were prevalent. It is suggested that patients be approached comprehensively carrying out behavioral and cognitive activities.
An Association Study of Candidate Gene Variants in Chinese Nonsyndromic Cleft Lip with or without Palate Subjects
Authors: Niu Zhenmin , Peng Li , Chen Jiapei , Wan Teng , Wu Dandan , Yang Yusheng , Wang Guomin , Yang Lin , Huang Wei , Chen Zhenqi 
Published: October 2020

Abstract
Background: Nonsyndromic cleft lip with or without palate is a common birth defect of complex etiology involving the interaction of genetic factors and environmental exposures. Previous reports identified several candidate genes and risk variants of the disease, and their functions were verified by model animal studies. Methods: In order to depict the composition of the orofacial cleft susceptibility loci in Chinese population, we genotyped ten common SNPs of six genes (VAX1, MAFB, PAX7, ABCA4, NTN1 and NOG) in 249 nonsyndromic cleft lip with or without palate individuals, 62 nonsyndromic cleft palate only individuals and 480 controls. Results: Three loci: VAX1 rs7078160, MAFB rs11696257 and NTN1 rs4791774 showed significant relevance with NSCL/P. Carrying both VAX1 rs7078160 and NTN1 rs4791774 further increased the risk, compared with carrying only one of them. Conclusions: This result supported that SNPs of genes VAX1, MAFB and NTN1 are associated with NSCL/P in Chinese subjects.
Cell-Free DNA and Circulating Tumor Cell Kinetics in a Pre-Clinical Head and Neck Cancer Model Undergoing Radiation Therapy
Authors: Muhanna Nidal , Eu Donovan , Chan Harley HL , Douglas Catriona , Townson Jason , Grappa Marco A Di , Mohamadi Reza M , Kelley Shana O. , Bratman Scott V , Irish Jonathan C 
Published: October 2020

Abstract
Background: Monitoring circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs), known as liquid biopsies, continue to be developed as diagnostic and prognostic markers for a wide variety of cancer indications, mainly due to their minimally invasive nature and ability to offer a wide range of phenotypic and genetic information. While liquid biopsies maintain significant promising benefits, there is still limited information regarding the kinetics of ctDNA and CTCs following radiation therapy which remains a vital treatment modality in head and neck cancers. This study aims to describe the kinetics of ctDNA and CTCs following radiation exposure in a preclinical rabbit model with VX2 induced buccal carcinoma. Methods: Seven rabbits were inoculated with VX2 cells in the buccal mucosa and subjected to radiation. At selected time points, blood sampling was performed to monitor differing levels of ctDNA and CTC. Plasma ctDNA was measured with quantitative PCR for papillomavirus E6 while CTCs were quantified using an immunomagnetic nanoparticles within a microfluidic device. Comparisons of CTC detection with EpCAM compared to multiple surface markers (EGFR, HER2 and PSMA) was evaluated and correlated with the tumor size.Results: Plasma ctDNA reflects the overall tumor burden within the animal model. Analysis of correlations between ctDNA with tumor and lymph node volumes showed a positive correlation (R= 0.452 and R = 0.433 [p <0.05]), respectively. Over the course of treatment, ctDNA levels declined and quickly becomes undetectable following tumor eradication. While during the course of treatment, ctDNA levels were noted to rise particularly upon initiation of radiation following scheduled treatment breaks. Levels of CTCs were observed to increase 1 week following inoculation of tumor to the primary site. For CTC detection, the use of multiple surface markers showed a greater sensitivity when compared to detection using only EpCAM. Plasma CTC levels remained elevated following radiation therapy which may account for an increased shedding of CTCs following radiation.Conclusion: This study demonstrates the utility of ctDNA and CTCs detection in response to radiation treatment in a preclinical head and neck model, allowing for better understanding of liquid biopsy applications in both clinical practice and research development.
Rare and Potentially Pathogenic Variants in Hydroxycarboxylic Acid Receptor Genes Identified in Breast Cancer Cases.
Authors: Sams Cierla McGuire , Shepp Kasey , Pugh Jada , Bishop Madison R. , Merner Nancy D. 
Published: October 2020

