[Show abstract][Hide abstract] ABSTRACT: Background and aim: Ursodeoxycholic acid (UDCA) is the standard treatment for primary biliary cirrhosis (PBC), but not all cases respond well. Evidence has shown that combination therapy of UDCA with bezafibrate significantly improved liver function. A meta-analysis was performed to assess the efficacy and safety of UDCA and bezafibrate combination therapy in the treatment of PBC. Results: Nine trials, with a total of 269 patients, were included in the analysis. The bias risk of these trials was high. Compared with UDCA alone, the combination with bezafibrate improved the Mayo risk score (mean difference [MD], 0.60; 95% confidence interval [CI], 0.25-0.95; P=0.0008) and liver biochemistry: alkaline phosphatase (MD, −238.21 IU/L; 95% CI, −280.83 to −195.60; P<0.00001); gamma-glutamyltransferase (MD, −38.23 IU/L; 95% CI, −50.16 to −25.85; P<0.00001); immunoglobulin M (MD, −128.63 IU/L; 95% CI, −151.55 to −105.71; P<0.00001); bilirubin (MD, −0.20 mg/dL; 95% CI, −0.33 to −0.07; P=0.002); triglycerides (MD, −26.84 mg/dL; 95% CI, −36.51 to −17.17; P<0.0001); total cholesterol (MD, −21.58 mg/dL; 95% CI, −30.81 to −12.34; P<0.0001), and serum alanine aminotransferase (MD, −10.24 IU/L; 95% CI, −12.65 to −78.5; P<0.00001). However, combination therapy showed no significant differences in the incidence of all-cause mortality or pruritus, and may have resulted in more adverse events (risk ratio [RR], 0.22; 95% CI, 0.07-0.67; P=0.008). Conclusion: Combination therapy improved liver biochemistry and the prognosis of PBC, but did not improve clinical symptoms or incidence of death. Attention should be paid to adverse events when using bezafibrate.
Drug Design, Development and Therapy 09/2015; 9:5407. DOI:10.2147/DDDT.S92041 · 3.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pharmacologic Relevance. Resveratrol, an antioxidant derived from grapes, has been reported to modulate the inflammatory process. In this study, we investigated the effects of resveratrol and its mechanism of protection on concanavalin-A- (ConA-) induced liver injury in mice. Materials and Methods. Acute autoimmune hepatitis was induced by ConA (20 mg/kg) in Balb/C mice; mice were treated with resveratrol (10, 20, and 30 mg/kg) daily by oral gavage for fourteen days prior to a single intravenous injection of ConA. Eight hours after injection, histologic grading, proinflammatory cytokine levels, and hedgehog pathway activity were determined. Results. After ConA injection, the cytokines IL-2, IL-6, and TNF-α were increased, and Sonic hedgehog (Shh), Glioblastoma- (Gli-) 1, and Patched (Ptc) levels significantly increased. Pretreatment with resveratrol ameliorated the pathologic effects of ConA-induced autoimmune hepatitis and significantly inhibited IL-2, IL-6, TNF-α, Shh, Gli-1, and Ptc. The effects of resveratrol on the hedgehog pathway were studied by western blotting and immunohistochemistry. Resveratrol decreased Shh expression, possibly by inhibiting Shh expression in order to reduce Gli-1 and Ptc expression. Conclusion. Resveratrol protects against ConA-induced autoimmune hepatitis by decreasing cytokines expression in mice. The decreases seen in Gli-1 and Ptc may correlate with the amelioration of hedgehog pathway activity.
Gastroenterology Research and Practice 06/2015; 2015:1-11. DOI:10.1155/2015/506390 · 1.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Hepatic ischemia reperfusion (IR) is an important issue in complex liver resection and liver transplantation. The aim of the present study was to determine the protective effect of astaxanthin (ASX), an antioxidant, on hepatic IR injury via the reactive oxygen species/mitogen-activated protein kinase (ROS/MAPK) pathway.
