Miracle-dz/UniFAR-FTUs huggingface dataset:
Repairing the efficiency loss due to varying cluster sizes in two‐level two‐armed randomized trials with heterogeneous clustering

In two‐armed trials with clustered observations the arms may differ in terms of (i) the intraclass correlation, (ii) the outcome variance, (iii) the average cluster size, and (iv) the number of clusters. For a linear mixed model analysis of the treatment effect, this paper examines the expected efficiency loss due to varying cluster sizes based upon the asymptotic relative efficiency of varying versus constant cluster sizes. Simple, but nearly cost‐optimal, correction factors are derived for the numbers of clusters to repair this efficiency loss. In an extensive Monte Carlo simulation, the accuracy of the asymptotic relative efficiency and its Taylor approximation are examined for small sample sizes. Practical guidelines are derived to correct the numbers of clusters calculated under constant cluster sizes (within each treatment) when planning a study. Because of the variety of simulation conditions, these guidelines can be considered conservative but safe in many realistic situations. Copyright © 2016 John Wiley & Sons, Ltd.
How do they do it: working women meeting physical activity recommendations.

OBJECTIVE To identify factors that facilitate adherence to physical activity among employed women. METHODS Participants were 103 employed women (Mean 44.4 years ±11.8). Measures included physical activity by accelerometry, location by global positioning systems, and psychosocial constructs, perception of worksite policies and the built environment by questionnaire. RESULTS Meeting physical activity recommendations was significantly associated with use of the built environment, self-regulation, perception of higher land-use mix diversity, and perception of lower infrastructure and safety for walking. Perception of worksite policies, self-efficacy, and social support were not associated with meeting recommendations. CONCLUSIONS The findings provide evidence that working women's physical activity behavior is influenced by both psychosocial and environmental factors.
Access to primary care affects the health of Deaf people.

> ‘On Wednesday, Hazel (a Deaf British Sign Language user) felt unwell at work. She went to a walk-in clinic, where she had to communicate with the nurse by writing notes (there were no interpreters on call). Hazel can read, but like many Deaf people this is at a basic level. The nurse diagnosed a problem with her knee but told her to go to her GP, which Hazel did first thing on Thursday, but had to sit around for a couple of hours to be seen. Again, as there was no interpreter at short notice, she had to tell the GP about her ‘stiffness’ on her left side by writing. She could not follow what the doctor was saying except ‘she should go to hospital’ to be checked. She went to the emergency department, which entailed another wait and more written communication, where she was kept in overnight and on Friday morning the doctor (at least she thinks it was a doctor) wrote down she ‘probably had a mild stroke’. Since she was feeling a bit better, she was told that she could go home and rest. Her condition worsened over the weekend until she could not hold a cup with her left hand. On Monday morning she went back to the GP, who took one look at her and sent her by ambulance straight to hospital for emergency admission. She was admitted for a week and was discharged back to the care of her GP, who had this time managed to get an interpreter. During this consultation it emerged that she had stopped her antihypertensives because she did not like the tablets, and she was unaware that this was meant to be a lifelong treatment. ’ This story was reported in a recent study of the health of Deaf sign …
Single step aerosol synthesis of nanocomposites by aerosol routes: γ-Fe_2O_3/SiO_2 and their functionalization

A single step gas phase method was developed to synthesize silica-coated iron oxide nanocomposite materials in a furnace aerosol reactor (FuAR) using premixed precursors. Synthesis of single component silica and magnetic iron oxide was studied to understand the decomposition mechanism of the precursors, identify the product crystal phase, and optimize the viable operating conditions for the controlled synthesis of nanocomposite material with desirable crystal phase, size, and morphology. The single component decomposition results are further extended to synthesize silica-coated magnetic iron oxide nanocomposite material using premixed precursor. A mechanism was proposed to explain the formation of SiO_2-coated γ-Fe_2O_3 nanocomposite in a single step in a FuAR based on chemical kinetics and was verified by supporting characterization results. The synthesized magnetic γ-Fe_2O_3/SiO_2 nanocomposite material was further tested for suspension stability, magnetic properties, and surface reactivity and was compared with uncoated γ-Fe_2O_3 nanoparticles to demonstrate improved surface properties.
A Dialysis , Opioids , and Pain Management : Where ’ s the Evidence ?

