bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined features based on MT1-MMP expression, CD11b + immunocytes density and LNR predict clinical outcomes of gastric cancer
Authors: Peng Chun-Wei , Wang Lin-Wei , Fang Min , Yang Gui-Fang , Li Yan , Pang Dai-Wen 
Published: June 2013

Abstract

Background
Given the complexity of tumor microenvironment, no single marker from cancer cells could adequately predict the clinical outcomes of gastric cancer (GC). The objective of this study was to evaluate the prognostic role of combined features including conventional pathology, proteinase and immune data in GC.

Methods
In addition to pathological studies, immunohistochemistry was used to assess membrane-type 1 matrix metalloproteinase (MT1-MMP) expression and CD11b + immunocytes density in three independent GC tissue microarrays containing 184 GC tissues. Separate and combined features were evaluated for their impact on overall survival (OS).

Results
We found that traditional factors including tumor size, histological grade, lymph node status, serosa invasion and TNM stage were associated with OS (P < 0.05 for all). Moreover, statistically significant differences in OS were found among lymph node ratio (LNR) subgroups (P < 0.001), MT1-MMP subgroups (P = 0.015), and CD11b + immunocytes density subgroups (P = 0.031). Most importantly, combined feature (MT1-MMP positive, low CD11b + immunocytes density and high LNR) was found by multivariate analysis to be an independent prognostic factors for OS after excluding other confounding factors (HR = 3.818 [95%CI: 2.223-6.557], P < 0.001). In addition, this combined feature had better performance in predicting clinical outcomes after surgery long before recurrence had occurred (Area under the curve: 0.689 [95%CI: 0.609-0.768], P < 0.001).

Conclusions
These findings indicate that better information on GC prognosis could be obtained from combined clinico-pathological factors, tumor cells and the tumor microenvironment.
The altered expression profile of microRNAs in cardiopulmonary bypass canine models and the effects of mir-499 on myocardial ischemic reperfusion injury
Authors: Qin Han , Chen Guang-xian , Liang Meng-ya , Rong Jian , Yao Jian-ping , Liu Hai , Wu Zhong-kai 
Published: June 2013

Abstract

Background
MicroRNAs were enrolled in various cardiovascular disease especially ischemic heart diseases, but the microRNA changes during myocardial ischemia reperfusion injury underwent cardiopulmonary bypass are still unknown. This study screens the microRNA differences in CPB canines and evaluates the relationship of microRNAs with myocardial ischemia reperfusion injury.

Methods
13 healthy canines received CPB with 60 minutes of aortic clamping and cardioplegic arrest, followed by 90 minutes reperfusion. Left ventricular myocardial samples, blood samples and hemodynamic data were taken at different time points. We performed microRNAs microarray experiments upon the left ventricle myocardium tissue of canines before CPB and after reperfusion for 90 minutes by pooling 3 tissue samples together and used qRT-PCR for confirmation.

Results
Statistically significant difference was found in mir-499 level before CPB and after reperfusion (T1 vs. T4, p = 0.041). We further examined the mir-499 levels by using qRT-PCR in all 13 canines at 4 different time points (T1 vs. T4, p = 0.029). Mir-499 expression was negatively correlated with cardiac troponin T (cTnT) and creatine kinase- MB (CK-MB) levels of canines in all time points samples (r = 0.469, p < 0.001 and r = 0.273, p = 0.050 respectively). Moreover, higher mir-499 expression level was associated with higher dP/dtmax at 25 minutes and 90 minutes after reperfusion.

Conclusion
Myocardial ischemic reperfusion injury with cardiopulmonary bypass results in declining level of mir-499 expression in left ventricle myocardium of canines, suggesting mir-499 would be a potential therapeutic target in cardiac protection during open heart surgery.
DNA damage strength modulates a bimodal switch of p53 dynamics for cell-fate control
Authors: Chen Xi , Chen Jia , Gan Siting , Guan Huaji , Zhou Yuan , Ouyang Qi , Shi Jue 
Published: June 2013

Abstract

Background
The p53 pathway is differentially activated in response to distinct DNA damage, leading to alternative phenotypic outcomes in mammalian cells. Recent evidence suggests that p53 expression dynamics play an important role in the differential regulation of cell fate, but questions remain as to how p53 dynamics and the subsequent cellular response are modulated by variable DNA damage.