Mice were randomized into a sham, IR, ASX or IR + ASX group. The mice received ASX at different doses (30 mg/kg or 60 mg/kg) for 14 days. Serum and tissue samples at 2 h, 8 h and 24 h after abdominal surgery were collected to assess alanine aminotransferase (ALT), aspartate aminotransferase (AST), inflammation factors, ROS, and key proteins in the MAPK family.
ASX reduced the release of ROS and cytokines leading to inhibition of apoptosis and autophagy via down-regulation of the activated phosphorylation of related proteins in the MAPK family, such as P38 MAPK, JNK and ERK in this model of hepatic IR injury.
Apoptosis and autophagy caused by hepatic IR injury were inhibited by ASX following a reduction in the release of ROS and inflammatory cytokines, and the relationship between the two may be associated with the inactivation of the MAPK family.
[Show abstract][Hide abstract] ABSTRACT: Background:
Although the effectiveness of treatment with ursodeoxycholic acid (UDCA) and fenofibrate for primary biliary cirrhosis (PBC) has been suggested by small trials, a systematic review to summarize the evidence has not yet been carried out.
A meta-analysis of all long-term randomized controlled trials comparing the combination of UDCA and fenofibrate with UDCA monotherapy was performed via electronic searches.
Six trials, which included 84 patients, were assessed. Combination therapy with UDCA and fenofibrate was more effective than UDCA monotherapy in improving alkaline phosphatase (mean difference [MD]: -90.44 IU/L; 95% confidence interval [CI]: -119.95 to -60.92; P<0.00001), gamma-glutamyl transferase (MD: -61.58 IU/L; 95% CI: -122.80 to -0.35; P=0.05), immunoglobulin M (MD: -38.45 mg/dL; 95% CI: -64.38 to -12.51; P=0.004), and triglycerides (MD: -0.41 mg/dL; 95% CI: -0.82 to -0.01; P=0.05). However, their effects on pruritus (odds ratio [OR]: 0.39; 95% CI: 0.09-1.78; P=0.23), total bilirubin (MD: -0.05 mg/dL; 95% CI: -0.21 to 0.12; P=0.58), and alanine aminotransferase (MD: -3.31 IU/L; 95% CI: -14.60 to 7.97; P=0.56) did not differ significantly. This meta-analysis revealed no significant differences in the incidence of adverse events (OR: 0.21; 95% CI: 0.03-1.25; P=0.09) between patients treated with combination therapy and those treated with monotherapy.
In this meta-analysis, combination therapy with UDCA and fenofibrate was more effective in reducing alkaline phosphatase than UDCA monotherapy, but it did not improve clinical symptoms. There did not appear to be an increase in adverse events with combination therapy.
Drug Design, Development and Therapy 05/2015; 9:2757. DOI:10.2147/DDDT.S79837 · 3.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cancer cells exhibit an altered metabolic phenotype known as the aerobic glycolysis. The expression of HK2 changes the metabolic phenotype of cells to support cancerous growth. In the present study, we investigated the inhibitory effect of resveratrol on HK2 expression and hepatocellular carcinoma (HCC) cell glycolysis. Aerobic glycolysis was observed in four HCC cell lines compared to the normal hepatic cells. Resveratrol sensitized aerobic glycolytic HCC cells to apoptosis, and this effect was attenuated by glycolytic inhibitors. The induction of mitochondrial apoptosis was associated with the decrease of HK2 expression by resveratrol in HCC cells. In addition, resveratrol enhanced sorafenib induced cell growth inhibition in aerobic glycolytic HCC cells. Combination treatment with both reagents inhibited the growth and promoted apoptosis of HCC-bearing mice. The reduction of HK2 by resveratrol provides a new dimension to clinical HCC therapies aimed at preventing disease progression.
