bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long noncoding RNA UPK1A-AS1 indicates poor prognosis of hepatocellular carcinoma and promotes cell proliferation through interacting with EZH2
Authors: Zhang Dong-Yan , Sun Qing-Can , Zou Xue-Jing , Song Yang , Li Wen-Wen , Guo Ze-Qin , Liu Shan-Shan , Liu Li , Wu De-Hua 
Published: October 2020

Abstract
Background: Dysregulations of lncRNA are responsible for cancer initiation and development, positioning lncRNAs as not only biomarkers but also promising therapeutic targets for cancer treatment. Growing number of lncRNAs have been reported in HCC but their functional and mechanistic roles remain unclear. Methods: Gene Set Enrichment Analysis was used to investigate the molecular mechanism of lncRNA UPK1A antisense RNA 1 (UPK1A-AS1). CCK-8 assay, EdU assay, flow cytometry, western blot, and xenograft assay were used to confirm the role of UPK1A-AS1 in the proliferation of HCC cells both in vitro and in vivo. Bioinformatics analysis and qRT-PCR were performed to explore the interplay between UPK1A-AS1 and Enhancer of Zeste Homologue 2 (EZH2). RNA immunoprecipitation (RIP), RNA-pull down assay, western blot, qRT-PCR, and were conducted to confirm the interaction between UPK1A-AS1 and EZH2. The interaction between UPK1A-AS1 and miR-138-5p was examined by luciferase reporter and RIP assays. Finally, the expression level and prognosis value of UPK1A-AS1 in HCC were analyzed using RNA-seq data from TCGA datasets.Results: We showed that UPK1A-AS1, a newly identified lncRNA, promoted cellular proliferation and tumor growth by accelerating cell cycle progression. Cell cycle related genes including CCND1, CDK2, CDK4, CCNB1 and CCNB2 were significantly upregulated in HCC cells with UPK1A-AS1 overexpression. Furthermore, overexpression of UPK1A-AS1 could protect HCC cells from cis-platinum toxicity. Mechanistically, UPK1A-AS1 interacted with EZH2 to mediate its nuclear translocation and reinforce its binding to SUZ12, leading to the increasing trimethylation of H27K3. Targeting EZH2 with specific siRNA impaired UPK1A-AS1-mediated upregulation of proliferation and cell cycle progression related genes. Moreover, miR-138-5p was identified as a direct target of UPK1A-AS1. Additionally, UPK1A-AS1 was significantly upregulated in HCC, and upregulation of UPK1A-AS1 predicted poor prognosis for patients with HCC. Conclusions: Our study reveals that UPK1A-AS1 promotes HCC development by accelerating cell cycle progression via interacting with EZH2 and sponging miR-138-5p, suggesting that UPK1A-AS1 possesses substantial potential as a novel biomarker for HCC prognosis and therapy.
Guidance for overviews of reviews continues to accumulate, but important challenges remain: A scoping review
Authors: Gates Michelle , Gates Allison , Guitard Samantha , Pollock Michelle , Hartling Lisa 
Published: October 2020

Abstract
Background. Overviews of reviews (overviews) provide an invaluable resource for healthcare decision-making by combining large volumes of systematic review (SR) data into a single synthesis. The production of high-quality overviews hinges on the availability of practical evidence-based guidance for conduct and reporting.Objectives. Within the broad purpose of informing the development of a reporting guideline for overviews, we aimed to provide an up-to-date map of existing guidance related to the conduct of overviews, and to identify common challenges that authors face when undertaking overviews.Methods. We updated a scoping review published in 2016 using the search methods that had produced the highest yield: ongoing reference tracking (2014 to March 2020 in Pubmed, Scopus, and Google Scholar), hand-searching conference proceedings and websites, and contacting authors of published overviews. Using a qualitative meta-summary approach, one reviewer extracted, organized, and summarized the guidance and challenges presented within the included documents. A second reviewer verified the data and synthesis.Results. We located 28 new guidance documents, for a total of 77 documents produced by 34 research groups. The new guidance helps to resolve some earlier identified challenges in the production of overviews. Important developments include strengthened guidance on handling primary study overlap at the study selection and analysis stages. Despite marked progress, several areas continue to be hampered by inconsistent or lacking guidance. There is ongoing debate about whether, when, and how supplemental primary studies should be included in overviews. Guidance remains scant on how to extract and use appraisals of quality of the primary studies within the included SRs and how to adapt GRADE methodology to overviews. The challenges that overview authors face are often related to the above-described steps in the process where evidence-based guidance is lacking or conflicting.Conclusion. The rising popularity of overviews has been accompanied by a steady accumulation of new, and sometimes conflicting, guidance. While recent guidance has helped to address some of the challenges that overview authors face, areas of uncertainty remain. Practical tools supported by empirical evidence are needed to assist authors with the many methodological decision points that are encountered in the production of overviews.
Molecular characteristics of rotavirus genotypes circulating in the south of Benin, 2016-2018
Authors: Agbla Jijoho Michel , Esona Mathew D , Agbankpé Alidéhou Jerrold , Capo-Chichi Annick , Gautam Rashi , Dougnon Tamègnon Victorien , Razack Osseni , Bowen Michael D , Bankolé Honoré Sourou 
Published: October 2020

