bluuebunny/crossref_metadata_2025_split 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.