Miracle-dz/UniFAR-FTUs huggingface dataset:
Metoprolol Increases Uric Acid and Risk of Gout in African Americans With Chronic Kidney Disease Attributed to Hypertension

BACKGROUND There is little evidence guiding selection of nondiuretic, antihypertensive agents with a goal of lowering uric acid (SUA) and minimizing gout risk. METHODS In the African American Study of Kidney Disease and Hypertension (AASK) trial, African Americans with chronic kidney disease were randomly assigned to metoprolol (a beta-blocker), ramipril (an angiotensin-converting enzyme inhibitors [ACEi]), or amlodipine (a dihydropyridine calcium-channel blocker). SUA was measured at baseline and 12 months. Gout-related hospitalizations were based on ICD9 codes. Gout-related medication use (GRMs) was based on active prescriptions of allopurinol, colchicine, or probenecid during the baseline visit of the AASK cohort phase. We examined the effect of drug assignment on 12-month SUA (linear regression), gout-related hospitalization (Cox regression), and GRM (logistic regression). RESULTS Of the 630 participants, 40% were female with a mean age of 55 years (SD, 10), mean SUA of 8.2 mg/dl (2.0), and mean serum creatinine of 1.8 mg/dl (0.6). After 12 months, metoprolol increased SUA by 0.3 mg/dl, while ramipril or amlodipine had no effect on SUA. Compared to ramipril, metoprolol significantly increased 12-month SUA (0.40; 0.10, 0.70 mg/dl; P = 0.009), nonsignificantly increased risk of gout-related hospitalization (hazard ratio: 3.87; 0.82, 18.26; P = 0.09), and significantly increased the odds of GRM (odds ratio: 1.62; 1.03, 2.54; P = 0.04). While metoprolol was associated with a higher 12-month SUA compared with amlodipine (0.57; 0.18, 0.95; P = 0.004), there was no difference in gout-related hospitalizations or GRM. CONCLUSIONS Metoprolol increased SUA and GRM in African American adults. Health professionals treating patients with kidney disease at risk for gout should avoid metoprolol and possibly consider an ACEi. CLINICAL TRIALS REGISTRATION Trial Number NCT00582777.
Influence Maximization over Large-Scale Social Networks: A Bounded Linear Approach

Information diffusion in social networks is emerging as a promising solution to successful viral marketing, which relies on the effective and efficient identification of a set of nodes with the maximal social influence. While there are tremendous efforts on the development of social influence models and algorithms for social influence maximization, limited progress has been made in terms of designing both efficient and effective algorithms for finding a set of nodes with the maximal social influence. To this end, in this paper, we provide a bounded linear approach for influence computation and influence maximization. Specifically, we first adopt a linear and tractable approach to describe the influence propagation. Then, we develop a quantitative metric, named Group-PageRank, to quickly estimate the upper bound of the social influence based on this linear approach. More importantly, we provide two algorithms Linear and Bound, which exploit the linear approach and Group-PageRank for social influence maximization. Finally, extensive experimental results demonstrate that (a) the adopted linear approach has a close relationship with traditional models and Group-PageRank provides a good estimation of social influence; (b) Linear and Bound can quickly find a set of the most influential nodes and both of them are scalable for large-scale social networks.
Predictors of length of stay in an acute psychiatric inpatient facility in a general hospital: a prospective study

Objective: There have been significant reductions in numbers of psychiatric beds and length of stay (LOS) worldwide, making LOS in psychiatric beds an interesting outcome. The objective of this study was to find factors measurable on admission that would predict LOS in the acute psychiatric setting. Methods: This was a prospective, observational study. Results: Overall, 385 subjects were included. The median LOS was 25 days. In the final model, six variables explained 14.6% of the variation in LOS: not having own income, psychiatric admissions in the preceding 2 years, high Clinical Global Impression and Brief Psychiatric Rating Scale scores, diagnosis of schizophrenia, and history of attempted suicide. All variables were associated with longer LOS, apart from history of attempted suicide. Conclusions: Identifying patients who will need to stay longer in psychiatric beds remains a challenge. Improving knowledge about determinants of LOS could lead to improvements in the quality of care in hospital psychiatry.
General sky models for illuminating terrains