life expectancy continues to increase, and those 65 years and older appear to be the greatest beneficiaries of this increased life expectancy, with growth in this group predicted to nearly double by 2030.1 Treating this growing elderly population presents many challenges. For example, the incidence of chronic kidney disease (CKD) in people ≥65 years old more than doubled from 2000 to 2008, and end-stage renal disease (ESRD) grew by 600% from 1980 to 2009.2 Mortality rates among patients with ESRD and dialysis peaked in 2001; since then, mortality rates in these patient groups have declined, with the rate among patients undergoing dialysis decreasing to early 1980s numbers.2 Increased survival for ESRD and dialysis patients requires a paradigm shift in the treatment approach of many difficult but common comorbid disease states that threaten their quality of life, in particular chronic pain. A decade ago, it was found that 50% of long-term dialysis patients reported suffering from chronic pain.3 Musculoskeletal pain is the most common type of pain reported, but neuropathy and peripheral vascular pain also is quite common.3,4 Approximately 75% of patients on dialysis describe their pain management as inadequate, with 55% reporting a severe pain episode during the last 24 hours.3 Unfortunately, there is an absence of pain management recommendations for dialysis patients. There are no published clinical practice guidelines addressing medications for chronic pain specifically for patients with ESRD or requiring dialysis. Nephrologists often are forced to address analgesic needs for their patients with ESRD or dialysis because primary care providers often feel uncomfortable prescribing analgesics and other therapies in this specialized population. This has become a catch-22, because neither provider is an expert at pain management. Likewise, certified pain clinicians who focus on interventional therapy often feel equally inadequate prescribing medications to this unique population. A Dialysis, Opioids, and Pain Management: Where’s the Evidence?
Impact of electronic health record transition on behavioral health screening in a large pediatric practice.

OBJECTIVE The objective was to determine whether transitioning from paper to electronic health records affected behavioral health screening rates in a large Northeastern pediatric practice. METHODS The study setting was a pediatric practice with seven pediatricians, serving about 6,000 patients. The patient population was diverse (54% nonwhite, 40% publicly insured or self-paying, and 31% non-English speakers). An interrupted times series design was used to evaluate the impact of electronic record implementation on behavioral health screening rates. The main outcome measure was the rate of such screening 18 months before and 36 months after implementation. RESULTS The rate of behavioral health screening increased from 70% to 91% during the baseline period. The training period-six months before electronic record implementation-was associated with a 28% decline in adjusted screening rates (from 83.3% to 55.5%). Only 50% of eligible youths were screened in the first month after implementation. The screening rate took more than three years to recover to baseline levels, climbing to 82% by April 2008. CONCLUSIONS Practice changes resulting from electronic record adoption were highly disruptive of care, and disruptions took several years to resolve completely. When medical assistants rather than physicians were tasked with transferring data from paper screening forms to the electronic record, reporting compliance improved. Compliance with Healthcare Effectiveness Data and Information Set standards and Medicaid performance measures will likely be similarly affected as electronic records are implemented nationwide. Although implementing a fully automated medical record has some benefits, the unintended effects on care after implementation must be acknowledged.
Coronavirus isolation from nasal swab samples in cattle with signs of respiratory tract disease after shipping.