Abstract
BackgroundThree genes, clustered together on chromosome 12, comprise a group of Hydroxycarboxylic Acid Receptors (HCARs), HCAR1, HCAR2, and HCAR3. These paralogous genes encode different G-protein coupled receptors that are responsible for detecting glycolytic metabolites and controlling fatty acid oxidation. Though better known for regulating lipid metabolism in adipocytes, more recently HCARs have been functionally associated with breast cancer proliferation/survival; HCAR2 has been described as a tumor suppressor, and HCAR1 and HCAR3 as oncogenes. Thus, we sought to identify genetic variants in HCAR1, HCAR2, and HCAR3 that could potentially be associated with breast cancer. MethodsDue to the extreme homology between HCAR1, HCAR2, and HCAR3, primers were carefully designed to amplify each gene separately through nested PCRs followed by Sanger sequencing. Forty-six unrelated breast cancer cases were screened for rare, non-synonymous coding variants. ResultsUpon screening, a total of four variants were identified in four different cases, each with estrogen receptor-positive (ER+) breast cancer. The variants were identified exclusively in HCAR1 and HCAR3. In HCAR1, two highly conserved and potentially damaging missense variants were identified, c.58C>G;p.Pro20Ala and c.721C>T;p.Leu241Phe. Statistical analyses revealed that c.58C>G;p.Pro20Ala was in significantly more cases than controls. In HCAR3, in addition to the breast cancer-associated missense variant c.560G>A;p.Arg187Gln, a frameshift mutation, c.1117delC;p.Gln373Lysfs*82, was detected that greatly extends the C-terminus and changes the secondary and tertiary protein structure. ConclusionsDue to the important role of HCARs in breast cancer, it is vital to understand how these genetic variants play a role in breast cancer risk and proliferation, as well as their consequences on treatment strategies. Due to the small sample size, additional and larger studies will be needed to validate these findings. Nevertheless, the identification of these potentially pathogenic variants supports the need to investigate their functional consequences.
Identification of repurposable cytoprotective drugs in Vanishing White Matter Disease patient-derived cells
Authors: Ng Neville , Cabral-da-Silva Mauricio Castro , Maksour Simon , Berg Tracey , Engel Martin , Silva Dina M. , Do-Ha Dzung , Lum Jeremy S. , Muñoz Sonia Sanz , Suarez-Bosche Nadia , Stevens Claire H. , Ooi Lezanne 
Published: October 2020

Abstract
Background Vanishing white matter disease (VWMD) is a rare leukodystrophy caused by mutations of the guanine exchange factor eIF2B. VWMD typically presents with juvenile onset, and there are few treatments for the disease. Recent progress in the field has established mitochondrial dysfunction and endoplasmic reticulum (ER) stress to be strongly implicated in observed glial cell pathology. Drug repurposing offers a rapid approach toward translation of therapeutics using already-licensed drugs. Objective The aim of this study was to use fibroblasts and induced pluripotent stem cell (iPSC)-derived astrocytes from patients bearing the EIF2B5R113H/A403V or EIF2B2G200V/E213G VWMD mutations to identify potentially repurposable FDA-approved drugs based on in vitro assays. Methods Cell viability in the presence or absence of stress was assessed by resazurin reduction activity and assays for mitochondrial membrane potential, and oxidative stress. Integrated stress response markers, including eIF2α phosphorylation, GADD34 and CHOP were quantified by fluorescent western blot. Results Dysregulated GADD34 and CHOP were identified in patient fibroblasts and iPSC-derived astrocytes under induced stress conditions. A drug screen from a 2,400 FDA-approved drug library with EIF2B5R113H/A403V VWMD patient fibroblasts identified 113 anti-inflammatory drugs as a major class of hits with cytoprotective effects. A panel of potential candidate drugs, including berberine, deflazacort, ursodiol, zileuton, guanabenz and Anavex 2-73, and preclinical ISRIB, increased cell survival of EIF2B5R113H/A403V or EIF2B2G200V/E213G VWMD astrocytes, and were further investigated for their effect on the integrated stress response and mitochondrial stress. Ursodiol demonstrated capacity to ameliorate oxidative stress and loss of mitochondrial membrane potential in VWMD patient iPSC-derived astrocytes in the presence or absence of stress conditions. Conclusion Patient-derived cells can be used to identify cellular phenotypes and for large-scale drug screening. Anti-inflammatory compounds, such as berberine, deflazacort, ursodiol and zileuton are potentially repurposable drug candidates for VWMD that should be further investigated for translation in vivo.
De novo profiling of long non-coding RNAs involved in MC-LR–induced liver injury in whitefish: discovery and perspectives
Authors: Florczyk Maciej , Brzuzan Paweł , Woźny Maciej 
Published: October 2020

