bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevated expression of lncRNA MEG3 induces endothelial dysfunction on HUVECs of IVF born offspring via epigenetic regulation
Authors: Jiang Ying , Zhu Hong , Chen Hong , Yang Meng-Meng , Yu Yi-Chen , He Sai-Nan , Xu Ye-Tao , Liu Fang , Sagnelli Matthew , Zhu Yi-Min , Luo Qiong 
Published: October 2020

Abstract
Background: The cardiovascular dysfunction in children born after in vitro fertilization (IVF) has been of great concern, in our study, we aim to explore potential molecular mechanism for such long-term outcomes.
Methods： Real-time qPCR was used to test long non-coding RNAMEG3and endothelium-derived factors, endothelial nitric oxide synthase (eNOS), endothelin-1(ET1), vascular endothelial growth factor (VEGF). Primary HUVEC after caesarean section was treated with different estradiol concentrations in vitro. Besides, knockdown ofMEG3on HUVEC provided further evidence between MEG3 expression and alteration of NO, ET1, VEGF. Then, by using pyrosequencing, we detectedMEG3promoter methylation status.
Results: We found that the expression level of MEG3was higher in human umbilical vein endothelial cells (HUVECs) of IVF offspring than that in spontaneously born offspring. Furthermore, we found decreased expression ofeNOS, VEGF, elevated expression of ET1in HUVECs from IVF offspring compared to spontaneously born offspring. We further confirmed the results from in-vivo experiments by demonstrating that high-estradiol intrauterine environments lead to abnormal expression of MEG3 and endothelium-derived factors. Meanwhile, silencing MEG3expression decreased ET1expression, and increased nitrite, nitrate, VEGFsecretion, which could correct the effect we observed in-vivo. With pyrosequencing technology, we found that elevated expression of MEG3in IVF offspring derived HUVECs was the result of hypomethylation of the MEG3promoter.
Conclusions: Our results demonstrated that higher expression ofMEG3in IVF-born HUVECs, accompanied by lower secretion of eNOS, VEGF, and higher secretion of ET1, which is closely related with endothelial dysfunction, which togetherprovide a potential mechanism addressing high-risk of hypertension in IVF offspring.
APOBEC3B and SPAG5, the Target Genes of miR-539, Involved into Imatinib-Resistant of Gastrointestinal Stromal Tumors
Authors: Zhang Qianqian , Liu Haiyun , Li Xingmin , Wang Hongxing 
Published: October 2020

Abstract
Background: Although imatinib can effectively treat gastrointestinal stromal tumor (GIST), some patients are still resistant to it or cannot tolerate the adverse reactions of the drug. This study aimed to investigate potential miRNAs, mRNA and tumor-infiltrating lymphocytes (TILs) associated with the prognosis of imatinib-resistant GIST.Methods: mRNA, miRNA sequencing data and patient clinic traits of primary (imatinib-naive) and imatinib-resistant GIST were obtained from GEO (Gene Expression Omnibus) database. A systems biology approach combining Weighted co-expression network analysis (WGCNA) and differential expression analysis were utilized to detect the imatinib-resistant-related miRNA and gene modules and construct a miRNA-gene network. Tumor-infiltrating immune cells were analyzed by Estimating the Proportion of Immune and Cancer cells (EPIC) and Tumor-Immune System Interactions (TISIDB). miR-539 was measured by qRT-PCR. SPAG5 and APOBEC3B was measured by qRT-PCR and WB. Transforming growth factor (TGF)-β and interleukin (IL)-10 were assessed with enzyme-linked immunosorbent assay (ELISA). The proportions of CD4+ T cells, CD8+ T cells , NK cells and B cells in tumor-infiltrating lymphocyteswere analyzed via flow cytometry (FCM).Results: Two gene modules (brown and yellow) and one miRNA module were associated with the imatinib-resistant. Two hub genes (APOBEC3B and SPAG5) were associated with the imatinib-resistant. Three hub miRNAs were identified to be related to imatinib-resistant (miR-539, miR-376b and miR-18b). G1/S transition of mitotic cell cycle, G2/M transition of mitotic cell cycle, and cell proliferation were common pathways of the gene modules and miRNA module. apolipoprotein B mRNA editing catalytic polypeptide-like 3B (APOBEC3B) and Sperm-associated antigen 5 (SPAG5), which were both target genes of miR-539 was located at the core of miRNA–gene network. APOBEC3B (rho=0.509, p < 2.2e-16) and SPAG5 (rho=0.468, p < 2.2e-16) was positive correlated with the infiltration levels of activated CD4+ T cells. he proportions of CD4+ T cells, and the mRNA and protein relative expression of APOBEC3B and SPAG5 in imatinib-resistant tumor samples significantly increased as compared with tumor samples in imatinib-naive group. Imatinib-resistant tumor samples exhibited significantly downregulation of miR-539 and TGF-β1. Over-expression of miR-539 sensitized imatinib resistant GIST48 cells and increased the secretion of TGF-β1 by inhibiting APOBEC3B and SPAG5.Conclusion: APOBEC3B and SPAG5, the target genes of miR-539 may play as key factor for imatinib-resistant GIST by increasing the proportion of tumor-infiltrated activated CD4+ T cells via TGF-β1. These findings help to advance the understanding of imatinib-resistant GIST and provide potential therapeutic targets.
Authorized, Clear and Timely Communication of Risk to Guide Public Perception and Action: Lessons of COVID-19 From China
Authors: Gong Ni , Liao Jing , Jin Xiaoyuan , Li Yundong , Zhang Meifen , Cheng Yu , Xu Dong 
Published: October 2020

