bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum levels of interleukins and S100A8/A9 correlate with clinical severity in patients with dermatomyositis-associated interstitial lung disease
Authors: Lou Yueyan , zheng yu , Tan Xiaoming , Fan Bijun , Zhang Liyan , Zhu Feng , Wang Xiaodong , Chen Zhiwei , Wei Qing
Published: March 2020

Background: Dermatomyositis (DM) is a systemic autoimmune inflammatory disorder that affects primarily skin, muscle and lung, frequently associated with interstitial lung disease (ILD). The objective of this study is to investigate the association between serum cytokines and clinical severity in patients with DM-ILD. Methods: Serum samples of 40 DM-ILD patients and 30 healthy controls were collected. Expressions of S100A8/A9 were analyzed by enzyme-linked immunosorbent assay (ELISA) and interleukins were analyzed by cytometric beads array (CBA). Results: Serum IL-4, IL-6 and S100A8/A9 were observably higher in DM-ILD than those in healthy controls ( p = 0.0013, 0.0017 and < 0.0001, respectively). Serum IL-10 level of patients was dramatically lower than that in controls ( p = 0.0001). IL-4 ( r = 0.1171, p = 0.0040), IL-6 ( r = 0.1174, p = 0.0040) and IL-10 ( r = -0.1829, p = 0.0003) were significantly correlated with S100A8/A9 in DM-ILD patients. S100A8/A9 was significantly correlated with high-resolution computed tomography (HRCT) ( r = 0.1642, p = 0.0157) and lung function (DLCO%: r = -0.2066, p = 0.0061, FVC%: r = -0.2156, p = 0.0050). Conclusions: Serum level of S100A8/A9 may be a valuable marker for assessing the clinical severity of DM-ILD patients. Serum IL-4, IL-6 and IL-10 levels were highly correlated with S100A8/A9, so these cytokines may play a synergistic effect on the progression of DM-ILD. Keywords : Dermatomyositis, Interstitial lung disease, S100A8/A9, Interleukin
An 8 week open-label interventional multicenter study to evaluate the lung clearance index as endpoint for clinical trials in cystic fibrosis patients ≥6 years of age, chronically infected with Pseudomonas aeruginosa
Authors: Sutharsan Sivagurunathan , Naehrig Susanne , Mellies Uwe , Sieder Christian , Zeigler joerg
Published: March 2020

Background Forced expiratory volume in 1 second (FEV 1 ) is the only parameter currently recognized as a surrogate endpoint in cystic fibrosis (CF) trials. However, FEV 1 is relatively insensitive to changes in the small airways of patients with milder lung disease. This pilot study aimed to evaluate the lung clearance index (LCI) as a marker for use in efficacy trials with inhaled antibiotics in CF. Methods This open-label, single-arm study enrolled CF patients with Pseudomonas aeruginosa infection, who were treated with tobramycin (28-day on/off regime). FEV 1 , LCI and bacterial load in sputum (CFU) were assessed at baseline, after 1, 4 and 8 weeks of treatment. Results All patients (n=17) showed elevated LCI of >11 despite 3 patients having normal FEV 1 (>90% predicted) at baseline. Overall, LCI improved in 8 (47%) patients and FEV 1 in 9 (53%) patients. At week 4, LCI decreased by 0.88, FEV 1 increased by 0.52%, and P. aeruginosa reduced by 30481.3 CFU/mL. These changes were however statistically non-significant. Six adverse events occurred in 5/17 (29.4%) patients, most of which were mild-to-moderate in severity. Conclusions Due to the low evaluable sample size, no specific trend was observed related to the changes between LCI, FEV 1 and CFU. Based on the individual data from this study and from recently published literature, LCI has been shown to be a more sensitive parameter than FEV 1 for lung function. However, LCI alone does not seem to be the ideal clinical endpoint for efficacy studies with antibiotic treatment in small groups of CF patients.Trial registration : The study is registered with ClinicalTrials.gov, identifier: NCT02248922
Use Of Leflunomide In Patients With Hypersensitivity Pneumonitis
Authors: Noh Sungryong , Yadav Ruchi , Li Manshi , Wang Xiaofeng , Sahoo Debasis , Culver Daniel A , Pande Aman
Published: March 2020

Prednisone has been shown to reverse lung function declines in hypersensitivity pneumonitis patients without established fibrosis. Second line immunosuppressants like azathioprine and mycophenolate mofetil have a steroid sparing effect and improve DLCO. There is no published literature on the use of leflunomide in such patients. We reviewed our experience with leflunomide for treatment of hypersensitivity pneumonitis in 40 patients. We stratified patients according to the presence or absence of significant (>20%) fibrosis. We studied the effect of leflunomide on FVC and DLCO trajectory and reported the changes at 12 months.Treatment with leflunomide tended to improve the estimated FVC slope from 0.18±1.90% (SEM) of predicted per year to 4.62±1.65% of predicted (NS, p=0.118). It significantly improved the FVC at 12 months of treatment by 4.4% of predicted (p=0.02). DLCO continued to increase at 1.45±1.44% (SEM) of predicted per year. Non-fibrotic HP patients had the largest gain in pulmonary function. Their FVC increased by 8.3% (p=0.001) and DLCO by 4.8% (p=0.011). Patients with fibrotic HP did not improve. Leflunomide treatment was associated with significant gastrointestinal and other adverse effects leading 40% of patients to discontinue therapy. It had a significant steroid sparing effect with half the patients weaned off prednisone entirely.Leflunomide appears to be a fairly well tolerated steroid sparing immunosuppressant that improves pulmonary function in HP patients. It is most effective in patients without significant fibrosis.
The Effects of One-lung Ventilation on the Production of Endogenous Melatonin and NLRP3 Inflammasome-Related Inflammatory Cytokines in Patients Undergoing Laparoscopic Esophagectomy: A Prospective Randomized Double-Blind Controlled Study
Authors: Wang Lixia , Li Jun , Huang Yuting , Zhu Yan , Shen Qiying , Zou Hongyun , Liu Xue-sheng
Published: March 2020