[Show abstract][Hide abstract] ABSTRACT: Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and the third leading cause of cancer-related mortality worldwide. Conflicting results have been reported regarding the use of serum Golgi protein 73 (GP73) as a promising serum marker for the diagnosis of HCC; therefore, the aim of the present study was to provide a systematic review of the diagnostic performance of GP73 for HCC. Following a systematic review of the relevant studies, a number of indices associated with the accuracy of the diagnostic performance of GP73, including the sensitivity and specificity, were pooled using Meta Disc 1.4 software. Data were presented as forest plots, and summary receiver operating characteristic (SROC) curve analysis was used to summarize the overall test performance. Eleven studies were included in this meta-analysis. The summary estimates for serum GP73 in diagnosing HCC were as follows: Sensitivity, 77% [95% confidence interval (CI), 75-79%]; specificity, 91% (95% CI, 90-92%); positive likelihood ratio, 4.34 (95% CI, 2.19-8.59); negative likelihood ratio, 0.30 (95% CI, 0.26-0.36) and diagnostic odds ratio, 15.78 (95% CI, 6.95-35.83). The area under the SROC curve was 0.8638, and the Q index was 0.7944. Significant heterogeneity was found. This meta-analysis indicates a moderate diagnostic value of GP73 in HCC; however, further studies with rigorous design, large sample size and multiregional cooperation are required.
Experimental and therapeutic medicine 04/2015; 9(4):1413-1420. DOI:10.3892/etm.2015.2231 · 1.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study was designed to study the protective effects and mechanisms of N-acetylcysteine (NAC) in concanavalin A-induced hepatitis in mice. In this study, pretreatment with NAC ameliorated the histopathological changes and suppressed inflammatory cytokines in ConA-induced hepatitis. The expression of IL-2, IL-6, TNF-α, and IFN-γ was significantly reduced in the NAC-treated groups. NAC activated PI3K/Akt pathway and inhibited the activation of NF-κB. Additionally, NAC reduced autophagosome formation, as assessed by detecting the expression of LC3 and Beclin 1. Our results demonstrate that NAC can alleviate ConA-induced hepatitis by regulating the PI3K/Akt pathway and reducing the late stages of autophagy. Our results described a new pharmaceutical to provide more effective therapies for immune hepatitis.
Mediators of Inflammation 03/2015; 2015:189785. DOI:10.1155/2015/189785 · 3.24 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Astaxanthin, a potent antioxidant, exhibits a wide range of biological activities, including antioxidant, atherosclerosis and antitumor activities. However, its effect on concanavalin A (ConA)-induced autoimmune hepatitis remains unclear. The aim of this study was to investigate the protective effects of astaxanthin on ConA-induced hepatitis in mice, and to elucidate the mechanisms of regulation.
Autoimmune hepatitis was induced in in Balb/C mice using ConA (25 mg/kg), and astaxanthin was orally administered daily at two doses (20 mg/kg and 40 mg/kg) for 14 days before ConA injection. Levels of serum liver enzymes and the histopathology of inflammatory cytokines and other maker proteins were determined at three time points (2, 8 and 24 h). Primary hepatocytes were pretreated with astaxanthin (80 μM) in vitro 24 h before stimulation with TNF-α (10 ng/ml). The apoptosis rate and related protein expression were determined 24 h after the administration of TNF-α.
Astaxanthin attenuated serum liver enzymes and pathological damage by reducing the release of inflammatory factors. It performed anti-apoptotic effects via the descending phosphorylation of Bcl-2 through the down-regulation of the JNK/p-JNK pathway.
This research firstly expounded that astaxanthin reduced immune liver injury in ConA-induced autoimmune hepatitis. The mode of action appears to be downregulation of JNK/p-JNK-mediated apoptosis and autophagy.
PLoS ONE 03/2015; 10(3):e0120440. DOI:10.1371/journal.pone.0120440 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this study, a meta-analysis of randomized controlled trials comparing ursodeoxycholic acid (UDCA) monotherapy with combination therapies utilizing UDCA and budesonide was performed. We found that combination therapy with UDCA and budesonide was more effective than UDCA monotherapy for primary biliary cirrhosis-autoimmune hepatitis overlap syndrome. Moreover, compared to prednisone, budesonide has fewer side effects.
Drug Design, Development and Therapy 01/2015; 9:567. DOI:10.2147/DDDT.S74515 · 3.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the role of probiotics in the standard triple Helicobacter pylori therapy.