Abstract
Backgrounds: This study examined the dynamic association between risk communication and public’s risk perception and action across the COVID-19 outbreak timeline in China.Methods: Publicly available information on COVID-19 was collected by Parehub tool for official channels (e.g. government websites and official media), and by Zhongyun Big Data Platform for mainstream Chinese social media (e.g. TikTok, Weibo, etc.). Information was examined by its release channels, content and release time. An online survey was conducted via WeChat across 33 provinces and municipalities of China to assess changes in participants’ risk perception and action against COVID-19. Information content and release-time trajectories were examined against the public’s risk perception and actions over time.Results: Altogether, 1,477 pieces of authorized information and 297,000 pieces of short videos on COVID-19 were retrieved from official channels and social media. Our online survey of 1,311 responds (25-60 years, 42% male) indicated that participants mainly relied on official channels to obtain information. Alongside the progress of the outbreak, there was a gradual rise in information quantity, publishing frequency, and content variation. Correspondingly, the public’s risk perception that “take it seriously" rose from 13% to 80%, 87.1% of who took “multiple actions” compared to 25.9% initially.Conclusions: Our findings indicated that insufficient information freely-accessible at the early stages of the outbreak may nevertheless lead to the lack of risk awareness and inadequate protective actions of the public. Given the current global situation of COVID-19, the study highlights authorized, transparent, and timely two-way risk communication is vital to guide public perception and actions.
Identifying Disincentives to Ethics Consultation Requests Among Physicians, Advance Practice Providers, and Nurses
Authors: Cederquist Lynette Carol , LaBuzetta Jamie , Cachay Edward , Friedman Lawrence , Yi Cassia , Dibsie Laura , Zhang Yiran 
Published: October 2020

Abstract
Background: Ethics consult services are well established, but often remain underutilized. Our aim was to identify the barriers and perceptions of the Ethics consult service at our urban academic medical center which might contribute to underutilization.Methods: This was a cross-sectional single-center, anonymous written online survey, developed by the UCSD Ethics committee, distributed by Survey Monkey, in January 2019, to a total of 3,800 clinicians at a tertiary care academic medical center. This was a quality improvement project, so IRB approval was waived. Results: Approximately 3,800 surveys were sent to physicians, advance practice providers (APPs) and nurses with a return rate of 5.5 - 10%. The majority of respondents had encountered an ethical dilemma although only half had ever requested an ethics consult. We found that there were 4 general reasons people did not consult Ethics: 1.) unawareness of the existence of or means of contacting the Ethics service. 2.) a priori perceptions that an Ethics consult would not be helpful or might slow down decision making. 3.) experiencing a poor quality consult in the past, including variability in knowledge and ability among various consultants, 4) a consult did not improve the situation, or lacked specific guidance from the consultant.Conclusions: Based on our survey results, we proposed the following methods of reducing barriers to use of an Ethics consult service: 1) Consults need to offer specific recommendations 2) set expectations for the consultation process and outcome; 3) ensure that Ethics consultants have strong training; 4) more actively engage nursing staff, and 5) better inform clinicians about the availability of the Ethics consult service.
Dynamic Changes in Blood PD-L1 Expression Predict the Efficacy and Overall Survival of Immune Checkpoint Inhibitor Treatment in Non-Small-Cell Lung Cancer Patients
Authors: Yang Qiao , Chen Mingjing , Gu Jiaoyang , Niu Kai , Zhao Xianlan , Zheng Linpeng , Xu Zihan , Yu Yongxin , Li Feng , Meng Lingxin , Zhu Bo , Chen Zhengtang , Zhuo Wenlei , Zhang Luping , Sun Jianguo 
Published: October 2020

