bluuebunny/crossref_metadata_2025_split huggingface dataset:
Different transcriptome profiles between human retinoblastoma Y79 cells and an etoposide-resistant subline reveal a chemoresistance mechanism
Authors: Song Wen-ping , Zheng Si , Yao Hong-juan , Zhou Xiao-fei , Li Rui , Zhang Cheng-yue , Zhao Jun-yang , Wang Lie-wei , Shao Rong-guang , Li Liang 
Published: January 2020

Abstract

Background: Retinoblastoma (RB) is the most frequent pediatric retinal tumor. In the present study, to elucidate chemoresistance mechanisms and identify potential biomarkers in RB, we utilized RNA sequencing (RNAseq) technological platforms to reveal transcriptome profiles and identify any differentially expressed genes (DEGs) between an etoposide drug-resistant subline (Y79/EDR) and parental Y79 cells. Methods: To test whether Y79/EDR cells showed resistance to antineoplastic agents for RB, we treated the cells with etoposide, carboplatin and vincristine and analyzed them with a Cell Counting Kit-8 (CCK-8). Y79/EDR and parental Y79 cells were used for RNAseq and bioinformatics analysis to enable a genome-wide review of DEGs between the two lines using the DESeq R package (1.10.1). Then, DEG enrichment in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was analyzed with KOBAS software. Next, real-time quantitative reverse transcription polymerase chain reaction (real time QRT-PCR) and cytotoxicity assays were performed to experimentally and functionally validate the identified candidate biomarkers. Results: Y79/EDR cells showed resistance to etoposide, carboplatin and vincristine at different concentrations. In total, 524 transcripts were differentially expressed in Y79/EDR cells based on analysis of fragments per kilobase of transcript per million fragments mapped (FPKM); among these, 57 genes were downregulated and 467 genes were upregulated in Y79/EDR cells compared to parental Y79 cells. We selected candidate DEGs, including ARHGAP9 , HIST1H4H , RELN , DDIT4 , HK2 , STC1 and PFKFB4, for mRNA expression validation with real time QRT-PCR assays and found that the expression levels determined by real time QRT-PCR were consistent with the RNAseq data. Further studies involving downregulation of ARHGAP9 with a specific siRNA showed that ARHGAP9 altered the cellular sensitivity of Y79 cells to etoposide and carboplatin.Conclusion: Our initial findings provided a genomic view of the transcription profiles of etoposide-induced acquired resistance in RB. Follow-up studies indicated that ARHGAP9 might be a chemoresistance biomarker in RB, providing insight into potential therapeutic targets for overcoming acquired chemoresistance in RB. These findings can aid in understanding and overcoming chemoresistance during treatment of RB in the clinic.
Functional and population genetic features of copy number variations in two dairy cattle populations
Authors: Lee Young-Lim , Bosse Mirte , Mullaart Erik , Groenen Martien A. M. , Veerkamp Roel F. , Bouwman Aniek C. 
Published: January 2020

Abstract
Background Copy Number Variations (CNVs) are gain or loss of DNA segments that are known to play a role in shaping a wide range of phenotypes. In this study, we used two dairy cattle populations, Holstein Friesian and Jersey, to discover CNVs using the Illumina BovineHD Genotyping BeadChip aligned to the ARS-UCD1.2 assembly. The discovered CNVs were investigated for their functional impact and their population genetics features.

Results We discovered 14,272 autosomal CNVs, which were aggregated into 1,755 CNV regions (CNVR) from 451 animals. These CNVRs together cover 2.8% of the bovine autosomes. The assessment of the functional impact of CNVRs showed that rare CNVRs (MAF < 0.01) are more likely to overlap with genes, than common CNVRs (MAF ≥ 0.05). The Population differentiation index (Fst) based on CNVRs revealed multiple highly diverged CNVRs between the two breeds. Some of these CNVRs overlapped with candidate genes such as MGAM and ADAMTS17 genes , which are related to starch digestion and body size, respectively. Lastly, linkage disequilibrium (LD) between CNVRs and BovineHD BeadChip SNPs was generally low, close to 0, although common deletions (MAF ≥ 0.05) showed slightly higher LD ( r 2 =~0.1 at 10kb distance) than the rest. Nevertheless, this LD is still lower than SNP-SNP LD ( r 2 =~0.5 at 10kb distance).

