Miracle-dz/UniFAR-FTUs huggingface dataset:
Preeclampsia and ESRD: The Role of Shared Risk Factors.

BACKGROUND Several registry-based studies, using diagnostic codes, have suggested that preeclampsia is a risk factor for end-stage renal disease (ESRD). However, because the 2 diseases share risk factors, the true nature of their association remains uncertain. Our goals were to conduct a population-based study to determine the magnitude of the association between preeclampsia and ESRD and evaluate the role of shared risk factors. STUDY DESIGN Population-based nested case-control study. SETTING & PARTICIPANTS The US Renal Data System was used to identify women with ESRD from a cohort of 34,581 women who gave birth in 1976 to 2010 in Olmsted County, MN. 44 cases of ESRD were identified and each one was matched to 2 controls based on year of birth (±1 year), age at first pregnancy (±2 years), and parity (±1 or ≥4). PREDICTOR Preeclamptic pregnancy, confirmed by medical record review. OUTCOME ESRD. MEASUREMENTS Prepregnancy serum creatinine and urine protein measurements were recorded. Comorbid conditions existing prior to pregnancy were abstracted from medical records and included kidney disease, obesity, diabetes, and hypertension. RESULTS There was evidence of kidney disease prior to the first pregnancy in 9 of 44 (21%) cases and 1 of 88 (<1%) controls. Per chart review, 8 of 44 (18%) cases versus 4 of 88 (5%) controls had preeclamptic pregnancies (unadjusted OR, 4.0; 95% CI, 1.21-13.28). Results were similar after independent adjustment for race, education, diabetes, and hypertension prior to pregnancy. However, the association was attenuated and no longer significant after adjustment for obesity (OR, 3.25; 95% CI, 0.93-11.37). LIMITATIONS The limited number of ESRD cases and missing data for prepregnancy kidney function. CONCLUSIONS Our findings confirm that there is a sizable association between preeclampsia and ESRD; however, obesity is a previously unexplored confounder. Pre-existing kidney disease was common, but not consistently coded or diagnosed.
Development of the carapacial ridge: implications for the evolution of genetic networks in turtle shell development

SUMMARY Paleontologists and neontologists have long looked to development to understand the homologies of the dermal bones that form the “armor” of turtles, crocodiles, armadillos, and other vertebrates. This study shows molecular evidence supporting a dermomyotomal identity for the mesenchyme of the turtle carapacial ridge. The mesenchyme of the carapace primordium expresses Pax3, Twist1, Dermo1, En1, Sim1, and Gremlin at early stages and before overt ossification expresses Pax1. A hypothesis is proposed that this mesenchyme forms dermal bone in the turtle carapace. A comparison of regulatory gene expression in the primordia of the turtle carapace, the vertebrate limb, and the vertebral column implies the exaptation of key genetic networks in the development of the turtle shell. This work establishes a new role for this mesodermal compartment and highlights the importance of changes in genetic regulation in the evolution of morphology.
Functional Consequences of RNA 5′-Terminal Deletions on Coxsackievirus B3 RNA Replication and Ribonucleoprotein Complex Formation

