bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of alpha thalassemia on clinical and laboratory parameters among nigerian children with sickle cell anemia
Authors: Olatunya Oladele S. , Albuquerque Dulcineia M. , Adekile Adekunle , Costa Fernando F. 
Published: August 2018

BackgroundThere is paucity of data on the influence of alpha thalassemia on the clinical and laboratory parameters among Nigerian sickle cell anemia (SCA) patients. This study aimed to determine the prevalence of alpha thalassemia and the influence of alpha thalassemia on laboratory parameters and clinical manifestations in a group of young NigerianSCApatients.MethodsThis was a cross‐sectional retrospective study conducted on 100 patients withSCAand 63 controls. The diagnosis ofSCAwas confirmed byDNAstudies. Alpha thalassemia genotyping was performed by multiplex gap‐PCRmethod. Laboratory parameters including complete blood count, hemoglobin quantitation, serum lactate dehydrogenase (LDH), and bilirubin were determined with standard techniques.ResultsAlpha thalassemia was found in 41 (41.0%) patients compared to 24 (38.1%) controls (P = 0.744), and all were due to the 3.7 κb α‐globin gene deletions. Alpha thalassemia was associated with more frequent bone pain crisis, higher hemoglobin concentration, red blood cell count, and HbA2level among the patients. On the contrary, patients with alpha thalassemia had lower mean corpuscular volume, mean corpuscular hemoglobin, and white blood cell count (WBC) (P ˂ 0.05). There were 6 (6.0%) patients with leg ulcers, and none of them had alpha thalassemia,P = 0.04.ConclusionThis study confirms that coexistence of alpha thalassemia withSCAsignificantly influences both the clinical and laboratory manifestations of young NigerianSCApatients. The coexistence of this genetic modifier is associated with increased bone pain crisis and protects against sickle leg ulcers among the patients.
Norepinephrine stimulation downregulates the β2‐adrenergic receptor–nitric oxide pathway in human pulmonary artery endothelial cells
Authors: Yu Wande , Gu Yue , Chen PeiP , Luo Jie , Liu Pengfei , Chao Yuelin , Chen Shao‐Liang , Zhang Hang 
Published: August 2018

BackgroundNorepinephrine (NE)‐mediated vasoconstriction plays an important role in pulmonary hypertension associated with left heart disease (PH‐LHD). However, the role of NE‐mediated endothelial cell dysfunction in the pathogenesis of PH‐LHD remains to be elucidated.Methods and ResultsAn enzyme‐linked immunosorbent assay showed that the NE concentration in the plasma of patients with PH‐LHD was higher and the nitrate–nitrite concentration was lower than those in the control group. NE treatment decreased phospho‐Ser633‐eNOS and β2‐adrenergic receptor (β2‐AR) levels in the membrane of human pulmonary artery endothelial cells (HPAECs) analysed by western blot analysis. Consistently, fluorescence microscopy and flow cytometry showed that nitric oxide (NO) production was also decreased in HPAECs. Coimmunoprecipitation confirmed a direct interaction between β2‐AR and endothelial NO synthase (eNOS). Overexpression of β2‐AR attenuated the decline in phospho‐Ser633‐eNOS and NO production. Additionally, the expression of phospho‐Ser633‐eNOS and β2‐AR was decreased in human pulmonary artery endothelium. Finally, our results indicate that NE stimulated HPAEC proliferation, which was blocked by protein kinase A inhibitor or protein kinase B (PKB–AKT) inhibitor.ConclusionsThese data provide a novel mechanism for NE‐decreased endothelium‐derived NO and NE‐induced HPAEC proliferation that leads to PH‐LHD, suggesting a potential therapeutic target for PH‐LHD.
Insulin promotes macrophage phenotype transition through PI3K/Akt and PPAR‐γ signaling during diabetic wound healing
Authors: Yu Tianyi , Gao Min , Yang Peilang , Liu Dan , Wang Di , Song Fei , Zhang Xiong , Liu Yan 
Published: August 2018

