Miracle-dz/UniFAR-FTUs huggingface dataset:
Relation Between Coronary Artery Disease, Risk Factors and Intima-Media Thickness of Carotid Artery, Arterial Distensibility, and Stiffness Index

Atherosclerosis is a diffuse process that involves vessel structures. In recent years, the relation of noninvasive parameters such as intima-media thickening (IMT), arterial distensibility (AD), and stiffness index (SI) to cardiovascular diseases has been researched. However, we have not found any study that has included all these parameters. The aim of this study is to examine the relation between the presence of coronary artery disease (CAD) and its risk factors to AD, SI, and IMT, which are the noninvasive predictors of atherosclerotic process in the carotid artery. Included in the study were 180 patients who were diagnosed as having CAD by coronary angiography (those with at least ≥ 30% stenosis in the coronary arteries) and, as a control group, 53 persons who had normal appearing coronary angiographies. IMT, AD, and SI values of all the patients in the study were measured by echo-Doppler imaging (AD formula = 2 × (AoS-AoD)/PP × AoD, SI formula = (SBP/DBP)/([AoS - AoD]/AoD). Significantly increased IMT (0.82 ±0.1, 0.57 ±0.1, p < 0.05), decreased AD (0.25 ±0.9, 0.37 ±0.1, p < 0.05), and increased SI (13 ±4, 8 ±3, p < 0.05) values were detected in the CAD group compared to the control group. A significant correlation was found between IMT and presence of diabetes mellitus (DM), systolic blood pressure, total cholesterol, and presence of plaque in carotids, and age. In the coronary artery disease group there was a significant correlation between AD and age, systolic blood pressure, and HDL cholesterol levels, while there was no significant correlation with plaque development. A significant correlation was also found between stiffness index and systolic blood pressure and age; however, there was no relation between number of involved vessels and IMT, AD, and SI. We found sensitivity, specificity, and positive predictive and negative predictive values for CAD diagnosis to be 70%, 75%, 77%, and 66%, respectively. In CAD cases, according to data in this study, IMT and SI increased while AD decreased, and this was detected by carotid artery Doppler ultrasonography. Therefore, it was concluded that these cheaper, noninvasive, and easily available parameters could be used in early diagnosis of CAD.
Influence of HDL Cholesterol on Preclinical Carotid Atherosclerosis in Familial Hypercholesterolemia

Objective—The effect of risk factors on carotid atherosclerosis in heterozygous familial hypercholesterolemia (FH) is unclear. We evaluated carotid intima-media thickness (IMT) by sonography in relation to classical and emergent risk factors in a large FH cohort. Methods and Results—Risk factors and carotid IMT were assessed in 196 asymptomatic subjects aged ≥25 years fulfilling strict diagnostic criteria for clinical FH who were either undertreated or treatment-naive. Conventional risk factors, but not lipoprotein(a), homocysteine, or apolipoprotein E (apoE) genotypes were univariately related to IMT. Age-adjusted and gender-adjusted IMT increased with increasing low-density lipoprotein (LDL) cholesterol and decreased with increasing high-density lipoprotein (HDL) cholesterol. Compared with a total cholesterol/HDL ratio >5.0, a ratio ≤5.0 was associated with a lower adjusted IMT, with a mean difference of −0. 09 mm (95% confidence interval, −0.13 to −0.04). By multivariate analysis, age, HDL cholesterol (negatively), physical exercise, family history of early-onset coronary heart disease, LDL cholesterol, and leukocyte count, in this order, were independent associations of IMT (r2=0.429, P<0.001). Conclusions—Traditional risk factors account for a sizeable proportion of variation in carotid IMT in FH. Because the HDL cholesterol level and the total cholesterol/HDL ratio are strong predictors of preclinical carotid atherosclerosis, HDL cholesterol-raising strategies should have an important therapeutic role in FH.
C/EBPβ Is Involved in the Amplification of Early Granulocyte Precursors during Candidemia-Induced “Emergency” Granulopoiesis