Abstract
Background Immune checkpoint inhibitors (ICIs) have become a high-profile treatment regimen for malignancy in recent years. However, only a small piece of patients obtain benefit. How to use reasonable biomarkers to optimally select suitable patients is currently a research hot topic.Methods Paired tissue samples and blood samples from 51 patients with various malignancies were collected for correlation analysis. Dynamic changes in bPD-L1 expression, including PD-L1 mRNA, soluble PD-L1 (sPD-L1) and exosomal PD-L1 (exoPD-L1) protein, were detected in non-small-cell lung cancer (NSCLC) patients treated with ICIs. The best cutoff values for progression-free survival (PFS) and OS of all three biomarkers were calculated with R software.Results In 51 malignancies patients, those with positive tPD-L1 expression had significantly higher PD-L1 mRNA expression than those with negative tPD-L1 expression. For sPD-L1 expression, only the TC1~2/IC1~2 group had higher expression than the TC0/IC0 group. In 40 NSCLC patients, those with a fold change (2 months compared to baseline) of PD-L1 mRNA over 2.03 had a better PFS, a better OS and the best objective response (bOR) rate. In addition, a fold change of exoPD-L1 over 1.85 was also found to be associated with better efficacy and OS in a small cohort. Furthermore, the combination of the biomarkers could better screen patients who could benefit from ICI treatment.Conclusion Blood PD-L1 expression was positively correlated with tPD-L1 expression. Increased expression of exoPD-L1, PD-L1 mRNA, or both during early treatment could serve as biomarkers for predicting efficacy and OS in NSCLC patients treated with ICIs.
miR-708-5p Enhances Erlotinib/paclitaxel Efficacy and Overcomes Chemoresistance in Lung Cancer Cells
Authors: Monteleone Nicholas , Lutz Carol S. 
Published: October 2020

Abstract
BackgroundLung cancer is a collection of aggressive tumors generally not diagnosed until late-stage, resulting in high mortality rates. The vast majority of non-small cell lung cancer (NSCLC) patients undergo combinatory chemotherapeutic treatment, which initially reduces tumor growth, but frequently becomes ineffective due to toxicity and resistance. Researchers have identified multiple signaling pathways involved in lung cancer chemoresistance, including cyclooxygenase-2 (COX-2)/microsomal prostaglandin E synthase-1 (mPGES-1) derived prostaglandin E2 (PGE2). While COX-2 inhibitors have shown promise in the clinic, their use is limited due to severe side effects. One novel approach to effectively suppress COX-2 signaling is through microRNA (miRNA). MiRNAs are small-noncoding RNAs commonly misexpressed in cancer. One tumor suppressive miRNA, miR-708-5p, has been shown to repress pro-resistant signaling pathways, including COX-2 and mPGES-1. MethodsmiR-708-5p expression was measured via RT-qPCR, while protein expression was assessed using western blotting. Biological changes in lung cancer cell proliferation and survival were evaluated using Ki-67 and Annexin V staining via flow cytometry, respectively. ResultsHere, we demonstrate that chemotherapies reduce COX-2 expression, possibly through induction of miR-708-5p. Moreover, combination treatment of erlotinib (ERL) or paclitaxel (PAC) with miR-708-5p enhances COX-2 and mPGES-1 protein suppression. We also show that combination chemotherapeutic and miR-708-5p treatment intensifies the anti-proliferative and pro-apoptotic effects of ERL and PAC. We also created ERL and PAC resistant lung cancer cell lines, which have increased COX-2 expression and diminished miR-708-5p levels compared to naïve lung cancer cells. While ERL and PAC treatments do not alter resistant cell phenotype alone, combination treatment with miR-708-5p partially restores the chemotherapies’ anti-proliferative effects and fully restores their pro-apoptotic qualities. ConclusionThese data suggest miR-708-5p may have potential combinatory therapeutic value to more efficaciously treat lung tumors while overcoming chemoresistance.
Longitudinal Prospective Study of Emergency Medicine Provider Wellness Across Ten Academic and Community Hospitals During the Initial Surge of the COVID-19 Pandemic
Authors: Kelker Heather , Yoder Kyle , Musey Paul , Harris Madison , Johnson Olivia , Sarmiento Elisa , Vyas Punit , Henderson Brooke , Adams Zachary , Welch Julie L 
Published: October 2020

