bluuebunny/crossref_metadata_2025_split huggingface dataset:
The mediating role of inflammation in the association between cigarette smoking and intima-media thickness: the Guangzhou biobank cohort study
Authors: Wang Tao , Jiang Chao Qiang , XU Lin , Zhang Wei Sen , Zhu Feng , Jin Ya Li , Thomas G. Neil , Cheng Kar Keung , Lam Tai Hing 
Published: August 2019

Abstract
Background: Cigarette smoking is associated with thicker carotid intima-media thickness (IMT), probably partly through inflammatory pathways. However, to what extent does inflammation mediate the smoking-carotid atherosclerosis association remains unclear. We investigated the mediating effect of inflammation on the association between cigarette smoking and carotid IMT, and quantified the respective contributions of inflammatory markers to this association.
Methods: A total of 1,752 participants from Guangzhou Biobank Cohort Study-Cardiovascular Disease Sub-cohort (GBCS-CVD) were included. Using causal mediation analysis under the counterfactual framework, we decomposed total effects of cigarette smoking on IMT into indirect effects (through inflammatory response) and direct effects (not through inflammatory response).
Results: After adjusting for traditional risk factors, the indirect effects of per 109/L increment in leukocyte and granulocyte, per mg/L increment in high-sensitivity C-reactive protein (hs-CRP) and per mg/dl increment in fibrinogen on carotid IMT was 0.0028 mm (95% confidence interval (CI), 0.0011, 0.0047), 0.0019 mm (95% CI, 0.0006, 0.0034), 0.0017 mm (95% CI, 0.0006, 0.003) and 0.001 mm (95% CI, 0.0001, 0.0021), respectively. No evidence for a mediating role of lymphocyte was found. The proportion of the smoking-IMT association mediated by leukocyte, granulocyte, hs-CRP and fibrinogen was 12.57% (95% CI, 8.50%, 22.11%), 8.50% (95% CI, 5.76%, 15.09%), 7.64% (95% CI, 5.20%, 13.79%) and 4.48% (95% CI, 3.04%, 8.03%), respectively. Restricting data analysis to men showed similar results.
Conclusions: The effects of cigarette smoking on IMT were partly mediated by leukocyte, hs-CRP and fibrinogen. The mediating role of leukocyte was likely mainly driven by higher granulocyte.
Eosinopenia as a diagnostic marker of bloodstream infection in a general internal medicine setting: A cohort study
Authors: Hirosawa Takanobu , Harada Yukinori , Morinaga Kohei , Takase Hiroshi , Nin Michihiro , Shimizu Taro 
Published: August 2019

Abstract
Background

Little is known about the potential use of the eosinophil count as a predictive marker of bloodstream infection. In this study, we aimed to assess the reliability of eosinopenia as a predictive marker of bloodstream infection.

Methods

This study was a retrospective cohort study. The outpatient department and general internal medicine department of a tertiary university hospital in Japan. A total of 189 adult patients with at least 2 sets of blood cultures obtained during January 1–December 31, 2018, after excluding those with the use of antibiotic therapy within 2 weeks prior to blood culture, steroid therapy, a history of haematological cancer, or eosinophilia. The diagnostic accuracies of each univariate variable and the multivariable logistic regression models were assessed by calculating the areas under the receiver operating characteristic curves (AUROCs). The primary outcome was a positive blood culture indicating bloodstream infection.

Results

Severe eosinopenia (<10 cells/mm3) alone yielded little overall predictive ability (AUROC: 0.606, 95% confidence interval (CI): 0.502–0.710, P=0.035), and only moderate sensitivity (50%, 95%CI: 29–70%) and specificity (71%, 95%CI: 63–78%). The model comprising baseline variables (age, sex) and the C-reactive protein level yielded an AUROC of 0.7384, and the further addition of eosinopenia yielded a slight improvement, with an AUROC of 0.7547 (P=0.4297) and a statistically significant net reclassification improvement (NRI) (P=0.03). However, the integrated discrimination index (IDI) (P=0.282) remained non-significant.