AbstractOveractivation and persistent chronic inflammation are the major pathogenic characteristics of diabetic‐impaired healing, and diabetic wound healing can be promoted by stimulating the transition of macrophage phenotype from pro‐inflammatory (M1) to anti‐inflammatory (M2). Our previous studies found that the application of insulin induced an advanced initiation and resolution of inflammatory response. To further explore the mechanism, we have investigated the effect of insulin on macrophage phenotype switch utilizing a diabetic rat model and a human monocytic THP‐1 cell. We have utilized the high glucose (HG) and HG plus insulin to stimulate the M1 macrophages derived from lipopolysaccharide‐treated THP‐1 cells. We studied the secretion of inflammatory mediator and related signaling pathways by using western blot test, immunofluorescence, and Rac1 pull‐down assay. We have found that the production of pro‐inflammatory mediators, which thereafter induced macrophage polarization toward M1 phenotype, has been elevated due to consistent HG exposure. HG plus insulin stimulation, on the other hand, promoted anti‐inflammatory effects. Experiments performed on diabetic burn wounds indicated that the insulin modulated macrophages transition from M1 to M2 phenotype. We found that PI3K/Akt/Rac‐1 and PPAR‐γ signaling pathways are involved in the anti‐inflammatory effect of insulin. Insulin inhibited HG‐induced activation of p38, NF‐κB, and STAT1 transcriptional activity by activating Akt‐Rac‐1 signaling. Moreover, insulin performs anti‐inflammatory effects through upregulation of PPAR‐γ expression and induced P38‐mediated dephosphorylation of PPAR‐γ (Ser112). In conclusion, insulin downregulates inflammatory response, regulates M1 macrophage transition in response to HG, and thus improves chronic wound healing.
Emerging role of SIRT3 in endothelial metabolism, angiogenesis, and cardiovascular disease
Authors: He Xiaochen , Zeng Heng , Chen Jian‐Xiong 
Published: August 2018

AbstractSirtuin 3 (SIRT3) a mitochondrial enzyme that plays an important role in energy homeostasis, cardiac remodeling, and heart failure (HF). The expression of SIRT3 declines with advanced age, cardiovascular, and metabolic diseases. Accumulating evidence suggests that SIRT3 plays a critical role in protecting the heart from cardiac hypertrophy, cardiac dysfunction associated with HF, and in the protection of cardiac cells from stress‐mediated cell death. Clinical studies have demonstrated that HF with preserved ejection fraction (HFpEF) in patients present with abnormalities in coronary microcirculation related to endothelial dysfunction and coronary microvascular rarefaction. Although SIRT3‐mediated regulation of mitochondrial homeostasis and heart function has been intensively investigated, the effect of SIRT3 on endothelial cell (EC) glycolytic metabolism and microvascular function has not been well studied. ECs utilize glycolysis for generating ATP rather than oxidative phosphorylation to maintain their normal functions and promote angiogenesis and EC–cardiomyocyte interactions. Emerging evidence indicates that SIRT3 is involved in the regulation of endothelial metabolism and angiogenesis and thus affects the development of cardiovascular diseases associated with aging. This review will discuss the current knowledge of SIRT3 and its functional role on endothelial metabolism, cardiac function, and cardiovascular diseases.
The mechanical and pharmacological regulation of glioblastoma cell migration in 3D matrices
Authors: Kaphle Pranita , Li Yongchao , Yao Li 
Published: August 2018

AbstractThe invasion of glioblastoma is a complex process based on the interactions of tumor cells and the extracellular matrix. Tumors that are engineered using biomaterials are more physiologically relevant than a two‐dimensional (2D) cell culture system. Matrix metalloproteinases and the plasminogen activator generated by tumor cells regulate a tumor’s invasive behavior. In this study, microtumors were fabricated by encapsulating U87 glioma cells in Type I collagen and then glioma cell migration in the collagen hydrogels was investigated. Crosslinking of collagen with 8S‐StarPEG increased the hydrogel viscosity and reduced the tumor cell migration speed in the hydrogels. The higher migration speed corresponded to the increased gene expression of MMP‐2, MMP‐9, urokinase plasminogen activator (uPA), and tissue plasminogen activator (tPA) in glioma cells grown in non‐crosslinked collagen hydrogels. Inhibitors of these molecules hindered U87 and A172 cell migration in collagen hydrogels. Aprotinin and tranexamic acid did not inhibit U87 and A172 migration on the culture dish. This study demonstrated the differential effect of pharmacologic molecules on tumor cell motility in either a 2D or three‐dimensional culture environment.
Prevalence of rheumatoid cachexia in rheumatoid arthritis: a systematic review and meta‐analysis
Authors: Santo Rafaela C.E. , Fernandes Kevin Z. , Lora Priscila S. , Filippin Lidiane I. , Xavier Ricardo M. 
Published: August 2018