Background: NLRP3 inflammasome has been confirmed to play a pivotal role in ventilator-induced lung injury (VILI), while exogenous melatonin can attenuate VILI by inhibiting NLRP3 inflammasome activation in mouse model. However, the relationship between endogenous melatonin and the NLRP3 inflammasome-related inflammatory cytokines in VILI induced by one-lung ventilation (OLV) remains unknown. In this study, we aimed to reveal the relationship between the NLRP3 inflammasome-related inflammatory cytokines: interleukin (IL)-1β, IL-18 and endogenous melatonin in OLV-induced VILI during esophageal cancer surgery.Methods: Twenty-eight patients were randomized to receive “conventional” ventilation (Vt=8 mL/kg) or lung protective ventilation (Vt=5 mL/kg along with 5 cm H 2 O positive end-expiratory pressure (PEEP)). Respiratory variables were evaluated. IL-1β, IL-18 and melatonin in bronchoalveolar lavage fluid (BALF) and plasma were measured.Results: we found that lung protective ventilation during OLV decreased peak airway pressure (Ppeak), plateau airway pressure (Pplat) and driving pressure (ΔP) compared with that in “conventional” ventilation group. Moreover, lung protective ventilation inhibited polymorphonuclear (PMN) cells invasion into BALF. Likewise, lung protective ventilation not only suppressed alveolar and plasma IL-1β secretion, but also reduced increased production of IL-18 in both BALF and plasma after OLV. Furthermore, we found that both alveolar and plasma endogenous melatonin levels in “conventional” ventilation group were lower than that in lung protection group.Conclusion: Taken together, the present study suggested that lung protective ventilation during OLV prevented VILI via suppressing NLRP3 inflammasome-related inflammatory cytokines secretion and restoring the level of endogenous melatonin in patients.Trial registration: the Chinese Clinical Trial Registry, ChiCTR1900026190. Registered 25 September 2019, http://www.chictr.org.cn/edit.aspx?pid=34677&htm=4
The Outcome of Self-expandable Metallic Stent for Malignant Tracheobronchial Stenosis Following Esophageal Stenting
Authors: Li Yahua , zhou zihe , Ren kewei , Lu Huibin , Li Zongming , Li Zhaonan , Liu Juanfang , Zhou Xueliang , Chen Jianjian , Han Xinwei , Ren Jianzhuang
Published: March 2020

Background: Tracheobronchial stenosis following esophageal stenting is rare. We aim to explore the outcome of SEMS for malignant tracheobronchial stenosis following esophageal stenting.Methods: Clinical and imaging data of 20 patients (12 males, 8 females) with malignant tracheobronchial stenosis following esophageal stenting from Jan 2014 to Jan 2019 were retrospectively analyzed. Data of the location of tracheobronchial stenosis, stent types, Borg score before and after airway stenting, indication of esophageal stent placement, interval between double stents placement and survival time after airway stenting were collected.Results: A total of 20 stents (13 Y-shaped stents, 7 tube stents) were successful placement in all patients without procedure-related complications happened. Seven of them are tracheal stenosis, 5 carina stenosis and 8 multiple stenosis. The mean Borg score before and after airway stenting are 6.6±1.1 and 1±0.5 (P<0.001). The interval between double stents placement in patients who received chemoradiotherapy is 146.29±106.77 days, while in palliation therapy is 41.83±146.29 days(P<0.05). The mean survival time after esophageal stenting in patients who received chemoradiotherapy is 232.79 ±97.71 days, while in palliation therapy is 163 ± 113.50 days(P=0.230). The mean survival time after airway stenting in patients who received chemoradiotherapy is 86.5 ±52.47 days, while in palliation therapy is 121.17 ± 113.48 days(P=0.461).Conclusion: The application of SEMS in malignant tracheobronchial stenosis following esophageal stenting is safe and effective. Chemoradiotherapy is a factor affect the interval between double stents placement.
Developing and implementing a community-based suicide prevention program in Iranian primary health care: study protocol
Authors: azizi Hosein , Fakhari Ali , Esmaeili Elham Davtalab , Barzegar Habibe , Farahbakhsh Mostafa , Mirzapour Mohammad , Aslrahimi Vahab
Published: March 2020

Background : Since 2013, WHO has had a global mental health action plan which includes reducing suicide rate by 10% in countries by 2020. However, only 18% of countries have a registry for suicide. The community-based Suicide Prevention Program (SPP) statistic is much lower than registry for suicide. Suicide is a growing concern in Iran. A health community assessment found that suicide and Suicidal Behaviors (SBs) are one of the most important public health problems in Malekan County, East Azerbaijan Province of Iran. This calls for a regional SPP effort in Primary Health Care (PHC). Methods: A regional community-based SPP was established during 2014-2017 in two phases including development and implementation. The development phase focuses on three pillars: 1) review of systematic reviews, 2) expert comments, and 3) report to the health care system. The implantation phase also carried out in five steps: 1) improving coverage of SBs registration, 2) identification of determinants of SBs, 3) follow up monitoring of SBs people, 4) treatment for depression and conducting research, and 5) developing public education campaigns. Primary outcome was reducing the rate of completed suicide. Secondary outcomes were considered Suicide Attempt (SA) and re-attempt. Our ultimate goal was considered to lower by 15%, 20% and 30% rates of suicide, SA, and re-attempt, respectively. Discussion : In this study protocol, we have been to outline and explain the steps of developing and implementing a regional community-based SPP by using the highly effective evidence and field expert's comments. Implementing SPP with low cost and easily adaptable in PHC is the most important site for the case management of SBs and materialization of interventions in the health system including various types of health service providers and coverage of a large number of people. This study is both research and action. It needs to involve and support of the health system and inter-sectoral collaborations to achieve the goal of such community-based Health System Research. This HSR was approved to number 60665 in an electronic system (Pajoohan) of Tabriz University of Medical Sciences.
Identification of immune prognostic signature of lung carcinoma based on Genome-wide immune expression profile
Authors: Ling Bo , Ye Guangbin , Zhao Qiuhua , Jiang Yan , Liang Lingling , Tang Qianli
Published: March 2020

