Miracle-dz/UniFAR-FTUs huggingface dataset:
Dietary fatty acids affect plasma markers of inflammation in healthy men fed controlled diets: a randomized crossover study.

BACKGROUND The effect of individual dietary fatty acids on emerging risk factors for cardiovascular disease that are associated with subclinical inflammation is unknown. OBJECTIVE The goal was to evaluate the role of dietary fat and specific fatty acids, especially trans fatty acids, in altering concentrations of markers of inflammation in humans fed controlled diets. DESIGN In a randomized crossover design, 50 men consumed controlled diets for 5 wk that provided 15% of energy from protein, 39% of energy from fat, and 46% of energy from carbohydrate. Eight percent of fat or fatty acids was replaced across diets with the following: cholesterol, oleic acid, trans fatty acids (TFAs), stearic acid (STE), TFA+STE (4% of energy each), and 12:0-16:0 saturated fatty acids (LMP). RESULTS Fibrinogen concentrations were higher after consumption of the diet enriched in stearic acid than after consumption of the carbohydrate diet. C-reactive protein concentrations were higher after consumption of the TFA diet than after consumption of the carbohydrate diet, but were not significantly different after consumption of the TFA and TFA+STE diets than after consumption of the LMP diet. Interleukin 6 concentrations were lower after consumption of the oleic acid diet than after consumption of the LMP, TFA, and STE diets. E-selectin concentrations were higher after consumption of the TFA diet than after consumption of the carbohydrate diet. Consumption of the TFA but not the TFA+STE diet resulted in higher E-selectin concentrations than did the LMP diet. CONCLUSIONS These data provide evidence that dietary fatty acids can modulate markers of inflammation. Although stearic acid minimally affects LDL cholesterol, it does appear to increase fibrinogen concentrations.
Novel late-onset Alzheimer disease loci variants associate with brain gene expression

Objective: Recent genome-wide association studies (GWAS) of late-onset Alzheimer disease (LOAD) identified 9 novel risk loci. Discovery of functional variants within genes at these loci is required to confirm their role in Alzheimer disease (AD). Single nucleotide polymorphisms that influence gene expression (eSNPs) constitute an important class of functional variants. We therefore investigated the influence of the novel LOAD risk loci on human brain gene expression. Methods: We measured gene expression levels in the cerebellum and temporal cortex of autopsied AD subjects and those with other brain pathologies (∼400 total subjects). To determine whether any of the novel LOAD risk variants are eSNPs, we tested their cis-association with expression of 6 nearby LOAD candidate genes detectable in human brain (ABCA7, BIN1, CLU, MS4A4A, MS4A6A, PICALM) and an additional 13 genes ±100 kb of these SNPs. To identify additional eSNPs that influence brain gene expression levels of the novel candidate LOAD genes, we identified SNPs ±100 kb of their location and tested for cis-associations. Results: CLU rs11136000 (p = 7.81 × 10−4) and MS4A4A rs2304933/rs2304935 (p = 1.48 × 10−4–1.86 × 10−4) significantly influence temporal cortex expression levels of these genes. The LOAD-protective CLU and risky MS4A4A locus alleles associate with higher brain levels of these genes. There are other cis-variants that significantly influence brain expression of CLU and ABCA7 (p = 4.01 × 10−5–9.09 × 10−9), some of which also associate with AD risk (p = 2.64 × 10−2–6.25 × 10−5). Conclusions: CLU and MS4A4A eSNPs may at least partly explain the LOAD risk association at these loci. CLU and ABCA7 may harbor additional strong eSNPs. These results have implications in the search for functional variants at the novel LOAD risk loci.
Association between the Glutathione-S-transferase T1 null genotype and esophageal cancer susceptibility: a meta-analysis involving 11,163 subjects

