bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exosomal microRNAs are novel circulating biomarkers in cigarette, waterpipe smokers, E-cigarette users and dual smokers
Authors: Singh Kameshwar P. , Maremanda Krishna P. , Li Dongmei , Rahman Irfan 
Published: September 2020

AbstractBackgroundElectronic cigarettes (e-cigs) vaping, cigarette smoke, and waterpipe tobacco smoking are associated with various cardiopulmonary diseases. microRNAs are present in higher concentration in exosomes that play an important role in various physiological and pathological functions. We hypothesized that the non-coding RNAs transcript may serve as susceptibility to disease biomarkers by smoking and vaping.MethodsPlasma exosomes/EVs from cigarette smokers, waterpipe smokers and dual smokers (cigarette and waterpipe) were characterized for their size, morphology and TEM, Nanosight and immunoblot analysis. Exosomal RNA was used for small RNA library preparation and the library was quantified using the High Sensitivity DNA Analysis on the Agilent 2100 Bioanalyzer system and sequenced using the Illumina NextSeq 500 and were converted to fastq format for mapping genes.ResultsEnrichment of various non-coding RNAs that include microRNAs, tRNAs, piRNAs, snoRNAs, snRNAs, Mt-tRNAs, and other biotypes are shown in exosomes. A comprehensive differential expression analysis of miRNAs, tRNAs and piRNAs showed significant changes across different pairwise comparisons. The seven microRNAs that were common and differentially expressed of when all the smoking and vaping groups were compared with non-smokers (NS) are hsa-let-7a-5p, hsa-miR-21-5p, hsa-miR-29b-3p, hsa-let-7f-5p, hsa-miR-143-3p, hsa-miR-30a-5p and hsa-let-7i-5p. The e-cig vs. NS group has differentially expressed 5 microRNAs (hsa-miR-224-5p, hsa-miR-193b-3p, hsa-miR-30e-5p, hsa-miR-423-3p, hsa-miR-365a-3p, and hsa-miR-365b-3p), which are not expressed in other three groups. Gene set enrichment analysis of microRNAs showed significant changes in the top six enriched functions that consisted of biological pathway, biological process, molecular function, cellular component, site of expression and transcription factor in all the groups. Further, the pairwise comparison of tRNAs and piRNA in all these groups revealed significant changes in their expressions.ConclusionsPlasma exosomes of cigarette smokers, waterpipe smokers, e-cig users and dual smokers have common differential expression of microRNAs which may serve to distinguish smoking and vaping subjects from NS. Among them has-let-7a-5p has high sensitivity and specificity to distinguish NS with the rest of the users, using ROC curve analysis. These findings will pave the way for the utilizing the potential of exosomes/miRNAs as a novel theranostic agents in lung injury and disease caused by tobacco smoking and vaping.
Dissecting the conformation of glycans and their interactions with proteins
Authors: Wang Sheng-Hung , Wu Tsai-Jung , Lee Chien-Wei , Yu John 
Published: September 2020

AbstractThe use of in silico strategies to develop the structural basis for a rational optimization of glycan-protein interactions remains a great challenge. This problem derives, in part, from the lack of technologies to quantitatively and qualitatively assess the complex assembling between a glycan and the targeted protein molecule. Since there is an unmet need for developing new sugar-targeted therapeutics, many investigators are searching for technology platforms to elucidate various types of molecular interactions within glycan-protein complexes and aid in the development of glycan-targeted therapies. Here we discuss three important technology platforms commonly used in the assessment of the complex assembly of glycosylated biomolecules, such as glycoproteins or glycosphingolipids: Biacore analysis, molecular docking, and molecular dynamics simulations. We will also discuss the structural investigation of glycosylated biomolecules, including conformational changes of glycans and their impact on molecular interactions within the glycan-protein complex. For glycoproteins, secreted protein acidic and rich in cysteine (SPARC), which is associated with various lung disorders, such as chronic obstructive pulmonary disease (COPD) and lung cancer, will be taken as an example showing that the core fucosylation of N-glycan in SPARC regulates protein-binding affinity with extracellular matrix collagen. For glycosphingolipids (GSLs), Globo H ceramide, an important tumor-associated GSL which is being actively investigated as a target for new cancer immunotherapies, will be used to demonstrate how glycan structure plays a significant role in enhancing angiogenesis in tumor microenvironments.
Navafenterol (AZD8871) in patients with mild asthma: a randomised placebo-controlled phase I study evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending doses of this novel inhaled long-acting dual-pharmacology bronchodilator
Authors: Jimenez Eulalia , Astbury Carol , Albayaty Muna , Wählby-Hamrén Ulrika , Seoane Beatriz , Villarroel Cristina , Pujol Helena , Bermejo Maria Jesus , Aggarwal Ajay , Psallidas Ioannis 
Published: September 2020

