Miracle-dz/UniFAR-FTUs huggingface dataset:
An 18-mo randomized trial of a low-glycemic-index diet and weight change in Brazilian women.

BACKGROUND Despite interest in the glycemic index diets as an approach to weight control, few long-term evaluations are available. OBJECTIVE The objective was to investigate the long-term effect of a low-glycemic-index (LGI) diet compared with that of a high-glycemic-index (HGI) diet; all other dietary components were equal. DESIGN After a 6-wk run-in, we randomly assigned 203 healthy women [body mass index (in kg/m2): 23-30] aged 25-45 y to an LGI or an HGI diet with a small energy restriction. The primary outcome measure was weight change at 18 mo. Secondary outcomes included hunger and fasting insulin and lipids. RESULTS Despite requiring a run-in and the use of multiple incentives, only 60% of the subjects completed the study. The difference in glycemic index between the diets was approximately 35-40 units (40 compared with 79) during all 18 mo of follow-up, and the carbohydrate intake from energy remained at approximately 60% in both groups. The LGI group had a slightly greater weight loss in the first 2 mo of follow-up (-0.72 compared with -0.31 kg), but after 12 mo of follow-up both groups began to regain weight. After 18 mo, the weight change was not significantly different (P = 0.93) between groups (LGI: -0.41 kg; HGI: -0.26 kg). A greater reduction was observed in the LGI diet group for triacylglycerol (difference = -16.4 mg/dL; P = 0.11) and VLDL cholesterol (difference = -3.7 mg/dL; P = 0.03). CONCLUSIONS Long-term weight changes were not significantly different between the HGI and LGI diet groups; therefore, this study does not support a benefit of an LGI diet for weight control. Favorable changes in lipids confirmed previous results.
Long-term effect of varying the source or amount of dietary carbohydrate on postprandial plasma glucose, insulin, triacylglycerol, and free fatty acid concentrations in subjects with impaired glucose tolerance.

BACKGROUND Reducing the glycemic load (GL) is considered beneficial for managing insulin resistance. The GL can be reduced either by reducing carbohydrate intake or by reducing the glycemic index (GI). OBJECTIVE We studied whether these 2 dietary maneuvers have the same long-term effects on postprandial plasma glucose, insulin, triacylglycerol, and free fatty acid (FFA) concentrations in subjects with impaired glucose tolerance (IGT). DESIGN Thirty-four subjects with IGT were randomly assigned to high-carbohydrate, high-GI (high-GI); high-carbohydrate, low-GI (low-GI); and low-carbohydrate, high-monounsaturated fatty acid (MUFA) diets for 4 mo. Plasma glucose, insulin, and FFAs were measured from 0800 to 1600 at baseline in response to high-GI meals (60% carbohydrate, GI = 61, GL = 63) and after 4 mo in response to meals representative of the study diet. RESULTS Carbohydrate intake (% of energy), GI, and GL in the high-GI, low-GI, and MUFA groups (breakfast and lunch meals combined), respectively, were 60%, 61, and 63; 60%, 53, and 55; and 49%, 61, and 52. Compared with the change after 4 mo of the high-GI diet, both the low-GI and MUFA diets reduced 0-8-h mean plasma glucose concentrations by 0.35 mmol/L (P < 0.05). Mean plasma insulin was approximately 20% higher (P < 0.05) and FFAs approximately 12% lower (P < 0.05) after the low-GI diet than after the high-GI diet, with no significant effect of MUFA. Changes in 0-8-h mean plasma triacylglycerols in the 3 treatment groups differed significantly: -0.14, 0.04, and 0.18 mmol/L, respectively, with the high-GI, MUFA, and low-GI diets. CONCLUSIONS In subjects with IGT, reducing the GI of the diet for 4 mo reduced postprandial plasma glucose by the same amount as did reducing carbohydrate intake. The 2 dietary maneuvers had different effects on postprandial plasma insulin, triacylglycerols, and FFAs.
Sensitivity of corneal biomechanical and optical behavior to material parameters using design of experiments method

