bluuebunny/crossref_metadata_2025_split huggingface dataset:
ELF5 inhibits migration and invasion of breast cancer cells via regulating CD24 expression
Authors: Qu Xinjian , Li Qianqian , Tu Simei 
Published: April 2020

Abstract
Objective: E74-like factor five (ELF5) is a basic transcriptional factor that plays a key role in breast tissue and glandular development. However, the molecular mechanism by which ELF5 mediates the biological functions of breast cancer cells has not been elucidated. We hypothesize that ELF5 regulate CD24 transcription though an E26 transforming sequence (ETS) cis-element in the CD24 promoter region.Methods: Human breast cancer cell line MCF-7 was transfected with Myc-ELF5 plasmid in over-expression experiment. T47D cells were transfected with ELF5-shRNA plasmid in knockout experiment. The expression level of ELF5 `protein was analyzed by Western blot. MTT assays and Clonal formation assays were used to assess the proliferation properties of cells. Scratch wound-healing assays were performed to determine cell migration and invasive activities. CD24 protein expression was analysis by flow cytometry. Using the bioinformatics tool JASPAR, we identified high-scoring ETS-like sequences in the CD24 gene promoter. To confirm the ETS, Chromatin immunoprecipitation (ChIP) analysis was used. DNA fragments of a putative or mutated ETS-like sequence were synthesized and ligated into a pGL3 basic plasmid to construct the CD24 promoter luciferase reporter systems which was used to detect ELF5 regulation of CD24 transcriptional activity.Results: In this study, we examined the effect of ELF5 on human breast cancer cell lines MCF-7 and T49D, and confirmed that ELF5 act as a suppressor of cell proliferation, migration and invasion. In further research, the interaction between ELF5 and CD24 was characterized in breast cancer cells. We found that CD24 was a target gene of ELF5 through ChIP-Sequence assays, and proved that ELF5 could bind to ETS cis-element on the proximal promoter of CD24 gene. Importantly, experiments verified that CD24 was upregulated after ELF5 overexpression in MCF-7 cells, while knockdown of CD24 expression caused MCF-7 cells to restore cell proliferation, migration and invasion activity in adaptive ELF5 expression.Conclusions: This study not only found that ELF5 can inhibit cell proliferation, migration and invasion in breast cancer cells, but also found that ELF5 induced CD24 expression by binding to the ETS cis element in the CD24 gene promoter sequence. This study provided a molecular mechanism for ELF5 to inhibit breast cancer from a new perspective, and provided further theoretical support for the treatment and prevention of breast cancer.
Osteopontin, Osteoprotegerin and Musculoskeletal Ultrasound findings in First-Degree Relatives of Rheumatoid Arthritis: Potential Markers of Preclinical Disease
Authors: Soliman Eiman , Ohrndorf Sarah , Zehairy Magdy , Matrawy Khaled , Alhadidy Abeer , Abdelati Abeer 
Published: April 2020

Abstract
Background: First-degree relatives (FDRs) of rheumatoid arthritis (RA) patients are known to have increased risk of developing the disease. The detection of altered bone metabolism in FDRs could be a predictor of the disease. Preclinical phase of RA is characterized by a state of autoimmunity and inflammation. Musculoskeletal ultrasound (MSUS) is known for its ability to detect subclinical joint inflammation in RA, but changes in FDRs are not yet described.Objectives: To study serum osteopontin (OPN) and osteoprotegerin (OPG) levels in first degree relatives (FDRs) of rheumatoid arthritis (RA) as markers of altered bone metabolism in relation to clinical, laboratory and musculoskeletal ultrasound (MSUS) findings. Methods: Fifty-five individuals were included, 20 had definite RA, 25 were FDRs of RA patients, and 10 healthy controls. Clinical evaluation for joint swelling/tenderness was performed for all. ESR, CRP, rheumatoid factor (RF), anti-citrullinated antibodies (ACPA), OPN, OPG, and MSUS by the US7 score were evaluated.Results: OPG was significantly higher in RA (143.89 pg/ml±365.47) than in FDRs (22.23 pg/ml±65.73; p=0.009) and controls (6.20 pg/ml±12.43; p=0.003). OPN was also higher in RA (3.66 ng/ml±4.20) than in FDRs (1.97 ng/ml±1.04) and controls (2.81 ng/ml±1.31), though not significant (p=0.102). Eight of 25 FDRs (32%) had arthralgia without clinical arthritis and 17/25 (68%) were asymptomatic. FDRs with arthralgia had significantly higher ESR and CRP levels than asymptomatic FDRs (9.82 mm/h±4.13; p=0.003, and 3.93 mg/l±3.58; p=0.003). OPG was higher in FDRs than in controls, and also in those with arthralgia (51.55 pg/ml±114.68) than in those without (8.44 pg/ml±9.67), though without significant difference. OPN was higher in FDRs with arthralgia (2.09 ng/ml±1.19) than in asymptomatics (1.70 ng/ml±0.55), also without significant difference. Pathologic findings by US7 were detected in 10/25 (40%) FDRs, of which three (12%) had arthralgia and seven (28%) were asymptomatic. Conclusions: The raised OPG and lower OPN in FDRs than in controls reflect an altered bone metabolism which could precede clinical disease phase. OPN and OPG could serve as markers of altered preclinical bone metabolism in FDRs of RA. US7 score might be a useful screening tool to identify ‘at-risk’ individuals.
Porcine model of sepsis-induced systemic inflammation and acute lung injury in donor lungs
Authors: Nasir Basil Saad , Menaouar Ahmed , Landry Caroline , Germain Jean-Francois , Laplante Patrick , Sarkissian Shant Der , Liberman Moishe , Cailhier Jean-Francois , Leduc Charled , Noiseux Nicolas , Ferraro Pasquale 
Published: April 2020