Granulopoiesis is tightly regulated to meet host demands during both “steady-state” and “emergency” situations, such as infections. The transcription factor CCAAT/enhancer binding protein β (C/EBPβ) plays critical roles in emergency granulopoiesis, but the precise developmental stages in which C/EBPβ is required are unknown. In this study, a novel flow cytometric method was developed that successfully dissected mouse bone marrow cells undergoing granulopoiesis into five distinct subpopulations (#1–5) according to their levels of c-Kit and Ly-6G expression. After the induction of candidemia, rapid mobilization of mature granulocytes and an increase in early granulocyte precursors accompanied by cell cycle acceleration was followed by a gradual increase in granulocytes originating from the immature populations. Upon infection, C/EBPβ was upregulated at the protein level in all the granulopoietic subpopulations. The rapid increase in immature subpopulations #1 and #2 observed in C/EBPβ knockout mice at 1 d postinfection was attenuated. Candidemia-induced cell cycle acceleration and proliferation of hematopoietic stem/progenitors were also impaired. Taken together, these data suggest that C/EBPβ is involved in the efficient amplification of early granulocyte precursors during candidemia-induced emergency granulopoiesis.
Effects of folic acid supplementation on serum homocysteine levels, lipid profiles, and vascular parameters in post-menopausal Korean women with type 2 diabetes mellitus

BACKGROUND/OBJECTIVES Complications of diabetes, such as cardiovascular disease, are associated with increased mortality among type 2 diabetes mellitus patients. Homocysteine has been recently identified as a predictor of cardiovascular disease-related complications in diabetes. We investigated whether or not supplementation with folic acid tablets can lower homocysteine levels and improve parameters related with vascular complications. SUBJECTS/METHODS We conducted a non-randomized 8-week trial involving postmenopausal diabetic women (n = 25) supplemented with 800 µg of folic acid (400 µg twice a day) daily. Subjects' serum levels of folate, homocysteine, and vitamin B12 were measured, along with vascular function and brachial-ankle pulse wave velocity. RESULTS Folic acid supplementation significantly increased serum folate levels (P < 0.0001), reduced homocysteine levels (P < 0.0001), and increased vitamin B12 levels (P = 0.0063). There were significant decreases in low-density lipoprotein cholesterol levels as well as the ratios of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol and total cholesterol to high-density lipoprotein cholesterol. Brachial-ankle pulse wave velocities were not altered by supplementation. Changes in serum vitamin B12 after folic acid supplementation were negatively correlated with changes in brachial-ankle pulse wave velocity. CONCLUSIONS In this study on postmenopausal Korean women with type 2 diabetes mellitus, folic acid supplementation reduced serum homocysteine levels, increased serum folate and vitamin B12 levels, and lowered lipid parameters.
Peroxisomal and Mitochondrial β-Oxidation Pathways Influence the Virulence of the Pathogenic Fungus Cryptococcus neoformans

ABSTRACT An understanding of the connections between metabolism and elaboration of virulence factors during host colonization by the human-pathogenic fungus Cryptococcus neoformans is important for developing antifungal therapies. Lipids are abundant in host tissues, and fungal pathogens in the phylum basidiomycota possess both peroxisomal and mitochondrial β-oxidation pathways to utilize this potential carbon source. In addition, lipids are important signaling molecules in both fungi and mammals. In this report, we demonstrate that defects in the peroxisomal and mitochondrial β-oxidation pathways influence the growth of C. neoformans on fatty acids as well as the virulence of the fungus in a mouse inhalation model of cryptococcosis. Disease attenuation may be due to the cumulative influence of altered carbon source acquisition or processing, interference with secretion, changes in cell wall integrity, and an observed defect in capsule production for the peroxisomal mutant. Altered capsule elaboration in the context of a β-oxidation defect was unexpected but is particularly important because this trait is a major virulence factor for C. neoformans. Additionally, analysis of mutants in the peroxisomal pathway revealed a growth-promoting activity for C. neoformans, and subsequent work identified oleic acid and biotin as candidates for such factors. Overall, this study reveals that β-oxidation influences virulence in C. neoformans by multiple mechanisms that likely include contributions to carbon source acquisition and virulence factor elaboration.
Matrix metalloprotease 16 expression is downregulated by microRNA‐146a in spontaneously differentiating Caco‐2 cells