In this meta-analysis, we investigated the efficacy of probiotics in a standard triple H. pylori therapy in adults. Searches were mainly conducted in MEDLINE/PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. Fourteen studies met our criteria, and the quality of these studies was assessed using the Jadad scale. We used STATA version 12.0 to extract data and to calculate the odds ratios (ORs), which are presented with the corresponding 95% confidence intervals (CIs). The data are presented as forest plots.
The pooled ORs for the eradication rates calculated by intention-to-treat analysis and per-protocol analysis in the probiotic group vs the control group were 1.67 (95%CI: 1.38-2.02) and 1.68 (95%CI: 1.35-2.08), respectively, using the fixed-effects model. The sensitivity of the Asian studies was greater than that of the Caucasian studies (Asian: OR = 1.78, 95%CI: 1.40-2.26; Caucasian: OR = 1.48, 95%CI: 1.06-2.05). The pooled OR for the incidence of total adverse effects was signiﬁcantly lower in the probiotic group (OR = 0.49, 95%CI: 0.26-0.94), using the random effects model, with significant heterogeneity (I (2) = 85.7%). The incidence of diarrhea was significantly reduced in the probiotic group (OR = 0.21, 95%CI: 0.06-0.74), whereas the incidence of taste disorders, metallic taste, vomiting, nausea, and epigastric pain did not differ significantly between the probiotic group and the control group.
Supplementary probiotic preparations during standard triple H. pylori therapy may improve the eradication rate, particularly in Asian patients, and the incidence of total adverse effects.
World Journal of Gastroenterology 12/2014; 20(47):18013-21. DOI:10.3748/wjg.v20.i47.18013 · 2.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the use of endoscopic ultrasound combined with endoscopic submucosal dissection (ESD) or endoscopic mucosal resection (EMR) for the diagnosis and treatment of protruding gastrointestinal lesions.
Endoscopic and clinicopathological data were available for 158 patients with protruding gastrointestinal lesions who underwent endoscopic ultrasound. We selected for ESD or EMR treatment 138 patients with gastrointestinal protruding lesions that did not reach the muscular layer of the mucosa according to their endoscopic ultrasound findings. We compared the consistency of the diagnoses made with normal gastrocoloscopy, endoscopic ultrasound, and pathology after the ESD or EMR treatment, and evaluated the therapeutic effects of ESD or EMR on protruding gastrointestinal lesions. We also performed follow-ups with gastrocoloscopy and endoscopic ultrasound one, three, and six months after surgery.
Of 158 patients who underwent endoscopic ultrasound, 138 were treated with ESD or EMR. Postoperative oozing of blood occurred in 12 patients and hemorrhage in four patients, and the complication rate was 2.9% (4/138). There were no serious complications. The pathological diagnoses were consistent their endoscopic ultrasound diagnoses, so the accuracy of endoscopic ultrasound was 97.8% (135/138).
Endoscopic ultrasound combined with ESD or EMR can improve the diagnosis of protruding gastrointestinal lesions.
[Show abstract][Hide abstract] ABSTRACT: Background
Hepatic ischemia–reperfusion injury (HIRI) remains a pivotal clinical problem after hemorrhagic shock, transplantation, and some types of toxic hepatic injury. Apoptosis and autophagy play important roles in cell death during HIRI. It is also known that N-acetylcysteine (NAC) has significant pharmacologic effects on HIRI including elimination of reactive oxygen species (ROS) and attenuation of hepatic apoptosis. However, the effects of NAC on HIRI-induced autophagy have not been reported. In this study, we evaluated the effects of NAC on autophagy and apoptosis in HIRI, and explored the possible mechanism involved.
A mouse model of segmental (70%) hepatic warm ischemia was adopted to determine hepatic injury. NAC (150 mg/kg), a hepatoprotection agent, was administered before surgery. We hypothesized that the mechanism of NAC may involve the ROS/JNK/Bcl-2 pathway. We evaluated the expression of JNK, P-JNK, Bcl-2, Beclin 1 and LC3 by western blotting and immunohistochemical staining. Autophagosomes were evaluated by transmission electron microscopy (TEM).