Conclusions

Severe eosinopenia can be considered an inexpensive marker of bloodstream infection in a general internal medicine setting.
Helicobacter pylori eradication according to sequencing-based 23S ribosomal RNA point mutation associated with clarithromycin resistance
Authors: Seo Seung In , Joo Byoung , Kang Jin Gu , Kim Hyoung Su , Jang Myoung Kuk , Kim Hak Yang , Shin Woon Geon 
Published: August 2019

Abstract
Background
Clarithromycin resistance in Helicobacter pylori (H. pylori) is associated with point mutations in the 23S ribosomal RNA (rRNA) gene. A sequencing-based method can detect more point mutations than a polymerase chain reaction (PCR)-based method. We investigated the point mutations in the 23S rRNA genes of patients infected with clarithromycin-resistant H. pylori and compared the H. pylori eradication rates based on the identified clinically significant point mutations.
Methods
A total of 431 adult patients with H. pylori infection were retrospectively recruited in Kangdong Sacred Heart Hospital in 2017 and 2018. Patients who did not have point mutations related to clarithromycin resistance and/or had clinically insignificant point mutations were treated with PAC (proton pump inhibitor, amoxicillin, clarithromycin) for 7 days, while patients with clinically significant point mutations were treated with PAM (proton pump inhibitor, amoxicillin, metronidazole) for 7 days. H. pylori eradication rates were compared between the two groups.
Results
Sequencing-based detection of point mutations identified four mutations that were considered clinically significant (A2142G, A2142C, A2143G, A2143C), while all the other mutations were considered clinically insignificant. The clarithromycin resistance rate was 21.3% in the overall group of patients. A2143G was the most clinically significant point mutation (84/431, 19.5%), while T2182C was the most clinically insignificant point mutation (283/431, 65.7%). The H. pylori eradication rate in the overall group of patients was 83.7%, and the 7-day PAM-treated clarithromycin-resistance group showed a significantly lower eradication rate than the 7-day PAC-treated nonresistance group [ITT; 55.4% (51/92) vs. 74.3% (252/339), P=0.001, PP; 66.2% (51/77) vs. 88.4% (252/285), P=0.0001].
Conclusions
There were significantly lower eradication rates in the patients with clarithromycin-resistant H. pylori as identified by the sequencing of point mutations in the 23S rRNA gene when treated with PAM for 7 days. A future study comparing treatment regimens in clarithromycin-resistant H. pylori-infected patients may be necessary.
Characteristics of peptic ulcer bleeding in cirrhosis with esophageal and gastric varices
Authors: Lu Zheng , Sun Xiaotian , Han Jingjing , Jin Bo , Zhang Wenhui , Wang Yanling , Han Jun , Ma Xuemei , Liu Bo , Yu Xiaoli , Wu Qin , Li Hanwei 
Published: August 2019

Abstract
Background

Upper gastrointestinal bleeding (UGIB) is common in liver cirrhosis. Although esophageal and gastric varices (EGV) is the main bleeding source, there were still a proportion of patients with peptic ulcer bleeding, which has been easily neglected. Thus, this study aimed to analyzed and compared the characteristic of variceal bleeding and peptic ulcer bleeding in liver cirrhosis patients.

Methods

Cirrhotic patients with confirmed UGIB by urgent endoscopy from July 2012 to June 2018 in our hospital were enrolled, and classified into peptic ulcer bleeding group (n=248) and variceal bleeding group (n=402) based on the bleeding cause. The clinical and endoscopic characteristics, therapeutic efficacy and prognosis were evaluated and compared, and independent risk factors for 42-day morality in peptic ulcer bleeding in cirrhotic EGV patients were determined.

Results

Compared with variceal bleeding group, peptic ulcer bleeding group were older (55.58±11.37 vs. 52.87±11.57, P<0.01) and more stable, and the most common symptom was melena. Hepatocellular carcinoma was more prevalent in peptic ulcer group (141 vs. 119, P<0.01). The success rate of endoscopic hemostasis for variceal bleeding and peptic ulcer bleeding was 89.05% and 94.35%, respectively (P=0.021). Univariate and multivariate analysis identified emergency intervention (P=0.018, OR [95% CI] 11.270 [1.503-84.501]), hepatic encephalopathy before bleeding (P=0.034, OR [95% CI] 6.831 [1.159-40.255]) and hepatic renal syndrome before bleeding (P=0.013, OR [95% CI] 8.482 [1.568-45.869]) as three independent predictors for 42-day mortality.

Conclusion

Peptic ulcer bleeding should be distinguished from variceal bleeding by clinical and endoscopic characteristics, and urgent endoscopic treatment is needed once diagnosed.
Clinicopathological profiling of small heterodimer partner, as a negative regulator of inflammatory responses in rectal cancer patients
Authors: Kim Sup , Joo MiNa , Yeo Min-Kyung , Cho Moon-June , Kim Jun-Sang , Jo Eun-Kyeong , Kim Jin-Man 
Published: August 2019

