bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emotional Stress and Tako-Tsubo Cardiomyopathy: Observations on 2 Distinct Clinical Phenotypes
Authors: Yaqub Yasir , Jenkins Leigh A. , Suarez Jose , Sutthiwan Piraon , Phy Michael , Nugent Kenneth M. , Kumar Ashwani 
Published: May 2016

Background Tako-tsubo syndrome is a transient cardiomyopathy usually precipitated by an acute emotional or physiological stress. Our study objectives were to review and analyze the impact of emotional stress on clinical variables, echocardiographic characteristics, and short-term outcomes in patients with tako-tsubo syndrome. Methods Retrospective chart review. Results Eleven patients presented with tako-tsubo syndrome (1 man and 10 women) during the 8-year period (January 2000 to January 2008). The patients were split into 2 groups, defined by presenting either after emotional stress (6/11, 54.5%) or after idiopathic/physical stress (5/11, 45.5%). The mean age was 53.8 (12.6) years. The mean peak troponin T level was 0.54 ng/mL (range, 0.03-2.06 ng/mL), and the mean left ventricular end-diastolic pressure was 15.8 (8.1) mm Hg. Emotional stress was associated with younger age ( P = 0.024), a lower left ventricular end-diastolic pressure ( P < 0.05), more ST segment changes on electrocardiogram (66.7% vs 40%), and a higher ejection fraction ( P = 0.012). The patients in the idiopathic/physical stress group required more frequent hemodynamic support. Conclusions We conclude that clinical, echocardiographic, and outcome characteristics can differentiate tako-tsubo patients presenting with emotional stress from those with idiopathic/physical stress into 2 distinct clinical phenotypes. Clinicians should monitor idiopathic/physically stressed tako-tsubo patients carefully for hemodynamic compromise.
Technical and Policy Approaches to Balancing Patient Privacy and Data Sharing in Clinical and Translational Research
Authors: Malin Bradley , Karp David , Scheuermann Richard H. 
Published: May 2016

Introduction Clinical researchers need to share data to support scientific validation and information reuse and to comply with a host of regulations and directives from funders. Various organizations are constructing informatics resources in the form of centralized databases to ensure reuse of data derived from sponsored research. The widespread use of such open databases is contingent on the protection of patient privacy. Methods We review privacy-related problems associated with data sharing for clinical research from technical and policy perspectives. We investigate existing policies for secondary data sharing and privacy requirements in the context of data derived from research and clinical settings. In particular, we focus on policies specified by the US National Institutes of Health and the Health Insurance Portability and Accountability Act and touch on how these policies are related to current and future use of data stored in public database archives. We address aspects of data privacy and identifiability from a technical, although approachable, perspective and summarize how biomedical databanks can be exploited and seemingly anonymous records can be reidentified using various resources without hacking into secure computer systems. Results We highlight which clinical and translational data features, specified in emerging research models, are potentially vulnerable or exploitable. In the process, we recount a recent privacy-related concern associated with the publication of aggregate statistics from pooled genome-wide association studies that have had a significant impact on the data sharing policies of National Institutes of Health-sponsored databanks. Conclusion Based on our analysis and observations we provide a list of recommendations that cover various technical, legal, and policy mechanisms that open clinical databases can adopt to strengthen data privacy protection as they move toward wider deployment and adoption.
Prostate Cancer, Comorbidity, and Participation in Randomized Controlled Trials of Therapy
Authors: Chao Herta H. , Mayer Tina , Concato John , Rose Michal G. , Uchio Edward , Kelly Wm Kevin 
Published: May 2016

Background Randomized controlled trials (RCTs) evaluate the potential benefits of chemotherapy regimens and guide clinical care for patients with cancer. Inclusion criteria for RCTs are usually stringent and may exclude many patients seen in clinical practice. Our objective was to determine the proportion of men with castrate-resistant prostate cancer (CRPC) in a clinical setting that would have been excluded from major phase 3 RCTs. Methods We reviewed eligibility criteria from 24 phase 3 clinical trials evaluating chemotherapy for CRPC active from January, 2004, through April, 2008. We created a common list of criteria used in at least 3 studies and separately considered the criteria from a prominent RCT (TAX 327). We applied these criteria to a population of patients with CRPC treated during 2004 to 2006 at the Veterans Affairs Connecticut Healthcare System. Results Among 106 patients with CRPC, 99 (93%) had complete medical records, and 45 (45%) of the 99 would have been excluded from RCTs. Common reasons for exclusion were abnormal laboratory values, other malignancies, and other serious medical conditions including cardiac disease. Conclusions Almost half of the CRPC patients examined in a clinical setting would have been ineligible for phase 3 RCTs, highlighting that such trials may not be applicable to general oncology practice.
Erythropoietin Markedly Attenuates Brain Infarct Size and Improves Neurological Function in the Rat
Authors: Yuen Chun-Man , Leu Steve , Lee Fan-Yen , Yen Chia-Hung , Lin Yu-Chun , Chua Sarah , Chung Sheng-Ying , Chai Han-Tan , Sheu Jiunn-Jye , Ko Sheung-Fat , Sun Cheuk-Kwan , Yip Hon-Kan 
Published: May 2016

