bluuebunny/crossref_metadata_2025_split huggingface dataset:
MiRNA Profiling: Mouse Blastocyst Extracellular&nbsp;Microvesicles Inhibit Melanoma Cell&nbsp;Invasion
Authors: Duan Ruxia , Liu Qing , Wang Yiting , Wei Zixin , Ba Xiaoyun , Fang Liaoqiong 
Published: November 2020

Abstract
Background: Microvesicles (MVs) mediate the transmission of information between cells through the miRNAs, proteins, lipids and mRNAs carried by MVs, which inhibit/promote the function of receptor cells. This study confirmed that blastocyst MVs inhibited the invasion of melanoma cells and showed a complex miRNA pedigree. Functional miRNAs were found, and the mechanism of inhibiting invasiveness was analyzed based on the miRNA lineage characteristics of mouse blastocyst MVs, combined with the miRNA bioinformatics information of miRBase, microRNA.org, NCBI and other databases.Methods: MVs derived from D3.5 mouse blastocysts were isolated and the miRNA gene expression of MV was detected by fluorescence quantitative polymerase chain reaction (qPCR). The dynamic changes in tumor cell invasiveness in the co-culture system of blastocyst MVs and melanoma B16-F10 cells were monitored in real time. The MV miRNAs expression profile of blastocyst was identified using the qPCR array. Bioinformatics tools were used to analyze the characteristics of miRNA pedigree in blastocyst MV to screen functional miRNAs, which reduce tumor cell invasiveness and to predict functional miRNA target genes. The target genes were analyzed by KEGG and GO pathway enrichment analyses using David and FunRich software.Results: The average diameter of round MVs extracted from mouse blastocysts was 196.4 ±7.8 nm. When B16-F10 melanoma cells were co-cultured with mouse blastocyst MVs, no significant difference in invasive ability was found between the two groups before 72 h, but increased significantly after 72 h (P < 0.05, P < 0.01). A total of 336 miRNAs were analyzed in mouse blastocyst MVs. Further analysis showed that 224 miRNAs were associated with invasion. Also, 32 invasion-related miRNAs with the strongest differential expression were verified by real-time quantitative polymerase chain reaction (qPCR). The GO analysis of the target genes showed that the 32 functional miRNAs were mainly related to 8 biological processes, including DNA binding, sequence-specific DNA binding, metal ion binding, chromatin binding, nucleotide binding, sequence specificity, DNA binding transcription factor activity and ubiquitin-protein ligase activity. The KEGG pathway analysis showed that the 32 functional miRNAs were mainly related to the PI3K-Akt signaling pathway.Conclusion: Blastocyst MVs carrying miRNAs regulated the decrease in the invasive ability of melanoma cells through the PI3K-Akt signaling pathway.
LncRNA ACTA2-AS1 Suppress Colon Adenocarcinoma Progression by Sponging miR-4428 Upregulation BCL2L11
Authors: Pan Qingyun , Huang Ying , Wang Yirui , Li Deke , Lei Changjiang 
Published: November 2020

Abstract
BackgroundLong non-coding RNA is considered to be essential to modulate the development and progression of human malignant cancers. And long non-coding RNA can act as crucial modulators by sponging the corresponding microRNA in tumorigenesis. We aimed to elucidate the function of ACTA2-AS1 and its molecular mechanism in colon adenocarcinoma. Materials and MethodsThe expression of ACTA2-AS1, miR-4428 and BCL2L11 in colon adenocarcinoma tissues were detected via qRT-PCR. SW480 and HT29 cells were transfected with shRNA ACTA2-AS1, OE ACTA2-AS1, miRNA mimics of miR-4428, miR-4428 inhibitor, si-BCL2L11 and over-expression of si-BCL2L11. Cell proliferation, colony formation and apoptosis were respectively assessed using CCK-8 assay, colony assay and flow cytometry. Luciferase reporter assay was performed to verify the targets of ACTA2-AS1 and miR-4428. Tumor subcutaneous xenograft mode was constructed to explore tumor growth in vivo. ResultsACTA2-AS1 was obviously downregulated in human colon adenocarcinoma tissues and colon adenocarcinoma cell lines. Silence or over-expression of ACTA2-AS1 promoted or inhibited cell proliferation and colony formation abilities, and regulated apoptosis. The silence of ACTA2-AS1 resulted in the decrease of Bax and increase of Bal2, while restored in OE ACTA2-AS1 group when compared with the control transfected cells. In addition, luciferase reporter assay revealed that ACTA2-AS1 interacted with miR-4428 and suppressed its expression. miR-4428 could bind to 3ʹ untranslated region of BCL2L11 and modulated the expression of BCL2L11 negatively. Knockdown of ACTA2-AS1 and over-expression of BCL2L11 reversed the biological function that ACTA2-AS1 mediated by knockdown ACTA2-AS1 alone. ConclusionOur data demonstrated that ACTA2-AS1 could suppress colon adenocarcinoma progression via sponging miR-4428 to regulate BCL2L11 expression.
Identification of Four Key Prognostic Genes and Three Potential Drugs in Human Papillomavirus Negative Head and Neck Squamous Cell Carcinoma
Authors: Tian Guocai , Fu You , Zhang Dahe , Li Jiang , Zhang Zhiyuan , Yang Xi 
Published: November 2020