Abstract
Objective Rotavirus remains the main causative agent of gastroenteritis in young children in countries that have not yet introduced the vaccine. In Benin, rotavirus vaccine was introduced late December 2019 into the EPI. This study aims to provide pre-vaccination era rotavirus genotyping data in Benin. These data can supplement data from the surveillance system of Ministry of Health of Benin which is supported by the World Health Organization (WHO). Results Of the 420 diarrheal stool samples, actively collected in southern Benin from July 2016 through November 2018 from children under five years old and suffering from gastroenteritis, 167 (39.8%) samples were rotavirus EIA positive. 186 (44.3%) samples contained amplifiable rotavirus RNA detected by qRT-PCR method and were genotyped using one-step RT-PCR multiplex genotyping method. G1P[8] represents the predominant genotype (32%) followed by the G2P[4] (26%), G3P[6] (16%), G12P[8] (13%) and mixed G and P types (1%). Four samples (2%) could not be assigned both G and P type speciﬁcity.
Effects of the socio-economic transition on health professions education: The case of Mongolia
Authors: Amgalan Nomin , Shin Jwa-Seop , Lee Seung-Hee , Badamdorj Oyungoo , Ravjir Oyungerel , Yoon Hyun Bae 
Published: October 2020

Abstract
BackgroundFormer socialist countries have undergone a socio-economic transition in recent decades. New challenges for the healthcare system have arisen in the transition economy, leading to demands for better management and development of the health professions. However, few studies have explored the effects of this transition on health professions education. Thus, we investigated the effects of the socio-economic transition on the three levels of health professions education system in Mongolia, a transition economy country. The changing requirements of three levels, including input, process, and output levels of health professions education system were explored. The input level refers to planning and management, the process level refers to the actual delivery of educational services, and the output level refers to issues related to the health professionals, produced by the system. This study utilized a qualitative research design, including document review and interviews with local representatives. Content analysis and the constant comparative method were used for data analysis. ResultsWe explored tensions in the three levels of the health professions education system. First, medical schools attained academic authority for planning and management without proper regulation and financial support. The government sets tuition fees, which are the only financial resource of medical schools; thus, medical schools attempt to enroll more students in order to adapt to the market environment. Second, the quality of educational services varies across institutions due to the absence of a core curriculum and differences in the learning environment. After the transition, the number of private medical schools rapidly increased without quality control, while hospitals started their own specialized training programs. Third, health professionals are struggling to maintain their professional values and development in the market environment. Fixed salaries lead to a lack of motivation, and quality evaluation measures more likely reflect government control than quality improvement.ConclusionMongolia continues to face the consequences of the socio-economic transition. Medical schools’ lack of financial authority, the varying quality of educational services, and poor professional development are the major adverse effects. Finding external financial support, developing a core curriculum, and introducing performance-based payments are recommended.
Lactic acidosis associated with metformin in diabetic patients with chronic kidney disease: a multicentre case-control study using electronic health records
Authors: Ávila Mónica , Videla Sebastian , Gómez-Lumbreras Ainhoa , Manriquez Marcela , Prat Oriol , Morros Rosa , Pedrós Consuelo 
Published: October 2020