Abstract
Background
Navafenterol (AZD8871) is an inhaled long-acting dual-pharmacology muscarinic antagonist/β2-adrenoceptor agonist (MABA) in development for the treatment of obstructive airways diseases. The safety, tolerability, pharmacodynamics, and pharmacokinetics of navafenterol were investigated in patients with mild asthma.

Methods
This was a randomised, single-blind, placebo-controlled, single-ascending-dose study. Patients were randomly assigned to one of two cohorts which evaluated escalating doses of navafenterol (50–2100 μg) in an alternating manner over three treatment periods. The primary pharmacodynamic endpoint was the change from pre-dose baseline in trough forced expiratory volume in 1 s (FEV1) for each treatment period.

Results
Sixteen patients were randomised; 15 completed treatment. Data from all 16 patients were analysed. The maximum tolerated dose was not identified, and all doses of navafenterol were well tolerated. The most frequently reported treatment-emergent adverse events (TEAEs) were headache (n = 10, 62.5%) and nasopharyngitis (n = 7, 43.8%). No TEAEs were serious, fatal, or led to discontinuation, and no dose dependency was identified. Navafenterol demonstrated a dose-ordered bronchodilatory response with a rapid onset of action (within 5 min post-dose). Doses ≥200 μg resulted in improvements in trough FEV1 (mean change from baseline range 0.186–0.463 L) with sustained bronchodilation for 24–36 h. Plasma concentrations increased in a dose-proportional manner, peaking ~ 1 h post-dose, with a derived terminal elimination half-life of 15.96–23.10 h.

Conclusions
In this study navafenterol was generally well tolerated with a rapid onset of action which was sustained over 36 h.

Trial registration
ClinicalTrials.gov; No.: NCT02573155
Nrf2 protects against seawater drowning-induced acute lung injury via inhibiting ferroptosis
Authors: Qiu Yu-bao , Wan Bin-bin , Liu Gang , Wu Ya-xian , Chen Dan , Lu Mu-dan , Chen Jun-liang , Yu Ren-qiang , Chen Dao-zhen , Pang Qing-feng 
Published: September 2020

Abstract
Background
Ferroptosis is a new type of nonapoptotic cell death model that was closely related to reactive oxygen species (ROS) accumulation. Seawater drowning-induced acute lung injury (ALI) which is caused by severe oxidative stress injury, has been a major cause of accidental death worldwide. The latest evidences indicate nuclear factor (erythroid-derived 2)-like 2 (Nrf2) suppress ferroptosis and maintain cellular redox balance. Here, we test the hypothesis that activation of Nrf2 pathway attenuates seawater drowning-induced ALI via inhibiting ferroptosis.

Methods
we performed studies using Nrf2-specific agonist (dimethyl fumarate), Nrf2 inhibitor (ML385), Nrf2-knockout mice and ferroptosis inhibitor (Ferrostatin-1) to investigate the potential roles of Nrf2 on seawater drowning-induced ALI and the underlying mechanisms.

Results
Our data shows that Nrf2 activator dimethyl fumarate could increase cell viability, reduced the levels of intracellular ROS and lipid ROS, prevented glutathione depletion and lipid peroxide accumulation, increased FTH1 and GPX4 mRNA expression, and maintained mitochondrial membrane potential in MLE-12 cells. However, ML385 promoted cell death and lipid ROS production in MLE-12 cells. Furthermore, the lung injury became more aggravated in the Nrf2-knockout mice than that in WT mice after seawater drowning.