Abstract
Background: Small heterodimer partner (SHP) is an orphan nuclear receptor family member that plays an essential role in the regulation of innate immune and inflammatory responses. However, the expression of SHP in rectal cancer and its prognostic significance have not been investigated. The aim of this study was to identify whether SHP levels are associated with cancer-related inflammation, treatment response and prognosis in rectal cancer patients.
Methods: First, we performed classic gene set enrichment analysis (GSEA) to detect the association between high and low SHP expression using TCGA data sets. Then, the correlation between the expression of SHP and the prognosis of rectal cancer patients was evaluated using online OncoLnc database. Finally, we performed immunohistochemistry and analysed the correlation between SHP expression and clinicopathological / haematolgic features or treatment response of rectal cancer patients treated with radiochemotherapy.
Results: Bioinformatics analysis indicated that low SHP mRNA expression was significantly associated with inflammatory response (NES = -1.67507) and poor prognosis (p = 0.0319). Nuclear expression of SHP was associated with cN stage (p = 0.003), Neutrophil (p = 0.023), Lymphocyte (p = 0.024), NLR (p = 0.023) and complete pathologic response after radiochemotherapy (p = 0.031). Low nuclear expression of SHP was associated with poor overall and distant metastasis-free survival for rectal cancer (p = 0.029 and p = 0.008) and retained significance as an independent prognostic factor for rectal cancer (p = 0.087 and p = 0.037).
Conclusions: These results inidcate that SHP may act as an antiinflammatory mediator by regulating systemic and local immune responses in rectal cancer. Moreover, SHP might be used a candidate markers or therapeutic target in rectal cancer.
Value of AFP and PIVKA-II in diagnosis of primary hepatocellular carcinoma and prediction of vascular invasion and tumor differentiation
Authors: Author) Yuan-Quan Si(Former Corresponding , Wang Xiu-qin , fan Gang , wang chang-yin , zheng yuan-wen , song xia , pan cui-cui , chu fu-lu , liu zhan-feng , Lu bing-ru , Lu Zhi-Ming 
Published: August 2019

Abstract
Background: To explore the value of alpha fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) in diagnosis of primary hepatocellular carcinoma (HCC) and their relationship with vascular invasion, tumor differentiation and size.
Methods: A total of 433 participants were enrolled in this study including 266 cases with HCC, 87 cases with liver cirrhosis and 80 healthy individuals. Then we explored the correlation between AFP, PIVKA-II serum level and several pathological features such as vascular invasion, tumor differentiation and size. The value of these two markers used singly or jointly in diagnosing HCC was evaluated by receiver operating characteristic (ROC) curve. The ROC curve was also plotted to identify AFP, PIVKA-II serum cut-off values that would best distinguish HCC patients with and without vascular invasion.
Results: The level of AFP and PIVKA-II in HCC group was significantly higher (Z was 7.428, 11.243 respectively, all P<0.01). When AFP and PIVKA-II were used as the individual tumor marker, the areas under the ROC curve (AUC) of HCC diagnosis were 0.765 (95% CI, 0.713～0.8170) for AFP, 0.901 (95% CI, 0.868～0.935) for PIVKA-II, and 0.917 (95% CI, 0.886～0.948) for AFP and PIVKA-II simultaneously.
The serum levels of AFP and PIVKA-II were positively correlated with tumor differentiation and size. High AFP and PIVKA-II expression was signiﬁcantly associated with the presence of vascular invasion (P was 0.007 and 0.014 respectively). The AFP level >64.4ng/ml or PIVKA-II level >957.61mAU/ml was the best critical value to predict the presence of vascular invasion.
Conclusion: The diagnostic value of AFP and PIVKA-II combined detection or single assay of PIVKA-II is higher than that of separate assay of AFP. And the proper concentration has important clinical value for judging tumor size, tumor cell differentiation and vascular invasion. Above results validate that AFP and PIVKA-II play a significant role in the diagnosis of HCC.
CX3CR1 regulates hepatocellular carcinoma(HCC) metastasis via PI3K/AKT pathway
Authors: Fan Mengtian , Weng Yaguang , Li Xian , Jiang Yingjiu , Wang Xiaowen , Bie Mengjun , An Liqin , Shi Qiong 
Published: August 2019

Abstract
Background

Fractalkine receptor CX3CR1 is differentially expressed in hepatocellular carcinoma and its function is unknown. As a special case of chemokine family, CX3CR1 only binds to its unique ligand CX3CL1, and CX3CL1 also only binds to its only receptor CX3CR1, the unique matching between ligands and receptors is not found in other chemokines, and this specificity is essential for diagnosis, prognosis and clinical target therapy.

Methods

CX3CR1 expression was analyzed by immunohistochemistry, migration and invasion abilities of SMMC-7721 cells were detected by wound-healing and transwell after overexpressing CX3CR1. In addition to overexpression experiments, interfering RNA siCX3CR1 was used for reverse validation in HepG2 cells. To further clarify the mechanism of CX3CR1 regulating HCC metastasis, the classical PI3K/AKT pathway were detected by Western blot.