Background Glutathione-S-Transferase T1 (GSTT1) null genotype has been shown to be associated with the risk of esophageal cancer. However, the results remain inconsistent. Thus a comprehensive meta-analysis was conducted to assess the strength of association between GSTT1 null genotype and the risk of esophageal cancer. Materials and Methods A literature search of PubMed, Embase, China National Knowledge Infrastructure (CNKI) and Wanfang databases up to March 31, 2017 was conducted and 30 eligible articles with 4482 cases and 6681 controls were finally recruited. The strength of correlation between GSTT1 polymorphism and the susceptibility of esophageal cancer was assessed by the crude odds ratios (ORs) with 95% confidence intervals (CIs). Subgroup analyses and sensitivity analyses were performed to further identify the association. Results GSTT1 null genotype significantly increased the risk of esophageal cancer (OR = 1.20; 95% CI 1.04–1.40; P < 0.05). In a subgroup analysis by ethnicity, GSTT1 null genotype was correlated with a significantly increased risk of esophageal cancer among Asians (OR = 1.33; 95% CI 1.12–1.58; P < 0.05), instead of Caucasians or Africans (OR = 0.91; 95% CI 0.65–1.26; P > 0.05 for Caucasians and OR = 1.32; 95% CI 0.98–1.77; P > 0.05 for Africans). In the analysis by histological type, GSTT1 null genotype was correlated with a significantly increased risk of esophageal squamous cell carcinoma (OR = 1.34; 95% CI 1.12–1.61; P < 0.05), particularly among Asians (OR = 1.54; 95% CI 1.30–1.82; P < 0.05), but not among Caucasians or Africans (OR = 0.87; 95% CI 0.48–1.57; P > 0.05 for Caucasians and OR = 1.32; 95% CI 0.98–1.77; P > 0.05 for Africans). In addition, there is no significant correlation between GSTT1 null genotype and the risk of esophageal adenocarcinoma (OR = 0.98; 95% CI 0.71–1.35; P > 0.05). Conclusions Our findings demonstrate that GSTT1 null genotype significantly increases esophageal cancer risk, particularly in Asians.
Exploration of the sequential gene changes in epithelial ovarian cancer induced by carboplatin via microarray analysis

The purpose of the current study was to explore the carboplatin-induced sequential changes in gene expression and screen out key genes, which were associated with effects of carboplatin on epithelial ovarian cancer (EOC). The microarray dataset GSE13525 was downloaded from the Gene Expression Omnibus database, including 6 EOC cell samples separately treated with carboplatin at 24, 30 and 36 h (case group), and 6 samples treated with phosphate-buffered saline at the same time points (control group). A total of 3 sets of differentially expressed genes (DEGs) were respectively identified in case samples at 24, 30 and 36 h compared with the control group via the Limma package, and separately recorded as DEG-24, DEG-30 and DEG-36. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the overlapped DEGs were performed via the Database for Annotation, Visualization and Integrated Discovery. The protein-protein interaction (PPI) network was constructed and analyzed by Cytoscape software. In addition, the survival curves were drawn to illustrate the association between the expression levels of certain critical genes and the prognosis of EOC. A total of 170, 605 and 1043 DEGs were separately obtained in DEG-24 DEG-30 and DEG-36, and 110 overlaps were identified. The overlaps were enriched in 77 GO terms and 3 KEGG pathways. A total of 152 pairs were involved in the PPI network, and the abnormal expression levels (high or low) of c-Jun and cyclin B1 (CCNB1) would reduce the survival time of patients with EOC. The study indicated that c-Jun and CCNB1 may be the prognostic biomarkers of EOC treated with carboplatin, and certain pathways (such as p53 signaling pathway, cell cycle and mitogen-activation protein kinase signaling pathway) may be involved in carboplatin-resistant EOC.
Environment vs. Plant Ontogeny: Arthropod Herbivory Patterns on European Beech Leaves along the Vertical Gradient of Temperate Forests in Central Germany

Environmental and leaf trait effects on herbivory are supposed to vary among different feeding guilds. Herbivores also show variability in their preferences for plant ontogenetic stages. Along the vertical forest gradient, environmental conditions change, and trees represent juvenile and adult individuals in the understorey and canopy, respectively. This study was conducted in ten forests sites in Central Germany for the enrichment of canopy research in temperate forests. Arthropod herbivory of different feeding traces was surveyed on leaves of Fagus sylvatica Linnaeus (European beech; Fagaceae) in three strata. Effects of microclimate, leaf traits, and plant ontogenetic stage were analyzed as determining parameters for herbivory. The highest herbivory was caused by exophagous feeding traces. Herbivore attack levels varied along the vertical forest gradient for most feeding traces with distinct patterns. If differences of herbivory levels were present, they only occurred between juvenile and adult F. sylvatica individuals, but not between the lower and upper canopy. In contrast, differences of microclimate and important leaf traits were present between the lower and upper canopy. In conclusion, the plant ontogenetic stage had a stronger effect on herbivory than microclimate or leaf traits along the vertical forest gradient.
Fracture risk assessment in postmenopausal women with diabetes: comparison between DeFRA and FRAX tools