We found that ALT, AST and pathological changes were significantly improved in the NAC group. Western blotting analysis showed that the expression levels of Beclin 1 and LC3 were significantly decreased in NAC-treated mice. In addition, JNK, p-JNK, Bax, TNF-α, NF-κB, IL2, IL6 and levels were also decreased in NAC-treated mice.
NAC can prevent HIRI-induced autophagy and apoptosis by influencing the JNK signal pathway. The mechanism is likely to involve attenuation of JNK and p-JNK via scavenged ROS, an indirect increase in Bcl-2 level, and finally an alteration in the balance of Beclin 1 and Bcl-2.
PLoS ONE 09/2014; 9(9):e108855. DOI:10.1371/journal.pone.0108855 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Hydrogen sulfide (H2S) is known to exert anti-inflammatory properties. Apoptosis and autophagy play important roles in concanavalin A (Con A)-induced acute hepatitis. The purpose of this study was to explore both the effect and mechanism of H2S on Con A-induced acute hepatitis.
BALB/c mice were randomized into sham group, Con A-injection group, and 14 μmol/kg of sodium hydrosulfide (NaHS, an H2S donor) pretreatment group.
Aspartate aminotransferase, alanine aminotransferase, and pathological damage were significantly ameliorated by NaHS pretreatment. NaHS pretreatment significantly reduced the levels of interleukin-6 and tumor necrosis factor-α compared with those of the Con A group. The expression of Bcl-2, Bax, Beclin-1, and LC3-2, which play important roles in the apoptosis and autophagy pathways, were also clearly affected by NaHS. Furthermore, NaHS affected the p-mTOR and p-AKT.
H2S attenuates Con A-induced acute hepatitis by inhibiting apoptosis and autophagy, in part, through activation of the PtdIns3K-AKT1 signaling pathway.
Drug Design, Development and Therapy 09/2014; 8:1277-86. DOI:10.2147/DDDT.S66573 · 3.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recent studies have shown that microRNAs, a class of small and noncoding RNA molecules, play crucial roles in the initiation and progression of pancreatic cancer. In the present study, the expression and roles of miR-191 were investigated. Through both gain-of function and loss-of function experiments, a pro-oncogenic function of miR-191 was demonstrated. At the molecular level, bioinformatic prediction, luciferase, and protein expression analysis suggested that miR-191 could inhibit protein levels of UPS10, which suppressed the proliferation and growth of cancer cells through stabilizing P53 protein. Collectively, these data suggest that miR-191 could promote pancreatic cancer progression through targeting USP10, implicating a novel mechanism for the tumorigenesis.
[Show abstract][Hide abstract] ABSTRACT: Background. There have been many reports on des-γ-carboxy prothrombin (DCP) as a promising serum marker in the diagnosis of hepatocellular carcinoma (HCC); however, the results are inconsistent and even conflicting. Methods. This meta-analysis was performed to investigate the performance of DCP in the diagnosis of HCC. Following a systematic review of relevant studies, Meta-DiSc 1.4 software was used to extract data and to calculate the overall sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). Data are presented as forest plots and summary receiver operating characteristic curve (SROC) analysis was used to summarize the overall test performance. Results. Twelve studies were included in our meta-analysis. The overall sensitivity, specificity, PLR, and NLR of DCP for the detection of HCC in the studies included were 71% (95%CI: 68%-73%), 84% (95%CI: 83%-86%), 6.48 (95%CI: 4.22-9.93), and 0.33 (95%CI: 0.25-0.43), respectively. The area under the SROC curve was 0.8930 and the Q index was 0.8238. Significant heterogeneity was found. Conclusion. This meta-analysis indicated that DCP had moderate diagnostic accuracy in HCC. Further studies with rigorous design, large sample size, and mmultiregional cooperation are needed in the future.
Gastroenterology Research and Practice 08/2014; 2014:529314. DOI:10.1155/2014/529314 · 1.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
More clinically meaningful diagnostic tests are needed in pancreatic cancer (PC). K-ras mutations are the most frequently acquired genetic alteration.
Original research articles involving the diagnostic accuracy of K-ras mutation detection in PC were selected. Data were presented as forest plots and summary receiver operating characteristic (SROC) curve analysis was used to summarize the overall test performance.