Abstract
Background: Several studies have assessed the risk of lactic acidosis with metformin use. However, data of this association in patients with renal impairment are still scarce and controversial. Our aim was therefore to assess the association between metformin and lactic acidosis in Spanish type 2 diabetic patients with chronic kidney disease.Methods: A case-control study (ALIMAR-C2) was performed using the electronic health records from hospitals linked to their corresponding primary healthcare regions. The cases were adult (≥18 years) diabetic patients with chronic kidney disease, admitted to seven Spanish hospitals from 2010 to 2016. Ten controls (≥18 years, diabetic patients with chronic kidney disease) per case were selected from the population within the same primary healthcare region of the hospital cases. The patients’ hospital health records were linked to their corresponding primary healthcare information. Analyses included multivariable logistic regression and adjustment for potential confounders. Results: Our study included 126 cases and 1,260 matched controls. The current use of metformin and administration at high doses (>2g) were associated with lactic acidosis (adjusted OR: 1.92, 95% CI: 1.21-3.03; OR: 3.13, 95% CI: 1.63-6.01, respectively). The estimated case fatality rate was 46.8% (95% CI: 38.3-55.5%). An increased risk of lactic acidosis was observed In patients with mild to moderate renal impairment (OR: 3.41, 95% CI: 1.48-7.85). As an unexpected finding, diuretic drugs use was also associated with lactic acidosis (OR: 2.73, 95% CI: 1.67 - 4.46).Conclusions: Metformin was associated with an increased risk of lactic acidosis in patients with type 2 diabetes mellitus and chronic kidney disease. New data is needed to confirm the association between diuretic drugs and lactic acidosis in this group of patients.
ZNF674-AS1 suppresses non-small cell lung cancer growth through the miR-423-3p/p21 axis
Authors: Liu Yu , Huang Risheng , Xie Deyao , Lin Xiaoming , Zheng Liangcheng 
Published: October 2020

Abstract
Background: ZNF674-AS1, a recently characterized long noncoding RNA, shows prognostic significance in hepatocellualar carcinoma and glioma. However, the expression and function of ZNF674-AS1 in non-small cell lung cancer (NSCLC) is unclear. Methods: In this work, we investigated the expression of ZNF674-AS1 in 83 pairs of NSCLC specimens and adjacent noncancerous lung tissues. The clinical significance of ZNF674-AS1 in NSCLC was analyzed. The role of ZNF674-AS1 in NSCLC growth and cell cycle progression was explored. Results: Our data show that ZNF674-AS1 expression is decreased in NSCLC compared to normal tissues. ZNF674-AS1 downregulation is significantly correlated with advanced TNM stage and decreased overall survival of NSCLC patients. Overexpression of ZNF674-AS1 inhibits NSCLC cell proliferation, colony formation, and tumorigenesis, which is accompanied by a G0/G1 cell cycle arrest. Conversely, knockdown of ZNF674-AS1 enhances the proliferation and colony formation of NSCLC cells. Biochemically, ZNF674-AS1 overexpression increases the expression of p21 through downregulation of miR-423-3p. Knockdown of p21 or overexpression of miR-423-3p blocks ZNF674-AS1-mediated growth suppression and G0/G1 cell cycle arrest. In addition, ZNF674-AS1 expression is negatively correlated with miR-423-3p in NSCLC specimens. Conclusions: ZNF674-AS1 suppresses NSCLC growth by downregulating miR-423-3p and inducing p21. This work suggests the therapeutic potential of ZNF674-AS1 in the treatment of NSCLC.
Monophasic Synovial Sarcoma Presenting as Infantile Hemangioma: A Case Report
Authors: Kandari Abdulrahman Fahad Al , Alkandari Abdulwahab Fahad , Alhendi Sarah Faisal , Almousawi Hussain Saleh , Burezq Hisham Adel 
Published: October 2020

Abstract
Objective: This report describes a case of a monophasic synovial sarcoma that was initially misdiagnosed as an infantile hemangioma in a 3-month-old female infant. We also discuss the basic elements of evaluating a soft-tissue mass and important radiological and clinical features that should raise the index of suspicion for a synovial sarcoma. Summary Background Data: Synovial sarcoma is a rare pathology that is often challenging to diagnose due to its similarities with more common vascular lesions that occur in infancy. Infantile hemangioma, in particular, is common, has distinctive clinical and radiological findings, and is frequently diagnosed without histological confirmation. This increases the risk of misdiagnosis of rare tumors in infancy. Case Report: A 3-month-old female infant presented with a soft-tissue mass on the left forearm. Physical examination showed a well-defined, subcutaneous mass on the left forearm, measuring approximately 3 cm × 5 cm, firm in consistency, with no cutaneous involvement and normal skin coverage. Imaging suggested an infantile hemangioma but, due to the atypical presentation, a trial of beta-blocker therapy was conducted to confirm the diagnosis. The patient showed no clinical response to beta-blocker therapy, and therefore an incisional biopsy was performed. Using histopathology, the tumor was diagnosed as a monophasic synovial sarcoma.Conclusions: We highlight a rare presentation of a synovial sarcoma in a neonate and caution against making a diagnosis without histopathologic analysis. Clinicians should include sarcoma in the differential diagnosis when assessing a mass in neonates, as early diagnosis and intervention can reduce morbidity and mortality.MINI ABSTRACT A 3-month-old infant presented with a left forearm soft-tissue mass, initially diagnosed as infantile hemangioma. Biopsy revealed a monophasic synovial sarcoma. We discuss the basic elements of evaluating a soft-tissue mass and important radiological and clinical features that should raise the index of suspicion for a synovial sarcoma.
Risk Factors for Critical-Ill Events of Patients With COVID-19 in Wuhan, China: A Retrospective Cohort Study
Authors: Yang Sen , Ma Le , Wang Yu-Lan , Wang Qian , Tong Qiang , Chen Miao , Zhang Hua , Yu De-Hua , Dai Sheng-Ming , Cui Ran 
Published: October 2020