Results
We identified a novel, bimodal switch of p53 dynamics modulated by DNA-damage strength that is crucial for cell-fate control. After low DNA damage, p53 underwent periodic pulsing and cells entered cell-cycle arrest. After high DNA damage, p53 underwent a strong monotonic increase and cells activated apoptosis. We found that the damage dose-dependent bimodal switch was due to differential Mdm2 upregulation, which controlled the alternative cell fates mainly by modulating the induction level and pro-apoptotic activities of p53.

Conclusions
Our findings not only uncover a new mode of regulation for p53 dynamics and cell fate, but also suggest that p53 oscillation may function as a suppressor, maintaining a low level of p53 induction and pro-apoptotic activities so as to render cell-cycle arrest that allows damage repair.
Impaired toll-like receptor 8 signaling in multiple sclerosis
Authors: Johnson Tory P , Tyagi Richa , Patel Karan , Schiess Nicoline , Calabresi Peter A , Nath Avindra 
Published: June 2013

AbstractBackgroundThe etiology and immunopathology of multiple sclerosis (MS) is not well understood. It is recognized that although autoreactive T cells are the main early mediators of disease, other cell types, including cells of the innate immune system contribute to MS pathogenesis. The objective of this study was to determine if Toll-like receptor (TLR) signaling is functionally altered in patients with MS.FindingsPeripheral blood mononuclear cells from healthy donors and patients with relapsing remitting MS were stimulated with specific agonists of TLRs 3, 7, 8 and 9. Using quantitative polymerase chain reaction transcript levels of tumor necrosis factor-α, interferon-α and interleukin (IL)-12β were quantified from patients with MS and healthy donors. TLR8-induced production ofIL12Btranscripts and protein was functionally impaired in patients with MS as compared to healthy controls (P<0.05 andP<0.005, respectively). Patients with MS also expressed lower baseline levels of TLR8 as compared to healthy controls (P<0.05).ConclusionsTLR8 expression and signaling is impaired in peripheral blood mononuclear cells from patients with MS. This finding suggests that loss of TLR8 signaling may be contributing to autoimmune processes in MS.
Multi-scale agent-based modeling on melanoma and its related angiogenesis analysis
Authors: Wang Jun , Zhang Le , Jing Chenyang , Ye Gang , Wu Hulin , Miao Hongyu , Wu Yukun , Zhou Xiaobo 
Published: June 2013

Abstract

Background
Recently, melanoma has become the most malignant and commonly occurring skin cancer. Melanoma is not only the major source (75%) of deaths related to skin cancer, but also it is hard to be treated by the conventional drugs. Recent research indicated that angiogenesis is an important factor for tumor initiation, expansion, and response to therapy. Thus, we proposed a novel multi-scale agent-based computational model that integrates the angiogenesis into tumor growth to study the response of melanoma cancer under combined drug treatment.

Results
Our multi-scale agent-based model can simulate the melanoma tumor growth with angiogenesis under combined drug treatment. The significant synergistic effects between drug Dox and drug Sunitinib demonstrated the clinical potential to interrupt the communication between melanoma cells and its related vasculatures. Also, the sensitivity analysis of the model revealed that diffusivity related to the micro-vasculatures around tumor tissues closely correlated with the spread, oscillation and destruction of the tumor.

Conclusions
Simulation results showed that the 3D model can represent key features of melanoma growth, angiogenesis, and its related micro-environment. The model can help cancer researchers understand the melanoma developmental mechanism. Drug synergism analysis suggested that interrupting the communications between melanoma cells and the related vasculatures can significantly increase the drug efficacy against tumor cells.
Quinolone prophylaxis for the prevention of BK virus infection in kidney transplantation: study protocol for a randomized controlled trial
Authors: Humar Atul , Gill John , Johnston Olwyn , Fergusson Dean , House Andrew A , Lebel Louise , Cockfield Sandra , Kim S Joseph , Zaltzman Jeff , Cantarovich Marcelo , Karpinski Martin , Ramsay Tim , Knoll Greg A 
Published: June 2013