ABSTRACT Group B coxsackieviruses are responsible for chronic cardiac infections. However, the molecular mechanisms by which the virus can persist in the human heart long after the signs of acute myocarditis have abated are still not completely understood. Recently, coxsackievirus B3 strains with 5′-terminal deletions in genomic RNAs were isolated from a patient suffering from idiopathic dilated cardiomyopathy, suggesting that such mutant viruses may be the forms responsible for persistent infection. These deletions lacked portions of 5′ stem-loop I, which is an RNA secondary structure required for viral RNA replication. In this study, we assessed the consequences of the genomic deletions observed in vivo for coxsackievirus B3 biology. Using cell extracts from HeLa cells, as well as transfection of luciferase replicons in two types of cardiomyocytes, we demonstrated that coxsackievirus RNAs harboring 5′ deletions ranging from 7 to 49 nucleotides in length can be translated nearly as efficiently as those of wild-type virus. However, these 5′ deletions greatly reduced the synthesis of viral RNA in vitro, which was detected only for the 7- and 21-nucleotide deletions. Since 5′ stem-loop I RNA forms a ribonucleoprotein complex with cellular and viral proteins involved in viral RNA replication, we investigated the binding of the host cell protein PCBP2, as well as viral protein 3CDpro, to deleted positive-strand RNAs corresponding to the 5′ end. We found that binding of these proteins was conserved but that ribonucleoprotein complex formation required higher PCBP2 and 3CDpro concentrations, depending on the size of the deletion. Overall, this study confirmed the characteristics of persistent CVB3 infection observed in heart tissues and provided a possible explanation for the low level of RNA replication observed for the 5′-deleted viral genomes—a less stable ribonucleoprotein complex formed with proteins involved in viral RNA replication. IMPORTANCE Dilated cardiomyopathy is the most common indication for heart transplantation worldwide, and coxsackie B viruses are detected in about one-third of idiopathic dilated cardiomyopathies. Terminal deletions at the 5′ end of the viral genome involving an RNA secondary structure required for RNA replication have been recently reported as a possible mechanism of virus persistence in the human heart. These mutations are likely to disrupt the correct folding of an RNA secondary structure required for viral RNA replication. In this report, we demonstrate that transfected RNAs harboring 5′-terminal sequence deletions are able to direct the synthesis of viral proteins, but not genomic RNAs, in human and murine cardiomyocytes. Moreover, we show that the binding of cellular and viral replication factors to viral RNA is conserved despite genomic deletions but that the impaired RNA synthesis associated with terminally deleted viruses could be due to destabilization of the ribonucleoprotein complexes formed.
Tribological Properties of Magnetron Sputtered Amorphous Silicon Carbide and Silicon Carbonitride Coatings

The tribological properties of magnetron sputtered amorphous silicon carbide (a-SiC) and silicon carbonitride coatings (a-SiCN) with thickness of 2.2 and 3.4 µm were investigated. Samples were additionally annealed at temperature of 700°C or 900°C in air. Progressive load scratch tests were performed on the annealed samples as well as on the as deposited ones. An acoustic emission signal was detected during all tests using the sample holder with embedded sensor of our own design. Results indicate no change in wear resistance of SiCN sample after high temperature exposure up to 900°C, unlike in the tests of SiC coatings. Detection of acoustic emission generated during the scratch test proved to be a significant improvement for the coating evaluation.
Analytical Advances in the Ex Vivo Challenge Efficacy Assay.

The ex vivo challenge assay is being increasingly used as an efficacy endpoint during early human clinical trials of HIV prevention treatments. There is no standard methodology for the ex vivo challenge assay, although the use of different data collection methods and analytical parameters may impact results and reduce the comparability of findings between trials. In this analysis, we describe the impact of data imputation methods, kit type, testing schedule and tissue type on variability, statistical power, and ex vivo HIV growth kinetics. Data were p24 antigen (pg/ml) measurements collected from clinical trials of candidate microbicides where rectal (n = 502), cervical (n = 88), and vaginal (n = 110) tissues were challenged with HIV-1BaL ex vivo. Imputation of missing data using a nonlinear mixed effect model was found to provide an improved fit compared to imputation using half the limit of detection. The rectal virus growth period was found to be earlier and of a relatively shorter duration than the growth period for cervical and vaginal tissue types. On average, only four rectal tissue challenge assays in each treatment and control group would be needed to find a one log difference in p24 to be significant (alpha = 0.05), but a larger sample size was predicted to be needed for either cervical (n = 21) or vaginal (n = 10) tissue comparisons. Overall, the results indicated that improvements could be made in the design and analysis of the ex vivo challenge assay to provide a more standardized and powerful assay to compare efficacy of microbicide products.
Distributions of Subclinical Cardiovascular Disease in a Socioeconomically and Racially Diverse Sample