We assessed 19 studies from 16 published articles. The reports were divided into three groups according to the process used to obtain the test material. The summary estimates for detecting K-ras status using an invasive method (fine needle aspiration (FNA), endoscopic retrograde cholangiopancreatography (ERCP), or surgery) were better than cytology: the pooled sensitivity was 77% (95% confidence interval (CI): 74-80%) versus 54% (95% CI: 47-61%); specificity was 88% (95% CI: 85-91%) versus 91% (95% CI: 83-96%); and diagnostic odds ratio (DOR) was 20.26 (11.40-36.03) versus 7.52 (95% CI: 2.80-20.18), respectively. When two procedures were combined, the diagnostic accuracy was markedly improved.
The analysis of K-ras mutations in pancreatic tissue has a promising diagnostic significance in PC. Further valuable studies are needed.
[Show abstract][Hide abstract] ABSTRACT: Objective. 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) reduces inflammation and has been identified as an anti-inflammatory prostaglandin in numerous animal models. In this study, we investigated both effects of 15d-PGJ2 and its protection mechanism in concanavalin A- (ConA-) induced autoimmune hepatitis in mice.
Materials and Methods. In vivo, Balb/C mice were injected with ConA (25 mg/kg) to induce acute autoimmune hepatitis, and 15d-PGJ2 (10 μg or 25 μg) was administered 1 h before the ConA injection. The histological grade, proinflammatory cytokine levels, and NF-κB and PPARγ activity were determined 6, 12, and 24 h after the ConA injection. In vitro, LO2 cells and RAW264.7 cells were pretreated with 15d-PGJ2 (2 μM) 1 h before the stimulation with ConA (30 μg/mL). The NF-κB and PPARγ activity were determined 30 min after the ConA administration.
Results. Pretreatment with 15d-PGJ2 reduced the pathological effects of ConA-induced autoimmune hepatitis and significantly reduced the levels of cytokines after injection. 15d-PGJ2 activated PPARγ, blocked the degradation of IκBα, and inhibited the translocation of NF-κB into the nucleus.
Conclusion. These results indicate that 15d-PGJ2 protects against ConA-induced autoimmune hepatitis by reducing proinflammatory cytokines. This reduction in inflammation may correlate with the activation of PPARγ and the reduction in NF-κB activity.
PPAR Research 07/2014; 2014:215631. DOI:10.1155/2014/215631 · 1.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction
Several studies have reported the relationship between the STAT4 rs7574865G > T polymorphism as a susceptibility factor to ulcerative colitis (UC). However, the results have been controversial. Therefore, we conducted this meta-analysis to obtain the most reliable estimate of the association.
Material and methods
PubMed, Embase and Web of Science databases were searched. Crude odds ratios (OR) with 95% confidence intervals (CI) were extracted and pooled to assess the strength of the association between the STAT4 rs7574865G > T polymorphism and risk of UC. A total of five eligible studies including 1532 cases and 3786 controls based on the search criteria were involved in this meta-analysis.
We observed that the STAT4 rs7574865G > T polymorphism was significantly correlated with UC risk when all studies were pooled into the meta-analysis (the allele contrast model: OR = 1.13, 95% CI = 1.02–1.25; the heterozygote codominant model: OR = 1.22, 95% CI = 1.04–1.43; the dominant model: OR = 1.25, 95% CI = 1.07–1.45). In the stratified analysis by ethnicity, significant associations were observed in Spanish for the allele contrast model (OR = 1.20; 95% CI = 1.04–1.39), for the homozygote codominant model (OR = 1.57; 95% CI = 1.07–2.31), for the dominant model (OR = 1.20; 95% CI = 1.01–1.43), and for the recessive model (OR = 1.50; 95% CI = 1.03–2.19).
This meta-analysis suggests that the STAT4 rs7574865G > T polymorphism is a low-penetrant risk factor for UC, especially in Spanish.
Archives of Medical Science 06/2014; 10(3):419-24. DOI:10.5114/aoms.2014.43735 · 2.03 Impact Factor