Conclusions Our analyses showed that CNVRs detected using BovineHD BeadChip arrays are likely to be functional. This finding indicates that CNVs can potentially disrupt the function of genes and thus might alter phenotypes. Also, the population differentiation index revealed two candidate genes, MGAM and ADAMTS17 , which hint at adaptive evolution between the two populations. Lastly, low CNVR-SNP LD implies that genetic variation from CNVs might not be fully captured in routine animal genetic evaluation, which relies solely on SNP markers.

Keywords : Copy number variations, Bos taurus , Linkage disequilibrium, population genetics
Hypoxic hepatocellular carcinoma cells acquire arsenic trioxide resistance through upregulating HIF-1α expression
Authors: Chen Yaoting , Li Huiqing , Chen Dong , Jiang Xiongying , Wang Weidong , Li Dan , Shan Hong 
Published: January 2020

Abstract
Background : Although arsenic trioxide (ATO) is used in the treatment of advanced hepatocellular carcinoma (HCC) in clinical trials, it is not satisfactory in terms of improving HCC patients’ overall survival. Intratumoral hypoxia and overexpression of hypoxia-inducible-1α (HIF-1α) may result in ATO-resistance and tumor progression. We investigated the mechanisms involving HIF-1α expression and acquired ATO chemoresistance in HCC cells and mice. Methods: The therapeutic effects of ATO in normoxic and hypoxic HCC cells were assessed using cell viability and apoptosis assays in vitro and a xenograft model in vivo . mRNA and protein expression of HIF-1α, P-glycoprotein, and VEGF were measured by qRT-PCR and western blotting. HIF-1α inhibition was performed to investigate the mechanism of ATO-resistance. VEGF secretion was tested using ELISA and tube-formation assays. Results : Compared to normoxic cells, hypoxic HCC cells were more resistant to ATO, with higher IC 50 values and less apoptosis, and upregulated HIF-1α protein expression, accompanied with the enhancement of P-glycoprotein and VEGF synthesis after ATO treatment. VEGF secretion was elevated in the supernatant of ATO-treated HCC cells, and this change can potentiate angiogenesis in vitro . HIF-1α inhibition attenuated ATO-resistance and angiogenesis, and promoted the anticancer effects of ATO both in vitro and in vivo by downregulating therapy-induced P-glycoprotein and VEGF overexpression. Conclusions : Hypoxic HCC cells acquire ATO resistance by upregulating HIF-1α levels; thus, combining ATO with a HIF-1α-targeting agent may lead to enhanced antitumor effects in HCC.
Association of cyberbullying with psychosocial difficulties, self-harm and helping-seeking behaviors: a cross section study in Singapore adolescents
Authors: Ong Say How , Tan Yi Ren , Khong Jerrine Z. N. , Elliott John M. , Sourander Andre , Fung Daniel S. S. 
Published: January 2020

Abstract
Background Social media use has constituted to significant time spent online by adolescents globally, with its untoward effects increasingly being reported in many countries. Bullying through the use of such media has afflicted many adolescents to cause severe mental health concerns including self-harm and suicide.Aims The aims of this study are to examine the prevalence of cyberbullying in Singapore adolescents, its associations with psychosocial issues including self-harm and suicidal behaviors, and how adolescents seek help after being cybervictimised.Methods A representative sample of 3,319 school students aged between 12 and 17 years were recruited in this cross-sectional study and responded to a survey with scales measuring cyberbullying, psychosocial difficulties, self-harm, suicidal and help-seeking behaviors. The prevalence rate of cyberbullying was first explored using descriptive statistics, followed by Pearson chi-square tests for independence, one-way ANOVA tests and multinomial logistics regressions to examine its associations with various psychosocial issues.Results In the present study, 7.3% of adolescents reported being cybervictims only, 1.8% were cyberbullies only and 4.8% were cyberbully-victims. Compared to the non-involved group, all three cyberbullying-involved groups were associated with higher externalising problems [ F (3, 3290) = 62.06, p <.001], but only both cybervictim and cyberbully-victim groups were associated with more internalising problems [ F (3, 3290) = 38.97, p < .001]. Similarly, both cybervictim and cyberbully-victim groups reported significantly higher incidence of self-harm behaviors, suicidal thoughts and attempts as compared to the non-involved group (Odds ratios = 2.6-5.0, all p s < .001). Cyberbullies, on the other hand, had increased odds in having suicidal attempts (Odds ratio = 3.9, p < .001). Approximately half of the cybervictimised participants reported that they have sought help, with most of them (81.7%) choosing to tell their friends.Conclusions Our findings are consistent with previous studies showing increased associations of psychosocial difficulties, self-harm and suicidal behaviors among adolescents who are involved in cyberbullying. Public awareness of the consequences of unhealthy cyber-usage could be raised to aid in early detection of cyberbullying among school children and adolescents. Moreover, cyberwellness programmes should be considered as a component of larger suicide prevention efforts in schools and in the community.
Depression, anxiety, and associated factors in patients with diabetes: evidence from the Anxiety, Depression, and Personality Traits in Diabetes Mellitus (ADAPT-DM) study
Authors: Abdullah Mohammad Farris Iman Leong Bin , Woon Sy-Cherng Luke , Sidi Hatta , Ravindran Arun , Gosse Paula Junggar , Mainland Roslyn Laurie , Kaunismaa Emily Samantha , Hatta Nurul Hazwani , Arnawati Puteri , Zulkifli Amelia Yasmin , Mustafa Norlaila 
Published: January 2020