Abstract The optical performance of the human cornea under intraocular pressure (IOP) is the result of complex material properties and their interactions. The measurement of the numerous material parameters that define this material behavior may be key in the refinement of patient-specific models. The goal of this study was to investigate the relative contribution of these parameters to the biomechanical and optical responses of human cornea predicted by a widely accepted anisotropic hyperelastic finite element model, with regional variations in the alignment of fibers. Design of experiments methods were used to quantify the relative importance of material properties including matrix stiffness, fiber stiffness, fiber nonlinearity and fiber dispersion under physiological IOP. Our sensitivity results showed that corneal apical displacement was influenced nearly evenly by matrix stiffness, fiber stiffness and nonlinearity. However, the variations in corneal optical aberrations (refractive power and spherical aberration) were primarily dependent on the value of the matrix stiffness. The optical aberrations predicted by variations in this material parameter were sufficiently large to predict clinically important changes in retinal image quality. Therefore, well-characterized individual variations in matrix stiffness could be critical in cornea modeling in order to reliably predict optical behavior under different IOPs or after corneal surgery.
Siderophore vaccine conjugates protect against uropathogenic Escherichia coli urinary tract infection

Significance Urinary tract infections (UTIs) are primarily caused by uropathogenic Escherichia coli (UPEC), and 1 in 40 women experience chronic UTIs during their lifetime. The antibiotic courses required to treat infections promote antibiotic resistance, and current vaccine options offer limited protection. We have pioneered a strategy using small iron-chelating compounds called siderophores as vaccine antigens. These siderophores are not produced by commensal bacteria and are required for UTI. The siderophore vaccines reported here are easy to formulate and reduce bacterial burdens in a murine model of UTI. This report highlights the untapped resource of bacteria-specific small molecules as potential vaccine antigens and provides a proof of principle for incorporating these compounds into multicomponent vaccines for the prevention of bacterial infections. Uropathogenic Escherichia coli (UPEC) is the primary cause of uncomplicated urinary tract infections (UTIs). Whereas most infections are isolated cases, 1 in 40 women experience recurrent UTIs. The rise in antibiotic resistance has complicated the management of chronic UTIs and necessitates new preventative strategies. Currently, no UTI vaccines are approved for use in the United States, and the development of a highly effective vaccine remains elusive. Here, we have pursued a strategy for eliciting protective immunity by vaccinating with small molecules required for pathogenesis, rather than proteins or peptides. Small iron-chelating molecules called siderophores were selected as antigens to vaccinate against UTI for this vaccine strategy. These pathogen-associated stealth siderophores evade host immune defenses and enhance bacterial virulence. Previous animal studies revealed that vaccination with siderophore receptor proteins protects against UTI. The poor solubility of these integral outer-membrane proteins in aqueous solutions limits their practical utility. Because their cognate siderophores are water soluble, we hypothesized that these bacterial-derived small molecules are prime vaccine candidates. To test this hypothesis, we immunized mice with siderophores conjugated to an immunogenic carrier protein. The siderophore–protein conjugates elicited an adaptive immune response that targeted bacterial stealth siderophores and protected against UTI. Our study has identified additional antigens suitable for a multicomponent UTI vaccine and highlights the potential use of bacterial-derived small molecules as antigens in vaccine therapies.
Novel methodology allows simultaneous measurement of true phosphorus digestibility and the gastrointestinal endogenous phosphorus outputs in studies with pigs.

Methodology was developed for measuring the gastrointestinal endogenous phosphorus (P) outputs and true P digestibility values in studies with piglets. Four barrows, average initial body weight 6.8 kg, were fitted with a simple T-cannula at the distal ileum and fed four diets according to a 4 x 4 Latin square design. Four cornstarch-based diets containing four levels of P (1.1, 2.1, 3.2 and 4.3 g/kg diet) on a dry matter (DM) basis were formulated from soybean meal (SBM). Each experimental period comprised 8 d with a 4-d adaptation and 4-d collection of ileal digesta and feces. The apparent ileal and fecal P digestibility values in SBM were affected (P < 0.05) by P levels in the assay diets. The ileal and fecal P digestibility values increased from -24.8 to 37.1% and from 18.8 to 42.5%, respectively, as P contents increased from 1.1 to 4.3 g/kg DM diet. Linear relationships (P < 0.05), expressed as g/kg DM diet intake, between ileal and fecal outputs and dietary inputs of P, suggested that the endogenous P outputs can be determined by linear regression analysis. The endogenous P output was higher (P < 0.05) in ileal digesta than in feces (0.86 +/- 0.09 vs. 0.31 +/- 0.06 g/kg DM diet intake). There was no difference (P > 0.05) between the true ileal (50.7 +/- 7.1%) and fecal (48.5 +/- 5.4%) P digestibility values in SBM. These results suggest that differences in P contents between assay diets are primarily responsible for the large variability in apparent P digestibility values reported within the same ingredient. Apparent digestibility values underestimate the true digestive utilization of P by approximately 25%. True rather than apparent P digestibility values should be determined and used in diet formulation for pigs. In addition, this study shows that the gastrointestinal endogenous P output is important in whole-body P requirement and homeostasis.
Genetic variants of PDGF signaling pathway genes predict cutaneous melanoma survival

