bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying Serum Exosomal-Associated lncRNA/circRNA-miRNA-mRNA Network in Coronary Heart Disease
Authors: Mao Jia , Zhou Yufei , Lu Licheng , Zhang Ping , Ren Runhua , Wang Yaqiong , Wang Jing 
Published: January 2021

Abstract
Background: Accumulating evidence has indicated that the importance of noncoding RNAs and exosomes in coronary heart disease (CHD). However, the exosomal-associated competing endogenous RNA (ceRNA)-mediated regulatory mechanism in CHD is still unknown. The present study aimed to explore exosomal-associated ceRNA network in CHD.Methods: The dataset, including 6 CHD patients and 32 normal controls, were downloaded from the ExoRBase database. Differentially expressed mRNAs (DEMs), lncRNAs (DELs) and circRNAs (DECs) in the serum exosomes between CHD and normal controls were screened. MicroRNAs (miRNAs) targeting DEMs were predicted by Targetscan and miRanda, miRNAs targeting DELs and DECs were predicted with miRcode and starBase, respectively. The biological functions and related signal pathways of DEMs were analyzed using David and KOBAS database. Subsequently, the protein-protein interaction (PPI) network was established to screen out hub genes, enrichment analyses of hub genes were performed and the ceRNA network (lncRNA/circRNA-miRNA-mRNA) was constructed to elucidate ceRNA axes in CHD.Results: A total of 312 DEMs, 43 DELs and 85 DECs were identified between CHD patients and normal controls. Functional enrichment analysis showed that DEMs were significantly enriched in “chromatin silencing at rDNA”, “telomere organization”, “negative regulation of gene expression, epigenetic”. The PPI network analysis showed that 25 hub DEMs were closely related to CHD, of which, ubiquitin C (UBC) was the most important. The biological function of hub genes showed that they were mainly enriched in “cellular protein metabolic process”. The exosomal-associated ceRNA regulatory network incorporated 48 DEMs, 72 predicted miRNAs, 10 DELs and 15 DECs. LncRNA/circRNA-miRNA-mRNA interaction axes (RPL7AP11/hsa-miR-17-5p/UBC, RPL7AP11/hsa-miR-20b-5p/UBC) were obtained from the network. Conclusions: Our findings have provided a novel perspective on the potential roles of exosomal-associated ceRNA network regulating the pathogenesis of CHD.
Frequency of metabolic syndrome and insulin resistance in epileptic patients treated with sodium valproate or carbamazepine monotherapy: A Case-Control Study
Authors: Bayat Mahnaz , Jalali Nasrin , Poursadeghfard Maryam , Nazeri Masomeh , Dabbaghmanesh Mohammad Hossein , Ashjazadeh Nahid 
Published: January 2021

Abstract
Background

Metabolic syndrome (MetS) represents a collection of metabolic risk factors such as obesity, dyslipidemia, hyperglycemia, and hypertension. Medications can increase the incidence rate of MetS and insulin resistance (IR).
Objective

This study aims to evaluate the effects of Carbamazepine (CBZ) or Valproate (VPA) as monotherapy on the development of MetS and IR in the adult Iranian epileptic patients.
Methods

In this observational analytic case-control study, 80 epileptic patients were treated with VPA (40 patients) or CBZ (40 patients) monotherapies for more than 6 months and 45 age and sex matched controls were included. MetS was assessed based on International Diabetes Federation (IDF) and National Cholesterol Education Program (NCEP) criteria.
Results

In the multiple regression analysis, in VPA-treated patients the risk of MetS (by IDF criteria) was increased 19 times higher than controls (OR = 19.20; 95% CI = 2.62-140.23, P = 0. 004) and risk of IR (by HOMA and QUICKI) was increased 15 and 9 times more than controls (OR = 14.83; 95% CI = 3.03–72.56, P = 0.001) and (OR = 9.13; 95% CI = 2.55–32.65, P = 0.001) respectively. Increase in waist, DBP, and insulin level were also showed as important factors in risk of MetS. In CBZ therapy, the risk of MetS (by IDF) depressed by 17% less than controls and the risk of IR (by HOMA) increased 7 times more than controls.
Conclusion

Treatment with VPA can increase the likelihood of developing MetS and IR while, CBZ therapy could decrease the risk of MetS and increase risk of IR in the epileptic patients in Iran compared to the general population.
An Innovative Approach to Improve the Detection and Treatment of Risk Factors in Poor Urban Settings: A Feasibility Study in Argentina
Authors: Poggio Rosana , Danaei Goodarz , Gutierrez Laura , Cavallo Ana , Lopez María , Irazola Vilma 
Published: January 2021