Background : Lung cancer is one of the most common types of cancer with low early diagnosis rate and poor prognosis. The integration of immune checkpoint gene expression data and patient prognosis information can help identify the immune subtypes of lung cancer and provide reference for individualized gene immunotherapy in patients with lung cancer. Methods : The data of immune gene expression for lung cancer patients were obtained from TCGA and GEO databases. The relationship between the expressions of 45 immune checkpoint genes (ICGs) and prognosis were analysed. In the other hand, the correlation between the expressions of 45 biomarkers , tumor mutation load (TMB), MMRs, neoantigens and other immunotherapy biomarkers were been identified. Ultimately, prognosis-related ICGs were combined with IDO1, CD274, and CTLA4 to divide lung cancer immune subgroups and the prognostic differences between lung cancer immune subgroups were identified. Results: Based on TCGA database and GEO database, 9 and 11 ICGs were obtained respectively, which were closely related to prognosis. There was a certain synergistic relationship between them. The expression of CD200R1 had a significant negative correlation with TMB and neoantigens. CD200R1 showed a significant positive correlation with CD8A, CD68 and GZMB genes, indicating that it may cause the expression disorder of adaptive immune resistance pathway genes. Based on CD200R1 and combination with IDO1, CD274 and CTLA4, the group with high expression of CD200R1 and low expression of IDO1, CD274 and CTLA4 had the best prognosis among the immune subtypes. Conclusion : Our research provides a method of integrating immune checkpoint gene expression profile and clinical prognosis information to identify immune subtypes of lung cancer, which can provide a unique reference for gene immunotherapy of lung cancer patients.
CD73 blockade enhances the local and abscopal effects of radiotherapy in a murine rectal cancer model
Authors: Tsukui Hidenori , Horie Hisanaga , Koinuma Koji , Ohzawa Hideyuki , Sakuma Yasunaru , Hosoya Yoshinori , Yamaguchi Hironori , Yoshimura Kotaro , Lefor Alan Kawarai , Sata Naohiro , KITAYAMA JOJI
Published: March 2020

Background Anti-tumor effects of radiation therapy (RT) largely depend on host immune function. Adenosine with its strong immunosuppressive properties is an important immune checkpoint molecule.Method We examined how intra-tumoral adenosine levels modify anti-tumor effects of RT in a murine model using an anti-CD73 antibody which blocks the rate-limiting enzyme to produce extracellular adenosine. We also evaluated CD73 expression in irradiated human rectal cancer tissue.Results LuM-1, a highly metastatic murine colon cancer, expresses CD73 with significantly enhanced expression after RT. After subcutaneous (sc) transfer of LuM-1, mice developed macroscopic sc tumors and microscopic pulmonary metastases within 2 weeks. Adenosine levels in the sc tumor were increased after RT. Selective RT (4Gyx3) suppressed the growth of the irradiated sc tumor, but did not affect the growth of lung metastases which were shielded from RT. Intraperitoneal administration of anti-CD73 antibody (200 μg x 6) alone did not produce antitumor effects. However, when combined with RT in the same protocol, anti-CD73 antibody further delayed the growth of sc tumors and suppressed the development of lung metastases presumably through abscopal effects. Splenocytes derived from RT+ CD73 antibody treated mice showed enhanced IFN-γ production and cytotoxicity against LuM-1 compared to controls. Immunohistochemical studies of irradiated human rectal cancer showed that high expression of CD73 in remnant tumor cells and/or stroma is significantly associated with worse outcome.Conclusion These results suggest that adenosine plays an important role in the anti-tumor effects mediated by RT and that CD73/adenosine axis blockade may enhance the anti-tumor effect of RT, and improve the outcomes of patients with locally advanced rectal cancer.
Diagnostic Value of Circulating microRNAs in Laryngeal Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis
Authors: Cheng Danni , Pang Wendu , Qiu Ke , Yang Wenjie , Rao Yufang , Deng Di , Yan Xiaohong , Song Yao , Yang Wen , Ren Jianjun , Zhao Yu
Published: March 2020