Abstract
Background: The shortage of organ donors is a major challenge in lung transplantation. To expand the lung donor pool, ex-vivo lung perfusion (EVLP) has emerged as a platform for assessment and reconditioning marginal donor lungs. In this study a stable and reproducible large animal model of lipopolysaccharide (LPS) induced systemic inflammation and acute lung injury (ALI) was developed.Methods: Pigs (n=6) were anesthetized and monitored. After infusion of LPS (20 μg/kg) for 1 hour, followed by a 90-minute response period, lungs were procured and kept on ice for 2 hours, followed by 4 hours of EVLP. Pulmonary function, inflammatory biomarkers and edema formation were measured in vivo before procurement and during EVLP. Pro and anti-inflammatory cytokines were assayed in blood and in EVLP perfusate, which were collected before and every 30 minutes after LPS administration and EVLP.Results: LPS infusion resulted in significant hemodynamic instability, characterized by marked pulmonary hypertension, decreased systemic blood pressure and increased heart rate. This was associated with increased levels of TNFα, IL-10, IL-6, but no change in IL-1β. Ex vivo assessment of injured lungs showed graft dysfunction characterized by impaired gas exchange and edema formation. The inflammatory profile showed stable but elevated TNFα levels, and continuous production of interleukins during EVLP.Conclusion: We describe a reproducible large animal model of LPS-induced systemic inflammation and ALI. EVLP alone was unable to recondition severely injured lungs. These findings suggest that the EVLP platform requires adjuncts such as targeted anti-inflammatory agents to allow reconditioning of marginal donor lungs.
Efficacy and Safety of Electro-Acupuncture (EA) on Insomnia in Patients with Lung Cancer: Study Protocol of a Randomized Controlled Trial
Authors: Yue Hongyu , Zhou Shuang , Wu Huangan , Yin Xuan , Li Shanshan , Liang Tingting , Li Yan , Fang Zhihong , Zhang Xufeng , Wang Linglin , Han Min , Chen Xiaolei , Zhang Ming , Zhang Wei , Zhang Zhangjin , Xu Shifen 
Published: April 2020

Abstract
Background : Cancer-related insomnia (CRI) is one of the most prevalent complaints among cancer survivors and severely impairs patients’ quality of life. As a popular non-pharmacological alternative treatment, acupuncture provides a good clinical curative effect on insomnia. The aim of this trial is to evaluate efficacy and safety of electro-acupuncture on insomnia in patients with lung cancer. Method : This is a protocol for a multicenter randomized single-blinded sham-controlled trial. We will randomly assign 252 eligible patients with lung cancer-related insomnia into two groups at a ratio of 1:1, the treatment group (EA) and the control group (sham EA). All treatment will be given 3 times per week for 8 weeks, and a 12-week follow-up will be conducted. The primary outcome will be measured by the Pittsburgh Sleep Quality Index (PSQI). The secondary outcomes will include sleep parameters recorded from the actigraphy, scores from Quality of Life Questionnaire Core-30 (QLQ-C30), and Patient Health Questionnaire-9 (PHQ-9). All adverse effects during the trial will be assessed by the Treatment Emergent Symptom Scale (TESS). The primary outcome will be assessed at baseline, week 4, week 8, week 12 and week 20. The secondary outcomes will only be assessed at baseline and week 8. Discussion : This large-sample trial protocol will evaluate the efficacy of electro-acupuncture on insomnia in patients with lung cancer. This protocol, if proven to be effective, will contribute to filling the gap in treatment options in the CRI field and provide a promising intervention for insomnia in lung cancer survivors. Trial registration: ChiCTR, ChiCTR1900026395, Registered 8 October 2019, http://www.chictr.org.cn/showproj.aspx?proj=44068
Comparative Efficacy and Mechanisms of a Single Session Behavioral Medicine Class among Patients with Chronic Pain Taking Prescription Opioids: Study Protocol for a Randomized Controlled Trial
Authors: Ziadni Maisa , Chen Abby L. , Winslow Tyler , Mackey Sean C. , Darnall Beth D. 
Published: April 2020