AbstractBackgroundBK virus infection has emerged as a major complication in kidney transplantation leading to a significant reduction in graft survival. There are currently no proven strategies to prevent or treat BK virus infection. Quinolone antibiotics, such as levofloxacin, have demonstrated activity against BK virus. We hypothesize that administration of a quinolone antibiotic, when given early post-transplantation, will prevent the establishment of BK viral replication in the urine and thus prevent systemic BK virus infection.Methods/designThe aim of this pilot trial is to assess the efficacy, safety and feasibility of a 3-month course of levofloxacin in the kidney transplant population. This is a multicenter, randomized, double-blind, placebo-controlled trial with two parallel arms conducted in 11 Canadian kidney transplant centers. A total of 154 patients with end-stage renal disease undergoing kidney transplantation will be randomized to receive a 3-month course of levofloxacin or placebo starting in the early post-transplant period. Levofloxacin will be administered at 500 mg po daily with dose adjustments based on kidney function. The primary outcome will be the time to occurrence of BK viruria within the first year post-transplantation. Secondary outcomes include BK viremia, measures of safety (adverse events, resistant infections,Clostridium difficile-associated diarrhea), measures of feasibility (proportion of transplanted patients recruited into the trial), proportion of patients adherent to the protocol, patient drop-out and loss to follow-up,and use of quinolone antibiotics outside of the trial protocol.DiscussionResults from this pilot study will provide vital information to design and conduct a large, multicenter trial to determine if quinolone therapy decreases clinically meaningful outcomes in kidney transplantation. If levofloxacin significantly reduces BK viruria and urine viral loads in kidney transplantation, it will provide important justification to progress to the larger trial. If the full trial shows that levofloxacin significantly reduces BK infection and improves outcomes, its use in kidney transplantation will be strongly endorsed given the lack of proven therapies for this condition.Trial registrationThis trial was funded by the Canadian Institutes of Health Research (grant number:222493) and is registered at ClinicalTrials.gov (NCT01353339).
Reduced expression of miR-22 in gastric cancer is related to clinicopathologic characteristics or patient prognosis
Authors: Wang Weibin , Li Fujun , Zhang Yong , Tu Yanyang , Yang Qi , Gao Xingchun 
Published: June 2013

Abstract

Objective
Involvements of microRNA-22 (miR-22) in cancer development have attracted much attention, but its role in tumorigenesis of gastric cancer is still largely unknown. Therefore, the aim of this study was to investigate the expression patterns and clinical implications of miR-22 in gastric cancer.

Methods
Quantitative RT-PCR was performed to evaluate the expression levels of miR-22 in 98 pairs of gastric cancer and normal adjacent mucosa.

Results
Compared with normal adjacent mucosa, miR-22 expression was significantly downregulated in gastric cancer tissues (P < 0.001). Of 98 patients with gastric cancer, 58 (59.2%) were placed in the low miR-22 expression group and 40 (40.8%) were placed in the high miR-22 expression group. In addition, tumors with low miR-22 expression had greater extent of lymph node metastasis (P = 0.02) and distant metastasis (P = 0.01), and were at a worse stage (P = 0.01) than the tumors with high miR-22 expression. Moreover, the gastric cancer patients with low miR-22 expression had shorter overall survival than those with high miR-22 expression (P = 0.03). MiR-22, determined by multivariate analysis, was an independent prognostic factor for patients with gastric cancer.

Conclusion
Our data offer the convincing evidence that the reduced expression of miR-22 was significantly associated with malignant development of gastric cancer and may be a novel prognostic marker of this disease. miR-22 might have potentials in the application of cancer therapy for patients with gastric cancer.
Nurr1 regulates Top IIβ and functions in axon genesis of mesencephalic dopaminergic neurons
Authors: Heng Xin , Jin Gang , Zhang Xin , Yang Dehuang , Zhu Mingzhe , Fu Shijun , Li Xuping , Le Weidong 
Published: June 2013

AbstractBackgroundNURR1 (also named as NR4A2) is a member of the steroid/thyroid hormone receptor family, which can bind to DNA and modulate expression of target genes. Previous studies have shown that NURR1 is essential for the nigral dopaminergic neuron phenotype and function maintenance, and the defects of the gene are possibly associated with Parkinson's disease (PD).ResultsIn this study, we used new bornNurr1knock-out mice combined with Affymetrix genechip technology and real time polymerase chain reaction (PCR) to identifyNurr1regulated genes, which led to the discovery of several transcripts differentially expressed in the nigro-striatal pathway ofNurr1knock-out mice. We found that an axon genesis gene calledTopoisomerase IIβ(Top IIβ) was down-regulated inNurr1knock-out mice and we identified two functional NURR1 binding sites in the proximalTop IIβpromoter. While inTop IIβnull mice, we saw a significant loss of dopaminergic neurons in the substantial nigra and lack of neurites along the nigro-striatal pathway. Using specific TOP II antagonist ICRF-193 orTop IIβsiRNA in the primary cultures of ventral mesencephalic (VM) neurons, we documented that suppression of TOP IIβ expression resulted in VM neurites shortening and growth cones collapsing. Furthermore, microinjection of ICRF-193 into the mouse medial forebrain bundle (MFB) led to the loss of nigro-striatal projection.ConclusionTaken together, our findings suggest thatTop IIβmight be a down-stream target ofNurr1, which might influence the processes of axon genesis in dopaminergic neurons via the regulation of TOP IIβ expression. TheNurr1-Top IIβinteraction may shed light on the pathologic role ofNurr1defect in the nigro-striatal pathway deficiency associated with PD.
American tegumentary leishmaniasis caused by Leishmania (Viannia) braziliensis: assessment of parasite genetic variability at intra- and inter-patient levels
Authors: Oliveira Fernanda S , Valete-Rosalino Cláudia M , Pacheco Sandro JB , Costa Filipe A Carvalho , Schubach Armando O , Pacheco Raquel S 
Published: June 2013