Background : Circulating microRNAs (miRNAs) play an important role in the biological processes of cancers and are promising biomarkers of cancer diagnosis. Objectives : To estimate the diagnostic value of microRNAs in laryngeal squamous cell carcinoma (LSCC) patients, comparing with the non-LSCC controls. Population : Six eligible LSCC studies including 1,585 LSCC patients with corresponding 2,095 non-LSCC controls from years 2000 to 2017 were analyzed. Methods : Medline, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, EMBASE, Cochrane Library and Web of Science were searched in this study. We conducted a meta-analysis to identify studies that reported the diagnostic data of miRNAs both in LSCC patients and controls. I n addition, we evaluated and compared the diagnostic value of upregulated miRNAs with downregulated miRNAs . Results : Six studies with corresponding specificity and sensitivity data were included in this study. The pooled sensitivity, specificity and AUC were 0.89 (95% CI: 0.79-0.94), 0.87 (95% CI: 0.77-0.93), and 0.94 (95% CI: 0.92-0.96), respectively. However, the heterogeneities of these studies were quite high, the value of I 2 for the pooled sensitivity, specificity were 96.82% and 97.08%, respectively. Subgroup analysis of upregulated and downregulated miRNAs showed a similar diagnostic value but the heterogeneity remained high. Publication bias was found in Funnel plot of pooled and upregulated miRNAs, while not obvious in downregulated miRNAs. Conclusions : Circulating miRNAs showed diagnostic significance in laryngeal cancer, however, the results of this meta-analysis revealed significant heterogeneity. Therefore, the diagnostic value of miRNAs in LSCC seems limited.
Meta-analysis examining overall survival in patients with pancreatic cancer treated with second-line 5-fluorouracil and oxaliplatin-based therapy after failing first-line gemcitabine-containing therapy: effect of performance status and comparison with other regimens
Authors: Wainberg Zev Aryeh , Feeney Kynan , Lee Myung Ah , Muñoz Andrés , Gracián Antonio Cubillo , Lonardi Sara , Ryoo Baek-Yeol , Hung Annie , Lin Yong , Bendell Johanna , Hecht J. Randolph
Published: March 2020

Background: Pancreatic cancer has a poor prognosis and few choices of therapy. For patients with adequate performance status, FOLFIRINOX or gemcitabine plus nab-paclitaxel are preferred first-line treatment. 5-Fluorouracil (5-FU)–based therapy (e.g. FOLFIRI, OFF, or FOLFOX) are often used in patients who previously received gemcitabine-based regimens. A systematic review was conducted of the safety and efficacy of FOLFOX for metastatic pancreatic cancer following prior gemcitabine-based therapy. A Bayesian fixed-effect meta-analysis with adjustment of patient performance status (PS) was conducted to evaluate overall survival (OS) and compare outcomes with nanoliposomal irinotecan combination therapy. Methods: PubMed.gov, FDA.gov, ClinicalTrials.gov, congress abstracts, Cochrane.org library, and EMBASE database searches were conducted to identify randomized controlled trials of advanced/metastatic disease, prior gemcitabine-based therapy, and second-line treatment with 5-FU and oxaliplatin. The database search dates were January 1, 1990–June 30, 2019. Endpoints were OS and severe treatment-related adverse events (TRAEs). Trial-level PS scores were standardized by converting Karnofsky grade scores to Eastern Cooperative Oncology Group (ECOG) Grade, and overall study-weighted PS was calculated based on weighted average of all patients. Results: Of 282 studies identified, 11 randomized controlled trials ( N = 454) were included in the meta-analysis. Baseline weighted PS scores predicted OS in 10 of the 11 studies, and calculated PS scores of 1.0 were associated with a median OS of 6.3 months (95% posterior interval, 5.4–7.4). After adjusting for baseline PS, FOLFOX had a similar treatment effect profile (median OS, range 2.6–6.7 months) as 5-FU/leucovorin plus nanoliposomal irinotecan therapy (median OS, 6.1 months; 95% confidence interval 4.8–8.9). Neutropenia and fatigue were the most commonly reported Grade 3–4 TRAEs associated with FOLFOX. Conclusions: Baseline PS is a strong prognostic factor when interpreting the efficacy of 5-FU and oxaliplatin-based therapy of pancreatic cancer after progression on first-line gemcitabine-based regimens. When baseline PS is considered, FOLFOX has a similar treatment effect as 5-FU and nanoliposomal irinotecan therapy and a comparable safety profile. These findings suggest that 5-FU and oxaliplatin-based therapies remain an acceptable and alternative second-line treatment option for patients with pancreatic cancer and adequate PS (e.g. ECOG 0–1) following gemcitabine treatment.
A propensity-matched analysis of stereotactic body radiotherapy and sublobar resection for stage I non-small cell lung cancer in patients at high risk for lobectomy: the results in a Chinese population
Authors: Chen Wu-Cheng , Yuan Xiao-Shuai , Lin Qing-Ren , Sun Xiao-Jiang , Liu Jin-Shi , Chen Qi-Xun , Xu Ya-Ping , Shang Jin-Biao
Published: March 2020

Objectives To investigated comparative effectiveness of stereotactic body radiotherapy (SBRT) and sublobar resection (SLR) in patients who had stage I non-small cell lung cancer (NSCLC) and a high risk for lobectomy. Methods From January 2008 to December 2015, patients who underwent SBRT or SLR for clinical stage I NSCLC were examined retrospectively. Propensity score matching (PSM) was performed to reduce selection biases in SBRT and SLR patients. Results 86 SBRT and 79 SLR patients were collected. Median follow-up periods of SBRT and SLR groups were 32 and 37 months, respectively. Patients treated with SBRT exhibited significant increased age, larger tumor diameter, lower FEV1, poorer PS and higher rates of male comparing with SLR. There were no significant differences in terms of 3-year overall survival (OS) (80.3% and 82.3%, P = 0.405), cause-specific survival (CSS) (81.3% and 83.4%, P = 0.383) and local control (LC) (89.7% and 86.0%, P = 0.501) were found in SBRT and SLR patients. 49 patients were identified from each group after performing PSM. The differences of matching factors were balanced based on age, gender, performance status, tumor characteristics and pulmonary function, as no significant differences in terms of 3-year OS (85.4% and 73.3%, P = 0.649), CSS (87.2% and 74.9%, P = 0.637) and LC (95.6% and 82.1%, P = 0.055) in matched SBRT and SLR patients were observed. The rate of grade 3 or the occurrence of worse adverse events was 0 and 10.2% in the matched SBRT and SLR groups (P = 0.056), respectively. Conclusion These results suggest that disease control and survival achieved by SBRT were equivalent to SLR in patients who had clinical stage I NSCLC and were at high risk for lobectomy. SBRT can be an alternative option to SLR in treating patients with a high operative risk.
Tracking the Features of CIMP-positive Glioma: A Systematic Review and Meta-Analysis
Authors: Xiao Huashi , Xu Yingying , Shen He-chun , Liu Wanjun , Tan Siyuan , Chen Ping , Yu Guo , Ren Chuanli , Sun Liangdan , Yu Duonan , Zong Liang
Published: March 2020