Background The impact of epoetin beta (recombinant human erythropoietin) on brain infarction area (BIA) and neurological status in a rat model of acute ischemic stroke (IS) induced by distal left internal carotid artery occlusion was investigated. Methods Adult male Sprague-Dawley rats (n = 30) were categorized into group 2 (IS only) and group 3 (IS plus intraperitoneal erythropoietin 5000 IU/kg at 0, 12, and 24 hours after IS). Healthy Sprague-Dawley rats (n = 10) served as group 1. Results Analysis of brain tissues showed larger BIA in group 2 than in group 3 ( P < 0.001). Corner test identified highest frequency of left turn in group 2 ( P < 0.05). The mRNA expressions of Bax, caspase 3, interleukin 18, toll-like receptor 4, and plasminogen activator inhibitor 1 were highest, whereas Bcl-2 was lowest in group 2 ( P < 0.05). Lower CXCR4 and stromal cell-derived factor 1 expressions were noted in group 2 than in group 3 ( P < 0.01). Immunohistofluorescence staining showed lower expressions of CXCR4, stromal cell-derived factor 1, von Willebrand factor, and doublecortin with higher number of apoptotic nuclei in group 2 than in group 3 ( P < 0.001). Immunohistochemical staining demonstrated lower cellular proliferation and number of small vessels with higher glial fibrillary acid protein expression in group 2 than in group 3 ( P < 0.01). Conclusions Erythropoietin significantly limited BIA and improved sensorimotor dysfunction after acute IS.
Cardiac Involvement in Patients with Hematologic Malignancies
Authors: Allegra Alessandro , Alonci Andrea , Russo Sabina , Cannavò Antonino , Penna Giuseppa , D'Angelo Arianna , Bellomo Giacomo , Musolino Caterina 
Published: May 2016

Authors have reviewed literature about the management of patients with cardiologic disease occurring secondary to hematologic pathology itself or its therapy, with a focus on infiltration of myocardium in acute and chronic leukemia, lymphoma, multiple myeloma, and hypereosinophilic syndrome. Moreover, they evaluated chemotherapy-associated toxicity, particularly for new drugs such as monoclonal antibody therapy, tyrosine kinase inhibitors, arsenic trioxide, bortezomib, and epigenetic therapy. In fact, cardiac toxicity may range from asymptomatic subclinical abnormalities, such as electrocardiographic changes and left ventricular ejection decline, to life-threatening events and lead to chemotherapy dose reduction and delay and, in some cases, for patients with severe side effects, discontinuation of treatment. Finally, they discussed on the identification of early markers of cardiac injury and on cardiac stem cell therapy as a promising approach to facilitate myocardial regeneration.
P-Glycoprotein Transporter Expression on A549 Respiratory Epithelial Cells is Positively Correlated with Intracellular Dexamethasone Levels
Authors: Cohen Joanna S. , Benton Angela S. , Nwachukwu Fisayo , Ozedirne Tugba , Teach Stephen J. , Freishtat Robert J. 
Published: May 2016

Background Several mechanisms of glucocorticoid resistance in asthma have been proposed. P-glycoprotein (P-gp), a ubiquitous efflux transport protein, is associated with variability in the disposition of many drugs and interindividual variability in drug treatment response. This study was undertaken to determine the effect of P-gp expression on glucocorticoid efflux from airway epithelial cells. Hypothesis Decreasing respiratory epithelial P-gp expression in dexamethasone-exposed airway epithelial cells in vitro will increase intracellular dexamethasone concentration. Methods A549 lung epithelial cells, transfected with small interfering RNA (siRNA) targeted at messenger RNA for the gene encoding P-gp, were exposed to 100-nM dexamethasone for 15 minutes. Transfection efficiency of siRNA, P-gp expression, and intracellular dexamethasone were measured with flow cytometry. Results Cells transfected with both negative siRNA and siRNA targeted at P-gp exhibited a positive correlation of P-gp expression with intracellular dexamethasone. The mean ± SEM correlation coefficients were 0.78 ± 0.07 for cells transfected with negative siRNA and 0.79 ± 0.08 for cells transfected with siRNA targeted at P-gp. Discussion Contrary to our hypothesis, the positive correlation between P-gp expression and intracellular dexamethasone suggests that P-gp is not a primary transporter of glucocorticoids from airway epithelial cells. Increased P-gp expression is unlikely to be an important mechanism of glucocorticoid resistance in asthma.
C-Reactive Protein in Acute Pulmonary Embolism
Authors: Abul Yasin , Karakurt Sait , Ozben Beste , Toprak Ahmet , Celikel Turgay 
Published: May 2016