Cellular differentiation in the gut is vital in maintaining the cellular and functional specialization of the epithelial layer. MicroRNAs (miRNAs) have recently emerged as one of the key players in orchestrating the differentiation process in the gut. Using the spontaneously differentiating Caco‐2 cell line, we observed an increased expression of miR‐146a but not miR‐146b in the course of differentiation. Bioinformatic analyses revealed that the membrane type matrix metalloprotease 16 (MMP16, MT3‐MMP) was a predicted target of miR‐146a and a decrease in the mRNA and protein expression of MMP16 was observed in the course of differentiation. Transfection of a luciferase reporter vector containing the 3′UTR of MMP16 showed decreased luciferase activity due to miR‐146a expression. With forced expression of miR‐146a in undifferentiated Caco‐2 cells, a decrease in the mRNA and protein levels of MMP16 and a lower gelatinase activity in a gelatin zymogram were observed. Additionally, forced expression of miR‐146a in HT‐29 colon cancer cells also resulted in decreased expression of MMP16, along with a decrease in the invasion through Matrigel. Taken together, we have shown here that MMP16 is regulated by miR‐146a in spontaneously differentiated Caco‐2 cells. As MMP16 activates the zymogen of MMP2, which is known to degrade extracellular matrix proteins, the regulation of MMP16 by miR‐146a may account, at least in part, for lower motility of well‐differentiated cells.
Management of respiration in MND/ALS patients: An evidence based review

This systematic review comprises an objective appraisal of the evidence in regard to the management of respiration in patients with motor neuron disease (MND/ALS). Studies were identified through computerised searches of 32 databases. Internet searches of websites of drug companies and MND/ALS research web sites, ‘snow balling’ and hand searches were also employed to locate any unpublished study or other ‘grey literature’ on respiration and MND/ALS. Since management of MND/ALS involves a number of health professionals and care workers, searches were made across multiple disciplines. No time frame was imposed on the search in order to increase the probability of identifying all relevant studies, although there was a final limit of March 2005. Recommendations for patient and carer‐based guidelines for the clinical management of respiration for MND/ALS patients are suggested on the basis of qualitative analyses of the available evidence. However, these recommendations are based on current evidence of best practice, which largely comprises observational research and clinical opinion. There is a clear need for further evidence, in particular randomised and non‐randomised controlled trials on the effects of non‐invasive ventilation and additional larger scale cohort studies on the issues of initial assessment of respiratory symptoms, and management and timing of interventions.
Influence of SENSE on image properties in high‐resolution single‐shot echo‐planar DTI

Limited spatial resolution is a key obstacle to the study of brain white matter structure with diffusion tensor imaging (DTI). In its frequent implementation with single‐excitation spin‐echo echo‐planar sequences, DTI's ability to resolve small structures is strongly restricted by T2 and T 2* decay, B0 inhomogeneity, and limited signal‐to‐noise ratio (SNR). In this work the influence of sensitivity encoding (SENSE) on diffusion‐weighted (DW) image properties is investigated. Computer simulations showed that the PSF becomes narrower with increasing SENSE reduction factors, R, enhancing the intrinsic resolution. After a brief theoretical discussion, we describe the estimation of SNR on a pixel‐by‐pixel basis as a function of R. The mean image SNR behavior is manifold: SENSE is capable of increasing SNR efficiency by reducing the echo time (TE). Each SNR(R) curve reveals a maximum that depends on the amount of partial Fourier encoding used. The overall best SNR efficiency for an eight‐element head coil array and a b‐factor of 1000 s/mm2 is achieved at R = 2.1 and partial Fourier encoding of 60%. In vivo tensor maps of volunteers and a patient, with an in‐plane resolution of 0.78 × 0.78 mm2, are also presented to demonstrate the practical implementation of the parallel approach. Magn Reson Med, 2006. © 2006 Wiley‐Liss, Inc.
Mitigation of Insulin Resistance by Mangiferin in a Rat Model of Fructose-Induced Metabolic Syndrome Is Associated with Modulation of CD36 Redistribution in the Skeletal Muscle