Backgrounds Controversy surrounding CpG island methylator phenotype (CIMP) in glioma exists with regard to its prognostic value.Methods PubMed, EMBASE, and Cochrane Library databases were searched for studies describing molecular and clinicopathological features, and overall survival of gliomas stratified by CIMP status. Associations of CIMP with outcome parameters were estimated using odds ratio (OR) or hazard ratios (HRs) with a 95% confidence interval (CI) using a fixed or random effects model.Results A total of 12 studies involving 2386 gliomas (1051 CIMP-positive and 1335 CIMP-negative) were included. Molecular analysis showed that CIMP is more frequent in IDH1-mutated gliomas (OR 229.07; 95% CI 138.72–378.26) and 1p19q LOH gliomas (OR 5.65; 95% CI 2.66–12.01), though CIMP was not associated with EGFR mutation (OR 0.14; 95% CI 0.05–0.43) or MGMT promoter methylation (OR 3.01; 95% CI 0.79–11.48). Clinicopathological analysis showed that CIMP is more frequent in oligodendroglioma (OR 5.51; 95% CI 3.95–7.70), but less frequent in glioblastoma (OR 0.14; 95% CI 0.10–0.19). However, CIMP was not associated with anaplastic oligoastrocytomas (OR 1.57; 95% CI 1.24-2.00) or oligoastrocytoma (OR 0.79; 95% CI 0.35–1.76). We found that CIMP-positive glioma was associated with a longer overall survival (HR -0.57; 95% CI -0.97– -0.16).Conclusions A CIMP-positive glioma has better prognosis and its own molecular features (such as IDH1 and 1p19q LOH mutations) and clinicopathological features. These conditions suggest CIMP could be used as an independent prognostic marker for glioma.
Intratumoral cycling hypoxia inhibits expression level of estrogen receptor to promote the formation of heterogeneous sub-clones in luminal A breast cancer
Authors: Song Bing , Zhang Gaofeng , Li Jianyi , Kang Ye , Kong Linna , Ma Yan , Shu Hong , Zhang Yang , Jia Shi , Wang Zhenrong
Published: March 2020

Background The expression level of estrogen receptor (ER) is positively correlated with chemoresistance in patients with Luminal A tumor (LAT). ER expression level alters frequently after neoadjuvant chemotherapy which may be related with hypoxia. The spatial and temporal heterogeneity of tumor sub-clones is one of the major contributors to treatment failure. It is essential to investigate how the intratumoral heterogeneous sub-clones survive hypoxic microenvironment in LAT. Material and Methods LAT with largest cross section was divided into micro-sections, the expressions of hypoxia inducible factor-1 (HIF-1) and ER were then detected by immunohistochemistry. The intratumoral distribution of micro-vessels was assessed by 3D reconstruction and stained CD34; the cycling hypoxia model of MCF-7 was established in a step fashion to investigate the changes in HIF-1 and ER expressions. All statistical analyses were performed using SPSS software (version 17.0 for Windows). Results There was a negative correlation between the expressions of ER-alpha and HIF-1alpha (c=-2.40; p=0.044) as assessed by mean optical density values in the maximal cross section of tumor. As shown by 3D ultrasound image, the center of tumor had less functional micro-vessels compared with the periphery (P<0.05). From the periphery to the center of tumors in the large sections from 8 patients with LAT, the expressions of ER, progesterone receptor and CD34 were gradually decreased with HIF-1alpha expression showing an opposite direction. There was a negative correlation between expressions of ER-alpha and HIF-1alpha, and between expressions of CD34 and HIF-1alpha. No significant difference was noted in the outcomes of cytometry between the hypoxia and control groups. ER-alpha expression gradually decreased with the time course of cycling hypoxia with HIF-1alpha showing an opposite direction. Conclusion LAT is composed of heterogeneous sub-clone cells which can be distinguished by ER-alpha and HIF-1alpha. The distribution of heterogeneous sub-clone cells was closely related with heterogeneous microenvironment of hypoxia / reoxygenation. Keywords: Luminal A breast cancer, cycling hypoxia, estrogen receptor, heterogeneous sub-clones.
Verteporfin Inhibits Cell Proliferation and Induces Apoptosis in Different Subtypes of Breast Cancer Cell Lines Without Light Activation
Authors: Wei Changran , Li Xiangqi
Published: March 2020

Background

Breast cancer (BC) can be separated into four molecular subclassifications including Lumina1 A, Lumina1 B, HER-2 overexpression and Basal-like subtype. These classifications are based on estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2) and cell proliferation antigen (Ki-67). The Hippo signaling pathway plays an indispensable role in BC. The YAP1 gene is a terminal effector of Hippo pathway, and hyperactivation of YAP mediates tumorigenesis. As an inhibitor of YAP, non-photoactivated verteporfin (VP) can inhibit YAP-mediated tumor proliferation and angiogenesis by eliminating its interaction with TEAD. This study set out to determine the effect and molecular mechanisms of VP-mediated inhibition of YAP in different subtypes of BC.