Background and Purpose— Differential subgroup vulnerability to subclinical cardiovascular disease is likely, and yet few, if any, studies have addressed interactive relations of age, sex, race, and socioeconomic status (SES) to these conditions to examine nuances of known health disparities. We examined distributions of carotid atherosclerosis and arterial stiffness in a socioeconomically diverse, biracial, urban sample. Methods— Participants (n=2270) in the population-based HANDLS study (Healthy Aging in Neighborhoods of Diversity Across the Life Span; 30–64 years old, 44% men, 57% African American, 39% with household income <125% federal poverty threshold) underwent carotid intimal medial thickness (IMT) and pulse wave velocity assessment. Results— In cross-sectional hierarchical regression analyses, interactive race×SES effects were identified for IMT and pulse wave velocity, such that high SES African Americans had significantly thicker IMTs and faster pulse wave velocities than all other subgroups (ie, low SES African Americans, low SES whites, and high SES whites). A race×sex effect was also identified for IMT, such that the IMT discrepancy between white men and women was more pronounced than the discrepancy between African American men and women. Finally, an SES×sex effect indicated that while IMTs of high SES and low SES men did not significantly differ, high SES women had marginally thicker IMTs than low SES women. Conclusions— High SES African Americans may be particularly vulnerable to subclinical cardiovascular diseases, placing them at enhanced risk for clinical cardiovascular diseases, including stroke. These findings suggest that male sex, low SES, and African American ancestry may represent imprecise generalizations as risk factors for subclinical cardiovascular disease.
IL‐10 distinguishes a unique population of activated, effector‐like CD8+ T cells in murine acute liver inflammation

Immune‐mediated liver injury is a central feature of hyperinflammatory diseases, such as hemophagocytic syndromes, yet the immunologic mechanisms underlying those processes are incompletely understood. In this study, we used the toll‐like receptor 9 (TLR9)–mediated model of a hemophagocytic syndrome known as macrophage activation syndrome (MAS) to dissect the predominant immune cell populations infiltrating the liver during inflammation. We identified CD8+ T cells that unexpectedly produce interleukin‐10 (IL‐10) in addition to interferon‐γ (IFN‐γ) as a major hepatic population induced by TLR9 stimulation. Despite their ability to produce this anti‐inflammatory cytokine, IL‐10+ hepatic CD8+ T cells in TLR9–MAS mice did not resemble CD8+ T suppressor cells. Instead, the induction of these cells occurred independently of antigen stimulation and was partially dependent on IFN‐γ. IL‐10+ hepatic CD8+ T cells demonstrated an activated phenotype and high turnover rate, consistent with an effector‐like identity. Transcriptional analysis of this population confirmed a gene signature of effector CD8+ T cells yet suggested responsiveness to liver injury–associated growth factors. Together, these findings suggest that IL‐10+ CD8+ T cells induced by systemic inflammation to infiltrate the liver have initiated an inflammatory, rather than regulatory, program and may thus have a pathogenic role in severe, acute hepatitis.
MYC‐driven inhibition of the glutamate‐cysteine ligase promotes glutathione depletion in liver cancer

How MYC reprograms metabolism in primary tumors remains poorly understood. Using integrated gene expression and metabolite profiling, we identify six pathways that are coordinately deregulated in primary MYC‐driven liver tumors: glutathione metabolism; glycine, serine, and threonine metabolism; aminoacyl‐tRNA biosynthesis; cysteine and methionine metabolism; ABC transporters; and mineral absorption. We then focus our attention on glutathione (GSH) and glutathione disulfide (GSSG), as they are markedly decreased in MYC‐driven tumors. We find that fewer glutamine‐derived carbons are incorporated into GSH in tumor tissue relative to non‐tumor tissue. Expression of GCLC, the rate‐limiting enzyme of GSH synthesis, is attenuated by the MYC‐induced microRNA miR‐18a. Inhibition of miR‐18a in vivo leads to increased GCLC protein expression and GSH abundance in tumor tissue. Finally, MYC‐driven liver tumors exhibit increased sensitivity to acute oxidative stress. In summary, MYC‐dependent attenuation of GCLC by miR‐18a contributes to GSH depletion in vivo, and low GSH corresponds with increased sensitivity to oxidative stress in tumors. Our results identify new metabolic pathways deregulated in primary MYC tumors and implicate a role for MYC in regulating a major antioxidant pathway downstream of glutamine.
Trajectory of Functional Recovery After Postoperative Delirium in Elective Surgery