Mangiferin is one of the prominent active components responsible for the antidiabetic property of many traditional herbs, but its underlying mechanisms of action remain unclear. CD36 in skeletal muscle is known to contribute to the etiology of insulin resistance by facilitating fatty acid uptake. This study investigated the effect of mangiferin on insulin resistance. The results showed that treatment of Wistar-Kyoto rats with mangiferin (15 mg/kg, once daily, by oral gavage) for 7 weeks inhibited chronic liquid fructose consumption–induced increases in plasma insulin concentrations at the baseline and during oral glucose tolerance test (OGTT), and the homeostasis model assessment of insulin resistance index. It also suppressed the increases in fasted plasma nonesterified fatty acid (NEFA) concentration and the adipose tissue insulin resistance index. Mechanistically, mangiferin neither affected intakes of fructose and chow, and the increase in epididymal and perirenal fat, nor attenuated fructose-induced hypertension. In contrast, mangiferin attenuated fructose-induced acceleration of plasma NEFA clearance during OGTT, and tended to decrease excessive triglyceride accumulation in gastrocnemius. Immunofluorescence staining and subsequent rating of CD36-expressing fibers in gastrocnemius revealed that mangiferin restored fructose-stimulated sarcolemmal CD36 overexpression and decreased intracellular CD36 distribution. In addition, the effects of mangiferin on the parameters associated with insulin resistance and abnormal fatty acid metabolism were absent in the spontaneously hypertensive rats carrying numerous nonfunctional mutations in the CD36 gene. Thus, these results suggest that mangiferin treatment mitigates insulin resistance in a rat model of fructose-induced metabolic syndrome by modulating sarcolemmal and intracellular CD36 redistribution in the skeletal muscle.
Assessing integrated measurement and evaluation strategies: A case study

This paper presents a case study aimed at understanding and comparing integrated strategies for software measurement and evaluation, considering a strategy as a resource from the assessed entity standpoint. The evaluation focus is on the quality of the capabilities of a measurement and evaluation strategy taking into account three key aspects: i) the conceptual framework, centered on a terminological base, ii) the explicit specification of the process, and iii) the methodological/technological support. We consider a strategy is integrated if to great extent these three capabilities are met simultaneously. In the illustrated case study two strategies i.e. GQM+Strategies (Goal-Question-Metric), and GOCAME (Goal-Oriented Context-Aware Measurement and Evaluation) are evaluated. The given results allowed us the understanding of strengths and weaknesses for both strategies, and planning improvement actions as well.
Reversion of epithelial-mesenchymal transition by a novel agent DZ-50 via IGF binding protein-3 in prostate cancer cells

Dysregulation of transforming growth factor-β1 (TGF-β1) and insulin-like growth factor (IGF) axis has been linked to reactive stroma dynamics in prostate cancer progression. IGF binding protein-3 (IGFBP3) induction is initiated by stroma remodeling and could represent a potential therapeutic target for prostate cancer. In previous studies a lead quinazoline-based Doxazosin® derivative, DZ-50, impaired prostate tumor growth by targeting proteins involved in focal adhesion, anoikis resistance and epithelial-mesenchymal-transition (EMT). This study demonstrates that DZ-50 increased expression of the epithelial marker E-cadherin, and decreased the mesenchymal marker N-cadherin in human prostate cancer cells. In DU-145 cells, the effect of DZ-50 on EMT towards mesenchymal epithelial transition (MET) was inhibited by talin1 overexpression, a focal adhesion regulator promoting anoikis resistance and tumor invasion. DZ-50 treatment of human prostate cancer cells and cancer-associated fibroblasts (CAFs) downregulated IGFBP3 expression at mRNA and protein level. In TGF-β1 responsive LNCaPTβRII, TGF-β1 reversed DZ-50-induced MET by antagonizing the drug-induced decrease of nuclear IGFBP3. Furthermore, co-culture with CAFs promoted prostate cancer epithelial cell invasion, an effect that was significantly inhibited by DZ-50. Our findings demonstrate that the lead compound, DZ-50, inhibited the invasive properties of prostate cancer epithelial cells by targeting IGFBP3 and mediating EMT conversion to MET. This study integrated the mechanisms underlying the effect of DZ-50 and further supported the therapeutic value of this compound in the treatment of advanced metastatic prostate cancer.
Prostate Cancer Education, Detection, and Follow-Up in a Community-Based Multiethnic Cohort of Medically Underserved Men