Abstract
BackgroundHead and neck squamous cell carcinoma (HNSCC) is a common tumor worldwide with poor prognosis. The pathogenesis of human papillomavirus (HPV)-positive and HPV-negative HNSCCs differs. However, few studies have considered the HPV status when identifying biomarkers for HNSCC. Thus, the identification of biomarkers for HPV-positive and HPV-negative HNSCCs is urgently needed.MethodsThree microarray datasets from Gene Expression Omnibus (GEO) were analyzed, and the differentially expressed genes (DEGs) were obtained. Then, functional enrichment pathway analysis was performed and protein-protein interaction (PPI) networks were constructed. The expression of hub genes at both the mRNA and protein level was determined in Oncomine, The Cancer Genome Atlas (TCGA) and the Human Protein Atlas (HPA). In addition, survival analysis of the patient stratified by HPV status and the expression levels of key genes were performed based on TCGA data. The role of AREG, STAG3, CAV1 and C19orf57 in cancer were analyzed through Gene set enrichment analysis (GSEA). Finally, the top ten small molecule drugs were identified and the therapeutic value of zonisamide, NVP-AUY922, PP-2 and fostamatinib was further evaluated in six HPV-negative HNSCC cell lines.ResultsIn total, 47 DEGs were obtained, 11 of which were identified as hub genes. Biological process analysis indicated that the hub genes were associated with the G1/S transition of the mitotic cell cycle. Survival analysis uncovered that the prognostic value of AREG, STAG3, C19orf57 and CAV1 differed between HPV-positive and HPV-negative patients. Gene set enrichment analysis (GSEA) showed the role of AREG, STAG3 and CAV1 in dysregulated pathways of tumor. Ten small molecules were identified as potential drugs specifically for HPV-positive or HPV-negative patients; three—NVP-AUY922, fostamatinib and PP-2—greatly inhibited the proliferation of six HPV-negative HNSCC cell lines in vitro, and NVP-AUY922 inhibited three HPV-negative HNSCC xenografts in vivo.ConclusionsIn conclusion, AREG, STAG3, C19orf57 and CAV1 are key prognostic factors and potential therapeutic targets in HPV-negative HNSCC. NVP-AUY922, fostamatinib and PP-2 may be effective drugs for HPV-negative HNSCC.
Impact of Covid-19 pandemic for patient care in an Interventional Radiology Unit
Authors: Veiga José , Amante Sofia , Costa Nuno Vasco , Luz José Hugo , Gomes Filipe Veloso , Coimbra Élia , Bilhim Tiago 
Published: November 2020

Abstract
Purpose: Assess the impact of Covid-19 pandemic in work volume in an Interventional Radiology Unit during the “State of Emergency” (16th March - 30th April) in 2020 and to analyse the short-term consequences for oncology patients.Materials and Methods: Single-centre retrospective analysis. The number and type of procedures performed during the “State of Emergency” was compared with the homologous period in 2019. The second analysis compared the impact on disease progression for oncology patients after the “State of Emergency”. All patients that had a scheduled loco-regional treatment (LRT) (74 hepatocellular carcinoma (HCC); 10 liver metastases) between 2nd May - 16th July 2020 were compared with the homologous period in 2019 (68 HCC; 11 liver metastases). The compared outcome measures included: baseline data, time from diagnostic imaging to LRT, LRT performed as planned, change in LRT.Results: There was a 55.2% reduction of procedures during the “State of Emergency” (n=77 in 2020; n=172 in 2019) with a significant increase in urgent procedures (48.1% in 2020; 33.1% in 2019; p=0.0120). Post-“State of Emergency”, in 2020, HCC patients had higher model of end-stage liver disease (MELD) scores (p=0.0124) and larger tumours (mean difference of 8.7 mm, p=0.0071). Mean time from diagnostic imaging to LRT increased 14.1 days (p=0.0439). More patients received different or no LRT due to disease progression (15.5% in 2020; 3.8% in 2019; p=0.0061).Conclusion: There was a reduction in interventional oncology treatments during the “State of Emergency” with more patients experiencing disease progression precluding LRTs in the following months.
Differential kinetics of T cell and antibody responses delineate dominant T cell epitopes in long-term immunity after COVID-19
Authors: Bilich Tatjana , Nelde Annika , Heitmann Jonas S. , Maringer Yacine , Roerden Malte , Bauer Jens , Rieth Jonas , Wacker Marcel , Peter Andreas , Hörber Sebastian , Rachfalski David , Märklin Melanie , Stevanović Stefan , Rammensee Hans-Georg , Salih Helmut R. , Walz Juliane S. 
Published: November 2020