Background Right ventricular dysfunction and N-terminal proB-type natriuretic peptide (NT-proBNP) are established determinants of prognosis in acute pulmonary embolism (PE). The aim of the study was to investigate the prognostic value of C-reactive protein (CRP) in PE. Methods Fifty-six patients (mean age, 64.4 ± 14.8years; 22 male subjects) with acute PE were consecutively enrolled and followed for 36 months after discharge. Serum CRP, NT-proBNP, and troponin T levels were determined. Right ventricular function was evaluated by transthoracic echocardiography. Results Right ventricular dysfunction was present in 31 patients and was more frequent in patients with higher CRP and NT-proBNP levels ( P = 0.020 and P = 0.045, respectively). During the 36-month follow-up, there were 15 terminal events (death due to recurrent PE). The mortality rate was 41.2% in patients with NT-proBNP levels greater than 1000 pg/mL, whereas it was 5.9% in patients with less than 500 pg/mL ( P = 0.011). Mortality rates also were higher in patients with elevated CRP and troponin T levels, but the differences did not reach clinical significance. The survival rate of acute PE patients with lower NT-proBNP and CRP levels was better than that of patients with higher NT-proBNP and CRP levels. Receiver operating characteristic curve analysis demonstrated cutoff values for NT-proBNP as 1800 pg/mL (sensitivity, 93.3%; specificity, 68.2%; positive predictive values, 66.7%; and negative predictive values, 93.8%) and for CRP as 48mg/L (sensitivity, 72.7%; specificity, 61.9%; positive predictive values, 50.0%; and negative predictive values, 81.3%) to predict mortality in PE patients. Conclusions C-reactive protein is associated with right ventricular dysfunction, which is a predictor of prognosis in PE and may become a promising biomarker for risk stratification of PE, although CRP is not found superior to NT-proBNP.
Interleukin 6 Promoter Polymorphisms in Normal Han Chinese Population: Frequencies and Effects on Inflammatory Markers
Authors: Pan Min , Gao Shu-Ping , Jiang Min-Hui , Guo Jing , Zheng Jin-Guo , Zhu Jian-Hua 
Published: May 2016

Background Interleukin 6 (IL-6) is a cytokine involved in different physiologic and pathophysiologic processes, and circulating levels of IL-6 differ greatly between individuals, but the results have not always been concordant among diverse populations. The aim of present study was to determine the prevalence of the 3 polymorphisms (−174G/C, −597G/A, and −634C/G) in the IL-6 gene promoter region and their effects on inflammatory markers in normal Han Chinese population. Methods A total of 232 subjects (143 men and 89 women; mean age, 51.37 ± 17.63 years; range, 22-88 years) of unrelated healthy Han Chinese in Jinangsu area (south of China) were enrolled. Genotyping of the 3 polymorphisms were performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis and then confirmed by direct sequencing. Results Among the 232 individuals studied, 231 carried the GG wild type of -174G/C; only 1 carried the GC genotype. For -597G/A polymorphism, individuals all carried the GG wild type; the GA or AA genotypes were not detected. The frequencies of -634C/G genotypes CC, CG, and GG were found to be 59.48%, 37.07%, and 3.45%, respectively, the derived allele frequencies for the C and G alleles were 78.02% and 21.98%. There were no significant differences in age, sex, body mass index, or lipids parameters between the -634 CC and CG+GG genotypes. However, individuals with CC genotype showed lower levels of high-sensitivity C-reactive protein and IL-6 than those with CG+GG genotype. Conclusions IL-6 -174G/C and -597G/A are rare, but -634C/G is common in Han Chinese population, and the -634G allele is associated with circulating levels of IL-6 and C-reactive protein.
Potential of Electron Beam Computed Tomography for Coronary Artery Calcium Screening to Evaluate Fatty Liver: Comparison with 1H Magnetic Resonance Spectroscopy in the Dallas Heart Study
Authors: Matulevicius Susan , Huff Laura C. , Szczepaniak Lidia S. , Ayers Colby R. , Budoff Matthew , McColl Roderick , Khera Amit , Peshock Ronald M. 
Published: May 2016