Abstract
Background To explore the risk factors for critical-ill events (intensive care, invasive ventilation, or death) in patients with COVID-19.Methods Patients with laboratory-confirmed COVID-19 admitted to the Wuhan Leishenshan Hospital from February 13 to March 14 was retrospectively analyzed. Demographic data, symptoms, laboratory values at baseline, comorbidities, treatments and clinical outcomes were extracted from electronic medical records and compared between patients with and without critical-ill events. The least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression models were developed to explore the risk factors for critical-ill events. A risk nomogram was established to predict the probability for the critical-ill events. Survival analysis of patients with critical-ill events was performed by the Kaplan-Meier method.Results 463 COVID-19 patients were included in this study, of whom 397 were non-critically ill and 66 were critically ill (all from the intensive care unit). The LASSO regression identified four variables (hypersensitive cardiac troponin I, blood urea nitrogen , haemoglobin, and interleukin-6) contributing to the critical-ill events. Multivariable regression showed increasing odds of in-hospital critical-ill events associated with hypersensitive cTnI greater than 0.04 ng/mL (OR 20.98,95% CI 3.51-125.31), blood urea nitrogen greater than 7.6 mmol/L (OR 5.22, 95% CI 1.52-17.81, decreased haemoglobin (OR 1.06, 95% CI 1.04-1.10), and higher interleukin-6 (OR 1.05, 95% CI 1.02-1.08) on admission. Conclusions Hypersensitive cTnI greater than 0.04 ng/mL, blood urea nitrogen greater than 7.6 mmol/L, decreased haemoglobin, and high IL-6 were risk factors of critical-ill events in patients with COVID-19.
Clinical and Deep-Learning Based Quantitative Serial Chest CT Features of The COVID-19 Disease: Association with Clinical Subtypes and A Follow-Up Study
Authors: Su Xiaoyun , Jia Yuxi , Zhu Qing , Liu Bo , Zhang Huiting , Wang Jing , Zheng Chuansheng 
Published: October 2020

Abstract
Background: To explore the clinical features and deep-learning (DL) based quantitative CT finding’s applications and evolution as well as the correlations in COVID-19.Methods: 273 chest CT scans (median interval, 6 days) from 75 COVID-19 RT-PCT positive patients (53 moderate and 22 severe) were included. Quantification parameters, such as CT value distribution, lesion (abnormal), GGO, consolidation rates, Hellinger distance and IOU, were automatically extracted from CT images by a combination of traditional image process algorithm and DL network. Clinical characteristics were also collected and analysed.Results: The hypertension and diabetes were more common in severity. The CRP, ESP, LDH and D-dimer were higher while LYM and LYM% lower in severity (P < 0.05). The DL network was detected the lesions to obtain quantitively CT indicators, with fast to process a chest CT images (average time, 2.2s) and high overlap with radiologist. The hellinger, abnormal, GGO, consolidation rates and HU values were higher and the IOU lower in severity than moderate patients (P < 0.05). The largest AUC was 0.943, using the cutoff value of 10.5% for abnormal rate. The CT score have postive correlations with CRP, D-dimer and ESR (P < 0.05). The increased levels of ESR and D-dimer were positively correlated with abnormal, consolidation and GGO rates (P < 0.05). Investigation for quantitative CT changes were performed in three periods: 1) 1-2 weeks, CT score and abnormal rate were increased. The GGO converted to consolidation in severity; 2) 2-5 weeks, CT scores stable trend, while abnormal and GGO rates had upward trend in severity; 3) > 5weeks, CT score and abnormal rate have decreased.Conclusions: There were three phases of two patterns’ evolutionary trends in quantitative CT findings with differences in two groups, and have correlations with laboratory markers, which helpful for evaluating severity and prognosis in COVID-19 patients.
Variants Translating Reduced Expression of the Beta Estrogen Receptor Gene Were Associated With Increased Carotid Intima Media Thickness. A Cross-Sectional Study in Late Postmenopausal Women.
Authors: Cano-Marquina Antonio-Jorge , García-Pérez Miguel-Ángel , Tarín Juan J , Maceira Alicia M , Cosín-Sales Juan , Cano Antonio 
Published: October 2020