Abstract
Background: While the coronavirus (COVID-19) has had far-reaching consequences on society and health care providers, there is a paucity of research exploring emergency medicine (EM) provider wellness over the course of a pandemic. The objective of this study was to assess the well-being, resilience, burnout, and wellness factors and needs of EM physicians and advanced practice providers (APPs) during the initial phase of the COVID-19 pandemic.Methods: A longitudinal, descriptive, prospective cohort survey study of 213 EM physicians and APPs was performed across ten emergency departments in a single state, including academic and community settings. Participants were recruited via email to complete four weekly, voluntary, anonymous questionnaires comprised of customized and validated tools for assessing wellness (Well Being Index), burnout (Physician Work Life Study item), and resilience (Brief Resilience Scale) during the initial acceleration phase of COVID-19. Univariate and multivariate analysis with Chi-squared, Fisher’s Exact, and logistic regression was performed.Results: Of 213 eligible participants, response rates ranged from 31 to 53% over four weeks. Women comprised 54 to 60% of responses. Nonrespondent characteristics were similar to respondents. Concern for personal safety decreased from 85% to 61% (p<0.001). Impact on basic self-care declined from 66% to 32% (p<0.001). Symptoms of stress, anxiety or fear was initially 83% and reduced to 66% (p=0.009). Reported strain on relationships and feelings of isolation affected >50% of respondents initially without significant change (p=0.05 and p=0.30 respectively). Women were nearly twice as likely to report feelings of isolation as men (OR 1.95; 95%CI 1.82-5.88). Working part-time carried twice the risk of burnout (OR, 2.45; 95% CI, 1.10-5.47). Baseline resilience was normal to high. Provider well-being improved over the four-weeks (30% to 14%; p=0.01), but burnout did not significantly change (30% to 22%; p=0.39).Conclusion: This survey of frontline EM providers during the initial surge of COVID-19 found that despite being a resilient group, the majority experienced stress, anxiety, fear, and concerns about personal safety due to COVID-19, with many at risk for burnout. The sustained impact of the pandemic on EM provider wellness deserves further investigation to guide targeted interventions.
Pseudomonas Aeruginosa Secreted Protein PA3611 Promotes Bronchial Epithelial Cells Epithelial-Mesenchymal Transition Through TGF-β1 Inducing p38/miRNA/NF-κB Pathway
Authors: Shu Lei , Chen Sixia , Chen Xiaolin , Lin Shaoqing , Du Xingran , Deng Kaili , Wei Jing , Cao Yang , Yan Jiaxin , Shen Ziyan , Feng Ganzhu 
Published: October 2020

Abstract
BackgroundPseudomonas aeruginosa (PA) is one of the important pathogens, which has been proven to colonize and cause infection in the respiratory tract of patients with structural lung diseases, and further lead to bronchial fibrosis. Epithelial-Mesenchymal Transition (EMT) of bronchial epithelial cells plays a vital role in the process of bronchial fibrosis. Up to the present, the research on bronchial epithelial cells EMT caused by secreted virulence factors of PA has not been reported. ResultsIn our present study, we found that PA3611 protein stimulation induced the bronchial epithelial cells EMT with up-regulation of mesenchymal cell markers and down-regulation of epithelial cell markers. Meantime, TGF-β1 secretion was markedly increased, IκBα expression was significantly decreased, and NF-κB p65 subunit phosphorylation was markedly enhanced, in addition, the levels of miR-3065-3p and miR-6802-3p expression and p38 MAPK phosphorylation were obviously increased in bronchial epithelial cells after PA3611 stimulation, furthermore, PA3611 was shown to promote EMT occur through TGF-β1 induced p38/miRNA/NF-Κb pathway. The function of PA3611 was also veriﬁed in PA-infected rats and results showed that △PA3611 could reduce lung inflammation and EMT. ConclusionsOverall, our results revealed that PA3611 promotes EMT via simulating the production of TGF-β1 induced p38/miRNA/NF-κB pathway-dependent manner, suggesting that PA3611 acts as a crucial virulence factor in bronchial epithelial cells EMT process and has potential use as a target for clinical treatment of bronchial EMT and fibrosis caused by chronic PA infection.
Obesity control by SHIP inhibition requires pan-paralog inhibition and an intact eosinophil compartment
Authors: Fernandes Sandra , Srivast Neetu , Pedicone Chiara , Sudan Raki , Luke Elizabeth , Dungan Otto , Pacherille Angela , Meyer Shea , Dormann Shawn , Chisholm John , Kerr William 
Published: October 2020