Abstract This study aimed to compare the performance of Fracture Risk Assessment Tool (FRAX) with that of Derived FRAX (DeFRA) in estimating fracture risk in a cohort of type-2 diabetes mellitus (T2DM) postmenopausal women. One hundred nineteen T2DM postmenopausal women and 118 consecutive healthy postmenopausal women were enrolled. Fracture risk was assessed with FRAX (adjusted or non- for trabecular bone score, TBS) and DeFRA. Bone mineral density (BMD) and TBS were evaluated by dual-energy X-ray absorptiometry (DXA). The outcome was the presence of vertebral/non-vertebral fragility fractures (FFs). T2DM women showed higher spinal BMD T-score (p < .05), but lower TBS (p < .05), than controls. Diabetic patients had higher prevalence of FFs compared to controls (p < .05), but no significant difference were found in the scores of any of the predictor tools. Differently, in the T2DM group, the scores of DeFRA, FRAX and adjusted-FRAX were significantly (p < .01 for all) higher in fractured compared with non-fractured women. DeFRA showed the best discriminative power among all fracture risk predictor tools (area under curves: DeFra: 0.89; adjusted FRAX: 0.80; non-adjusted FRAX: 0.73). In summary, all fracture risk assessment tools appeared to be effective in predicting bone fractures in T2DM postmenopausal women, with DeFRA showing a slightly better diagnostic accuracy.
Control of Thiol-Maleimide Reaction Kinetics in PEG Hydrogel Networks

Michael-type addition reactions are widely used to polymerize biocompatible hydrogels. The thiol-maleimide modality achieves the highest macromer coupling efficiency of the reported Michael-type pairs, but the resulting hydrogel networks are heterogeneous, because polymerization is faster than the individual components can be manually mixed. The reactivity of the thiol dictates the overall reaction speed, which can be slowed in organic solvents and acidic buffers. Since these modifications also reduce the biocompatibility of resulting hydrogels, we investigated a series of biocompatible buffers and crosslinkers to decelerate gelation while maintaining high cell viability. We found that lowering the polymer weight percentage (wt%), buffer concentration, and pH slowed gelation kinetics, but crosslinking with an electronegative peptide was optimal for both kinetics and cell viability. Slowing the speed of polymerization resulted in more uniform hydrogels, both in terms of visual inspection and the diffusion of small molecules through the network. However, reactions that were too slow resulted in non-uniform particle dispersion due to settling, thus there is a trade-off in hydrogel network uniformity versus cell distribution in the hydrogels when using these networks in cell applications.
Energy expenditure and free-living physical activity in black and white women: comparison before and after weight loss.

BACKGROUND The prevalence of obesity is higher in black than in white women. Differences in energy economy and physical activity may contribute to this difference. OBJECTIVE The objective of this study was to compare free-living energy expenditure and physical activity in black and white women before and after weight loss. DESIGN Participants were 18 white and 14 black women with body mass indexes (in kg/m(2)) between 27 and 30. Diet, without exercise, was used to achieve a weight loss of >/=10 kg and a body mass index <25. After 4 wk of energy balance in overweight and normal-weight states, body composition was assessed by using a 4-compartment model, sleeping and resting energy expenditures were assessed by using a chamber calorimeter, physiologic stress of exercise and exercise economy were measured by using standardized exercise tasks, and daily energy expenditure was assessed by using doubly labeled water. RESULTS Weight loss averaged 12.8 kg. Sleeping and resting energy expenditures decreased in proportion to changes in body composition. Weight reduction significantly improved physiologic capacity for exercise in both groups of women, making it easier for them to be physically active. Black women had lower body composition-adjusted energy requirements than did white women-both before and after weight loss-during sleep (9% lower, 519 kJ/d; P < 0.001), at rest (14% lower, 879 kJ/d; P < 0.001), during exercise (6% lower; P < 0. 05), and as a daily total (9% lower, 862 kJ/d; P < 0.06). By contrast, free-living physical activity was similar between the groups. CONCLUSIONS Weight-reduced women had metabolic rates appropriate for their body sizes. Black women had lower resting and nonresting energy requirements in both overweight and normal-weight states than did white women and did not compensate with greater physical activity, potentially predisposing them to greater weight regain.
hMENA is a key regulator in endothelin-1/β-arrestin1–induced invadopodial function and metastatic process