Sky models are quantitative representations of natural luminance of the sky under various atmospheric conditions. They have been used extensively in studies of architectural design for nearly a century, and more recently for rendering objects in the field of computer graphics. The objectives of this paper are to (1) describe sky models, (2) demonstrate how map designers can render terrain under various sky models in a typical geographic information system (GIS), (3) illustrate potential enhancements to terrain renderings using sky models, and (4) discuss how sky models, with their well-established standards from a different discipline, might contribute to a virtual geographic environment (VGE). Current GIS hill-shading tools use the Lambertian assumption which can be related to a simple point light source at an infinite distance to render terrain. General sky models allow the map designer to choose from a gamut of sky models standardized by the International Commission on Illumination (CIE). We present a computer application that allows the map designer to select a general sky model and to use existing GIS tools to illuminate any terrain under that model. The application determines the orientations and weights of many discrete point light sources that, in the aggregate, approximate the illumination provided by the chosen sky model. We discuss specific enhancements to terrains that are shaded and shadowed with these general sky models, including additional detail of secondary landforms with soft shadows and more realistic shading contrasts. We also illustrate how non-directional illumination models result in renderings that lack the perceptual relief effect. Additionally, we argue that this process of creating hill-shaded visualizations of terrain with sky models shows parallels to other geo-simulations, and that basing such work on standards from the computer graphics industry shows potential for its use in VGE.
FXR-Gankyrin axis is involved in development of pediatric liver cancer

The development of hepatoblastoma (HBL) is associated with failure of hepatic stem cells (HSC) to differentiate into hepatocytes. Despite intensive investigations, mechanisms of the failure of HSC to differentiate are not known. We found that oncogene Gankyrin (Gank) is involved in the inhibition of differentiation of HSC via triggering degradation of tumor suppressor proteins (TSPs) Rb, p53, C/EBPα and HNF4α. Our data show that the activation of a repressor of Gank, farnesoid X receptor, FXR, after initiation of liver cancer by Diethylnitrosamine (DEN) prevents the development of liver cancer by inhibiting Gank and rescuing tumor suppressor proteins. We next analyzed FXR-Gank-Tumor suppressor pathways in a large cohort of HBL patients which include 6 controls and 53 HBL samples. Systemic analysis of these samples and RNA-Seq approach revealed that the FXR-Gank axis is activated; markers of hepatic stem cells are dramatically elevated and hepatocyte markers are reduced in HBL samples. In the course of these studies, we found that RNA binding protein CUGBP1 is a new tumor suppressor protein which is reduced in all HBL samples. Therefore, we generated CUGBP1 KO mice and examined HBL signatures in the liver of these mice. Micro-array studies revealed that the HBL-specific molecular signature is developed in livers of CUGBP1 KO mice at very early ages. Thus, we conclude that FXR-Gank-TSPs-Stem cells pathway is a key determinant of liver cancer in animal models and in pediatric liver cancer. Our data provide a strong basis for development of FXR-Gank-based therapy for treatment of patients with hepatoblastoma.
Morphologic characterization of residual DNA methylation in the gastric mucosa after Helicobacter pylori eradication

Residual DNA methylation in the gastric mucosa after Helicobacter pylori (H. pylori) eradication may have a role in gastric carcinogenesis. We examined the association between morphologic features and promoter methylation status of non‐neoplastic gastric mucosa especially after H. pylori eradication. A total of 140 gastric specimens from 99 participants who had at least 6 months of post‐eradication period were examined. The magnifying narrow‐band imaging (NBI) endoscopic feature of gastric mucosa was divided into two types: restored‐small, round pits, accompanied with honeycomb‐like subepithelial capillary networks; atrophic‐well‐demarcated oval or tubulovillous pits with clearly visible coiled or wavy vessels. Methylation status of five candidate genes (MYOD1, SLC16A12, IGF2, RORA, and PRDM5) were examined by bisulfite pyrosequencing. The atrophic type, informative endoscopic features of intestinal metaplasia, demonstrated higher methylation levels in all five genes compared to the restored type (all P < 0.0001). In the restored type, methylation levels were significantly lower among the samples with longer post‐eradication period (for all genes, P < 0.0001), which was not observed in atrophic type (for all genes, P > 0.1). Multivariate analysis demonstrated that atrophic type or presence of intestinal held an independent factor for hyper methylation (odds ratio: 24.69, 95% confidence interval: 6.95–87.76, P < 0.0001). The atrophic type by the magnifying NBI and presence of intestinal metaplasia are the morphologic characteristics of residual DNA methylation of after H. pylori eradication, regardless of the post‐eradication period and it might be considered as the epigenetic irreversible point with H. pylori eradication.
Abdominal obesity and coronary artery calcification in young adults: the Coronary Artery Risk Development in Young Adults (CARDIA) Study.