Methods

Luminal A, Luminal B and Basal-like BC cells were cultivated in vitro in order to study effect of VP on proliferation and apoptosis on these three molecular BC subtypes.

Results

Our experimental results show that VP inhibits cell proliferation, YAP-TEAD interaction and its downstream target expression. VP also induces tumor cell apoptosis, and promotes the cleavage of Caspase-9 and PARP in various molecular subtypes of BC cells.

Conclusion

These findings provide a basis for VP as a potential anti-tumor therapeutic for BC by targeting the Hippo pathway effector YAP.
HIV understanding, experiences and perceptions of HIV-positive men who have sex with men in Amazonian Peru: A qualitative study.
Authors: Tattsbridge Jasmine , Wiskin Connie , De Wildt Gilles , Llavall Anna Clavé , Ramal-Asayag César
Published: March 2020

Background HIV-related incidence and mortality is increasing across Peru, with highest mortality rates recorded in Amazonian Loreto. This epidemic is concentrated in MSM, a population with 14% HIV treatment adherence despite free national provision. This study investigates barriers and facilitators to following healthcare advice through experiences and perceptions of HIV-positive MSM and healthcare professionals in Loreto. Methods Twenty qualitative interviews with HIV-positive MSM and one focus group with HIV-specialist healthcare professionals were conducted in Loreto, January-February 2019. Thematic content analysis was used. Results A culture of isolation and discrimination was identified, propagated by poor public knowledge surrounding HIV transmission and treatment. Employment potential was hampered and 7/20 patients had suicidal thoughts post-diagnosis. Barriers to care included: shame, depression, travel cost/times, a preference for traditional plant-based medicine and side-effects of ART. Facilitators included: education, family and clinic support, disease acceptance and lifestyle changes.Conclusion More targeted community education and workplace discrimination investigations are recommended.
Measuring Character Strengths as Possible Protective Factors against Suicidal Ideation in Older Chinese Adults: A Cross-Sectional Study
Authors: Cheng Xinfeng , Bu He , Duan Wenjie , He Along , Zhang Yaping
Published: March 2020

Background: Suicide is a global issue among the elderly. The number of older people committing suicide is proliferating, and the elderly suicide rate is the highest among all age groups in China. The possible protective factors against suicidal ideation should be investigated for prevention and intervention efforts. The objectives of the present study are as follows: (1) to examine the psychometric properties of the three-dimensional inventory of character strengths (TICS) with a sample of older adults; (2) to investigate correlations among suicide ideation, wellbeing, and character strengths; and (3) to explore the possible protective roles of the three character strengths and wellbeing in explaining suicidal ideation among older adults. Methods: A cross-sectional study comprising 308 older adults aged at least 50 years old from nursing homes was conducted. Four questionnaires, namely, the TICS, the Geriatric Suicide Ideation Scale—10 items, the Brief Inventory of Thriving, and the Satisfaction with Life Scale, were used. Exploratory structural equation modeling, intraclass correlation coefficients, partial correlations, and sets of hierarchical regressions were adopted to estimate and report the results. Results: TICS could be used to assess the character strengths (i.e., caring, inquisitiveness, and self-control) among older adults with an acceptable goodness-of-fit (chi square = 157.30, df = 63, p < 0.001, CFI = 0.94, TLI = 0.90, RMSEA = 0.07, 90% CI = [0.06, 0.08]). Wellbeing (life satisfaction: B = −0.14, t = −2.55, p = 0.01; thriving: B = −0.52, t = −9.64, p < 0.001) and character strengths (caring: B = −0.45, t = −11.84, p < 0.001; inquisitiveness: B = −0.33, t = −7.89, p < 0.001; self-control: B = −0.45, t = − 10.83, p < 0.001) have exhibited a significant association with suicidal ideation among older adults. Moreover, character strengths have shown an independently cross-sectional relationship with suicidal ideation, explaining 65.2% of the variance of suicidal ideation after controlling for the wellbeing and demographics. Conclusion: This study indicated that character strengths were associated with low levels of suicidal ideation. Therefore, the protective factors against suicidal ideation among older adults should be given additional attention.
Rapid development of a synthetic DNA vaccine for COVID-19
Authors: Smith Trevor R.F. , Patel Ami , Ramos Stephanie , Elwood Dustin , Zhu Xizhou , Yan Jian , Yang Maria , Chokkalingam Neethu , Gary Ebony N. , Schultheis Katherine , Pezzoli Patrick , Walters Jewell , Walker Susanne N. , Parzych Elizabeth , Reuschel Emma L. , Doan Arthur , Tursi Nicholas , Vasquez Miguel , Choi Jihae , Maricic Igor , Bah Mamadou A. , Wu Yuanhan , Amante Dinah , Park Daniel , Dia Yaya , Ali Ali Raza , Zaidi Faraz I. , Generotti Alison , Kim Kevin Y. , Herring Timothy A. , Reeder Sophia , Brown Ami Shah , Khoshnejad Makan , Wang Nianshuang , Chu Jacqueline , Wrapp Daniel , McLellan Jason S , Muthumani Kar , Kim J Joseph , Boyer Jean , Kulp Daniel W. , Humeau Laurent M.P.F. , Weiner David B. , Broderick Kate E.
Published: March 2020