Objective: To describe functional recovery after elective surgery and to determine whether improvements differ among individuals who develop delirium. Background: No large studies of older adults have investigated whether delirium influences the trajectory of functional recovery after elective surgery. The prospective observational study assessed this association among 566 individuals aged 70 years and older. Methods: Patients undergoing major elective surgery were assessed daily while in hospital for presence and severity of delirium using the Confusion Assessment Method, and their functional recovery was followed for 18 months thereafter. The Activities of Daily Living and Instrumental Activities of Daily Living Scales and the Physical Component Summary of the Short Form-12 were obtained before surgery and at 1, 2, 6, 12, and 18 months. A composite index (standard deviation 10, minimally clinically significant difference 2) derived from these scales was then analyzed using mixed-effects regression. Results: Mean age was 77 years; 58% of participants were women and 24% developed postoperative delirium. Participants with delirium demonstrated lesser functional recovery than their counterparts without delirium; at 1 month, the covariate-adjusted mean difference on the physical function composite was −1.5 (95% confidence interval −3.3, −0.2). From 2 to 18 months, the corresponding difference was −1.8 (95% confidence interval −3.2, −0.3), an effect comparable with the minimally clinically significant difference. Conclusions: Delirium was associated with persistent and clinically meaningful impairment of functional recovery, to 18 months. Use of multifactorial preventive interventions for patients at high risk for delirium and tailored transitional care planning may help to maximize the functional benefits of elective surgery.
Tensile Properties of the Individual Phases in Unreacted Multifilament Nb$_{3}$Sn Wires

The room temperature elastic and plastic properties under uniaxial tensile loading of the different phases of an un-reacted, internal-tin process, Nb3Sn wire have been determined by tensile tests of whole wires and of extracted Ta, Nb and Nb alloy filaments, as well as by indentation hardness measurements in metallographic wire cross sections
Expression of CD68 and macrophage chemoattractant protein-1 genes in human adipose and muscle tissues: association with cytokine expression, insulin resistance, and reduction by pioglitazone.

To examine the role of adipose-resident macrophages in insulin resistance, we examined the gene expression of CD68, a macrophage marker, along with macrophage chemoattractant protein-1 (MCP-1) in human subcutaneous adipose tissue using real-time RT-PCR. Both CD68 and MCP-1 mRNAs were expressed in human adipose tissue, primarily in the stromal vascular fraction. When measured in the adipose tissue from subjects with normal glucose tolerance, covering a wide range of BMI (21-51 kg/m2) and insulin sensitivity (S(I)) (0.6-8.0 x 10(-4)min(-1). microU(-1). ml(-1)), CD68 mRNA abundance, which correlated with the number of CD68-positive cells by immunohistochemistry, tended to increase with BMI but was not statistically significant. However, there was a significant inverse relation between CD68 mRNA and S(I) (r=-0.55, P=0.02). In addition, there was a strong positive relationship among adipose tissue CD68 mRNA, tumor necrosis factor-alpha (TNF-alpha) secretion in vitro (r=0.79, P<0.005), and plasma interleukin-6 (r=0.67, P < 0.005). To determine whether improving S(I) in subjects with impaired glucose tolerance (IGT) was associated with decreased CD68 expression, IGT subjects were treated for 10 weeks with pioglitazone or metformin. Pioglitazone increased S(I) by 60% and in the same subjects reduced both CD68 and MCP-1 mRNAs by >50%. Furthermore, pioglitazone resulted in a reduction in the number of CD68-positive cells in adipose tissue and reduced plasma TNF-alpha. Metformin had no effect on any of these measures. Thus, treatment with pioglitazone reduces expression of CD68 and MCP-1 in adipose tissue, apparently by reducing macrophage numbers, resulting in reduced inflammatory cytokine production and improvement in S(I).
A method for characterizing phenotypic changes in highly variable cell populations and its application to high content screening of Arabidopsis thaliana protoplasts

Quantitative image analysis procedures are necessary for the automated discovery of effects of drug treatment in large collections of fluorescent micrographs. When compared to their mammalian counterparts, the effects of drug conditions on protein localization in plant species are poorly understood and underexplored. To investigate this relationship, we generated a large collection of images of single plant cells after various drug treatments. For this, protoplasts were isolated from six transgenic lines of A. thaliana expressing fluorescently tagged proteins. Eight drugs at three concentrations were applied to protoplast cultures followed by automated image acquisition. For image analysis, we developed a cell segmentation protocol for detecting drug effects using a Hough transform‐based region of interest detector and a novel cross‐channel texture feature descriptor. In order to determine treatment effects, we summarized differences between treated and untreated experiments with an L1 Cramér‐von Mises statistic. The distribution of these statistics across all pairs of treated and untreated replicates was compared to the variation within control replicates to determine the statistical significance of observed effects. Using this pipeline, we report the dose dependent drug effects in the first high‐content Arabidopsis thaliana drug screen of its kind. These results can function as a baseline for comparison to other protein organization modeling approaches in plant cells. © 2017 International Society for Advancement of Cytometry
Edited 1H magnetic resonance spectroscopy in vivo: Methods and metabolites