BACKGROUND Whether abdominal obesity is related to coronary artery calcification (CAC) is not known. OBJECTIVE We investigated the relations of waist girth and waist-hip ratio (WHR) to CAC in 2951 African American and white young adults from the Coronary Artery Risk Development in Young Adults Study. DESIGN The present study was a cross-sectional and observational cohort study. Using standardized protocols, we measured CAC in 2001-2002 by using computed tomography and measured waist and hip girths in 1985-1986 (baseline), 1995-1996 (year 10), and 2001-2002 (year 15, waist girth only). CAC was classified as present or absent, whereas waist girth and WHR were placed in sex-specific tertiles. RESULTS After adjustment for age, sex, race, clinical center, physical activity, cigarette smoking, education, and alcohol intake, baseline waist girth and WHR were directly associated with a higher prevalence of CAC 15 y later (P for trend < 0.001 for both). The odds ratios (ORs) for CAC in the highest versus lowest tertiles of waist girth and WHR were 1.9 (95% CI: 1.36, 2.65) and 1.7 (1.23, 2.41), respectively. Waist girth and WHR at year 10 and waist girth at year 15 similarly predicted CAC. These associations persisted after additional adjustment for systolic blood pressure, fasting insulin concentrations, diabetes, and antihypertensive medication use but became nonsignificant after additional adjustment for blood lipids. CONCLUSIONS Abdominal obesity measured by waist girth or WHR is associated with early atherosclerosis as measured by the presence of CAC in African American and white young adults. This is consistent with an involvement of visceral fat in the occurrence of coronary artery calcium in young adults.
Spatially dependent alkyl quinolone signaling responses to antibiotics in Pseudomonas aeruginosa swarms

There is a general lack of understanding about how communities of bacteria respond to exogenous toxins such as antibiotics. Most of our understanding of community-level stress responses comes from the study of stationary biofilm communities. Although several community behaviors and production of specific biomolecules affecting biofilm development and associated behavior have been described for Pseudomonas aeruginosa and other bacteria, we have little appreciation for the production and dispersal of secreted metabolites within the 2D and 3D spaces they occupy as they colonize, spread, and grow on surfaces. Here we specifically studied the phenotypic responses and spatial variability of alkyl quinolones, including the Pseudomonas quinolone signal (PQS) and members of the alkyl hydroxyquinoline (AQNO) subclass, in P. aeruginosa plate-assay swarming communities. We found that PQS production was not a universal signaling response to antibiotics, as tobramycin elicited an alkyl quinolone response, whereas carbenicillin did not. We also found that PQS and AQNO profiles in response to tobramycin were markedly distinct and influenced these swarms on different spatial scales. At some tobramycin exposures, P. aeruginosa swarms produced alkyl quinolones in the range of 150 μm PQS and 400 μm AQNO that accumulated as aggregates. Our collective findings show that the distribution of alkyl quinolones can vary by several orders of magnitude within the same swarming community. More notably, our results suggest that multiple intercellular signals acting on different spatial scales can be triggered by one common cue.
Minimal model of arterial chaos generated by coupled intracellular and membrane Ca2+oscillators.

We have developed a mathematical model of arterial vasomotion in which irregular rhythmic activity is generated by the nonlinear interaction of intracellular and membrane oscillators that depend on cyclic release of Ca2+ from internal stores and cyclic influx of extracellular Ca2+, respectively. Four key control variables were selected on the basis of the pharmacological characteristics of histamine-induced vasomotion in rabbit ear arteries: Ca2+ concentration in the cytosol, Ca2+ concentration in ryanodine-sensitive stores, cell membrane potential, and the open state probability of Ca2+-activated K+ channels. Although not represented by independent dynamic variables, the model also incorporates Na+/Ca2+exchange, the Na+-K+-ATPase, Cl- fluxes, and Ca2+ efflux via the extrusion ATPase. Simulations reproduce a wide spectrum of experimental observations, including 1) the effects of interventions that modulate the functionality of Ca2+ stores and membrane ion channels, 2) paradoxes such as the apparently unpredictable dual action of Ca2+ antagonists and low extracellular Na+ concentration, which can abolish vasomotion or promote the appearance of large-amplitude oscillations, and 3) period-doubling, quasiperiodic, and intermittent routes to chaos. Nonlinearity is essential to explain these diverse patterns of experimental vascular response.
Effects of short-term submaximal training in humans on muscle metabolism in exercise.