Abstract

BackgroundMicrocystin-LR (MC-LR) is a potent hepatotoxin for which a substantial gap in knowledge persists regarding the underlying molecular mechanisms of liver toxicity and injury. Although long non-coding RNAs (lncRNAs) have been extensively studied in model organisms, and their roles have been identified in various cellular processes including participation in regulation of gene expression together with microRNAs, our knowledge concerning the role of lncRNAs in liver injury is limited even in mammals. Given that lncRNAs show low levels of sequence conservation, their role becomes even more unclear in non-model organisms without an annotated genome, like whitefish (Coregonus lavaretus). The objective of this study was to discover and profile aberrantly expressed polyadenylated lncRNAs that are involved in MC-LR–induced liver injury in whitefish.ResultsUsing polyA-enriched RNA-Seq data, we de novo assembled a high quality whitefish liver transcriptome. This enabled us to find 94 differentially expressed (DE) putative evolutionary-conserved lncRNAs (orthologous to known lncRNAs in other species), such as MALAT1, HOTTIP, HOTAIR or HULC and 4,429 DE putative novel whitefish lncRNAs, which differed from annotated protein-coding transcripts (PCTs) in terms of minimum free energy, GC base-pair content and length. Additionally, we identified DE non-coding transcripts that might be 3’ autonomous untranslated regions of mRNAs (3’UTRs). We found that, in response to MC-LR treatment, these potential 3’UTRs could either be coexpressed with PCTs from the same mRNA, or the 3’UTRs were upregulated while the corresponding PCTs were downregulated, suggesting 3’UTR-dependent gene regulation.ConclusionsTo our knowledge this is the first report on aberrantly expressed lncRNAs in MC-LR–induced liver injury in whitefish. We found both evolutionary conserved lncRNAs as well as novel whitefish lncRNAs that could serve as biomarkers of severe and chronic liver injury. The lncRNA sequence data files and raw sequence files are available in the Dryad Digital Repository and the NCBI Sequence Read Archive, respectively.
Sustainable Development in the Wake of Covid-19
Authors: Nerini Francesco Fuso , Henrysson Maryna , Swain Ashok , Swain Ranjula Bali 
Published: October 2020

Abstract
The ´decade of action´ to achieve the ambitious 17 Sustainable Development Goals by 2030 is off to a very challenging start. With progress on the achievement of most SDGs already lagging behind even before the Covid-19 crisis – our analysis finds that the pandemic negatively affects the achievement of 144 targets (almost 90%) of the SDGs. However, 66 targets (ca. 40%) could potentially benefit from the changes spurred by the crisis, given that the appropriate decisions are made. Holistic response and leadership are needed to ensure an inclusive economic recovery while protecting the environment. Furthermore, our analysis of the literature documents the unprecedented speed of the international community to assess the impacts of the pandemic. Future research should gather data to better understand the impacts of the pandemic locally and globally, and produce long-term analyses to inform the sustainable recovery across all SDGs.
Genome-Wide DNA Methylation Variations Between Grass Carp with Different Ages
Authors: He Libo , Zhu Denghui , Chu Pengfei , Li Yongming , Liao Lanjie , Huang Rong , Zhu Zuoyan , Wang Yaping 
Published: October 2020