Abstract
Long-term immunity to SARS-CoV-2 is crucial for the development of herd immunity and the aim of vaccination approaches. Reports on rapidly decreasing antibody titers question the efficacy of humoral immunity. The relevance of T cell memory after COVID-19 is yet unclear. Longitudinal analysis of SARS-CoV-2 immunity in convalescents up to six months post-infection revealed decreasing and stable spike and nucleocapsid antibody responses, respectively. In contrast, T cell responses remained robust and even increased in frequency and intensity. Single epitope mapping of T cell diversity over time identified ORF-independent, dominant T cell epitopes mediating long-term SARS-CoV-2 T cell responses and may be fundamental for vaccine design.
Web-based, rapid and contactless management of ambulatory patients for SARS-CoV-2-testing
Authors: Stemler Jannik , Cornely Oliver A. , Noack-Schönborn Torsten , Forholz Corinna , Schumacher Sofie , Poluschkin Leonard , Binder Bernd , Lehmann Clara , Langebartels Georg 
Published: November 2020

Abstract
BackgroundDuring the SARS-CoV-2 pandemic a mass casualty incident of ambulatory patients occurred at the COVID-19 rapid response infrastructure (CRRI) facility at the University Hospital of Cologne (UHC). We report the development of a patient-centred mobile-device solution to support efficient management of the facility, triage of patients and rapid delivery of test results.MethodsThe UHC-Corona Web Tool (CWT) was developed as a web-based application useable on each patient's smartphone. It provides, among others, a self-reported medical history including type and duration of symptoms and potential risk contacts and links all retrieved information to the digital patient chart via a QR code. It provides scheduling of outpatient appointments and automated transmission of SARS-CoV-2 test results.ResultsThe UHC-CWT was launched on April 9th, 2020. It was used by 28652 patients until August 31st,2020. Of those, 15245 (53,2%) consulted the CRRI, representing 43,1% of all CRRI patients during the observed period.There were 8304 (29,0%) specifications concerning travel history and 17145 (59,8%) indications of ≥1 symptom of SARS-CoV-2 infection. The most frequently indicated symptoms were sore throat (60,0%), headache (50,7%), common cold (45,1%) and cough (42,6%) while 11057 (40,2%) patients did not report any symptoms. After implementation of the UHC-CWT, the number of patient contacts per physician rose from 38 to 98,7 per day. The personnel for communication of test results was reduced from four on seven days to one on five days.ConclusionThe UHC-CWT is an effective digital solution for management of large numbers of outpatients for SARS-CoV-2 testing.
Altered Gut Microbiota Associated with Hemorrhage in Chronic Radiation Proctitis
Authors: Liu Liangzhe , Chen Chaoyun , Ding Chen , Chen Bingcheng , Liang Jinjun 
Published: November 2020

Abstract
Background: Pelvic cancer radiotherapy may cause chronic radiation proctitis (CRP) that adversely affects patient’s quality of life, especially in patients with prolonged hematochezia. However, previous studies of radiation enteropathy mainly focused on acute irradiation hazards, and the detail pathogenesis process and mechanism of prolonged hematochezia associated with radiation-induce toxicity remain unclear. Methods: The 16S DNA of gut microbiota of 32 CRP patients with or without hematochezia were sequenced. The diversities and densities of gut microbiota were analyzed. Findings: Differential patterns of dysbiosis were observed. The abundance of Peptostreptococcaceae, Eubacterium and Allisonella were significantly higher in CRP patients with hematochezia, while the compositions of the Lachnospiraceae, Megasphera, Megamonas and Ruminococcaceae were lower in the microbiota of non-hematochezia patients. Functional prediction suggested significant difference in the expression of mineral absorption and the Arachidonic Acid metabolism proteins between hematochezia and non-hematochezia patients, possibly interdependent on radiation-induced inflammation. Interpretation: This study provides new insight to the function of gut microbiota in hemorrhage symptom of CRP patients. Further study is required to select probiotics and prebiotics to improve intestinal homoeostasis and relief prolonged hematochezia in CRP patients.
How do parents deal with their children's chronic kidney disease? A qualitative study for identifying factors related to parent's adaptation
Authors: Khorsandi Fatemeh , Parizad Naser , Feizi Aram , maslakpak Masumeh Hemmati 
Published: November 2020