Abstract
Background The effective management of cardiovascular (CVD) prevention among the uninsured population in Argentina is low since less than 30% of the individuals with predicted 10-year CVD risk ≥10% attend a clinical visit for CVD risk factors control in the primary care clinics (PCCs). Methods We conducted a non-controlled feasibility study using a mixed methods approach to evaluate acceptability, adoption and fidelity of a multi-component intervention implemented in the public healthcare system. The eligibility criteria were being uninsured, age ≥ 40 years, residence in the PCC´s catchment area and 10-year CVD risk ≥ 10%. The multi-component intervention addressed (1) system barriers through task shifting among the PCC´s staff, protected medical appointments slots and a new CVD form and (2) Provider barriers through training for primary care physicians and CHW and individual barriers through a home-based intervention delivered by community health workers (CHWs).Results A total of 185 participants were included in the study. Of the total number of the eligible participants, 82.2% of eligible participants attended to at least one clinical visit for risk factor control. Physicians intensified drug treatment in 77% of participants with BP ≥140/90 mmHg and 79.5% of participants with diabetes, increased the proportion of participants treated according to GCP from 21% to 32.6% in hypertensive participants, 7.4% to 33.3% in high CVD risk and 1.4% to 8.7% in very high CVD risk groups. Mean systolic and diastolic blood pressure were lower at the end of follow up (156.9 to 145.4 mmHg and 92.9 to 88.9 mmHg, respectively) and control of hypertension (BP<140/90 mmHg) increased from 20.3% to 35.5%.Conclusion The proposed CHWs-led intervention was feasible and well accepted in improving the detection and treatment of risk factors in the uninsured and poor population with moderate or high CVD risk at the primary care setting in Argentina. Task sharing activities with CHWs not only stimulated teamwork among PCC staff, but it also improved quality of care. This study showed that community health workers could have a more active role in the detection and clinical management of CVD risk factors in low-income communities.
Selection and Evaluation of Reference Genes for ddPCR-Based Transcript Abundance Studies in Oidiodendron Maius Across Varying Carbon Sources
Authors: Feldman Erin , Martino Elena , Kohler Annegret , Durall Daniel , Jones Melanie 
Published: January 2021

Abstract
Background When identifying transcript abundance in response to treatment, accurate quantification is critical, especially when examining subtle differences in expression. In particular, data normalization is necessary to account for differences among samples including those associated with RNA quantity and quality. Due to the capacity of droplet digital PCR to absolutely quantify the copy number of the target gene in a given sample, normalization, such as the use of an internal control gene, has not customarily been considered obligatory. Decades of quantitative PCR research have shown, however, that the use of endogenous controls undoubtedly aid in correcting sample variability. With our limited knowledge of gene function in many fungi, typical ‘housekeeping genes’ commonly used as internal references may not be relevant in these organisms. This study aimed to identify and validate suitable reference genes for transcript abundance studies in Oidiodendron maius, a globally distributed, model ericoid mycorrhizal fungus. Results A shortlist of 251 non-differentially expressed genes was generated from RNA-Seq analyses of O. maius grown on three different carbon sources or in symbiosis with Vaccinium myrtillus. Subsequently, a set of criteria (stable expression, valid annotation and relatively high expression) was applied to select three candidate reference genes. These three genes were validated across a further eleven carbon sources using ddPCR and the application of geNorm and NormFinder stability analysis algorithms. Expression stability analysis of three genes - EfTu, vma, and sar - confirmed their reliability as internal references; the geometric mean of their expression values demonstrated the highest stability as a normalization factor.Conclusions We propose the use of the geometric mean of O. maius genes EfTu, vma and sar as a reference tool to normalize RNA expression in ddPCR assays. These newly selected and validated reference genes will increase reliability and reproducibility when studying transcriptional responses of O. maius at different developmental stages and/or under a range of physiological conditions. In addition, the list of 251 non-differentially expressed genes can serve as a valuable resource for selecting reference genes for related experiments and enhances the limited information available on O. maius.
Take-Home Naloxone Programs for Suspected Opioid Overdose in Community Settings: A Scoping Umbrella Review
Authors: Moustaqim-Barrette Amina , Dhillon Damon , Ng Justin , Sundvick Kristen , Ali Farihah , Elton-Marshall Tara , Leece Pamela , Rittenbach Katherine , Ferguson Max , Buxton Jane 
Published: January 2021