To investigate whether genetic variants of platelet-derived growth factor (PDGF) signaling pathway genes are associated with survival of cutaneous melanoma (CM) patients, we assessed associations of single-nucleotide polymorphisms in PDGF pathway with melanoma-specific survival in 858 CM patients of M.D. Anderson Cancer Center (MDACC). Additional data of 409 cases from Harvard University were also included for further analysis. We identified 13 SNPs in four genes (COL6A3, NCK2, COL5A1 and PRKCD) with a nominal P < 0.05 and false discovery rate (FDR) < 0.2 in MDACC dataset. Based on linkage disequilibrium, functional prediction and minor allele frequency, a representative SNP in each gene was selected. In the meta-analysis using MDACC and Harvard datasets, there were two SNPs associated with poor survival of CM patients: rs6707820 C>T in NCK2 (HR = 1.87, 95% CI = 1.35-2.59, Pmeta = 1.53E-5); and rs2306574 T>C in PRKCD (HR = 1.73, 95% CI = 1.33-2.24, Pmeta = 4.56E-6). Moreover, CM patients in MDACC with combined risk genotypes of these two loci had markedly poorer survival (HR = 2.47, 95% CI = 1.58-3.84, P < 0.001). Genetic variants of rs6707820 C>T in NCK2 and rs2306574 T>C in PRKCD of the PDGF signaling pathway may be biomarkers for melanoma survival.
On the modelling of electro-viscoelastic response of electrostrictive polyurethane elastomers

Electroactive polymers (EAP) deform under electric fields. This effect in fact generates various new fields of engineering applications of high technological interest. As an advantage, EAP may undergo deformations much larger than those capable by electroactive ceramics—however, to the price of acting at comparatively low forces. As common for polymers, EAP exhibit time-dependent material behaviour. The model proposed in this contribution, on the one hand, captures these electro-viscoelastic effects and, on the other hand, also nicely fits into iterative finite element formulations in order to simulate general boundary value problems. While the deformation itself as well as the electric potential are introduced as global degrees of freedom, the internal variables accounting for the viscous response are incorporated at the so-called local integration point level. Apart form calibrating the model against experimental data, a simple coupled finite element example is studied to show the applicability of the finite deformation electro-viscoelastic formulation proposed.
Dietary choline and betaine assessed by food-frequency questionnaire in relation to plasma total homocysteine concentration in the Framingham Offspring Study.

BACKGROUND Epidemiologic studies of choline and betaine intakes have been sparse because a food-composition database was not available until recently. The physiologic relevance of a variation in dietary choline and betaine in the general population and the validity of intake assessed by food-frequency questionnaire (FFQ) have not been evaluated. OBJECTIVE This study was conducted to examine the physiologic relevance and validity of choline and betaine intakes measured by an FFQ. DESIGN We examined the relations between choline and betaine intakes measured by FFQ and plasma total homocysteine (tHcy) concentrations in 1960 participants from the Framingham Offspring Study. RESULTS Higher intakes of dietary choline and betaine were related to lower tHcy concentrations independent of other determinants, including folate and other B vitamins. For the lowest and highest quintiles of dietary choline plus betaine, the multivariate geometric means for tHcy were 10.9 and 9.9 mumol/L (P for trend < 0.0001). The inverse association was manifested primarily in participants with low folate intakes (P for interaction < 0.0001). Among participants with folate intakes < or =250 microg/d, the geometric mean tHcy concentrations in the lowest and highest quintiles of choline plus betaine intakes were 12.4 and 10.2 micromol/L (P for trend < 0.0001). Except for choline from phosphatidylcholine, individual forms of choline were inversely associated with tHcy concentrations. CONCLUSIONS Our findings provide support for a physiologically important variation in choline and betaine intakes in the general population and for the validity of intake measured by FFQ.
Butyrate-Producing Probiotics Reduce Nonalcoholic Fatty Liver Disease Progression in Rats: New Insight into the Probiotics for the Gut-Liver Axis