Abstract
Background: Parents’ adaptation affects the health outcomes of children with chronic kidney diseases (CKD). Identifying factors that affect parents’ adaptation is necessary to understand their adaptation status. This study aims to explore factors related to the adaptation of parents who have children with CKD.Methods: This was a qualitative study with a content analysis approach. Seventeen parents of children with CKD were selected by using purposive sampling. The leading researcher performed semi-structured, in-depth, face-to-face interviews to collect data. Conventional content analysis was used to analyze data.Results: Two main categories extracted from the data were “adaptation facilitators” and “adaptation barriers.” Adaptation facilitators were supported by three sub-categories: "social support", "family capability" and "spiritual beliefs". Four sub-categories of “adaptation barriers” were revealed as: “family-related barriers,” “mental stress by others,” “the chronic nature of the disease,” and “unfavorable treatment conditions.”Conclusions: Identifying the factors influencing parental adaptation helps the medical staff to make the necessary interventions to support the parents. According to this study, increasing parent access to the required information, supporting them financially and emotionally, and helping them identify support resources can facilitate their adaptation to their child's chronic illness. Also, identifying and eliminating adaptation barriers can help parents deal better with their child’s chronic disease.
Hydroxysafflor yellow A promotes osteogenesis and bone development via epigenetically regulating β-catenin and prevents ovariectomy-induced bone loss
Authors: Wang Peng , Min Wang , Zhuo Tingling , Li Ying , Weiping Lin , Lingli Ding , Zhang Meng , Zhou Chi , Zhang Jinfang , Li Gang , Wang Haibin , Xu Liangliang 
Published: November 2020

Abstract
In clinical treatment, there is increasingly prevalent that traditional Chinese medicine treats common bone diseases including osteoporosis. Hydroxy safflor yellow A (HSYA), one of the essential compounds of Safflower, has strong effects to scavenge oxidative stress and inhibit apoptosis. It has been used as the therapy for thrombus, myocardial ischemia, and inflammation, but its effect on osteoporosis has not been explored. In this study, we found HSYA could enhance the cell viability and promote osteogenesis of hBMSC in vitro. Mechanistically, HSYA could increase the expression of β-catenin leading to its accumulation in the nucleus and activation of down-stream targets to promote osteogenesis. In addition, RNAseq and quantitative RT-PCR showed KDM7A was significantly increased by HSYA.The occupancy of H3K27me2 on β-catenin promoter was significantly decreased by HSYA, which could be reversed by silencing endogenous KDM7A. More importantly, HSYA could promote bone development in chick embryos and prevent ovariectomy(OVX)-induced bone loss in SD rats. Taken together, our study has shown convincing evidence that HSYA can promote osteogenesis and bone development via epigenetically regulating β-catenin and prevents ovariectomy-induced bone loss. HSYA might be used to treat some skeletal diseases such as osteoporosis.
Abnormal rich club organization in end-stage renal disease patients before dialysis initiation and undergoing maintenance hemodialysis
Authors: Ma Shaohui , Zhang Ming , Liu Yang , Ding Dun , Li Peng , Ma Xueying , Liu Hongjuan , Mu Junya 
Published: November 2020