Conclusions
These results suggested that Nrf2 can inhibit ferroptosis and therefore alleviate ALI induced by seawater drowning. The effectiveness of ferroptosis inhibition by Nrf2 provides a novel therapeutic target for seawater drowning-induced ALI.
OIP5-AS1 contributes to tumorigenesis in hepatocellular carcinoma by miR-300/YY1-activated WNT pathway
Authors: Wang Yu , Dou Lei , Qin Yun , Yang Huiyuan , Yan Peng 
Published: September 2020

AbstractBackgroundIt has reported that long non-coding RNAs (lncRNAs) exerted regulatory functions by targeting specific genes through a competing endogenous RNA (ceRNA) pathway. LncRNA OIP5-AS1 has been identified as a tumor-enhancer in several tumor types. Nonetheless, its molecular mechanism in HCC remains to be masked.Aim of the studyThis study was aimed at exploring whether and how OIP5-AS1 exert functions in HCC.MethodsqRT-PCR and western blot were employed for detecting gene expression. CCK-8, colony formation and EdU assays were implemented to evaluate the proliferative ability of HCC cells. Caspase-3 activity and flow cytometry analyses were implemented to determine cell apoptosis and cell cycle distribution. RNA pull down, ChIP, RIP and luciferase reporter assays explored the interplays between molecules.ResultsYY1 was upregulated in HCC cells, and silenced YY1 restrained HCC cell proliferation in vitro and hampered tumor growth in vivo. Later, we discovered that miR-300 could regulate WNT pathway via targeting YY1. Furthermore, OIP5-AS1 was identified as the sponge of miR-300 and promoted cell growth in HCC. Importantly, YY1 transcriptionally activate OIP5-AS1 in turn. Rescue experiments indicated that miR-300 inhibition or YY1 overexpression abrogated the inhibitive effect of OIP5-AS1 silencing on the malignant growth of HCC cells.ConclusionsOIP5-AS1/miR-300/YY1 feedback loop facilitates cell growth in HCC by activating WNT pathway.
MicroRNA-221-3p is related to survival and promotes tumour progression in pancreatic cancer: a comprehensive study on functions and clinicopathological value
Authors: Wu Xuejiao , Huang Jia , Yang Zilin , Zhu Ying , Zhang Yongping , Wang Jiancheng , Yao Weiyan 
Published: September 2020

Abstract
Background
The microRNA miR-221-3p has previously been found to be an underlying biomarker of pancreatic cancer. However, the mechanisms of miR-221-3p underlying its role in pancreatic cancer pathogenesis, proliferation capability, invasion ability, drug resistance and apoptosis and the clinicopathological value of miR-221-3p have not been thoroughly studied.

Methods
Based on microarray and miRNA-sequencing data extracted from Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), relevant literature, and real-time quantitative PCR (RT-qPCR), we explored clinicopathological features and the expression of miR-221-3p to determine its clinical effect in pancreatic cancer. Proliferation, migration, invasion, apoptosis and in vitro cytotoxicity tests were selected to examine the roles of mir-221-3p. In addition, several miR-221-3p functional analyses were conducted, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Protein–protein interaction (PPI) network analyses, to examine gene interactions with miR-221-3p.

Results
The findings of integrated multi-analysis revealed higher miR-221-3p expression in pancreatic cancer tissues and blood than that in para-carcinoma samples (SMD of miR-221-3p: 1.52; 95% CI 0.96, 2.08). MiR-221-3p is related to survival both in pancreatic cancer and pancreatic ductal adenocarcinoma patients. Cell experiments demonstrated that miR-221-3p promotes pancreatic cancer cell proliferation capability, migration ability, invasion ability, and drug resistance but inhibits apoptosis. Further pancreatic cancer bioinformatics analyses projected 30 genes as the underlying targets of miR-221-3p. The genes were significantly distributed in diverse critical pathways, including microRNAs in cancer, viral carcinogenesis, and the PI3K-Akt signalling pathway. Additionally, PPI indicated four hub genes with threshold values of 5: KIT, CDKN1B, RUNX2, and BCL2L11. Moreover, cell studies showed that miR-221-3p can inhibit these four hub genes expression in pancreatic cancer.