Results

The CX3CR1 levels were positive correlated with pathological TNM stage, meanwhile a negative correlation between high expression of CX3CR1 and survival rate was found among patients at stageII-III. In our study, overexpression of CX3CR1 promoted migration and invasion ability of SMMC-7721 cells, whereas knockout of CX3CR1 inhibited these abilities of HepG2 cells. Mechanistically, CX3CR1 regulates the metastasis of HCC cells via PI3K/AKT pathway, and the PI3K inhibitor LY294002 could stop the promoting effect of CX3CR1 on SMMC-7721 cells.

Conclusion

CX3CR1 regulated HCC cell metastasis via PI3K/AKT signaling and this effect might be a new target for clinical diagnosis and treatment.
Anti-PD-1 antibody decreases tumour-infiltrating regulatory T cells
Authors: Yoshida Kazushige , Okamoto Masanori , Sasaki Jun , Kuroda Chika , Ishida Haruka , Ueda Katsuya , Ideta Hirokazu , Kamanaka Takayuki , Sobajima Atsushi , Takizawa Takashi , Tanaka Manabu , Aoki Kaoru , Uemura Takeshi , Kato Hiroyuki , Haniu Hisao , Saito Naoto 
Published: August 2019

Abstract
Background: There are many types of therapies for cancer. In these days, immunotherapies, especially immune checkpoint inhibitors, are focused on. Though many types of immune checkpoint inhibitors are there, the difference of effect and its mechanism are unclear. Some reports suggest the response rate of anti-PD-1 antibody is superior to that of anti-PD-L1 antibody and could potentially produce different mechanisms of action. On the other hand, Treg also express PD-1; however, their relationship remains unclear. Methods: In this study, we used osteosarcoma cell lines in vitro and osteosarcoma mouse model in vivo. In vitro, we analyzed the effect of IFNγ for expression of PD-L1 on the surface of cell lines by flowcytometry. In vivo, murine osteosarcoma cell line LM8 was subcutaneously transplanted into the dorsum of mice. Mouse anti-PD-1 antibody was intraperitoneally administered. we analysed the effect for survival of anti-PD-1 antibody and proportion of T cells in the tumor by Flowcytometry. Results: We discovered that IFNγ increased PD-L1 expression on the surface of osteosarcoma cell lines. In assessing the relationship between anti-PD-1 antibody and Treg, we discovered the administration of anti-PD-1 antibody suppresses increases in tumour volume and prolongs overall survival time. In the tumor microenvironment, we found that the administration of anti-PD-1 antibody decreased Treg within the tumour and increased tumour-infiltrating lymphocytes. Conclusions: Here we clarify for the first time an additional mechanism of anti-tumour effect—as exerted by anti-PD-1 antibody decreasing Treg— we anticipate that our findings will lead to the development of new methods for cancer treatment.
keywords: PD-1, Treg, osteosarcoma, anti-PD-1 antibody.
Effects of cordycepin, gold nanostar and their combination on endometrial cancer cells
Authors: Fong Pedro , Cheong Chicheng , Mak Kawai , Lei Chicheng , Ho Manhei , Ao Chengngok , Meng Lirong 
Published: August 2019

Abstract
Background: The incidence rate of endometrial cancer has increased significantly in the past two decades. The current chemotherapy of endometrial cancer can cause intolerable side effects. Recently, both cordycepin and gold nanostars have demonstrated the ability to inhibit the growth and differentiation of cancers. The aim of this study was to investigate the anti-endometrial cancer effects of cordycepin, gold nanostars and the combination of two.
Methods: The gold nanostars were made by seed-mediated reduction, and their morphology was confirmed by laser particle size analysis, spectrophotometry and electron microscopy. MTT cytotoxicity assays, clonogenic assays and flow cytometry were employed to evaluate the inhibition rate, survival fraction and apoptosis in HEC-1A cells under different concentrations of cordycepin, Au NS and their combination. Results: This study revealed that both cordycepin and Au NS with 808 nm light exposure could inhibit cell proliferation, cause cell apoptosis, and inhibit clone ability of endometrial cancer cells. The combined Au NS-cordycepin solution produced greater anti-cancer effects than each treatment alone.
Conclusion: This study supports further investigations into Au NS-cordycepin in the development of new treatments for endometrial cancer.
A battery of self-screening instruments and self-reported body frame could not detect eating disorders among college students
Authors: Hayakawa Norika , Tanaka Satoshi , Hirata Naoko , Ogino Sachiko , Ozaki Norio 
Published: August 2019