Muscle metabolism, including the role of pyruvate dehydrogenase (PDH) in muscle lactate (Lac-) production, was examined during incremental exercise before and after 7 days of submaximal training on a cycle ergometer [2 h daily at 60% peak O2 uptake (V˙o 2 max)]. Subjects were studied at rest and during continuous steady-state cycling at three stages (15 min each): 30, 65, and 75% of the pretraining V˙o 2 max. Blood was sampled from brachial artery and femoral vein, and leg blood flow was measured by thermodilution. Biopsies of the vastus lateralis were obtained at rest and during steady-state exercise at the end of each stage. V˙o 2 max, leg O2 uptake, and the maximum activities of citrate synthase and PDH were not altered by training; muscle glycogen concentration was higher. During rest and cycling at 30% V˙o 2 max, muscle Lac- concentration ([Lac-]) and leg efflux were similar. At 65%V˙o 2 max, muscle [Lac-] was lower (11.9 ± 3.2 vs. 20.0 ± 5.8 mmol/kg dry wt) and Lac- efflux was less [-0.22 ± 0.24 (one leg) vs. 1.42 ± 0.33 mmol/min] after training. Similarly, at 75%V˙o 2 max, lower muscle [Lac-] (17.2 ± 4.4 vs. 45.2 ± 6.6 mmol/kg dry wt) accompanied less release (0.41 ± 0.53 vs. 1.32 ± 0.65 mmol/min) after training. PDH in its active form (PDHa) was not different between conditions. Calculated pyruvate production at 75%V˙o 2 max fell by 33%, pyruvate reduction to lactate fell by 59%, and pyruvate oxidation fell by 24% compared with before training. Muscle contents of coenzyme A and phosphocreatine were higher during exercise after training. Lower muscle lactate production after training resulted from improved matching of glycolytic and PDHafluxes, independently of changes in muscle O2 consumption, and was associated with greater phosphorylation potential.
Total-body and regional bone mineral content and areal bone mineral density in children aged 8-18 y: the Fels Longitudinal Study.

BACKGROUND Techniques for cross-calibration of bone mineral content (BMC) and bone mineral density (BMD) between manufacturers of dual-energy X-ray absorptiometry (DXA) instruments are currently inadequate for total body measurements. Therefore, manufacturer-specific data for BMC and BMD in children are needed. OBJECTIVE We provided age- and sex-specific means and SDs for total-body and regional BMC and areal BMD in 8-18-y-old white children. DESIGN BMC and BMD of the head, arms, legs, pelvis, spine, and total body were determined by DXA. Data include 465 annual measurements from 148 healthy children with body weights between 30 and 100 kg and statures <190 cm. RESULTS There were significant sex differences in BMC at ages 15-18 y for the total body and legs, at ages 12 and 15-18 y for arms and pelvis, at ages 11-13 and 16-18 y for the spine, and at ages 10-11 y for the head. There were significant sex differences in BMD at ages 16-18 y for total body, arms, and legs; at ages 12-13 and 16-18 y for the pelvis; at ages 12-14 and 18 y for the spine; and at ages 13-18 y for the head. CONCLUSIONS Data presented in this investigation can be used to compare the BMC and BMD of 8-18-y-old white children (with statures <190 cm and body weights between 30 and 100 kg) using DXA.
Loss-of-function PCSK9 mutants evade the unfolded protein response sensor GRP78 and fail to induce endoplasmic reticulum stress when retained