Nonalcoholic fatty liver disease (NAFLD) includes simple steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. The gut-derived endotoxin plays an essential role in the pathophysiological development and progression of NAFLD. By using rat models of choline-deficient/L-amino acid-defined (CDAA)-diet-induced NAFLD, we examined whether MIYAIRI 588–a butyrate-producing probiotic – prevents the progression of pathophysiological changes from steatosis to hepatocarcinogenesis. In vivo experiments showed that treatment with MIYAIRI 588 reduced CDAA-diet-induced hepatic lipid deposition and significantly improved the triglyceride content, insulin resistance, serum endotoxin levels, and hepatic inflammatory indexes. We also found that MIYAIRI 588 substantially increased the activation of hepatic adenosine 5′-monophosphate-activated protein kinase (AMPK) and AKT and the expression of lipogenesis- or lipolysis-related proteins. MIYAIRI 588 also improved CDAA-diet-induced delocalization and substantially decreased the expression of the tight-junction proteins intestinal zonula occluden-1 and occludin in CDAA-diet-fed rats. Further, the MIYAIRI 588-treated rats also showed remarkable induction of nuclear factor erythoid 2-related factor 2 (Nrf2) and its targeted antioxidative enzymes, which suppressed hepatic oxidative stress. In vitro studies revealed that treatment with sodium butyrate (NaB) also activated AMPK and AKT and enhanced Nrf2 expression by precluding ubiquitination, thereby increasing the half-life of the Nrf2 protein. Pharmacological studies and siRNA knockdown experiments showed that NaB-mediated AMPK activation induced the phosphorylation and nuclear translocation of Sirtuin 1, leading to the increased assembly of mammalian TOR complex 2 and phosphorylation of AKT at Ser473 and subsequent induction of Nrf2 expression and activation. These favorable changes caused an obvious decrease in hepatic fibrous deposition, GST-P-positive foci development, and hepatocarcinogenesis. Our data clearly established that the probiotic MIYAIRI 588 has beneficial effects in the prevention of NAFLD progression.
Determination of lung regions on chest ct images with diffuse lung diseases by use of anatomical structures and pulmonary textures

To analyze diffuse lung diseases based on chest region computed tomography (CT) imaging by using a computer-aided diagnosis (CAD) system, it is necessary to first determine the lung regions subject to analysis. The lung regions can be selected relatively easily for healthy individuals, by applying a threshold. Selecting an area by using a threshold-based method can be difficult when dealing with lungs with diffuse lung diseases, owing to the abnormal opacities that characterize the diseases. Trials for determining the lung regions were conducted in this study, through texture analysis and machine learning, by narrowing down the lung regions to rough regions, and by referring to ribs and the diaphragm. This method can be used for determining lung regions for analysis of diffuse lung diseases.
A dynamic and intricate regulatory network determines Pseudomonas aeruginosa virulence

Pseudomonas aeruginosa is a metabolically versatile bacterium that is found in a wide range of biotic and abiotic habitats. It is a major human opportunistic pathogen causing numerous acute and chronic infections. The critical traits contributing to the pathogenic potential of P. aeruginosa are the production of a myriad of virulence factors, formation of biofilms and antibiotic resistance. Expression of these traits is under stringent regulation, and it responds to largely unidentified environmental signals. This review is focused on providing a global picture of virulence gene regulation in P. aeruginosa. In addition to key regulatory pathways that control the transition from acute to chronic infection phenotypes, some regulators have been identified that modulate multiple virulence mechanisms. Despite of a propensity for chaotic behaviour, no chaotic motifs were readily observed in the P. aeruginosa virulence regulatory network. Having a ‘birds-eye’ view of the regulatory cascades provides the forum opportunities to pose questions, formulate hypotheses and evaluate theories in elucidating P. aeruginosa pathogenesis. Understanding the mechanisms involved in making P. aeruginosa a successful pathogen is essential in helping devise control strategies.
Polynitroxylated pegylated hemoglobin: A novel neuroprotective hemoglobin for acute volume-limited fluid resuscitation after combined traumatic brain injury and hemorrhagic hypotension in mice*