AbstractBackgroundThe genetic variability ofLeishmania(Viannia)braziliensiswas assessed at intra and interpatient levels of individuals with different clinical manifestations of American tegumentary leishmaniasis (ATL).MethodsFifty-two samples, of which 13 originated from cutaneous lesions and 39 from mucosal lesions, provided by 35 patients, were examined by low-stringency single-specific-primer PCR (LSSP-PCR) and phenetic analysis. Genetic variability ofL. (V.)braziliensis, in kinetoplast DNA (kDNA) signatures, was compared both from different patients and from different lesions of the same patient. Phenetic analysis was performed to evaluate the degree of heterogeneity of the kDNA minicircles. In order to evaluate inter and intrapatientL. (V.)braziliensisgenetic variability, the percentage of shared bands and analysis of the coefficients of similarity were analyzed.ResultsDifferent genetic profiles, representing kDNA signatures of the parasite, were obtained by LSSP-PCR analysis of each sample. Phenetic analysis grouped genetic profiles of different levels of differentiation from more similar to most divergent. The percentage of shared bands at the inter and intrapatient levels was 77% and 89%, respectively. Comparison of the average inter and intrapatient coefficients of similarity and their standard deviations were statistically significant (p < 0.001).ConclusionGenetic variability at the intrapatient level was less pronounced than that between different patients. A conceptual model was proposed to better understand the complexity at both levels.
Astragalus polysaccharide enhances immunity and inhibits H9N2 avian influenza virus in vitro and in vivo
Authors: Kallon Sanpha , Li Xiaorong , Ji Jun , Chen Cuiying , Xi Qianyun , Chang Shuang , Xue Chunyi , Ma Jingyun , Xie Qingmei , Zhang Youngliang 
Published: June 2013

Abstract
This study investigated the humoral immunization of Astragalus polysaccharide (APS) against H9N2 avian influenza virus (H9N2 AIV) infection in chickens.
The effects of APS treatment on H9N2 infection was evaluated by an MTT [3(4, 5-dimethylthiazol-2-yl)-2, 3-diphenyl tetrazolium bromide] assay and analysis of MHC and cytokine mRNA expression. The effect on lymphocyte and serum antibody titers in vivo was also investigated. IL-4, IL-6, IL-10, LITAF, IL-12 and antibody titers to H9N2 AIV were enhanced in the first week after APS treatment. The results indicated that APS treatment reduces H9N2 AIV replication and promotes early humoral immune responses in young chickens.
Peripheral regulatory cells immunophenotyping in Primary Sjögren's Syndrome: a cross-sectional study
Authors: Furuzawa-Carballeda Janette , Hernández-Molina Gabriela , Lima Guadalupe , Rivera-Vicencio Yahaira , Férez-Blando Karen , Llorente Luis 
Published: June 2013

Abstract
Introduction
IL-10--producing B cells, Foxp3-expressing T cells (Tregs) and the IDO-expressing dendritic cells (pDC) are able to modulate inflammatory processes, to induce immunological tolerance and, in turn, to inhibit the pathogenesis of autoimmune disease.
The aim of the study was to characterize and to enumerate peripheral IL-10--producing B cells, Tregs and pDCregs in primary Sjögren's Syndrome (pSS) patients in regard of their clinical and serologic activity.

Methods
Fifty pSS patients and 25 healthy individuals were included in the study. CD19+--expressing peripheral B lymphocytes were purified by positive selection. CD19+/CD24hi/CD38hi/IL-10--producing B cells, CD4+/CD25hi/Foxp3+ and CD8+/CD28-/Foxp3+ Tregs, as well as CCR6+/CD123+/IDO+ DCs, were quantitated by flow cytometry.