AbstractBackgroundLow muscle mass occurs in patients with rheumatoid arthritis without weight loss; this condition is referred as rheumatoid cachexia. The aim of the current study was to perform a systematic review with meta‐analysis to determine the rheumatoid cachexia prevalence.MethodsA systematic review with meta‐analysis of observational studies published in English, between 1994 and 2016, was conducted using MEDLINE (via PubMed) and other relevant sources. Search strategies were based on pre‐defined keywords and medical subject headings. The methodological quality of included studies was assessed using the Newcastle‐Ottawa Scale. Meta‐analysis was used to estimate the prevalence, and because studies reported different methods and criteria to estimate body composition and prevalence of rheumatoid cachexia, subgroup analyses were performed. Meta‐regression adjusted for the 28‐joint disease activity score and disease duration (years) was performed (significance level at P ≤ 0.05).ResultsOf 136 full articles (one duplicate publication) screened for inclusion in the study, eight were included. The estimated overall prevalence of rheumatoid cachexia was 19% [95% confidence interval (CI) 07–33%]. This prevalence was 29% (95% CI 15–46%) when body composition was measured by dual‐energy X‐ray absorptiometry. When the diagnostic criteria were fat‐free mass index below the 10th percentile and fat mass index above the 25th percentile, rheumatoid cachexia prevalence was 32% (95% CI 14–52%). The 28‐joint disease activity score and disease duration had no influence on the estimated prevalence of rheumatoid cachexia (P > 0.05). Most studies were rated as having moderate methodological quality.ConclusionsMeta‐analysis showed a prevalence of rheumatoid cachexia of 15‐32%, according to different criteria, demonstrating that this condition is a frequent comorbidity of rheumatoid arthritis. To better understand its clinical impact, more studies using standardized definitions and prospective evaluations are urgently needed.
Spleen and liver stiffness for noninvasive assessment of portal hypertension in cirrhotic patients with large esophageal varices
Authors: Tseng Yujen , Li Feng , Wang Jian , Chen Shiyao , Jiang Wei , Shen Xizhong , Wu Shengdi 
Published: August 2018

PurposeNoninvasive evaluation of portal hypertension is needed for cirrhotic patients with large esophageal varices. This study was aimed at assessing the diagnostic value of liver/spleen stiffness in predicting hepatic vein pressure gradient (HVPG) in this special population.MethodsIn the present prospective cohort study, liver/spleen stiffness was measured by transient elastography. Patients also underwent HVPG assessment, upper gastrointestinal endoscopy, and other noninvasive serum models.ResultsNinety‐nine cirrhotic patients with large esophageal varices were enrolled. Liver/spleen stiffness strongly correlated with HVPG. In regards to significant portal hypertension, area under receiver operating characteristic curves (AUROCs) for liver/spleen stiffness were 0.74 and 0.91. Accuracy for detecting significant portal hypertension was 79% for spleen stiffness of 48.9 kPa (sensitivity: 76%, specificity: 100%, positive predictive value: 100%, negative predictive value: 38%) and 75% for liver stiffness of 16.0 kPa (sensitivity: 78%, specificity: 54%, positive predictive value: 92%, negative predictive value: 27%). Similarly, spleen stiffness had significant higher AUROCs for predicting HVPG ≥16 and ≥20 mm Hg than that of liver stiffness and other noninvasive serum models.ConclusionIn cirrhotic patients with large esophageal varices, liver stiffness and spleen stiffness correlate with HVPG, and spleen stiffness is superior to liver stiffness in predicting portal hypertension.
Comparison of the Diagnostic Performance of Synthetic Versus Acquired High b‐Value (1500 s/mm2) Diffusion‐Weighted MRI in Women With Breast Cancers
Authors: Park Jung Hyun , Yun Bo La , Jang Mijung , Ahn Hye Shin , Kim Sun Mi , Lee Soo Hyun , Kang Eunyoung , Kim Eun‐Kyu , Park So Yeon 
Published: August 2018