Objective:Resuscitation of hemorrhagic hypotension after traumatic brain injury is challenging. A hemoglobin-based oxygen carrier may offer advantages. The novel therapeutic hemoglobin-based oxygen carrier, polynitroxylated pegylated hemoglobin (PNPH), may represent a neuroprotective hemoglobin-based oxygen carrier for traumatic brain injury resuscitation. Hypotheses:1) PNPH is a unique non-neurotoxic hemoglobin-based oxygen carrier in neuronal culture and is neuroprotective in in vitro neuronal injury models. 2) Resuscitation with PNPH would require less volume to restore mean arterial blood pressure than lactated Ringer's or Hextend and confer neuroprotection in a mouse model of traumatic brain injury plus hemorrhagic hypotension. Design:Prospective randomized, controlled experimental study. Setting:University center. Measurements and Main Results:In rat primary cortical neuron cultures, control bovine hemoglobin was neurotoxic (lactate dehydrogenase release; 3-[4,5-dimethylthiazol-2-yl-]-2,5-diphenyltetrazolium bromide assay) at concentrations from 12.5 to 0.625 &mgr;M, whereas polyethylene glycol-conjugated hemoglobin showed intermediate toxicity. PNPH was not neurotoxic (p < .05 vs. bovine hemoglobin and polyethylene glycol hemoglobin; all concentrations). PNPH conferred neuroprotection in in vitro neuronal injury (glutamate/glycine exposure and neuronal stretch), as assessed via lactate dehydrogenase and 3-[4,5-dimethylthiazol-2-yl-]-2,5-diphenyltetrazolium bromide (all p < .05 vs. control). C57BL6 mice received controlled cortical impact followed by hemorrhagic hypotension (2 mL/100 g, mean arterial blood pressure ∼35–40 mm Hg) for 90 min. Mice were resuscitated (mean arterial blood pressure >50 mm Hg for 30 min) with lactated Ringer's, Hextend, or PNPH, and then shed blood was reinfused. Mean arterial blood pressures, resuscitation volumes, blood gasses, glucose, and lactate were recorded. Brain sections at 7 days were examined via hematoxylin and eosin and Fluoro-Jade C (identifying dying neurons) staining in CA1 and CA3 hippocampus. Resuscitation with PNPH or Hextend required less volume than lactated Ringer's (both p < .05). PNPH but not Hextend improved mean arterial blood pressure vs. lactated Ringer's (p < .05). Mice resuscitated with PNPH had fewer Fluoro-Jade C positive neurons in CA1 vs. Hextend and lactated Ringer's, and CA3 vs. Hextend (p < .05). Conclusions:PNPH is a novel neuroprotective hemoglobin-based oxygen carrier in vitro and in vivo that may offer unique advantages for traumatic brain injury resuscitation.
Design of universal parallel‐transmit refocusing kT‐point pulses and application to 3D T2‐weighted imaging at 7T

T2‐weighted sequences are particularly sensitive to the radiofrequency (RF) field inhomogeneity problem at ultra‐high‐field because of the errors accumulated by the imperfections of the train of refocusing pulses. As parallel transmission (pTx) has proved particularly useful to counteract RF heterogeneities, universal pulses were recently demonstrated to save precious time and computational efforts by skipping B1 calibration and online RF pulse tailoring. Here, we report a universal RF pulse design for non‐selective refocusing pulses to mitigate the RF inhomogeneity problem at 7T in turbo spin‐echo sequences with variable flip angles.
Embedding multilevel survival analysis of dyadic social interaction in structural equation models: hazard rates as both outcomes and predictors.

OBJECTIVE Demonstrate multivariate multilevel survival analysis within a larger structural equation model. Test the 3 hypotheses that when confronted by a negative parent, child rates of angry, sad/fearful, and positive emotion will increase, decrease, and stay the same, respectively, for antisocial compared with normal children. This same pattern will predict increases in future antisocial behavior. METHODS Parent-child dyads were videotaped in the fall of kindergarten in the laboratory and antisocial behavior ratings were obtained in the fall of kindergarten and third grade. RESULTS Kindergarten antisocial predicted less child sad/fear and child positive but did not predict child anger given parent negative. Less child positive and more child neutral given parent negative predicted increases in third-grade antisocial behavior. CONCLUSIONS The model is a useful analytic tool for studying rates of social behavior. Lack of positive affect or excess neutral affect may be a new risk factor for child antisocial behavior.