Abstract
Background Depression and anxiety are common psychiatric complications affecting patients with diabetes mellitus. However, data on the prevalence of depression, anxiety, and associated factors among Malaysian diabetic patients is scarce. The Anxiety, Depression, and Personality Traits in Diabetes Mellitus (ADAPT-DM) study aimed to determine the prevalence of depression and anxiety, and their associated factors in the Malaysian diabetic population. Methods This cross-sectional study recruited 300 diabetic patients via convenience sampling from the Endocrine outpatient clinic of Universiti Kebangsaan Malaysia Medical Centre, a tertiary referral healthcare facility in Kuala Lumpur. Socio-demographic characteristics and clinical history were obtained from each participant. The Generalised Anxiety Disorder-7 (GAD-7) was administered to assess anxiety symptoms, the Beck Depression Inventory (BDI) to assess depressive symptoms, the Big Five Inventory (BFI) to evaluate personality traits, and the World Health Organization Quality of Life-BREF (WHOQOL-BREF) to measure quality of life (QOL). Multivariate logistic regression analyses were performed to determine the association between various factors, and depression and anxiety. Results The prevalence of depression was 20% (n = 60) while anxiety was 9% (n = 27). Co-morbid depression (adjusted OR = 24.91, 95% CI = 5.67–109.42, p < 0.001), neuroticism (adjusted OR = 9.24, 95% CI = 2.03–42.03, p = 0.004), and greater physical health-related QOL (adjusted OR = 1.67, 95% CI = 1.07–2.59, p = 0.024) increased the odds of developing anxiety, while psychological QOL (adjusted OR = 0.41, 95% CI = 0.21–0.79, p = 0.008) was protective. Co-morbid anxiety (adjusted OR = 20.06, 95% CI = 4.70–85.57, p < 0.001) increased the odds of depression, while older age (adjusted OR = 0.96, 95% CI = 0.92–0.99, p = 0.012), regular religious practice (adjusted OR= 0.08, 95% CI= 0.01-0.56, p= 0.011) and physical health-related QOL (adjusted OR = 0.72, 95% CI = 0.59–0.89, p = 0.002) were protective. Conclusions The study findings signify the need to screen for co-morbid depression and anxiety, as well as personality traits and QOL, and to include psychosocial interventions when planning a multidisciplinary approach to managing diabetes.
The brain structural and functional anomaly associated with simultanagnosia in patients with posterior cortical atrophy
Authors: Liu Yang , Yang Caishui , Cui Chunlei , Cui Yue , Jing Donglai , Liang Zhigang , Zhang Xuxiang , Chen Yaojing , Li Bingkun , Liu Jia , Li Dan , Rosa-Neto Pedro , Gauthier Serge Studies in Aging , Chen Kewei , Zhang Zhanjun , Wu Liyong 
Published: January 2020