Objectives Electron beam computed tomography (EBCT) for coronary artery calcification can potentially evaluate liver fat, another marker of cardiovascular risk. We compared quantitative estimates of hepatic steatosis measured by EBCT with those obtained by a well-validated, accurate-measure, magnetic resonance spectroscopy (1H MRS). Methods EBCT and 1H MRS were performed in 2159 subjects from the Dallas Heart Study. Forty subjects were randomly selected from each of 5 subgroups of liver fat percent by 1H MRS (n = 200). EBCT average liver attenuation (HU) was determined in a 1- to 2-cm circular region of interest over the liver lobes. Pearson correlation coefficients were calculated. Using a previously defined 1H MRS hepatic steatosis cut point (>5.5%), an optimized EBCT liver attenuation cut point was determined by receiver operating characteristic analysis. Results 1H MRS liver fat content and EBCT average right lobe liver attenuation were moderately negatively correlated ( r = −0.64, P < 0.0001) in all subjects and in those with 1H MRS hepatic steatosis ( r = −0.71, P < 0.0001). This correlation did not improve with attenuation correction of the EBCT data using a standard calcium phantom or statistical transformation. Using an optimized receiver operating characteristic EBCT cut point (64.5 HU), sensitivity was 78% and specificity was 72% for detecting 1H MRS hepatic steatosis, with a high false negative rate. Risk factors for hepatic steatosis (obesity, diabetes mellitus, insulin resistance, metabolic syndrome) were more strongly correlated with 1H MRS than EBCT liver fat measures. Conclusions Liver attenuation on EBCT acquired for coronary artery calcification screening correlates modestly with 1H MRS measures of liver fat content, with a high false negative rate.
Computational Approaches for Translational Clinical Research in Disease Progression
Authors: McGuire Mary F. , Iyengar Madurai Sriram , Mercer David W. 
Published: May 2016

Today, there is an ever-increasing amount of biological and clinical data available that could be used to enhance a systems-based understanding of disease progression through innovative computational analysis. In this article, we review a selection of published research regarding computational methods, primarily from systems biology, which support translational research from the molecular level to the bedside, with a focus on applications in trauma and critical care. Trauma is the leading cause of mortality in Americans younger than 45 years, and its rapid progression offers both opportunities and challenges for computational analysis of trends in molecular patterns associated with outcomes and therapeutic interventions. This review presents methods and domain-specific examples that may inspire the development of new algorithms and computational methods that use both molecular and clinical data for diagnosis, prognosis, and therapy in disease progression.
Differential Association of Cytochrome P450 3A4 Genotypes with Onsets of Breast Tumors in African American versus Caucasian Patients
Authors: McDaniel D. Olga , Thurber Tonya , Lewis-Traylor Angela , Berry Crystal , Barber William Henry , Zhou Xinchun , Bigler Steven , Vance Ralph 
Published: May 2016

Introduction Malignant breast tumors are often hormone-dependent, and to this end, both estrogen and progesterone receptors are good prognostic markers for evaluation of the outcomes after therapy. In addition, HER-2/neu, whose expression is increasingly being associated with poor prognosis of breast cancer, has predictive potential after immunotherapy. Cytochrome P450 3A4 is highly involved in the metabolism of steroids. Thus, we investigated the impact of CYP 3A4 gene variants in association with clinical outcomes in African American (AFAM) versus Caucasian (CAU) patients with breast cancer diagnosis. Methods Patients who had undergone biopsy procedures for diagnosis or for partial or radical mastectomy were recruited. The CYP 3A4 genotypes (A or G) were detected using polymerase chain reaction amplification and primers designed for a single nucleotide polymorphism. The messenger RNA (mRNA) transcripts were screened by reverse transcription-polymerase chain reaction. Clinical data including tumor staging, pathology grades, and family history were evaluated. Results Frequency of the CYP 3A4-G (mutated variant) was significantly increased in AFAM patients as compared with controls ( P < 0.001). No statistically significant difference was observed between the genotypes comparing the benign versus ductal carcinomas in situ (DCIS) or infiltrating ductal carcinomas (IDCAs). In AFAM patients, GG alleles were increased in IDCA with stage III tumors, and in CAU patients, the AA alleles were increased with stage III tumors. The mRNA expression was reduced in patients with IDCA versus DCIS or benign tumors (benign vs IDCA, P < 0.0009; DCIS vs IDCA, P < 0.005), as well in HER-2/neu-positive tumors versus samples negative for receptors ( P < 0.0024). Conclusions Genotype association was affected by race. Expression levels of total CYP 3A4 mRNA were inversely correlated with clinical diagnosis. This may suggest mRNA testing as an additional tool that accelerates improvement in the diagnosis of the onsets of breast cancer.
Melanoma Antigen Encoding Gene-A3 Expression, Its Clinical Significance, and Its Risk of Developing Acute Myeloid Leukemia
Authors: Makhlouf Manal Mohamed 
Published: May 2016