Abstract
Background: Opioid related overdoses and overdose deaths continue to constitute an urgent public health crisis. The implementation of naloxone programs, such as ‘take-home naloxone’ (THN), has emerged as a key intervention in reducing opioid overdose deaths. These programs aim to train individuals at risk of witnessing or experiencing an opioid overdose to recognize an opioid overdose and respond with naloxone. Naloxone effectively reverses opioid overdoses on a biological level; however, there are outstanding questions on community THN program effectiveness (adverse events, dosing requirements, dose-response between routes of administration) and implementation (accessibility, availability, and affordability). The objective of this scoping review is to identify existing systematic reviews and best practice guidelines relevant to clinical and operational guidance on the distribution of THN.Methods: Using the Arksey & O’Malley framework for scoping reviews, we searched both academic literature and grey literature databases using keywords (Naloxone) AND (Overdose) AND (Guideline OR Review OR Recommendation OR Toolkit). Only documents which had a structured review of evidence and/or provided summaries or recommendations based on evidence were included (systematic reviews, meta-analyses, scoping reviews, short-cut or rapid reviews, practice/clinical guidelines, and reports). Data were extracted from selected evidence in two key areas: (1) study identifiers; and (2) methodological characteristics. Results: A total of 47 articles met inclusion criteria: 20 systematic review; 10 grey literature articles; 8 short-cut or rapid reviews; 4 scoping reviews; and 5 other review types (e.g. mapping review and comprehensive reviews). The most common subject themes were: naloxone effectiveness, safety, provision feasibility/acceptability of naloxone distribution, dosing and routes of administration, overdose response after naloxone administration, cost-effectiveness, naloxone training and education, and recommendations for policy, practice and gaps in knowledge. Conclusions: Several recent systematic reviews address the effectiveness of take-home naloxone programs, naloxone dosing/route of administration, and naloxone provision models. Gaps remain in the evidence around evaluating cost-effectiveness, training parameters and strategies, and adverse events following naloxone administration. As THN programs continue to expand in response to opioid overdose deaths, this review will contribute to understanding the evidence 60 base for policy and THN program development and expansion.
Relationship Between Renal Function and Blood Pressure Dipping Status in Renal Transplant Recipients: A Longitudinal Study.
Authors: Jaques David , Saudan Patrick , Martinez Chantal , Andres Axel , Martin Pierre-Yves , Pechère-Bertschi Antoinette , Ponte Belen 
Published: January 2021

Abstract
Background Hypertension (HT) is associated with adverse outcomes in renal transplant (RTX) recipients. Blunting of physiological decrease in nighttime compared to daytime blood pressure (non-dipping status) is frequent in this setting. However, weather non-dipping is independently associated with renal function decline in RTX patients is unknown.Methods We retrospectively screened RTX outpatients attending for a routine ambulatory blood pressure monitoring (ABPM) (T1) at a single tertiary hospital. Patients had two successive follow-up visits, one (T2) and two (T3) years later respectively. Routine clinical and laboratory data were collected at each visit. Mixed linear regression models were used with estimated glomerular filtration rate (eGFR) as the dependent variable.Results A total of 123 patients were included with a mean follow-up of 2.12 +/- 0.45 years after ABPM. Mean age and eGFR at T1 were 56.0 +/- 15.1 and 54.9 +/- 20.0 mL/min/1.73m2 respectively. 61 patients (50.4%) had sustained HT and 81 (65.8%) were non-dippers. In multivariate analysis, systolic dipping status was positively associated with eGFR (p=0.009) and compared to non-dippers, dippers had a 10.4 mL/min/1.73m2 higher eGFR. HT was negatively associated with eGFR (p=0.003).Conclusions We confirm a high prevalence of non-dippers in RTX recipients. We show that preserved systolic dipping is associated with improved renal function in this setting independently of potential confounders, including HT and proteinuria. Whether modification of dipping status by chronotherapy would preserve renal function remains to be tested in clinical trials.
Vaccine monitoring shows that focused immunization with SARS-CoV-2 receptor-binding domain provides a better neutralizing antibody response than full-length spike protein
Authors: Bayarri-Olmos Rafael , Idorn Manja , Rosbjerg Anne , Pérez-Alós Laura , Hansen Cecilie , Johsen Laust , Helgstrand Charlotte , Öberg Fredrik Kryh , Søgaard Max , Paludan Søren , Bak-Thomsen Theresa , Jardine Joseph , Skjoedt Mikkel-Ole , Garred Peter 
Published: January 2021