Abstract
Background: Grass carp is an important farmed fish in China that infected by many pathogens, especially grass carp reovirus (GCRV). Notably, grass carp showed age-dependent susceptibility to GCRV, while the mechanism remains unclear. Herein, we performed a genome-wide survey of differences in DNA methylation and gene expression between five months old grass carp (FMO, sensitive to GCRV) and three years old grass carp (TYO, resistant to GCRV) aim to uncover the mechanism.Results: Colorimetric quantification revealed global methylation level of TYO fish was higher than that of FMO fish. Whole-genome bisulfite sequencing (WGBS) of two groups revealed 6,214 differentially methylated regions (DMRs) and 4,052 differentially methylated genes (DMGs), with most of DMRs and DMGs showed hypermethylation patterns in TYO fish. Correlation analysis indicated that DNA hypomethylation in promoter negative correlated with gene expression, whereas positive correlation was found between gene-body DNA hypermethylation and gene expression. Enrichment analysis revealed that promoter hypo-DMGs in TYO fish were significant enriched in pathways involved in immune response while gene-body hyper-DMGs in TYO fish were significant enriched in terms related to RNA transcription, biosynthetic, and energy production. RNA-seq indicated these terms or pathways involved in immune response, biosynthetic, and energy production also significant enriched for the up-regulated genes in TYO fish. Conclusions: Collectively, these results revealed the genome-wide DNA methylation variations between grass carp with different ages. DNA methylation and gene expression variations in genes involved in immune response, biosynthetic, and energy production may contributed to the age-dependent susceptibility to GCRV in grass carp. Our results will provide important information for the disease-resistant breeding programs of grass carp and may also benefit to the research of age-dependent diseases in human.
The role of Garlic and Honey on Nicotine-Induced Toxicity on the Cerebellum of adult Wistar Rats
Authors: Augustine Ibegbu O , Gertrude Okechukwu N. , Loveth Anosike N. , Al-Rashed Sarah , Obinna Uchewa O. , Uchenna Ezemagu K. , USMAN IBE MICHAEL , Ogugua Egwu A. , Batiha Gaber El-Saber 
Published: October 2020

Abstract
Background

Nicotine form the major constituent of consumed tobacco and cigarettes throughout the World resulting in oxidative stress while garlic and honey have been shown to contain numerous natural antioxidants. We investigated the role of combined effects of garlic and honey on nicotine induced Cerebellar and behavioral toxicity in Wistar rats.
Method

: Forty rats were divided into eight groups of five rats each. Group 1 received water only, Group 2 and 3 received 50 mg/kg of nicotine with garlic and honey at (300 mg/kg and 1000 mg/kg) and (600 mg/kg and 2000 mg/kg) respectively. Group 4 received 50 mg/kg of nicotine only, Group 5 received garlic 300 mg/kg and honey 1000 mg/kg before 50 mg/kg nicotine, Group 6 received garlic 600 mg/kg and honey 2000 mg/kg before 50 mg/kg nicotine. Group 7 and 8 received 50 mg/kg nicotine + 450 mg/kg garlic only and 1500 mg/kg honey only respectively. The administration was through oral route and lasted for 21 days respectively. Limb impairment and grip were conducted. After the administration, blood and cerebellum were harvested for lactate dehydrogenase assay, oxidative stress and histopathological analyses.
Result

There was significant decrease in body weight, grip strength and limb impairment in Group 4 with increase in Group 2 compared to the Control (p < 0.001). There was significant increase in LDH in Groups 2, 4, 7 and 8 with significant decrease in Group 3 compared to Group 1. The result showed significant decrease in SOD and CAT activities in all the groups compared to Group 1 (p < 0.001). Groups 1, 7 and 8 showed normal histology of the cerebellum while Group 4 showed areas of neuronal degeneration with distortions in histology and Groups 3, 5 and 6 showed few neural changes.
Conclusion