The Proton magnetic resonance (1H‐MRS) spectrum contains information about the concentration of tissue metabolites within a predefined region of interest (a voxel). The conventional spectrum in some cases obscures information about less abundant metabolites due to limited separation and complex splitting of the metabolite peaks. One method to detect these metabolites is to reduce the complexity of the spectrum using editing. This review provides an overview of the one‐dimensional editing methods available to interrogate these obscured metabolite peaks. These methods include sequence optimizations, echo‐time averaging, J‐difference editing methods (single BASING, dual BASING, and MEGA‐PRESS), constant‐time PRESS, and multiple quantum filtering. It then provides an overview of the brain metabolites whose detection can benefit from one or more of these editing approaches, including ascorbic acid, γ‐aminobutyric acid, lactate, aspartate, N‐acetyl aspartyl glutamate, 2‐hydroxyglutarate, glutathione, glutamate, glycine, and serine. Magn Reson Med 77:1377–1389, 2017. © 2017 International Society for Magnetic Resonance in Medicine.
National Trends in Antidepressant, Benzodiazepine, and Other Sedative-Hypnotic Treatment of Older Adults in Psychiatric and Primary Care.

OBJECTIVE To describe how use of antidepressants, benzodiazepines, and other anxiolytic/sedative-hypnotics among older adults (age ≥ 65 years) has changed over time among visits to primary care providers and psychiatrists. METHODS Data were from the National Ambulatory Medical Care Survey (years 2003-2005 and 2010-2012), a nationally representative cross-section of outpatient physician visits. Analysis focused on visits to primary care providers (n = 14,282) and psychiatrists (n = 1,095) at which an antidepressant, benzodiazepine, or other anxiolytic/sedative-hypnotic was prescribed, which were stratified by demographic and clinical characteristic (including ICD-9-CM diagnosis) and compared across study intervals. Odds of medication use were calculated for each stratum, adjusting for demographic and clinical characteristics. RESULTS The visit rate by older adults to primary care providers where any of the medications were prescribed rose from 16.4% to 21.8% (adjusted odds ratio [AOR] = 1.43, P < .001) while remaining steady among psychiatrists (75.4% vs 68.5%; AOR = 0.69, P = .11). Primary care visits rose for antidepressants (9.9% to 12.3%; AOR = 1.28, P = .01) and other anxiolytic/sedative-hypnotics (3.4% to 4.7%; AOR = 1.39, P = .01), but the largest growth was among benzodiazepines (5.6% to 8.7%; AOR = 1.62, P < .001). Among patients in primary care, increases primarily occurred among men, non-Hispanic white patients, and those with pain diagnoses as well as those with no mental health or pain diagnoses. CONCLUSIONS From 2003 to 2012, use of the most common psychotropic medications among older adults seen in primary care increased, with concentration among patients with no mental health or pain diagnosis. As the population of older adults grows and receives mental health treatment in primary care, it is critical to examine the appropriateness of psychotropic use.
Local and Global Regressive Mapping for Manifold Learning with Out-of-Sample Extrapolation

Over the past few years, a large family of manifold learning algorithms have been proposed, and applied to various applications. While designing new manifold learning algorithms has attracted much research attention, fewer research efforts have been focused on out-of-sample extrapolation of learned manifold. In this paper, we propose a novel algorithm of manifold learning. The proposed algorithm, namely Local and Global Regressive Mapping (LGRM), employs local regression models to grasp the manifold structure. We additionally impose a global regression term as regularization to learn a model for out-of-sample data extrapolation. Based on the algorithm, we propose a new manifold learning framework. Our framework can be applied to any manifold learning algorithms to simultaneously learn the low dimensional embedding of the training data and a model which provides explicit mapping of the out-of-sample data to the learned manifold. Experiments demonstrate that the proposed framework uncover the manifold structure precisely and can be freely applied to unseen data.