Results
Immature/transitional circulating IgA+ IL-10--producing B cells had higher levels in pSS patients versus control group, whereas CD19+/CD38hi/IgG+/IL-10+ cells had lower percentage versus control. Indeed CD19+/CD24hi/CD38hi/CD5+/IL-10+, CD19+/CD24hi/CD38hi/CD10+/IL-10+, CD19+/CD24hi/CD38hi/CD20+/IL-10+, CD19+/CD24hi/CD38hi/CD27-/IL-10+, and CD19+/CD24hi/CD38hi/CXCR7+/IL-10+ cells had higher frequency in clinical inactive pSS patients when compared with control group. Remarkably, only percentages of CD19+/CD24hi/CD38hi/CD10+/IL-10+ and CD19+/CD24hi/CD38hi/CD27-/IL-10+ subsets were increased in pSS serologic inactive versus control group (P < 0.05). The percentage of IDO-expressing pDC cells was higher in pSS patients regardless of their clinical or serologic activity. There were no statistically significant differences in the percentage of CD4+/CD25hi/Foxp3+ Tregs between patient groups versus controls. Nonetheless, a decrease in the frequency of CD8+/CD28-/Foxp3+ Tregs was found in inactive pSS patients versus controls (P < 0.05).

Conclusions
The findings of this exploratory study show that clinical inactive pSS patients have an increased frequency of IL-10--producing B cells and IDO-expressing pDC cells.
Species-specific PAMP recognition by TLR2 and evidence for species-restricted interaction with Dectin-1
Authors: Willcocks Sam , Offord Victoria , Seyfert Hans-Martin , Coffey Tracey J , Werling Dirk 
Published: June 2013

ABSTRACTTLRs mediate recognition of a wide range of microbial products, including LPS, lipoproteins, flagellin, and bacterial DNA, and signaling through TLRs leads to the production of inflammatory mediators. In addition to TLRs, many other surface receptors have been proposed to participate in innate immunity and microbial recognition, and signaling through some of these, for example, C-type lectins, is likely to cooperate with TLR signaling in defining inflammatory responses. In the present study, we examined the importance of the ECD and intracellular TIR domain of boTLR2 and huTLR2 to induce a species-specific response by creating a chimeric TLR2 protein. Our results indicate that the strength of the response to any TLR2 ligand tested was dependent on the extracellular, solenoid structure, but not the intracellular TIR domain. Furthermore, we examined whether the recognition of two PAMPs by Dectin-1, a CLR, depends on the interaction with TLR2 from the same species. TLR2 expression seemed to affect the Dectin-1-dependent production of CXCL8 to β-glucan containing zymosan as well as Listeria monocytogenes. Furthermore, the interaction of Dectin-1 with TLR2 seemed to require that both receptors are from the same species. Our data demonstrate that the differences in the TLR2 response seen between the bovine and human system depend on the ECD of TLR2 and that collaborative recognition of distinct microbial components by different classes of innate-immune receptors is crucial in orchestrating inflammatory responses.
Collaborative stepped care v. care as usual for common mental disorders: 8-month, cluster randomised controlled trial
Authors: Oosterbaan Desiree B. , Verbraak Marc J. P. M. , Terluin Berend , Hoogendoorn Adriaan W. , Peyrot Wouter J. , Muntingh Anna , van Balkom Anton J. L. M. 
Published: June 2013

BackgroundThus far collaborative stepped care (CSC) studies have not incorporated self-help as a first step.AimsTo evaluate the effectiveness of CSC in the treatment of common mental disorders.MethodAn 8-month cluster randomised controlled trial comparing CSC to care as usual (CAU) (Dutch Trial Register identifier NTR1224). The CSC consisted of a stepped care approach guided by a psychiatric nurse in primary care with the addition of antidepressants dependent on the severity of the disorder, followed by cognitive–behavioural therapy in mental healthcare.ResultsTwenty general practitioners (GPs) and 8 psychiatric nurses were randomised to provide CSC or CAU. The GPs recruited 163 patients of whom 85% completed the post-test measurements. At 4-month mid-test CSC was superior to CAU: 74.7% (n = 68) v. 50.8% (n = 31) responders (P = 0.003). At 8-month post-test and 12-month follow-up no significant differences were found as the patients in the CAU group improved as well.ConclusionsTreatment within a CSC model resulted in an earlier treatment response compared with CAU.