Abstract
Background There is debate on the role of estrogens in modulating the risk for atherosclerosis in women. Our purpose was to investigate whether the size of the estrogenic impact was independently associated with variation of carotid intima-media thickness (IMT) in healthy late postmenopausal women. The levels of circulating estrogens have been used in previous studies but the influence of SNPs of the estrogen receptors (ER) α and β has not been investigated.Methods We performed a crossed-sectional study of 91 women in a university hospital. We used a double approach in which, in addition to the measurement of estradiol levels by ultrasensitive methods, genetic variants (SNPs) associated with differing expression of the ER α and β genes were assessed. Multivariable analysis was used to examine the association of candidate factors with the value of IMT and plaque detection at both the carotid wall and the sinus.Results The levels of glucose were directly associated with IMT at both the carotid wall (p<0.001) and the sinus (p=0.001), while age was positively associated with IMT at the sinus (p=0.003) and vitamin D with IMT at the carotid wall (P=0.035). A genotype combination translating reduced gene expression of the ERβ was directly associated with IMT at both the carotid wall (p=0.001) and the sinus (p=0.002).Conclusions Poorer estrogenic impact, as concordant with a SNP variant imposing reduced expression of the ERβ, was directly associated with IMT at both the carotid wall and the sinus. Glucose level, vitamin D only for the carotid wall, and age only for the sinus, also emerged as independent factors in the IMT variance.
Transfer of Rhodamine-123 into the Brain and Cerebrospinal Fluid of Fetal, Neonatal and Adult Rats
Authors: Koehn Liam , Dziegielewska Katarzyna M , Habgood Mark D , Huang Yifan , Saunders Norman R 
Published: October 2020

Abstract
Background: Adenosine triphosphate binding cassette transporters such as P-glycoprotein (PGP) play an important role in drug pharmacokinetics by actively effluxing their substrates at barrier interfaces, including the blood-brain, blood-cerebrospinal fluid (CSF) and placental barriers. For a molecule to access the brain during fetal stages it must bypass efflux transporters at both the placental barrier and brain barriers themselves. Following birth, placental protection is no longer present and brain barriers remain the major line of defense. Understanding developmental differences that exist in the transfer of PGP substrates into the brain is important for ensuring that medication regimes are safe and appropriate for all patients. Methods: In the present study PGP substrate rhodamine-123 (R123) was injected intraperitoneally into E19 dams, postnatal (P4, P14) and adult rats. Naturally fluorescent properties of R123 were utilized to measure its concentration in blood-plasma, CSF and brain by spectrofluorimetry (Clariostar). Statistical differences in R123 transfer (ratios between tissue and plasma concentrations) were determined using Kruskal-Wallis tests with Dunn’s corrections. Results: Following maternal injection the transfer of R123 across the E19 placenta from maternal blood to fetal blood was around 20%. Of the R123 that reached fetal circulation 41% transferred into brain and 38% into CSF. The transfer of R123 from blood to brain and CSF was lower in postnatal pups and decreased with age (brain: 43% at P4, 22% at P14 and 9% in adults; CSF: 8% at P4, 8% at P14 and 1% in adults). Transfer from maternal blood across placental and brain barriers into fetal brain was approximately 8%, similar to the transfer across adult blood-brain barriers (9%). Following birth when placental protection was no longer present, transfer of R123 from blood into the newborn brain was significantly higher than into adult brain (3 fold, p<0.05). Conclusions: Administration of a PGP substrate to infant rats resulted in a higher transfer into the brain than equivalent doses at later stages of life or equivalent maternal doses during gestation. Toxicological testing of PGP substrate drugs should consider the possibility of these patient specific differences in safety analysis. Trial Registration: N/A.