Significance Discovering new targets and novel determinants of metastatic spread is an unmet need in ovarian cancer, which is plagued by high rates of recurrence. Endothelin-1 receptors (ET-1R), belonging to the G-protein–coupled receptor family, represent important targets critically involved in malignant progression. Here we identify a mechanistic link between ET-1R and the actin regulatory protein hMENA/hMENAΔv6 through the specific interaction with the multifunctional protein β-arrestin1 (β-arr1), which initiates signaling cascades as part of the molecular complex crucial for invadopodial maturation and malignant dissemination. Targeting ET-1R by using macitentan, a Food and Drug Administration-approved antipulmonary arterial hypertension drug, can impair the β-arr1–mediated signaling network controlling ovarian cancer progression and therefore represents a therapeutic option for ovarian cancer patients. Aberrant activation of endothelin-1 receptors (ET-1R) elicits pleiotropic effects relevant for tumor progression. The network activated by this receptor might be finely, spatially, and temporarily orchestrated by β-arrestin1 (β-arr1)–driven interactome. Here, we identify hMENA, a member of the actin-regulatory protein ENA/VASP family, as an interacting partner of β-arr1, necessary for invadopodial function downstream of ET-1R in serous ovarian cancer (SOC) progression. ET-1R activation by ET-1 up-regulates expression of hMENA/hMENAΔv6 isoforms through β-arr1, restricted to mesenchymal-like invasive SOC cells. The interaction of β-arr1 with hMENA/hMENAΔv6 triggered by ET-1 leads to activation of RhoC and cortactin, recruitment of membrane type 1-matrix metalloprotease, and invadopodia maturation, thereby enhancing cell plasticity, transendothelial migration, and the resulting spread of invasive cells. The treatment with the ET-1R antagonist macitentan impairs the interaction of β-arr1 with hMENA and inhibits invadopodial maturation and tumor dissemination in SOC orthotopic xenografts. Finally, high ETAR/hMENA/β-arr1 gene expression signature is associated with a poor prognosis in SOC patients. These data define a pivotal function of hMENA/hMENAΔv6 for ET-1/β-arr1–induced invadopodial activity and ovarian cancer progression.
Role of adenosine in the regulation of coronary blood flow in swine at rest and during treadmill exercise.

A pivotal role for adenosine in the regulation of coronary blood flow is still controversial. Consequently, we investigated its role in the regulation of coronary vasomotor tone in swine at rest and during graded treadmill exercise. During exercise, myocardial O2 consumption increased from 167 ± 18 μmol/min at rest to 399 ± 27 μmol/min at 5 km/h ( P ≤ 0.05), which was paralleled by an increase in O2 delivery, so that myocardial O2 extraction (76 ± 1 and 78 ± 1% at rest and 5 km/h, respectively) and coronary venous[Formula: see text] (24.5 ± 1.0 and 22.8 ± 0.3 mmHg at rest and 5 km/h, respectively) remained unchanged. After adenosine receptor blockade with 8-phenyltheophylline (5 mg/kg iv), the relation between myocardial O2consumption and coronary vascular resistance was shifted toward higher resistance, whereas myocardial O2extraction rose to 81 ± 1 and 83 ± 1% at rest and 5 km/h and coronary venous [Formula: see text] fell to 19.2 ± 0.8 and 18.9 ± 0.8 mmHg at rest and 5 km/h, respectively (all P ≤ 0.05). Thus, although adenosine is not mandatory for the exercise-induced coronary vasodilation, it exerts a vasodilator influence on the coronary resistance vessels in swine at rest and during exercise.
Serum 25-hydroxyvitamin D concentrations in girls aged 4-8 y living in the southeastern United States.