Abstract
Effective tools to monitor SARS-CoV-2 transmission and humoral immune responses are highly needed. Protective humoral immunity involves neutralizing antibodies and will be a hallmark for the evaluation of a vaccine response efficacy. Here we present a sensitive, fast and simple neutralization ELISA method to determine the levels of antibody-mediated virus neutralization. We can show that it is strongly correlated with the more elaborate plaque reduction neutralization test (PRNT) (ρ = 0.9231, p < 0.0001). Furthermore, we present pre-clinical vaccine models using recombinant receptor binding domain (RBD) and full-length spike antigen as immunogens showing a profound antibody neutralization capacity that exceeds the highest neutralization titers from convalescent individuals. Using a panel of novel high-affinity murine monoclonal antibodies (mAbs) we also show that majority of the RBD-raised mAbs have inhibitory properties while only a few of the spike-raised mAbs do. In conclusion, the ELISA-based viral neutralization test offers a time- and cost-effective alternative to the PRNT. The immunization results indicate that vaccine strategies focused only on the RBD region may have major advantages over those based on the full spike sequence.
On the Impact of Vessel Wall Stiffness on Quantitative Flow Dynamics in a Synthetic Model of the Thoracic Aorta
Authors: Zimmermann Judith , Loecher Michael , Kolawole Fikunwa , Bäumler Kathrin , Gifford Kyle , Dual Seraina , Levenston Marc , Marsden Alison , Ennis Daniel 
Published: January 2021

Abstract
Aortic wall stiffening is a predictive marker for morbidity in hypertensive patients. Arterial pulse wave velocity (PWV) correlates with the level of stiffness and can be derived using non-invasive 4D-flow magnetic resonance imaging (MRI). The objectives of this study were twofold: to develop subject-specific thoracic aorta models embedded into an MRI-compatible flow circuit operating under controlled physiological conditions; and to evaluate how a range of aortic wall stiffness impacts 4D-flow-based quantification of hemodynamics, particularly PWV. Three aorta models were 3D-printed using a novel photopolymer material at two compliant and one nearly rigid stiffnesses and characterized via tensile testing. Luminal pressure and 4D-flow MRI data were acquired for each model and cross-sectional net flow, peak velocities, and PWV were measured. In addition, the confounding effect of temporal resolution on all metrics was evaluated. Stiffer models resulted in increased systolic pressures (112, 116, and 133 mmHg), variations in velocity patterns, and increased peak velocities, peak flow rate, and PWV (5.8 to 7.3 m/s). Lower temporal resolution (20 ms down to 62.5 ms per image frame) impacted estimates of peak velocity and PWV (7.31 down to 4.77 m/s). Using compliant aorta models is essential to produce realistic flow dynamics and conditions that recapitulated in vivo hemodynamics.
Clinical Characteristics of Severe Neonatal Enterovirus Infection: A Systematic Review
Authors: Zhang Meng , Wang Haoran , Tang Jun , He Yang , Xiong Tao , Li Wenxing , Qu Yi , Mu Dezhi 
Published: January 2021