Abstract
Backgroud Posterior cortical atrophy (PCA) is a rare neurodegenerative disease characterized by impairments in visual processing and in other relatively selective posterior cortical functions, mainly involving occipito-parietal regions. As the most common and important clinical manifestation, simultanagnosia is a profound inability of a patient with PCA to integrate multiple visual elements and to precept the global precedence within a scene. With few reports, the structural and functional changes in the brain associated with simultanagnosia are still yet comprehended more fully.Methods This study recruited 18 PCA patients with simultanagnosia, 29 patients with Alzheimer’s disease (AD) and 20 cognitively normal controls (NC). All subjects underwent a full neuropsychological evaluation, picture-/computer-based simultanagnosia tests, structural and resting-state functional MRI. Grey matter volume (GMV) was assessed by voxel-based morphometry, while seed based intrinsic functional connectivity (iFC) was evaluated based on the PCA-specific grey matter injuries in contrast to AD. Finally, the correlations between the statistically significant structural or functional MRI features and the simultanagnosia were evaluated in PCA patients.Results We found that, between PCA and AD patients, there was no significant difference in clinical dementia rating, immediate memory and delayed memory, while the marked difference was exhibited in neuropsychological assessments, and also in the picture-based and computer-based test score (P<0.01). In addition to brain areas where both PCA and AD patients had compatible regional GMV reduction each in contrast with NC group, the left middle occipital gyrus and ventral occipital areas were specifically affected by PCA relative to AD. Also in contrast to AD, PCA had lower iFC from left middle occipital gyrus, left lingua gyrus and right middle occipital gyrus. Moreover, we found that GMV of left middle occipital gyrus, its functional coupling to right superior occipital gyrus, the GMV of left inferior occipital gyrus and the iFC from right middle occipital gyrus to left superior parietal gyrus were each correlated to simultanagnosia (r=0.670, p=0.002; r=-0.517, p<0.001; r=0.605 p=0.008; r=0.778, p<0.001, respectively) in PCA patients.Conclusions Simultanagnosia is associated with the lower structural GMV and lower iFC in the left middle occipital gyrus and the left inferior occipital gyrus in PCA.
Higher Prevalence of Obesity among Children with Functional Abdominal Pain Disorders
Authors: Galai Tut , Moran-Lev Hadar , Cohen Shlomi , Ben-Tov Amir , Levy Dina , Weintraub Yael , Amir Achiya , Segev Or , Yerushalmy-Feler Anat 
Published: January 2020

Abstract
Background Functional abdominal pain (FAP) disorders are one of the most common gastrointestinal disorders in children. We aimed to define the association between obesity and functional abdominal pain (FAP) disorders and to assess differences between overweight/obese children and normal weight children with FAP disorders.Methods We conducted a retrospective study of children (2-18 years old) with a clinical diagnosis of FAP who were followed-up in our pediatric gastroenterology unit between 1/2016-10/2018. FAP disorders were defined according to the ROME IV criteria. Body mass index (BMI) percentiles were defined by CDC standards. Patients with BMIs ≥85% were designated as being overweight/obese. A healthy control group was obtained from the 2015-2016 Israel national health survey.Results Data from 173 children with FAP disorders (median age 11.5 years, 114 females) were included. Seventy-one children (41%) were classified as having abdominal pain-NOS, 67 (38.7%) as having irritable bowel syndrome (IBS), and 35 (20.2%) has having functional dyspepsia. Fifty-three children (30.6%) were classified as being overweight/obese. Adolescents with FAP disorders had a significantly higher prevalence of overweight/obesity compared to controls (39.5% vs. 30%, respectively, p = 0.04). Overweight FAP children were older [12.4 (range 9.8-15.3) vs. 10.8 (7.4-14.1) years, p = 0.04] and had more hospitalizations due to FAP (20.8% vs. 7.6%, p = 0.01) compared to normal weight FAP children.Conclusions Children with FAP had higher prevalence of overweight/obesity compared to healthy controls. Future studies are warranted to raise awareness of weight issues in FAP and determine the effect of weight loss on FAP.
Effects of shading on lignin biosynthesis in the leaf of tea plant (Camellia sinensis (L.) O. Kuntze)
Authors: Teng Rui-Min , Wang Yong-Xin , Li Hui , Lin Shi-Jia , Liu Hao , Wang Yu , Zhuang Jing 
Published: January 2020