Abstract
Background: Independent of pain intensity, pain-specific distress is highly predictive of pain treatment needs, including prescription opioids. Given the inherently distressing nature of chronic pain, there is a need to equip individuals with pain education and self-regulatory skills that are shown to improve adaptation and improve response to medical treatments. Brief, targeted behavioral medicine interventions may efficiently address the key individual factors, improve self-regulation in the context of pain, and reduce need for opioid therapy. This highlights the critical need for targeted, cost-effective interventions that efficiently address the key psychological factors that can amplify the need for opioids and increased risk for misuse. In this trial, the primary goal is to test the comparative efficacy of a single-session skills-based pain management class to a health education active control group among patients with chronic pain who are taking opioids. Methods: Our study is a randomized, double-blind clinical trial testing the superiority of our 2-hour single-session skills-based pain management class against a 2-hour health education class. We will enroll 136 adult patients with mixed etiology chronic pain who are taking opioid prescription medication and randomize 1:1 to one of the two treatment arms. We hypothesize superiority for the skills-based pain class for pain control, self-regulation of pain-specific distress, and reduced opioid use measured by daily morphine equivalent. Team researchers masked to treatment assignment will assess outcomes up to 12 months post-treatment. Discussion: This study aims to test the utility of a single-session, 2-hour skills-based pain management class to improve self-regulation of pain and reduce opioid use. Findings from our project have the potential to shift current research and clinical paradigms by testing a brief and scalable intervention that could reduce need for opioids and prevent misuse effectively, efficiently and economically. Further, elucidation of mechanisms of opioid use can facilitate refinement of more targeted future treatments.
Surgical outcomes of acute acquired comitant esotropia of adulthood
Authors: Kim Dae Hyun , Noh Ha Jeong 
Published: April 2020

Abstract
Background: To analyze the surgical outcomes for adult patients diagnosed with acute acquired comitant esotropia (AACE).

Methods: Medical records of 21 patients who had undergone surgery for AACE were retrospectively analyzed. The main outcome measures were the final motor and sensory success rate after surgery and factors affecting motor and sensory outcomes. Motor success was considered alignment within 8 prism diopter (PD) at both near and distance and sensory success was stereoacuity ≥60 sec/arc.

Results: The preoperative mean esodeviation angles were 33.0 ± 11.6 PD at distance and 32.6 ± 10.8 PD at near. The mean period of postoperative follow up was 8.1 ± 4.5 months (range 3–8 months). The postoperative mean esodeviation angles at final follow-up time were 4.1 ± 5.7 PD at distance and 3.9 ± 5.6 PD at near. The surgical motor success rate at final follow-up was 76.2% (16/21). The sensory success rate at final follow-up was 55.5% (11/21). The factor affecting the motor outcome was the type of surgery ( p < 0.05). The factor affecting sensory outcome was postoperative follow-up time ( p < 0.05).

Conclusions: Surgery type appears to affect surgical motor outcomes in adults with AACE. Although the sensory outcome was favorable, it seems that regaining bifoveal fixation takes time.
Monocyte-derived Macrophages: the Supplements of Hepatic Macrophage in Echinococcus Multilocularis Infected Mice
Authors: Li Bin , Qi Xinwei , Liu Yumei , Yan Yi , Shan Jiaoyu , Cai Xuanlin , Lv Jie , Zhou Xuan , Luo Li , Ma Xiumin 
Published: April 2020