The study showed that garlic and honey may be useful in ameliorating nicotine toxicity dose-dependently which may be due to their antioxidant activity.
Corticomedullary Shunting After Ischaemia and Reperfusion in The Porcine Kidney?
Authors: Rehling Michael , Skjøth Stine Gram , Keller Anna Krarup , Nielsen Lene Elsebeth , Flø Christian , Jespersen Bente , Frøkiær Jørgen 
Published: October 2020

Abstract
Background: An animal model offers the opportunity to study organs in vivo and the porcine model was chosen to simulate a renal transplantation with complications. Renal perfusion may redistribute from cortex to medulla during systemic hypovolaemia and after renal ischaemia for other reasons, but there is no consensus on this matter. We studied renal perfusion after renal ischaemia and reperfusion.Methods: Renal perfusion distribution was examined by use of 153Gadolinium-labeled microspheres (MS) after 2 hours (hrs) and 4 hrs ischaemia of the pig kidney followed by 4 hrs of reperfusion. Intra-arterial injected MS are trapped in the glomeruli in renal cortex, which means that MS are not present in the medulla under normal physiological conditions.Results: Visual evaluation after reperfusion demonstrated that MS redistributed from the renal cortex to the medulla in 6 out of 16 pigs (38%) subjected to 4 hrs ischaemia and in one out of 18 pigs subjected to 2 hrs ischaemia. Central renal uptake of MS covering the medullary/total renal uptake was significantly higher in kidneys subjected to 4 hrs ischaemia compared with pigs subjected to 2 hrs ischaemia (69±5% vs. 63±1%, p<0.001), and also significantly higher than in the contralateral kidney (69±5% vs. 63±2, p<0.001). Analysis of blood and urine demonstrated no presence of radioactivity. Conclusion: The study demonstrated the presence of MS in the renal medulla in response to renal ischaemia and reperfusion suggesting that severe ischaemia and reperfusion of the pig kidney leads to opening of functional shunts bypassing glomeruli.
The genotypic and genetic diversity of enset (Ensete ventricosum) landraces used in traditional medicine is similar to the diversity found in starchy landraces
Authors: Nuraga gizachew Woldesenbet , Feyissa Tileye , Tesfaye Kassahun , Biswas Manosh Kumar , Schwarzacher Trude , Borrell James , Wilkin Paul , Demissew Sebsebe , Tadele Zerihun , Heslop-Harrison J.S. (Pat) 
Published: October 2020

Abstract
Background

Enset (Ensete ventricosum) is a multipurpose crop extensively cultivated in southern and southwestern Ethiopia for human food, animal feed and fiber. It contributes to the food security and rural livelihoods of 20 million people. Several distinct enset landraces are cultivated for their uses in traditional medicine. Socio-economic changes and the loss of indigenous knowledge might lead to the decline of important medicinal landraces and their associated genetic diversity. However, it is currently unknown whether medicinal landraces are genetically differentiated from other landraces. Here, we characterize the genetic diversity of medicinal enset landraces to support effective conservation and utilization of their diversity
Results

We evaluated the genetic diversity of 51 enset landraces of which 38 have reported medicinal value. A total of 38 alleles were detected across the 15 SSR loci. AMOVA revealed that 97.6% of the total genetic variation is among individual with an FST of 0.024 between medicinal and non-medicinal landraces. A neighbor-joining tree showed four separate clusters with no correlation to the use values of the landraces. Principal coordinate analysis also confirmed the absence of distinct clustering between the groups, showing low differentiation among landraces used in traditional medicine and those having other use values.
Conclusion

We found that enset landraces were clustered irrespective of their use value, showing no evidence for genetic differentiation between enset grown for ‘medicinal’ uses and non-medicinal landraces. This suggests that enset medicinal properties may be restricted to a more limited number of genotypes, a product of interaction with the environment or management practice, or partly misreported. The study provide baseline information that promotes further investigations in exploiting the medicinal value of these specific landraces