Abstract
Background: Enterovirus (EV) is a common cause of infection in neonates. Neonates are at high risk of enterovirus infection with serious clinical manifestations and high mortality. This review systematically summarized the clinical characteristics of neonates with severe enteroviral infection to provide evidence for the identification and treatment of severe neonatal EV infection. Methods: PubMed, Embase, and Web of Science were searched for original studies on neonates with severe EV infections from January 1, 2000, to November 27, 2020. Two reviewers independently screened the literature, extracted the data, and performed a descriptive analysis.Results: In total, 66 articles with 237 cases of severe neonatal enterovirus infection were included. All patients developed severe complications. Among them, 46.0% patients had hepatitis or coagulopathy, 37.1% had myocarditis, 11.0% had meningoencephalitis, and 5.9% had other complications such as hemophagocytic lymphohistiocytosis and pulmonary hemorrhage. The mortality rate of patients with severe infection was 30.4%. The highest mortality rate was 38.6%, which was observed in patients with myocarditis. In 70.5% patients, the age at the onset of symptoms was less than 7 days. Coxsackievirus B infection was seen in 52.3% patients. The most common symptoms included temperature abnormalities (127, 53.6%), rash (88, 37.1%), poor feeding (58, 24.5%), and respiratory symptoms (52, 21.9%). The main treatment included transfusion of blood components (42.2%), intravenous immunoglobulin (IVIG; 40.9%), mechanical ventilation (21.5%), and extracorporeal membrane oxygenation (ECMO; 18.1%). Additionally, antiviral medications pleconaril (14, 5.9%) and pocapavir (3, 1.3%) were administered. Conclusions: Mortality was high in patients with severe enterovirus infection, especially in those complicated with myocarditis. The most common symptoms included temperature abnormalities, rash, and poor feeding. The chief supportive treatment consisted of transfusion of blood components, mechanical ventilation, and ECMO. IVIG were widely used. Antiviral medications included pocapavir and pleconaril; however, more clinical evidence regarding their efficacy is needed.
Prediction of A Positive Surgical Margin and Biochemical Recurrence After Robot-Assisted Radical Prostatectomy&nbsp;
Authors: Yang Ching-Wei , Wang Hsiao-Hsien , Hassouna Mohamed , Chand Manish , Chung Hsiao-Jen 
Published: January 2021

Abstract
A positive surgical margin (PSM) detected in a prostatectomy specimen is associated with poor oncotherapeutic outcomes. Certain aspects regarding the determination of surgical margins and their effects on biochemical recurrence (BCR) remain unclear. This study investigated the predictive factors for PSM and BCR. We prospectively included 419 robot-assisted radical prostatectomy cases. The number of PSM cases was 126 (30.1%), stratified as 22 (12.2%) in stage T2 and 103 (43.6%) in stage T3. Preoperative prostate-specific antigen (PSA) > 10 ng/mL (p = 0.047; odds ratio [OR] 1.712), intraoperative blood loss > 200 mL (p = 0.006; OR 4.01), and postoperative pT3 stage (p < .001; OR 6.901) were three independent predictors for PSM in multivariate analysis. PSA > 10 ng/mL (p < 0.015; hazard ratio [HR] 1.8), pT3 stage (p = 0.012; HR 2.264), ISUP grade > 3 (p = 0.02; HR 1.964), and PSM (p = 0.027; HR 1.725) were four significant predictors for BCR in multivariate analysis. Among PSM cases, ISUP grade > 3 (p = 0.002; HR 2.689) was a significant BCR predictor. These results indicate that PSA level and pathological stage markedly influence the PSM and BCR.
A roadmap to using randomization in clinical trials
Authors: Berger Vance , Bour Louis , Carter Kerstine , Chipman Jonathan , Everett Colin , Heussen Nicole , Hewitt Catherine , Hilgers Ralf-Dieter , Luo Y. Abigail , Renteria Jone , Ryeznik Yevgen , Sverdlov Oleksandr , Uschner Diane 
Published: January 2021

Abstract
Background: Randomization is the foundation of any clinical trial involving treatment comparison. It helps mitigate selection bias, promotes similarity of treatment groups with respect to important known and unknown confounders, and contributes to the validity of statistical tests. Various restricted randomization procedures with different probabilistic structures and different statistical properties are available.Methods: We survey available restricted randomization procedures for sequential allocation of subjects in a randomized, comparative, parallel group clinical trial with equal (1:1) allocation. We explore statistical properties of these procedures, including balance/randomness tradeoff, type I error rate and power. We perform head-to-head comparisons of different procedures through simulation under various experimental scenarios, including cases when common model assumptions are violated. We also provide some real-life clinical trial examples to illustrate the thinking process for selecting a randomization procedure for implementation in practice. Results: Restricted randomization procedures targeting 1:1 allocation vary in the degree of balance/randomness they induce, and more importantly, they vary in terms of validity and efficiency of statistical inference when common model assumptions are violated (e.g. when outcomes are affected by a linear time trend; measurement error distribution is misspecified; or selection bias is introduced in the experiment). Some procedures are more robust than others. Covariate-adjusted analysis may be essential to ensure validity of the results. Special considerations are required when selecting a randomization procedure for a clinical trial with very small sample size.Conclusions: The choice of randomization design, data analytic technique (parametric or nonparametric), and analysis strategy (randomization-based or population model-based) are all very important considerations. Randomization-based tests are robust and valid alternatives to likelihood-based tests and should be considered more frequently by clinical investigators.