Abstract
Objective

Although studies have shown inconsistent results in terms of prevalence of eating disorders, the Eating Attitudes Test (EAT-26) was used to screen students for abnormal eating behaviors. The results of the self-reported EAT-26 and body frame, as well as the efficacy of using self-administered questionnaires (SAQs) were examined to detect eating disorders in new college students.Results

An anonymous questionnaire (EAT-26) was provided to 7738 new students; 4552 (58.8%) responders were included in the final analysis. Semi-structured interviews were conducted for 131 (1.7%) students. Among them, 6 students showed a high EAT-26 score, but were not diagnosed with an eating disorder based on the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). Three students were diagnosed with an eating disorder using SCID-I, but their EAT-26 scores were below the threshold. From these results, in a non-clinical population, findings on EAT-26 do not agree with those on SCID-I in terms of the diagnosis of eating disorders, and this battery is not appropriate for detecting eating disorders.
Road crash by public transport: Analysis from a bus accident case in Benin in 2019
Authors: AHANHANZO Yolaine GLELE , Daddah Donatien , Kpozèhouen Alphonse , Santos Bella Hounkpè Dos , Quenum Kisito , Bato Michael , Levêque Alain 
Published: August 2019

Abstract
Objective : Although public transport is not the highest contributor to road crashes in Benin, the morbidity and mortality associated with such accidents are very high. The work aimed to analyze a road crash involving an intercity bus that occurred on February 23, 2019 in Benin. Results : Mortality rate was 21.2%. The median age of patients admitted to the hospital was 36 years (27-45). The primary areas affected by the accident were the cephalic pole (51%) and more than 20% had a high injury severity score. The main risk factor contributing to the accident was speeding. Wearing a seatbelt was a factor found to impact the severity of the injuries endured. In order to implement intervention aimed at prevention, there needs to be sufficient research to identify the most pressing risk factors involved in accidents occurring on public transportation.
The Effect of Pro-Inflammatory Conditions on Neutrophil Rolling Adhesion
Authors: Taverner Keith , Murad Yousif , Yasunaga Adam , Furrer Christine , Little Jonathan , Li Isaac TS 
Published: August 2019

Abstract
Objective: Type 2 diabetes mellitus (T2D) is the result of a dysregulation of insulin concentrations and signaling, leading to an increase in both glucose concentration and proinflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α. Previous work showed that T2D patients exhibited immune dysfunction associated with increased adhesion molecule expression on endothelial cell surfaces, accompanied by decreased neutrophil rolling velocity on the endothelial cell surface. Changes in cell rolling adhesion have direct vascular and immune complications such as atherosclerosis and decreased healing time seen in T2D patients. While previous studies focused primarily on how endothelial cells affect neutrophil rolling under T2D conditions, little is known on changes to neutrophils that affect their rolling. In this study, we aim to show how the rolling behaviour of neutrophils are affected by T2D conditions on a controlled substrate. Results: We found that neutrophils cultured in T2D-serum mimicking media showed an increase in cell rolling velocity compared to neutrophils under normal conditions. Specifically, glucose alone is responsible for higher rolling velocity. While cytokines further increase the rolling velocity, they also reduce the cell size. It is likely that both glucose and cytokines reduce the PSGL-1 expression level on neutrophils.
Reliability and correlation of mixture cell correction in methylomic and transcriptomic blood data
Authors: Chaumette Boris , Kebir Oussama , Dion Patrick A. , Rouleau Guy A. , Krebs Marie-Odile 
Published: August 2019

Abstract
Objectives: DNA methylome and RNA transcriptome studies are growing, but investigators have to consider the cell type composition of tissues used. In blood samples, for instance, data reflect picture of mixture of cells. Specialized algorithms address the cell-type heterogeneity issue. We tested if the estimation of cell type composition in the blood are correlated between two heterogeneous datasets.
Results: We used methylome and transcriptome datasets obtained from a cohort of ten individuals whose blood were sampled at two different timepoints and examined how the cell composition derived from these omics correlated with each other using “CIBERSORT” for transcriptome and “EstimateCellCounts function” for the methylome. The correlation coefficients between the two omic datasets range from 0.45 to 0.81. There was minimal correlation between the two timepoints using the same algorithm. Our results suggest that a posteriori corrections of a mixture of cells present in blood samples are reliable. Using an omic dataset to correct a second dataset for relative fractions of cells seems to be appropriate, but only when the samples are simultaneously collected. Such approach could be beneficial when there are difficulties to control the cell types in the second dataset, even when the sample size is limited.