Abstract

Previously a small molecule SHIP inhibitor, K118, was shown to reverse high-fat diet induced obesity and improve blood glucose regulation in obese mice. K118 treatment was also found to increase the frequency and number of IL-4 producing eosinophils in the visceral fat as well as two potent immunoregulatory myeloid cell populations: M2-polarized macrophages and myeloid derived suppressor cells (MDSC) suggesting an immune regulatory mechanism. However, the cell(s) or SHIP paralog that should be targeted to improve metabolic regulation were not defined. Here we extend our understanding of how chemical inhibition of SHIP paralogs improves metabolic regulation during excess caloric intake. We compare different SHIP inhibitors in an obesity prevention model and find that selective inhibitors for SHIP1 or SHIP2 lack the ability to prevent weight gain and body fat accumulation during increased caloric intake. Surprisingly, only pan-SHIP1/2 inhibitors could prevent diet-induced obesity. We confirm that both SHIP1 and SHIP2 must be targeted by showing that dual treatment with the SHIP1 and SHIP2 selective inhibitors can reduce adiposity caused by excess caloric consumption. We also show that pan-SHIP1/2 inhibitors of two different chemical classes can control diet-induced obesity and improve blood glucose regulation. Intriguingly, we find that both classes of pan-SHIP1/2 inhibitors require an intact eosinophil compartment to prevent diet-related fat accumulation demonstrating pan-SHIP1/2 inhibitors act via the VAT innate immune compartment to control adiposity However, improved blood glucose regulation by pan-SHIP1/2 inhibition is not dependent upon eosinophils, indicating a separate mechanism of action for diet-related loss of glucose regulation.
Antiﬁbrotic activity of Hypocrellin A united LED red light irradiation on Keloid Fibroblasts through counteracting TGF-β/Smad/autophagy/apoptosis signaling pathway
Authors: Niu Tianhui , Tian Yan , Shi Ying , Guo Guangjin , Tong Ying , Wang Guangyun 
Published: October 2020

Abstract
Keloid disease is characterized by abnormal proliferation of fibroblast and continuous deposition of extracellular matrix (ECM) components. More and more attention in dermopathic is paid to photodynamic therapy (PDT) with visible light. The natural photosensitizer Hypocrellin A (HA) is identified to develop a splendid light induced anticancer, antimicrobial and antiviral activity. In this experiment, we investigated the impacts of HA united light-emitting diode (LED) red light irradiation on human keloid fibroblast cells (KFs). Our results showed that HA united red light irradiation treatment (HA-R-PDT) decreased KFs viability, reduced KFs collagen production and ECM accumulation, inhibited cell proliferation, suppressed cell invasion and induced cell apoptosis. Moreover, our observations demonstrated that TGF-β/Smad signaling pathway and autophagy were restrained by HA-R-PDT. TGF-β1 could accommodate autophagy in KFs through both Smad and ERK pathway, while inhibiting autophagy could mediate TGF-β1 level by the negative feedback. Therefore, HA-R-PDT could suppress cell hyper-proliferation, collagen synthesis and ECM accumulation in KFs via regulating TGF-β1-ERK-autophagy-apoptosis signaling pathway. HA-R-PDT deserves systematic investigation as a potential therapeutic strategy for keloid treatment and autophagy might be a promising candidate in the therapy of KFs.
Longitudinal analysis of blood markers reveals progressive loss of resilience and predicts ultimate human lifespan limit
Authors: Pyrkov Timothy , Avchaciov Konstantin , Tarkhov Andrei , Menshikov Leonid , Gudkov Andrei , Fedichev Peter 
Published: October 2020

Abstract
We investigated the dynamic properties of the organism state fluctuations along individual aging trajectories in a large longitudinal database of CBC measurements from a consumer diagnostics laboratory. To simplify the analysis, we used a log-linear mortality estimate from the CBC variables as a single quantitative measure of aging process, henceforth referred to as dynamic organism state index (DOSI). We observed, that the age-dependent population DOSI distribution broadening could be explained by a progressive loss of physiological resilience measured by the DOSI auto-correlation time. Extrapolation of this trend suggested that DOSI recovery time and variance would simultaneously diverge at a critical point of 120-150 years of age corresponding to a complete loss of resilience. The observation was immediately confirmed by the independent analysis of correlation properties of intraday physical activity levels fluctuations collected by wearable devices. We conclude that the criticality resulting in the end of life is an intrinsic biological property of an organism that is independent of stress factors and signifies a fundamental or absolute limit of human lifespan.