The Prostate Outreach Project (POP) provided free prostate cancer (PCa) education and early detection to medically underserved communities. POP recruited participants in medically underserved communities. PCa education and detection events occurred in POP locations (static) or natural gathering places (mobile) within the community. PCa education was delivered by video and evaluated using a questionnaire. Screening consisted of serum prostate-specific antigen and digital rectal examination. A navigated follow-up strategy was utilized to provide medical care for participants with abnormal screening examinations (ASE). POP recruited 4,420 men, 62.8% (2,667) were African American (AA). Most participants had a high school education and no prior screening. Fifty-four percent (2,159) were uninsured and 41% (1,811) had no access to a physician. PCa knowledge increased following the educational video. Prostate-specific antigen levels were elevated in 9.8% (436), while 6.9% (233) had an abnormal digital rectal examination. Follow-up among 609 men with ASE was successful in 40% (244), despite a navigated approach. Overall, 3.3% (144) cancers were diagnosed among the POP with AA participants exhibiting a significantly higher incidence. Recruitment, education, and PCa testing among a medically underserved cohort was successful. However, failure to follow through on ASE could contribute to maintaining the disparity in PCa outcomes noted among AAs and the medically underserved if not addressed.
Bis(hydroxyphenyl)methane—bisphenol F—metabolism by the HepG2 human hepatoma cell line and cryopreserved human hepatocytes

Bisphenol F (BPF) is present in the environment and as a contaminant of food. Humans may, therefore, be exposed to BPF, and an assessment of this risk is required. BPF has been shown to have genotoxic and endocrine-disruptor properties in a human hepatoma cell line (HepG2), which is a model system for studies of xenobiotic toxicity. In this study, we investigated the ability of HepG2 cells to biotransform BPF, because metabolism may affect the observed effects of BPF, and we compared this metabolic capacity with that of human hepatocytes. Cells were incubated for 24 hours with [3H]-BPF. The culture medium was then concentrated and its metabolites were isolated by high-performance liquid chromatography and identified by mass spectrometry. BPF was largely metabolized into the corresponding sulfate by the HepG2 cell line. BPF was metabolized into both sulfate and glucuronide by human hepatocytes, but with differences between individuals. The metabolism of BPF in both HepG2 cells and human hepatocytes suggests the existence of a detoxification pathway. Thus, these two cell models differ in metabolic capacity. It is, therefore, very important, when assessing the toxic effects of substances in vitro, to determine, in parallel, the biotransformation capacities of the model used to extrapolate in vivo.
Comparison Study between the Mechanisms of Allergic Asthma Amelioration by a Cysteinyl-Leukotriene Type 1 Receptor Antagonist Montelukast and Methylprednisolone

We investigated the effects of cysteinyl-leukotriene (cysLT) type 1 receptor antagonist montelukast (MK) and compared them with those of methylprednisolone (MP) in an allergic asthma model. Rats sensitized to ovalbumin (OVA) received repeated intratracheal exposure to OVA for up to 3 consecutive days. Pretreatment with MK or MP before OVA exposure inhibited late airway response (LAR) and reduced cellular infiltration into the bronchial submucosa after the triple OVA. The amount of N-acetyl-leukotriene E4 in the bile was significantly reduced by pretreatment with MK or MP, suggesting that both drugs reduced the production of cysLTs in the lungs. In the in vitro study, when the fragments of lungs that had been repeatedly pretreated with MK or MP and exposed to OVA were removed and incubated with OVA, the coaddition of either drug significantly reduced cysLT production. In contrast, the cysLT production following the addition of OVA to the lung fragments that had not received in vivo pretreatment with either drug was inhibited by MK but not by MP. These results indicate that MK and MP inhibit LAR by suppressing the infiltration of inflammatory cells into the bronchial submucosa, thereby inhibiting the production of cysLTs in the lungs, and that MK but not MP may inhibit cysLT production directly. The different effects on cysLT production between the two drugs may provide a rationale for the use of combination therapy with cysLT1 receptor antagonists and steroids for the treatment of asthma.