BACKGROUND Evidence suggests that adults and adolescents throughout the United States are at risk of poor vitamin D status. However, vitamin D concentrations in young American children have not been assessed. OBJECTIVE The relations between serum 25-hydroxyvitamin D [25(OH)D] and bone were examined in prepubertal girls. DESIGN In the present cross-sectional study, serum 25(OH)D concentration was assessed in 168 prepubertal girls aged 4-8 y living in the southeastern United States with the use of radioimmunoassay. Bone area, bone mineral content, and areal bone mineral density were measured from total body, lumbar spine, proximal femur, and forearm with dual-energy X-ray absorptiometry. Data were analyzed with analysis of variance, analysis of covariance, stepwise multiple regression, and partial correlations. RESULTS The mean (+/-SD) serum 25(OH)D was 93.8 +/- 28.1 nmol/L (range: 31.1-181.4 nmol/L). In a multiple regression analysis, race and season were the strongest predictors of vitamin D status. The black girls had lower mean 25(OH)D values than did the white girls (P < 0.01), and 25(OH)D values were significantly different in the total sample between the seasons (P < 0.001), ranging from 74.4 nmol/L during the winter months to 107 nmol/L during the summer. After adjustment for season, age, race, and body mass index, 25(OH)D values were negatively correlated with forearm bone mineral content (r = -0.18; P = 0.02). CONCLUSIONS Unlike prior reports of adults and adolescents living in the southeastern United States, vitamin D status was adequate in the children of the present study. 25(OH)D concentrations were not positively associated with higher bone mineral.
Alterations in basal nutrient metabolism increase resting energy expenditure in sickle cell disease.

Basal rates of whole body protein, glucose, and lipid metabolism and resting energy expenditure (REE) were measured in eight African-American sickle cell disease (SCD) patients and in six African-American controls. Catheters were placed 1) in an antecubital vein for stable isotope infusion and 2) in a heated hand vein for arterialized venous blood. Breath and blood were collected during the last 30 min of the 2.5-h study, and REE was measured by indirect calorimetry. REE [128 ± 5 vs. 111 ± 1 kJ ⋅ kg fat-free mass (FFM)-1 ⋅ day-1; P < 0.05 vs. controls] was 15% greater in the SCD patients. Whole body protein breakdown (5.0 ± 0.3 vs. 3.8 ± 0.2 mg ⋅ kg FFM-1 ⋅ min-1; P < 0.05 vs. controls) and protein synthesis (4.4 ± 0.3 vs. 3.2 ± 0.2 mg ⋅ kg FFM-1 ⋅ min-1; P< 0.05 vs. controls) were 32 and 38% greater, respectively, in the SCD patients, but whole body amino acid oxidation was similar (0.58 ± 0.03 vs. 0.66 ± 0.03 mg ⋅ kg FFM-1 ⋅ min-1). Measures of whole body glucose and lipid metabolism were not significantly different between the groups. The additional energy required for the greater rates of whole body protein breakdown and synthesis caused by SCD contributes significantly to the observed increase in REE, suggesting that dietary energy and protein requirements are enhanced in SCD patients.
Is percentage body fat differentially related to body mass index in Hispanic Americans, African Americans, and European Americans?

BACKGROUND Limited research has been done to explore differences between ethnic groups, including Hispanic Americans (HAs), in the association between percentage body fat (PBF) and body mass index (BMI; in kg/m(2)); the numbers of HAs are increasing in the US population. OBJECTIVE We investigated whether the relation between PBF and BMI in adult HAs differed from that of African Americans (AAs) and European Americans (EAs). DESIGN We used a multiple regression model in which PBF measured with dual energy X-ray absorptiometry was predicted by the reciprocal of BMI (1/BMI; in m(2)/kg) in a sample of 487 men (n(EA) = 192, n(AA) = 148, and n(HA) = 147) and 933 women (n(EA) = 448, n(AA) = 304, and n(HA) = 181). RESULTS For men, our results showed no significant differences between HAs and EAs, AAs and EAs, or HAs and AAs in the slope of the line relating 1/BMI to PBF. In women, there were significant differences in PBF as predicted by BMI between HAs and EAs (P < 0.002) and AAs and HAs (P = 0.020), but not between AAs and EAs. When PBF was estimated on the basis of predicting equations, the trend of the predicted PBF value in women differed according to ethnic group and BMI category. At a BMI < 30, HAs tended to have more body fat than did EAs and AAs, and at a BMI > 35, EAs tended to have more body fat than did the other groups. CONCLUSIONS Our results show that the relation between PBF and BMI in HA women differs from that of EA and AA women.