The coronavirus family member, SARS-CoV-2 has been identified as the causal agent for the outbreak of viral pneumonia disease, COVID-19 which first emerged in mid-December 2019 in the city of Wuhan in central China. As of February 25, 2020 there are 80,994 people infected and 2,760 deaths, and documented human-to-human transmission across multiple continents. At this time, no vaccine is available to control further dissemination of the disease. We have previously developed a synthetic DNA vaccine targeting the MERS coronavirus Spike (S) protein that was deployed in response to the MERS outbreak in South Korea. This vaccine induced potent antibody and CTL responses, and provided protection in a NHP challenge model. In the clinic, the vaccine generated humoral immunity including neutralizing antibody responses, as well as T cell immunity. Here we build on this prior work and report on the rapid development of a synthetic DNA-based vaccine targeting the major surface antigen Spike protein of SARS-CoV-2. The engineered construct, INO-4800 induced robust expression of the Spike protein in vitro, and generated antibody and T cell responses following a single immunization in mice and guinea pigs. This preliminary dataset identifies INO-4800 as a potential COVID-19 vaccine candidate, supporting further study for mobilization against this emerging disease threat.
THE EUROPEAN UNION EXPERIENCE REGARDING THE EDUCATION POLICY FOR INTERCULTURAL CITY DEVELOPMENT
Authors: Petrushenko Yu.M. , Vasilyeva Т.А. , Shvindina H.О. , Mayboroda Т.М. , Zaichyk K.O.
Published: March 2020

The article analyzes the trends of the European Union's education policy in the field of intercultural dialogue and intercultural development. The chronology of the intercultural education, the transformation of the terms interculturalism is presented, the main legislative acts of the Council of Europe, European conventions, UNESCO documents are analyzed. The basic principles of intercultural education, which form the basis for the development of appropriate education policies, are summarized. The paper proposes the next stage of the interculturalism evolution – the intercultural cities network movement. Sumy city has joined the network but there is a new stage of intercultural education is needed.
Keywords: intercultural dialogue, education policy, Council of Europe, intercultural urban development, intercultural education, intercultural cities network.
STAKEHOLDER APPROACH TO MONITORING THE ENTERPRISE'S ACTIVITIES IN THE STRATEGIC MANAGEMENT SYSTEM
Authors: Vasilyeva Т. , Boronos V. , Zakharkin O. , Bilous Iu.
Published: March 2020

The article discusses approaches to monitoring the activity of an enterprise as part of its strategic management system. The positions of modern scientists on the issues of monitoring the activity of the enterprise are analyzed and the conclusion is made about the necessity of participation in it of all stakeholders of the enterprise to take into account their interests. The stakeholder approach to monitoring the activity of the enterprise in the strategic management system is proposed and the role of different stakeholder groups in its implementation is defined.
Metals futures market: a comparative analysis of investment and arbitrage strategies
Authors: Guryanova Lidiya , Chernova Natalia
Published: March 2020

The article deals with the application of optimal portfolio theory and pair trading theory on the metals futures market. Advantages of the futures market over the spot market include relatively small initial price, low transaction costs, and high volatility. The main aim of the study is to explore the potential of both strategies for effective trading. The following financial instruments were chosen as the inputs of the models: futures on industrial metals (aluminum, copper, nickel, zinc, lead, tin), futures on precious metals (gold and silver). When building the optimal portfolio, it was decided to include Dow Jones Index futures and S&P Index futures among metals. This is because these instruments are extremely volatile and may play the role of a hedge in the portfolio. A drawdown indicator was used to assess the effectiveness of each strategy. The results show that both strategies can be applied on the real-life market. The final choice will depend on the level of risk taking by investors and the desired value of return.
Decision-making process of tomatoes purchase by generation Z: case study in the Slovak Republic
Authors: Šugrova Michaela , Plachy Marek , Nagyova Ľudmila , Šumichrast Jozef
Published: March 2020

The paper aims to investigate and assess the decision-making process of young Slovak consumers – generation Z – in the purchase of tomatoes. The respondents participatet in a questionnaire survey and blind testing of four tomato samples (two samples were Slovak and another two were foreign tomatoes). For a deeper analysis of the collected data, five scientific hypotheses were formulated. The accuracy of provided hypotheses was verified using the following mathematical-statistical methods: Chi-Square test of independence, Mann-Whitney U-test, and as Chi test for equality of proportions between two samples. The research results show that generation Z buys tomatoes once a week or several times a month. Moreover, it was found out that most young consumers are mostly influenced by freshness, taste, quality of tomatoes, and general appearance, the least by packaging, brand/specific tomato grower, information on the packaging and references. According to all observed attributes within the blind testing of tomato by the respondents, the best-evaluated sample was the Slovak sample of tomatoes – the sample B. Subsequently, all respondents were provided with information about the tested tomatoes, and it can be stated that they would also actually buy Slovak sample B in the store. Finally, one can state that the higher price of this sample has no significant impact on the respondents of generation Z.
Local government in Russia: de jure and de facto
Authors: Kazantseva Olesya L.
Published: March 2020

The analysis of the RF Federal Law of 6 October 2003 No 131-FZ, which enshrines the general principles of the organization of local self-government in the Russian Federation, demonstrates the consistent introduction of amendments aimed at restricting the autonomy of local self-government, which clearly contradicts the constitutional provisions on local self-government. In this regard, it seems necessary to determine the presence of the lower level of public authority (local self-government), for which it is necessary to reveal the conformity of the modern realities of local self-government with constitutional provisions and normative legal acts adopted for their development, that is, correlate de jure and de facto.
The Constitutional Court of the Russian Federation, the highest constitutional justice body, has a great influence on the formation of local self-government in the Russian state. It forms the legal position on the organizational, legal, competence, territorial, financial and economic foundations of local self-government. In this regard, researchers are interested in the legal positions of the RF Constitutional Court regarding the autonomy of local self-government and its relations with state authorities, which have undergone significant changes throughout the entire period of reforming local self-government.
Based on the analysis of changes in the legislation on local self-government and the legal positions of the RF Constitutional Court, this article shows the inconsistency of local self-government at the present stage of its development. Thus, the author proves that there are no working mechanisms for the implementation of local self-government by the population.
This article concludes that the current situation requires special attention and attitude from the state, since without purposeful changes in the state policy in the sphere of local self-government it is impossible to preserve such postulates enshrined in the Russian Constitution, as democracy and local government.
Subject-oriented approach to quality of life management
Authors: Lyovkin Vadim E. , Lyovkina Anastasia O.
Published: March 2020