Background Melanoma antigen encoding gene A3 (MAGE-A3) gene, also called cancer/testis (CT) antigen, is a member of MAGE multigene family, which is located on the long arm of the X chromosome, and its expression can be caused by promoter region demethylation. The MAGE-A3 proteins’ functions are unknown, but they were found to play a role in cell cycle progression, transcriptional regulation, and drug resistance. The aims of this study were to determine the expression of the MAGE-A3 gene in an Egyptian cohort of de novo acute myeloid leukemia (AML) patients and to define its role in the development of AML and its correlation with clinical presentation, laboratory data, as well as treatment outcome. Patients and Methods This study included 40 de novo AML patients as well as 30 age- and sex-matched normal healthy subjects as a control group. They were all subjected to reverse transcription-polymerase chain reaction assay for the detection of MAGE-A3 gene expression. Results Our study revealed that 23 AML patients (57.5%) expressed the MAGE-A3 gene, whereas none of the control group subjects (0%) expressed this gene. It was found that the expression of MAGE-A3 gene was associated with an increased risk of AML (odds ratio = 2.763; 95% confidence interval, 1.890-8.041). Regarding treatment outcome, a highly statistical significant difference was found between MAGE-A3-positive and -negative AML patients with P < 0.001, as the MAGE-A3-positive AML patients had a higher incidence of unfavorable treatment outcome, whereas the MAGE-A3-negative patients had a higher incidence of favorable outcome. This clarifies that the MAGE-A3 gene expression was found to have a significant impact on the risk of treatment failure (odds ratio = 3.591; 95% confidence interval, 1.273-10.462). Conclusions The expression of MAGE-A3 gene may have a clinical relevance and important role as a risk factor in the development of AML. It may be considered as a prognostic marker and may be useful as a predictive test for treatment outcome in AML.
Association between Serum Vitamin B12 Levels and the Degree of Steatosis in Patients with Nonalcoholic Fatty Liver Disease
Authors: Koplay Mustafa , Gulcan Erim , Ozkan Fuat 
Published: May 2016

Purpose A relationship between liver diseases and serum vitamin B12 levels was observed in previous reports. The purpose of this study was to determine if a similar relationship existed between vitamin B12 and nonalcoholic fatty liver disease (NAFLD), a common chronic liver disorder. Materials and Methods A total of 45 consecutive patients with NAFLD formed the NAFLD group, whereas 30 healthy controls (HC) formed the HC group. The subjects in all of the groups were of similar age and body mass index (BMI). A fatty liver is described in 3 ultrasonographic grades. Fasting blood samples were obtained, and serum vitamin B12 levels were measured. In addition, liver enzymes including aspartate aminotransferase, alanine aminotransferase (ALT), and alkaline phosphatase, and folic acid and other serum parameters were evaluated. The Mann-Whitney U test, χ2 test, and Spearman correlation analysis were used to compare the vitamin B12 levels and other serum parameters in both groups. Results The mean ± SD age and BMI of the NAFLD were 47.2 ± 11.2 and 28.8 ± 3.5. The mean ± SD age and BMI of the HC were 47.1 ± 8.8 and 27.7 ± 2.9, respectively. The serum aspartate aminotransferase and ALT levels of the patients with NAFLD were statistically higher compared with those of the controls ( P = 0.001). The levels of vitamin B12 and folate were statistically lower in the NAFLD patients compared with those of the controls ( P < 0.05). We found that there was a reduction of vitamin B12 levels, especially in grade 2 to grade 3 hepatosteatosis. In addition, in the Spearman correlation analysis between the vitamin B12 levels and ALT, the grade of fatty liver and the liver dimension were found to have an important negative correlation. Conclusion The serum vitamin B12 levels were significantly lower in the patients with NAFLD than in those of the control group; however, these still remain in the reference range. Consequently, low vitamin B12 levels may be associated with NAFLD especially in grade 2 to grade 3 hepatosteatosis.