Conclusions
Our research revealed that pancreatic cancer expresses a high-level of miR-221-3p, indicating a potential miR-221-3p role as a prognosis predictor in pancreatic cancer. Moreover, miR-221-3p promotes proliferation capacity, migration ability, invasion ability, and drug resistance but inhibits apoptosis in pancreatic cancer. The function of miR-221-3p in the development of pancreatic cancer may be mediated by the inhibition of hub genes expression. All these results might provide an opportunity to extend the understanding of pancreatic cancer pathogenesis.
Melatonin and urological cancers: a new therapeutic approach
Authors: Pourhanifeh Mohammad Hossein , Hosseinzadeh Azam , Juybari Kobra Bahrampour , Mehrzadi Saeed 
Published: September 2020

AbstractUrological cancers are responsible for thousands of cancer-related deaths around the world. Despite all developments in therapeutic approaches for cancer therapy, the absence of efficient treatments is a critical and vital problematic issue for physicians and researchers. Furthermore, routine medical therapies contribute to several undesirable adverse events for patients, reducing life quality and survival time. Therefore, many attempts are needed to explore potent alternative or complementary treatments for great outcomes. Melatonin has multiple beneficial potential effects, including anticancer properties. Melatonin in combination with chemoradiation therapy or even alone could suppress urological cancers through affecting essential cellular pathways. This review discusses current evidence reporting the beneficial effect of melatonin in urological malignancies, including prostate cancer, bladder cancer, and renal cancer.
Covid-19 in Israel: socio-demographic characteristics of first wave morbidity in Jewish and Arab communities
Authors: Birenbaum-Carmeli Daphna , Chassida Judith 
Published: September 2020

Abstract
Background
The first wave of the Covid-19 pandemic hit Israel in late February 2020. The present study examines patterns of the first wave of Covid-19 morbidity in Israel at the macro level, during the period of late February to early June 2020, when the first wave has faded out. The analysis focuses on the significance of four sociodemographic variables: socioeconomic status, population density, rate of elderly population and minority status (Jewish / Arab identity) of the population in cities with 5000 residents or more. Additionally, we take a closer look into the association between morbidity rates and one SES component – home Internet access.

Methods
The article is a cross sectional study of morbidity rates, investigated on a residential community basis. Following the descriptive statistics, we move on to present multivariate analysis to explore associations between these variables and Covid-19 morbidity in Israel.

Results
Both the descriptive statistics and regressions show morbidity rates to be positively associated with population density. Socioeconomic status as well as the size of elderly population were both significantly related to morbidity, but only in Jewish communities. Interestingly, the association was inverse in both cases. i.e., the higher the SES the lower the morbidity and the larger the elderly population, the lower the community’s morbidity. Another interesting result is that overall, morbidity rates in Jewish cities were consistently higher than in Arab communities.

Conclusions
We attribute the low morbidity rates in communities with relatively small elderly populations to the exceptionally high fertility rates in ultra-orthodox communities that sustained increased rates of morbidity; the lower morbidity in Arab communities is attributed to several factors, including the spatial Jewish-Arab segregation.
Chitosan-miRNA functionalized microporous titanium oxide surfaces via a layer-by-layer approach with a sustained release profile for enhanced osteogenic activity
Authors: Wu Kaimin , Liu Mengyuan , Li Nan , Zhang Li , Meng Fanhui , Zhao Lingzhou , Liu Min , Zhang Yumei 
Published: September 2020

Abstract
Background
The biofunctionalization of titanium implants for high osteogenic ability is a promising approach for the development of advanced implants to promote osseointegration, especially in compromised bone conditions. In this study, polyelectrolyte multilayers (PEMs) were fabricated using the layer-by-layer approach with a chitosan-miRNA (CS-miRNA) complex and sodium hyaluronate (HA) as the positively and negatively charged polyelectrolytes on microarc-oxidized (MAO) Ti surfaces via silane-glutaraldehyde coupling.

Methods
Dynamic contact angle and scanning electron microscopy measurements were conducted to monitor the layer accumulation. RiboGreen was used to quantify the miRNA loading and release profile in phosphate-buffered saline. The in vitro transfection efficiency and the cytotoxicity were investigated after seeding mesenchymal stem cells (MSCs) on the CS-antimiR-138/HA PEM-functionalized microporous Ti surface. The in vitro osteogenic differentiation of the MSCs and the in vivo osseointegration were also evaluated.

Results
The surface wettability alternately changed during the formation of PEMs. The CS-miRNA nanoparticles were distributed evenly across the MAO surface. The miRNA loading increased with increasing bilayer number. More importantly, a sustained miRNA release was obtained over a timeframe of approximately 2 weeks. In vitro transfection revealed that the CS-antimiR-138 nanoparticles were taken up efficiently by the cells and caused significant knockdown of miR-138 without showing significant cytotoxicity. The CS-antimiR-138/HA PEM surface enhanced the osteogenic differentiation of MSCs in terms of enhanced alkaline phosphatase, collagen production and extracellular matrix mineralization. Substantially enhanced in vivo osseointegration was observed in the rat model.