The problem of quality of life management is primarily associated with defining the object and subject of management, which in relation to the quality of life is definitely not easy due to the large number of different interpretations.
This article newly defines the quality of life phenomenon and develops the principles for its managing through clarification of the methodological and prescriptive position. This reveals the content of the category “quality of life” and criteria distinguishing good quality of life from bad in the context of sustainable development goals regardless of the current cultural structure. The concept of “a way of human interaction with the world” (namely, the specificity in the objects, mechanisms, and results of human interaction with the world at different levels or spheres of life) introduces a system of principles for managing quality of life, consistent with the current leading achievements in understanding the quality of life. This system of principles is represented by three main criteria for evaluating any innovations that change the quality of life of people (rationality, humanity, significance). Basing in these principles, the authors have developed twelve criteria for good quality of life management, two for each of the six areas human life: continuum (cultural), circumstances, physical, emotional, intellectual, and spiritual.
Role of Grina/Nmdara1 in the Central Nervous System Diseases
Authors: Chen Kai , Yang Liu Nan , Lai Chuan , Liu Dan , Zhu Ling-Qiang
Published: March 2020

Glutamate receptor, ionotropic, N-methyl-D-aspartate associated protein 1 (GRINA) is a
member of the NMDA receptors (NMDARs) and is involved in several neurological diseases, which
governs the key processes of neuronal cell death or the release of neurotransmitters. Upregulation of
GRINA has been reported in multiple diseases in human beings, such as major depressive disorder
(MDD) and schizophrenia (SCZ), with which the underlying mechanisms remain elusive. In this
review, we provide a general overview of the expression and physiological function of GRINA in
the central nervous system (CNS) diseases, including stroke, depression ,epilepsy, SCZ, and Alzheimer’s
disease (AD).
Effects of Probiotics on Diabetic Nephropathy: A Systematic Review
Authors: Vlachou Eugenia , Ntikoudi Anastasia , Govina Ourania , Lavdaniti Maria , Kotsalas Nikolaos , Tsartsalis Athanasios , Dimitriadis George
Published: March 2020

Background:

Diabetic Nephropathy is a frequent complication of diabetes mellitus due
to functional and structural modifications in multiple kidney compartments. Probiotics have risen
lately as a forthcoming therapeutic intervention but they have not been systematically evaluated in
diabetic nephropathy so far. The aim of this systematic review was to evaluate randomized controlled
trials and experimental studies assessing the effect of probiotic supplements on diabetic
nephropathy.

Methods:

An extensive literature search was conducted through electronic databases (PubMed,
Scopus, Cinahl and Medline) with the Medical Subject Headings and entry terms of “diabetic nephropathy”,
“diabetic renal disease” and “probiotics”. The search yielded 116 results, 9 of which met
the inclusion criteria for this systematic review.

Results:

Most of the microorganisms used in the studies belonged to the Lactobacillus and Bifidobacterium
genus. The dosage ranged from 2×107 to 6×1010 CFU/ g. The form of the probiotics
varied across the studies (capsules, sachets, soy milk, kefir and honey). The majority of the studies
demonstrated the benefits of probiotic supplementation on the reduction of inflammation, oxidative
stress and on the amelioration of renal function biomarkers in subjects with diabetic nephropathy. No
major gastrointestinal adverse events were observed during the intervention time with probiotics.

Conclusion:

: Findings of this systematic review demonstrate the positive impact of probiotics on
Diabetic Nephropathy without any major adverse events. Moreover, future larger randomized controlled
trials with bigger samples and longer follow-up time are deemed necessary for further valid
results on the effectiveness of probiotic supplementation on Diabetic Nephropathy.
Risk Analysis of Lurasidone in Patients with Schizophrenia and Bipolar Depression
Authors: Modugula Harika , Kumar Anoop
Published: March 2020

Lurasidone was approved by the United States Food and Drug Administration (FDA) for the treatment of schizophrenia, as well as for the treatment of bipolar depression. However, emerging reports have indicated various adverse drug reactions with the use of lurasidone. Thus, in this article, we have analyzed the risk profile of lurasidone in the established therapeutic indication. A total of 419 studies were published from October 2010-July 2019 regarding lurasidone. After the inclusion and exclusion criteria, 17 studies were selected for the analysis of risk. The adverse drug reactions (ADRs) of these studies were categorized as per the innovator summary of product characteristics (SmPC). Finally, the unlisted ADRs were analyzed by using the Naranjo probability algorithm. Telogen effluvium, thrombocytopenia, restless leg syndrome and hypersexuality were found with the use of lurasidone and fall under the unlisted category. The causality assessment has shown a probable correlation of lurasidone with hypersexuality, restless leg syndrome, thrombocytopenia and possible relation with telogen effluvium. In conclusion, lurasidone is a novel and efficacious pharmacological treatment for bipolar depression and schizophrenia. However, more data regarding the safety of this drug in a large population is needed.