Abstract
Background Alveolar echinococcosis (AE) is a potentially lethal zoonosis caused by the cestode Echinococcus multilocularis. The aim of this study is to study the dynamic changes of monocytes, macrophages and related cytokines in animal models of persistent infection of Echinococcus multilocularis. To explore the possible connection between them and the persistent infection of Echinococcus multilocularis.Methods An infection model was established by intraperitoneal injection of a protoscolex suspension. The pathological changes of mice liver were observed by HE staining and the score scale of infection was established. The ratio of Ly6Chi and Ly6Clo Monocytes in peripheral blood of mice was detected by flow cytometry. The distribution and expression of CX3CL1, CX3CR1, iNOS, CD163 and CD11b in mouse liver were detected by immunohistochemistry. The mRNA expression levels of TNF-α and Arg1 in mouse liver were detected by qRT-PCR. The expression levels of INF-γ, IL-17, IL-4 and IL-10 in peripheral blood of mice were detected by ELISA.Results The results of HE staining showed that in the later stages of infection, significant lesions appear in the liver.The results of the infection degree score scale show that with the extension of the infection time, the severity score value increases. The results of flow cytometry showed that the proportion of Ly6Chi monocytes in the peripheral blood of the experimental group mice was decreased after a brief rise, Ly6Clo monocytes decreased first and then increased.. The results of immunohistochemistry showed that the expression of CX3CL1, CX3CR1, CD11b , CD163 and iNOS in the mice liver of the experimental group was increased. The results of qRT-PCR showed that the expression level of TNF-α and Arg1 mRNA in the liver of the experimental group mice were increased. The results of ELISA showed that the expression level of IFN-γ, IL-17, IL-4 and IL-10 increased with the duration of infection.Conclusions Monocytes as a supplement to hepatic macrophage, it and kupffer cells (KCs) participate in Th1 and Th2 immune responses of the body by differentiating into M1 or M2 at different stages of Echinococcus multilocularis infection.
GPR30 negatively regulates inflammation in gout by inhibiting IL-1β production
Authors: Qian Hongyan , Chen Rongjuan , Chen Shiju , He Yan , Liu Yuan , Shi Guixiu 
Published: April 2020

Abstract
Background: Gout is the most common inflammatory arthritis induced by monosodium urate crystal (MSU) precipitation.The incidence of gout attack was significantly higher in men than women, indicating the important role of oestrogen system in pathogenesis of gout, but the specific mechanisms underlying remained to be explored. GPR30, the newly defined estrogen receptor, had been proved participated in regulating inflammation in some diseases. As different estrogen receptors paly different role in inflammation regulation, how GPR30 was involved in the inflammation induced by MSU in gout was still unknown. Methods: In this work, we investigated the function of GPR30 in inflammation induced by MSU in cultured macrophages and in mouse model by using G-1(the agonist of GPR30). We further tested the expression of the TLR and NOD like receptor protein3 (NLRP3), which are the key receptor involved in pathogenesis of gout. ROS and cleaved-caspase-1 expression were also detected to confirm the regulation role in NLRP3 pathway. Seahorse analysis was used to detect the metabolism profile in macrophages by G-1 to investigate the mechanism of GPR30 in inflammation. The relative expression of GPR30 were detected according to the inflammation state to confirm the role of GPR30 in gout. Results: Negative regulation role of G-1 in IL-1β expression and NLRP3 expression were found both in vitro and in vivo. Moreover, the negative regulation of ROS production and NLRP3 as well as cleaved-caspase-1 expression were also found in G-1 stimulated macrophages. Our data also showed that G-1 inhibited aerobic glycolysis in LPS activated macrophages, which might be responsible for IL-1β and NLRP3 expression. Higher expression levels of GPR30 were found in patients with remitted gout inflammation. Conclusion: Together, our data suggested that GPR30 was involved in the negative inflammation regulation induced by MSU and high expression of GPR30 might contribute to part of the mechanism of inflammation remission of gout.
Assessment of a dried blood spot C-reactive protein method to identify disease flares in rheumatoid arthritis patients
Authors: D’Cruz Leon G , McEleney Kevin G , Cochrane Chris , Tan Boon C , Shukla Priyank , Gardiner Philip V , Small Dawn , Zhang Shu-Dong , Gibson David Samuel 
Published: April 2020