Conclusions
The findings demonstrated that the novel CS-antimiR-138/HA PEM-functionalized microporous Ti implant exhibited sustained release of CS-antimiR-138, and notably enhanced the in vitro osteogenic differentiation of MSCs and in vivo osseointegration. This novel miRNA-functionalized Ti implant may be used in the clinical setting to allow for more effective and robust osseointegration.
Impact of pre-transplant dialysis modality on the outcome and health-related quality of life of patients after simultaneous pancreas-kidney transplantation
Authors: Scheuermann Uwe , Rademacher Sebastian , Jahn Nora , Sucher Elisabeth , Seehofer Daniel , Sucher Robert , Hau Hans-Michael 
Published: September 2020

Abstract
Background
Simultaneous pancreas-kidney transplantation (SPKT) profoundly improves the health-related quality of life (HRQoL) of recipients. However, the influence of the pre-transplant dialysis modality on the success of the SPKT and post-transplant HRQoL remains unknown.

Methods
We analyzed the surgical outcome, long-term survival, as well as HRQoL of 83 SPKTs that were performed in our hospital between 2000 and 2016. Prior to transplant, 64 patients received hemodialysis (HD) and nineteen patients received peritoneal dialysis (PD). Physical and mental quality of life results from eight basic scales and the physical and mental component summaries (PCS and MCS) were measured using the Short Form 36 (SF-36) survey.

Results
Peri- and postoperative complications, as well as patient and graft survival were similar between the two groups. Both groups showed an improvement of HRQoL in all SF-36 domains after transplantation. Compared with patients who received HD before transplantation, PD patients showed significantly better results in four of the eight SF-36 domains: physical functioning (mean difference HD - PD: − 12.4 ± 4.9, P = < 0.01), bodily pain (− 14.2 ± 6.3, P < 0.01), general health (− 6.3 ± 2.8, P = 0.04), vitality (− 6.8 ± 2.6, P = 0.04), and PCS (− 5.2 ± 1.5, P < 0.01) after SPKT. In the overall study population, graft loss was associated with significant worsening of the HRQoL in all physical components (each P < 0.01).

Conclusions
The results of this analysis show that pre-transplant dialysis modality has no influence on the outcome and survival rate after SPKT. Regarding HRQoL, patients receiving PD prior to SPKT seem to have a slight advantage compared with patients with HD before transplantation.
Modeling the Cost-effectiveness of Esophageal Cancer Screening in China
Authors: Li Yuanyuan , Du Lingbin , Wang Youqing , Gu Yuxuan , Zhen Xuemei , Hu Xiaoqian , Sun Xueshan , Dong Hengjin 
Published: September 2020

Abstract
Background
This study aimed to examine the cost-effectiveness of one-time standard endoscopic screening with Lugol’s iodine staining for esophageal cancer (EC) in China.

Methods
A Markov decision analysis model with eleven states was built. Individuals aged 40 to 69 years were classified into six age groups in five-year intervals. Three different strategies were adopted for each cohort: (1) no screening; (2) one-time endoscopic screening with Lugol’s iodine staining with an annual follow-up for low-grade intraepithelial neoplasia (LGIN); and (3) one-time endoscopic screening with Lugol’s iodine staining without follow-up. Quality-adjusted life-years (QALYs) indicated the effectiveness of the model. The incremental cost-effectiveness ratio (ICER) was used as the evaluation indicator. Sensitivity analysis was performed to assess the robustness of the model.

Results
One-time screening with follow-up was the undominated strategy for individuals aged 40–44 and 45–49 years, which saved USD 10,942.57 and USD 6611.73 per QALY gained compared to nonscreening strategy. For those aged 50–69 years, the nonscreening scenarios were undominated. One-time screening without follow-up was the extended dominated strategy. Compared to screening strategies without follow-up, all the screening strategies with follow-up were more cost-effective, with the ICER increasing from 299.57 USD/QALY for individuals aged 40–44 years to 1617.72 USD/QALY for individuals aged 65–69 years. Probabilistic sensitivity analysis (PSA) supported the results of the base case analysis.

Conclusions
One-time EC screening with follow-up targeting individuals aged 40–49 years was the most cost-effective strategy.