The proprotein convertase subtilisin/kexin type-9 (PCSK9) plays a central role in cardiovascular disease (CVD) by degrading hepatic low-density lipoprotein receptor (LDLR). As such, loss-of-function (LOF) PCSK9 variants that fail to exit the endoplasmic reticulum (ER) increase hepatic LDLR levels and lower the risk of developing CVD. The retention of misfolded protein in the ER can cause ER stress and activate the unfolded protein response (UPR). In this study, we investigated whether a variety of LOF PCSK9 variants that are retained in the ER can cause ER stress and hepatic cytotoxicity. Although overexpression of these PCSK9 variants caused an accumulation in the ER of hepatocytes, UPR activation or apoptosis was not observed. Furthermore, ER retention of endogenous PCSK9 via splice switching also failed to induce the UPR. Consistent with these in vitro studies, overexpression of PCSK9 in the livers of mice had no impact on UPR activation. To elucidate the cellular mechanism to explain these surprising findings, we observed that the 94-kDa glucose-regulated protein (GRP94) sequesters PCSK9 away from the 78-kDa glucose-regulated protein (GRP78), the major activator of the UPR. As a result, GRP94 knockdown increased the stability of GRP78–PCSK9 complex and resulted in UPR activation following overexpression of ER-retained PCSK9 variants relative to WT secreted controls. Given that overexpression of these LOF PCSK9 variants does not cause UPR activation under normal homeostatic conditions, therapeutic strategies aimed at blocking the autocatalytic cleavage of PCSK9 in the ER represent a viable strategy for reducing circulating PCSK9.
Ability of new octapolar bioimpedance spectroscopy analyzers to predict 4-component-model percentage body fat in Hispanic, black, and white adults.

BACKGROUND New, vertical, 8-electrode bioimpedance spectroscopy (BIS) analyzers provide detailed body-composition and nutritional information within 2 min. This is the first report on BIS's accuracy in predicting relative fatness [percentage body fat (%BF)] in a heterogeneous sample according to a multicomponent model criterion. OBJECTIVE We compared %BF measurements from 2 BIS devices with those from a multicomponent model in a sample of Hispanic, black, and white adults. DESIGN Equal numbers of apparently healthy men and women (n = 75 of each) from each racial-ethnic group, diverse in body mass index and age, volunteered. Reference %BF (%BF(4C)) was computed by using a 4-component (4C) model with total bone mineral content obtained from dual-energy X-ray absorptiometry, body density from underwater weighing with measured residual lung volume, and total body water from traditional BIS. Estimations from InBody 720 (%BF(720)) and InBody 320 (%BF(320)) BIS analyzers were validated against %BF(4C). RESULTS The %BF(720) (r = 0.85, SEE = 5.19%BF) and %BF(320) (r = 0.84, SEE = 5.17%BF) correlations were significant (P < 0.05) in the men; main effects were nonsignificant. Correlations for %BF(720) (r = 0.88, SEE = 4.85%BF) and %BF(320) (r = 0.89, SEE = 4.82%BF) also were significant in the women (P < 0.05); there was a main effect for method but not race-ethnicity. There were no sex-specific overestimations or underestimations at the extremes of the distributions. CONCLUSIONS BIS estimates of %BF(4C) were well correlated in men and women. There were no significant methodologic differences in the men. The %BF(4C) was significantly underestimated by %BF(720) and %BF(320) in the women.
Homocysteine and cognitive function in healthy elderly community dwellers in Italy.

BACKGROUND Elevated plasma total homocysteine (tHcy) concentrations are common in the elderly and have been suggested to be a risk factor for dementia. OBJECTIVE In an elderly population, we examined the relation between plasma tHcy and scores on the Mini-Mental State Examination (MMSE), a commonly used screening measure of cognitive impairment in general practice. DESIGN Fasting plasma tHcy concentrations were measured in 650 healthy, cognitively normal Italian community dwellers aged > or = 65 y (x +/- SD: 72.8 +/- 6.0 y). Socioeconomic status; serum folate, vitamin B-12, and creatinine; other potential dietary and lifestyle determinants of tHcy; and conventional vascular disease risk factors were also assessed. RESULTS Subjects with MMSE scores of 26-28 had higher plasma tHcy concentrations (12.7 micromol/L; range: 12.2-13.2 micromol/L) than did those with scores > 28 (11.9 micromol/L; 11.4-12.3 micromol/L; P < 0.01). Subjects with scores of 24-25 had higher plasma tHcy concentrations (14.5 micro mol/L; 13.5-15.6 micromol/L) than did subjects with scores of 26-28 (P < 0.01) or > 28 (P < 0.001). The risk of hyperhomocysteinemia (plasma tHcy > 15 micromol/L) was higher in subjects with scores of 24-25 (odds ratio: 3.81; 95% CI: 1.9, 7.5) or 26-28 (odds ratio: 1.96; 95% CI: 1.3, 3.0) than in those with scores > 28. The results did not change after adjustment for conventional vascular risk factors and for age, medical, dietary, and lifestyle determinants of plasma tHcy. CONCLUSION Elevated plasma tHcy has an independent, graded association with concurrent cognitive impairment as measured with the MMSE in healthy elderly community dwellers.