Abstract
Background Rheumatoid arthritis (RA) is characterised by painful, stiff and swollen joints. RA features sporadic ‘flares’ or inflammatory episodes – mostly occurring outside clinics - where symptoms worsen and plasma C-reactive protein (CRP) becomes elevated. Poor control of inflammation results in higher rates of irreversible joint damage, increased disability, and poorer quality of life. Flares need to be accurately identified and managed. A method comparison study was designed to assess agreement between CRP values obtained by dried blood spot (DBS) versus conventional venepuncture sampling. The ability of a weekly DBS sampling and CRP test regime to detect flare outside the clinic was also assessed. Methods Matched venepuncture and finger lancet DBS samples were collected from n=100 RA patients with active disease at baseline and 6 weeks (NCT02809547). A subset of n=30 RA patients submitted weekly DBS samples over the study period. Patient demographics, including self-reported flares were recorded. DBS sample CRP measurements were made by enzyme-linked immunosorbent assay, and venepuncture samples by a reference immunoturbometric assay. Data was compared between sample types by Bland-Altman and weighted Deming regression analyses. Flare detection sensitivity and specificity were compared between ‘minimal’ baseline and 6 week sample CRP data and the ‘continuous’ weekly CRP data. Results Baseline DBS ELISA assay CRP measures yielded a mean positive bias of 2.693 ± 8.640 (95% limits of agreement -14.24% to 19.63%), when compared to reference assay data. Deming regression revealed good agreement between the DBS ELISA method and reference assay data, with baseline data slope of 0.978 and intercept -0.153. The specificity of ‘continuous’ area under the curve (AUC) CRP data (72.7%) to identify flares, was greater than ‘minimal’ AUC CRP data (54.5%). Conclusions This study indicates reasonable agreement between DBS and the reference method, especially at low to mid-range CRP values. Importantly, longitudinal CRP measurement in RA patients helps to clearly identify flare and thus could assist in remote monitoring strategies and may facilitate timely therapeutic intervention.
Prevalence, characteristics and survival of pulmonary hypertension due to chronic heart failure: a national multicenter prospective registry study
Authors: Quan Ruilin , Huang Shian , Pang Lingpin , Shen Jieyan , Wu Weifeng , Tang Fangming , Zhu Xiulong , Su Weiqing , Sun Jingzhi , Yu Zaixin , Wang Lemin , Zhu Xianyang , Changming Xiong , He Jianguo 
Published: April 2020

Abstract
Background The prevalence, characteristics and survival of pulmonary hypertension due to left heart disease (PH-LHD) in heart failure with reduced and preserved ejection fraction (HFrEF, HFpEF) has yet to be explored. Methods Consecutive patients with chronic heart failure undergoing first right heart catheterization (RHC) were prospectively enrolled from October 2012 to August 2016 in 11 participating medical centers. Follow-up was performed every 6 months ± 2 weeks. The primary endpoint was all-cause mortality. Results A total of 500 patients were enrolled. The prevalence of PH was 67.2% in HFrEF and 40.2% in HFpEF, respectively. Predictors of PH differed between PH etiologies, but left ventricular end diastolic diameter (LVEDD) was a consistent both in HFrEF (P=0.031) and HFpEF (P=0.003). During a median follow-up time of 33.39 months, 69 patients (13.8%) met the primary endpoint. The survival of PH patients was significantly worse than that of patients without PH (P=0.001). Diastolic pressure gradient (DPG) was a significant prognostic variable both in HFrEF (HR=1.057, 95% CI=1.007-1.108, P=0.024) and HFpEF (HR=1.094, 95% CI=1.009-1.187, P=0.030). Patients with a DPG ≥ 7 mmHg had a worse survival compared to those whose DPG < 7 mmHg both in HFrEF (log rank test, P=0.047) and in HFpEF (P=0.016). Conclusion Though the prevalence, characteristics and prognosis of PH differ between HFrEF and HFpEF, PH-LHD is a common complication and has an adverse effect on the prognosis. Study registration NCT02164526.
Targeting the Coronavirus SARS-CoV-2: computational insights into the mechanism of action of the protease inhibitors Lopinavir, Ritonavir, and Nelfinavir
Authors: Bolcato Giovanni , Bissaro Maicol , Pavan Matteo , Sturlese Mattia , Moro Stefano 
Published: April 2020

Abstract
Coronavirus SARS-CoV-2 is a recently discovered single-stranded RNA (ssRNA) betacoronavirus, responsible for a severe respiratory disease known as coronavirus disease 2019 (COVID-19), which is rapidly spreading. Chinese health authorities, as a response to the lack of an effective therapeutic strategy, started to investigate the use of lopinavir and ritonavir, previously optimized for the treatment and prevention of HIV/AIDS viral infection. Despite the clinical use of these two drugs, no information regarding their possible mechanism of action at the molecular level is still known for SARS-CoV-2. Very recently, the crystallographic structure of the SARS-CoV-2 main protease (Mpro), also known as C30 Endopeptidase, was published. Starting from this essential structural information, in the present work we have exploited Supervised Molecular Dynamics (SuMD), an emerging computational technique that allows investigating at an atomic level the recognition process of a ligand from its unbound to the final bound state. In this research, we provided molecular insight on the whole interaction pathway of lopinavir, ritonavir, and nelfinavir, three potential C30 Endopeptidase inhibitors, with the last one taken into consideration due to the promising in-vitro activity shown against the structurally related SARS-CoV protease.