Abstract
Background: End-stage renal disease (ESRD) patients are at a substantially higher risk for developing cognitive impairment compared with the healthy population. Dialysis is an essential way to maintain the life of ESRD patients. Based on previous research, there isn’t an uncontested result whether cognition was improved or worsened during dialysis.Methods: To explore the impact of dialysis treatment on cognitive performance, we recruited healthy controls (HCs), predialysis ESRD patients (predialysis group), and maintenance hemodialysis ESRD patients (HD group). All ESRD patients performed six blood biochemistry tests (hemoglobin, urea, cystatin C, Na+, K+, and parathyroid hormone). Neuropsychological tests were used to measure cognitive function. By using diffusion tensor imaging and graph-theory approaches, the topological organization of the whole-brain structural network was investigated. Generalized linear models (GLMs) were performed to investigate blood biochemistry predictors of the neuropsychological tests and the results of graph analyses in the HD group and predialysis group. Results: Neuropsychological analysis showed the HD group exhibited better cognitive function than the predialysis group, but both were worse than HCs. Whole-brain graph analyses revealed that increased global efficiency and normalized shortest path length remained in the predialysis group and HD group than the HCs. Besides, a lower normalized clustering coefficient was found in the predialysis group relative to the HCs and HD group. For the GLM analysis, only the Cystatin C level was significantly associated with the average fiber length of rich club connections in the predialysis group. Conclusions: Our study revealed that dialysis had a limited effect on cognitive improvement.
Association between Chronic Kidney Disease and the Most Common Corneal Ectasia Disease (Keratoconus): a Nationwide Cohort Study
Authors: Jan Ren-Long , Weng Shih-Feng , Wang Jhi-Joung , Chang Yuh-Shin 
Published: November 2020

Abstract
Background: Both keratoconus (KCN) and chronic kidney disease (CKD) are multifactorial conditions with multiple aetiologies and share several common pathophysiologies. However, the few studies that have described the relationship between KCN and CKD are limited to case reports and small case series. This study aimed to evaluate the association between KCN and CKD.Methods: The study cohort included 4,609 new-onset keratoconus patients ≥ 12 years identified by the International Classification of Diseases, Ninth Revision, Clinical Modification, code 371.6 and recruited between 2004 and 2011 from the Taiwan National Health Insurance Research Database. The age- , sex- , and comorbidity-matched control group included 27,654 non-KCN patients, selected from the Taiwan Longitudinal Health Insurance Database, 2000. Information for each patient was collected and tracked from the index date until December 2013. The incidence and risk of CKD were compared between the two groups. The adjusted hazard ratios (HRs) for CKD were calculated with Cox proportional hazard regression analysis. Kaplan–Meier analysis was used to calculate the cumulative CKD incidence rate. Results: The incidence rate of CKD was 1.36 times higher in KCN patients than in controls without statistically significant difference (95% confidence interval [CI] = 0.99–1.86, p = 0.06). In total, 29 male KCN patients and 90 male controls developed CKD during the follow-up period. The incidence rate of CKD was 1.92 times (95% [CI] = 1.26–2.91; p = 0.002) higher in male KCN patients than in controls. After adjusting for potential confounders, including age, hypertension, hyperlipidaemia, and diabetes mellitus, male KCN patients were 1.75 times (adjusted HR = 1.75, 95% [CI] = 1.14–2.68, p < 0.05) more likely to develop CKD. Conclusions: We found that male KCN patients have an increased risk of CKD. Therefore, it is recommended that male KCN patients should be aware of CKD.
DASSI: Differential Architecture Search for Splice Identification from DNA Sequences
Authors: Moosa Shabir , Amira Abbes , Boughorbel Sabri 
Published: November 2020

Abstract
Background: The data explosion caused by unprecedented advancements in the field of genomics is constantly challenging the conventional methods used in the interpretation of the human genome. The demand for robust algorithms over the recent years has brought huge success in the field of Deep Learning (DL) in solving many difficult tasks in image, speech and natural language processing by automating the manual process of architecture design. This has been fueled through the development of new DL architectures. Yet genomics possesses unique challenges that requires customization and development of new DL models. Methods: We proposed a new model, DASSI, by adapting a differential architecture search method and applying it to the Splice Site (SS) recognition task on DNA sequences to discover new high-performance convolutional architectures in an automated manner. We evaluated the discovered model against state-of-the-art tools to classify true and false SS in Homo sapiens (Human), Arabidopsis thaliana (Plant), Caenorhabditis elegans (Worm) and Drosophila melanogaster (Fly). Results: Our experimental evaluation demonstrated that the discovered architecture outperformed baseline models and fixed architectures and showed competitive results against state-of-the-art models used in classification of splice sites. The proposed model - DASSI has a compact architecture and showed very good results on a transfer learning task. The benchmarking experiments of execution time and precision on architecture search and evaluation process showed better performance on recently available GPUs making it feasible to adopt architecture search based methods on large datasets. Conclusions: We proposed the use of differential architecture search method (DASSI) to perform SS classification on raw DNA sequences, and discovered new neural network models with low number of tunable parameters and competitive performance compared with manually engineered architectures. We have extensively benchmarked DASSI model with other state-of-the-art models and assessed its computational efficiency. The results have shown a high potential of using automated architecture search mechanism for solving various problems in the field of genomics.