BackgroundAcquired high b‐value (>1000 s/mm2) diffusion‐weighted imaging (DWI) has its strength in lesion detection. However, it is not easily used, due to a lower signal‐to‐noise ratio, eddy current distortions, and prolonged acquisition times. Synthetic DWI does not have these disadvantages because it is based on indirect acquisition, calculated in a voxel‐wise manner.PurposeTo compare the diagnostic performance of synthetic and acquired high b‐value (1500 s/mm2) DWI in women with breast cancer.Study TypeRetrospective.PopulationA total of 108 patients (median age 49 years [range 32–77]) with 133 breast cancers.Field Strength/Sequence3T, echo‐planar imaging.AssessmentThree radiologists independently reviewed image sets of both synthetic (S‐b1500) and acquired (A‐b1500) high b‐value DWI. Malignancy confidence of the lesion was scored using a 6‐point Likert‐type scale.Statistical TestJack‐knife alternative free‐response receiver‐operating characteristic 1 (JAFROC1) analysis was used. Sensitivity and positive predictive value (PPV) were compared using generalized estimating equations. An independent t‐test was used to compare the confidence. An intraclass correlation coefficient was calculated to compare interobserver agreement.ResultsThe JAFROC1 figures of merit values were 0.816 and 0.808 in S‐b1500 and A‐b1500, respectively, with no statistically significant difference (P = 0.637). Sensitivity was higher in synthetic than in A‐b1500 for readers 2 (P = 0.015) and 3 (P = 0.037). Although sensitivity was higher in S‐b1500 than in A‐b1500 for reader 1, the difference was not significant (P = 0.487). The PPV of S‐b1500 was not significantly different from that of A‐b1500 (P = 0.397). The malignancy confidence of true‐positive tumors was higher in S‐b1500 than in A‐b1500 (P = 0.013). Interobserver agreement was good for both sequences.Data ConclusionsThe synthetic high b‐value DWI may improve the diagnostic sensitivity for breast cancer detection without affecting PPV compared with acquired high b‐value DWI.Level of Evidence: 3Technical Efficacy: Stage 2J. Magn. Reson. Imaging 2019;49:857–863.
Role of phenol red in the stabilization of the Sabin type 2 inactivated polio vaccine at various pH values
Authors: Huijuan Yang , Xiaohu Dai , Ze Liu , Wei Cai , Jian Zhou , Lei Ma , Shaohui Song , Weidong Li , Guoyang Liao 
Published: August 2018

AbstractTo analyze the effects of phenol red at various pH values on the Sabin type 2 inactivated polio vaccine (sIPV2), several biophysical techniques were used to evaluate the particle size and capsid protein for conformation. sIPV2’s size was assessed via transmission electron microscopy and dynamic light scattering. The effects of various pH values (from 4.0 to 7.0) on the biophysical characters of sIPV2 particles in solution were determined by dynamic light scattering and zeta potential. The results clearly indicated that aggregation and instability occurred in the solution of sIPV2 particles at a pH of 6.0. Under similar conditions, by dynamic light scattering and zeta potential, the virus particles in solution showed more dispersion and were stable with the addition of 0.05 mM phenol red. According to circular dichroism and intrinsic tryptophan fluorescence data, it was observed that the secondary and tertiary structures of the sIPV2 particles were more stable with the protection of phenol red. At a pH below 6.0, the sIPV2 solution with phenol red had more D‐antigen content, which was confirmed by enzyme‐linked immunosorbent assay and rat experiments. These results strongly suggested that phenol red improved the pH stability of the sIPV2. The study indicated the potential of phenol red in preserving vaccine potency of the sIPV2 at various pH values.
Predictors of appropriate ICD therapy in Japanese patients with structural heart diseases: A major role of prior sustained ventricular tachycardia in secondary prevention
Authors: Nagahara Daigo , Fujito Takefumi , Mochizuki Atsushi , Shimoshige Shinya , Hashimoto Akiyoshi , Miura Tetsuji 
Published: August 2018