Abstract
BackgroundLignin is one of the most important secondary metabolite that play vital functions in plant growth and development. Shading is an effective method to improve tea quality. However, little is known about the relationship between shading and xylogenesis in tea plant. ResultsIn this study, tea plant cultivar ‘Longjing 43’ was treated with no shading (S0), 40% (S1) and 80% (S2) shading treatments. The leaf area and lignin content of tea plant leaves decreased under shading treatments (especially S2). The lignin distribution and anatomical characteristics of the tea plant leaves showed that lignin is mainly distributed in the xylem. Promoter analysis indicated that the genes involved in lignin pathway contain several light recognition elements. The transcript abundances of 12 lignin-associated genes were altered under shading treatments. Correlation analysis indicated that the most genes showed strong positive correlation with lignin content, and CsPAL, Cs4CL, CsF5H, and CsLAC exhibited significant positively correlation under 40% and 80% shading treatments. ConclusionsIn this study, we evaluated the effect of shading on leaves growth, xylem development, and lignin accumulation in tea plant. Shading treatment inhibited leaves growth and lignin content. Safranin-O/fast green staining and autofluorescence indicated lignin was mostly deposited in the xylem. Shading may affect tea plant leaves lignification by regulating the transcript levels of lignin biosynthesis genes. This study provided potentially useful information for understanding the mechanism of lignin biosynthesis under shading treatments in tea plant.
Metabolic responses of Carlina acaulis L. to chronic and acute cadmium stress: insights into chelation mechanisms, non-enzymatic antioxidants, and specialized metabolism
Authors: Dresler Sławomir , Strzemski Maciej , Kováčik Jozef , Sawicki Jan , Staniak Michał , Wójciak Magdalena , Sowa Ireneusz , Hawrylak-Nowak Barbara 
Published: January 2020

Abstract
BackgroundChronic and acute stress can lead to completely different metabolic responses of plants exposed to the same abiotic factor. The effect of long-term chronic cadmium stress (ChS, 0.1 µM Cd, 85 days) or short-term acute cadmium stress (AS, 10 µM Cd, 4 days) on the physiology of Carlina acaulis L. (Asteraceae) and selected secondary metabolites was compared to identify specific physiological and biochemical reactions.ResultsThe bioconcentration of Cd in all analyzed organs was higher under AS in comparison with ChS (130 vs. 16 µg g-1 DW, 7.9 vs. 3.2 µg g-1 DW, and 11.5 vs. 2.4 µg g-1 DW in roots, leaves, and trichomes, respectively). The high concentration of Cd in the trichomes in the AS treatment might be an anatomical adaptation mechanism. ChS evoked an increase in the root biomass, whereas its impact on shoot biomass was not significant in any treatment. The amounts of ascorbic acid and the sum of phytochelatins were higher in the shoots, whilst organic acids (malic and citric) reached higher levels in the roots of plants from the ChS treatment. Glutathione depletion occurred in the shoots, but there was no change in its root level in both treatments. The amount of chlorogenic acid, but not that of ursolic and oleanolic acids, was increased under ChS. On the other hand, AS exposure elevated the level of ursolic and oleanolic acids, but not chlorogenic acid in the shoots. ConclusionsThese data indicate that ChS and AS induce different physiological and biochemical defense mechanisms. Both chelation and enhancement of the antioxidative machinery contribute to protection of C. acaulis exposed to long-term (chronic) Cd exposure and alleviate Cd toxicity effectively. However, triterpene acids were elevated only under AS treatment, which may suggest an instantaneous action of these metabolites under short-term acute Cd stress.
Unraveling the Molecular Heterogeneity in type 2 Diabetes: A Potential Subtype Discovery Study Followed by Metabolic Modeling
Authors: Khoshnejat Maryam , Kavousi Kaveh , Moghaddam Ali Mohammad Banaei , Moosavi-Movahedi Ali Akbar 
Published: January 2020

Abstract
Background Type 2 diabetes mellitus (T2DM) is a complex multifactorial disease with a high prevalence in the world. Insulin resistance and impaired insulin secretion are the two major abnormalities in the pathogenesis of T2DM. Skeletal muscle is responsible for over 75% of the glucose uptake thus plays a critical role in T2DM. Here, we attempt to provide a better understanding of abnormalities in this tissue. We have explored the muscle gene expression pattern in healthy and newly-diagnosed T2DM individuals using supervised and unsupervised classification along with the discovery of potential subtypes of type 2 diabetes.Results A machine-learning technique applied to identify a pattern of gene expression that could potentially discriminate between normoglycemic and diabetic groups. A gene set comprises of 26 genes identified which was able to discriminate healthy from diabetic individuals with the 94% accuracy after 10-fold stratified cross-validation. In addition, three distinct potential subtypes with different dysregulated genes and metabolic pathways identified in diabetic patients.Conclusion This study implies that it seems the disease has triggered through different cellular/molecular mechanisms. Therefore, subtyping of T2DM patients will provide a better understanding of abnormalities in each group and lead to the recommendation of the appropriate precision therapy for each subtype in the future.