AbstractBackgroundImplantable cardioverter defibrillator (ICD) and cardiac resynchronization with a defibrillator (CRT‐D) are established therapies for secondary prevention of sudden cardiac death (SCD) in patients with structural heart disease (SHD), but the rates of subsequent ICD/CRT‐D therapy widely differ among patients with SHD. The aim of this study was to determine clinical factors associated with appropriate therapy for preventing SCD in patients with SHD.MethodsWe enrolled 147 patients with SHD (mean age, 59 ± 15 years; mean ejection fraction [EF], 45 ± 15%) who underwent ICD/CRT‐D implantation for secondary prevention of SCD (ischemic heart disease, n = 50; nonischemic heart disease, n = 97). ICD/CRT‐D was implanted for aborted cardiopulmonary arrest (CPA, n = 65) or sustained ventricular tachycardia (VT, n = 82).ResultsDuring a follow‐up period of 3.2 ± 3.6 years, 79 of the 147 patients had appropriate ICD/CRT‐D therapies. A Kaplan‐Meier survival curve showed that the rate of appropriate therapy was 54% at 5‐year follow‐up. Prior sustained VT, lower EF, and use of a class I antiarrhythmic drug were significantly more frequent in patients with appropriate therapy. In multivariate analysis, prior sustained VT (hazard ratio, 2.8; 95% CI, 1.60‐4.46; P = .001) was the only independent predictor for appropriate ICD/CRT‐D therapy. Kaplan‐Meier survival curves showed that rates of appropriate therapy during a 5‐year follow‐up period were 70% and 34% in patients with sustained VT and those with CPA, respectively (P = .001).ConclusionsIn SHD patients implanted with an ICD/CRT‐D, prior sustained VT as an indication of ICD/CRT‐D implantation, but not EF or an antiarrhythmic drug, predicts a high rate of appropriate therapy.
Abnormal loading of the hip and knee joints in unilateral hip osteoarthritis persists two years after total hip replacement
Authors: Stief Felix , Schmidt André , van Drongelen Stefan , Lenarz Katharina , Froemel Dara , Tarhan Timur , Lutz Frederick , Meurer Andrea 
Published: August 2018

ABSTRACTA total hip replacement (THR) is a common and routine procedure to reduce pain and restore normal activity. Gait analysis can provide insights into functional characteristics and dynamic joint loading situation not identifiable by clinical examination or static radiographic measures. The present prospective longitudinal study tested whether 2 years after surgery a THR would restore dynamic loading of the knee and hip joints in the frontal plane to normal. Instrumented gait analysis was performed shortly before surgery and approximately 2 years after THR on 15 unilateral hip osteoarthritis (OA) patients. 15 asymptomatic matched individuals were recruited as healthy controls. Results showed that abnormal joint loading persisted 2 years after THR. The 2nd external knee adduction moment in terminal stance in the affected (−34%, p = 0.002, d = 1.22) and non‐affected limb (−25%, p = 0.035, d = 0.81) was lower compared to controls and thus indicated a shift in the knee joint load distribution from medial to lateral. A correlation analysis revealed that a smaller hip range of motion explained 46% of 2nd knee adduction moment alterations. In contrast, the 2nd external hip adduction moment in terminal stance was postoperatively higher in the affected (+22%, p = 0.007, d = 1.04) and non‐affected limb (+22%, p = 0.005, d = 1.05). Here, 51% of 2nd hip adduction moment alterations can be explained with a greater hip adduction angle. Patients with a THR may therefore be at higher risk for abnormal joint loading and thus for the development of OA in other joints of the lower extremities. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2167–2177, 2018.
Macrophage‐derived inflammatory cytokines regulate growth factors and pain‐related molecules in mice with intervertebral disc injury
Authors: Miyagi Masayuki , Uchida Kentaro , Takano Shotaro , Fujimaki Hisako , Aikawa Jun , Sekiguchi Hiroyuki , Nagura Naoshige , Ohtori Seiji , Inoue Gen , Takaso Masashi 
Published: August 2018

ABSTRACTUpregulation of inflammatory cytokines and various growth factors is a significant contributor to discogenic low back pain. The aim of this study was to investigate possible regulation of pain‐related molecules by macrophages and the role of macrophage‐derived molecules in injured intervertebral disc (IVD)s. C57BL/6J mice were used in this study. We characterized the expression profiles of genes for tumor necrosis factor (TNF)‐alpha, interleukin (IL)‐1beta, nerve growth factor (NGF), and vascular endothelial growth factor (VEGF) in both intact and injured IVDs. We examined whether macrophage depletion, induced by systemic injection of clodronate‐laden liposomes, affected the expression of these molecules in injured IVDs. The effect of TNF‐alpha on cultured F4/80‐CD11b‐cells in injured IVDs was investigated. Expression of TNF‐alpha and IL‐1beta was significantly increased in injured IVDs, but decreased by macrophage depletion. Expression of NGF and VEGF was also significantly increased, but by contrast was not decreased by macrophage depletion. TNF‐alpha treatment of F4/80‐cells from injured IVDs upregulated NGF, VEGF, cyclooxygenase (COX)‐2, and microsomal prostaglandin E synthase‐1 (mPGES1). IVD injury upregulated inflammatory cytokines and various growth factors. Macrophages in the injured IVDs produced inflammatory cytokines, but not growth factors. Macrophage‐derived inflammatory cytokines regulate growth factors and pain‐related molecules. These findings demonstrate further complexity in the pathogenesis of discogenic pain. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2274–2279, 2018.