OBJECTIVE To monitor the prevailing viral respiratory tract infections in cattle after transportation to feedlots. ANIMALS 100 cattle with signs of respiratory tract disease on arrival at 2 feedlots. PROCEDURES Nasal swab samples were obtained from each animal and were used for inoculation of defined cell culture systems that detected bovine viruses known to cause respiratory tract infections, as well as viruses previously not recognized as respiratory pathogens for cattle. RESULTS Bovine respiratory coronaviruses were isolated from 38 of the 100 cattle, including 6 of 50 cattle from California, 22 of 31 cattle from Oklahoma, 6 of 11 cattle from Texas, and 4 of 8 cattle of unknown origin. Parainfluenza 3 viruses also were isolated from 5 California cattle, but other bovine viruses were not detected. CLINICAL IMPLICATIONS The high rate of coronavirus isolations from feedlot cattle with signs of respiratory tract disease implied wide distribution and high susceptibility among cattle to this infection, which had not been detected by use of viral isolation systems in previous etiologic evaluations of feedlot cattle affected with bovine respiratory disease complex.
Cytoskeleton/Endoplasmic Reticulum Collapse Induced by Prostaglandin J2 Parallels Centrosomal Deposition of Ubiquitinated Protein Aggregates*

Many neurodegenerative disorders, such as Parkinson disease, exhibit inclusion bodies containing ubiquitinated proteins. The mechanisms implicated in this aberrant protein deposition remain elusive. In these disorders signs of inflammation are also apparent in the affected central nervous system areas. We show that prostaglandin J2 (PGJ2), an endogenous product of inflammation, disrupts the cytoskeleton in neuronal cells. Furthermore, PGJ2 perturbed microtubule polymerization in vitro and decreased the number of free sulfhydryl groups on tubulin cysteines. A direct effect of PGJ2 on actin was not apparent, although actin filaments were altered in cells treated with PGJ2. This cyclopentenone prostaglandin triggered endoplasmic reticulum (ER) collapse and the redistribution of ER proteins, such as calnexin and catechol-O-methyltransferase, into a large centrosomal aggregate containing ubiquitinated proteins and α-synuclein. The PGJ2-dependent cytoskeletal rearrangement paralleled the development of the large centrosomal aggregate. Both of these events were replicated by treating cells with colchicine, which disrupts the microtubule/ER network, but not with brefeldin A, which impairs ER/Golgi transport. PGJ2 also perturbed 26 S proteasome assembly and activity, which preceded the accumulation of ubiquitinated proteins as detergent/salt-insoluble aggregates. Our data support a mechanism by which, upon PGJ2 treatment, cytoskeleton/ER collapse coincides with the relocation of ER proteins, other potentially neighboring proteins, and ubiquitinated proteins into centrosomal aggregates. Development of these large perinuclear aggregates is associated with disruption of the microtubule/ER network. This aberrant protein deposition, triggered by a product of inflammation, may be common to other compounds that disrupt microtubules and induce protein aggregation, such as MPP+ and rotenone, found to be associated with neurodegeneration.
Dual effect of lysine‐rich polypeptides on the activity of protein kinase CK2

Protein kinase CK2 (casein kinase II) is normally a heterotetramer composed of catalytic (α, α′) and regulatory subunits (β). CK2 is able to phosphorylate a large number of protein substrates but the physiological mechanisms of its regulation are still unresolved. Lysine‐rich peptides such as polylysine and histone H1 are known to stimulate the catalytic activity of the holoenzyme. This activation is mediated through the CK2β regulatory subunit. In this communication, we report that the same concentrations of lysine‐rich peptides or proteins that activate the holoenzyme cause strong inhibition of the phosphorylation of proteins catalyzed by the free catalytic CK2α subunit. The inhibitory effect of polylysine and histone H1 is observed with several protein substrates of CK2α (casein, adeno E1A, transcription factor II A, and CK2β itself). With calmodulin, however, the inhibition of CK2α phosphorylation caused by polylysine is much lower while with a model peptide substrate of CK2 the inhibition caused by this polycation is negligible. The inhibition of CK2α by polylysine is observed only at limiting concentrations of the target substrate proteins. The dual effect of polylysine and of histone H1, which results in the inhibition of CK2α and stimulation of the CK2 α2β2 tetrameric holoenzyme, has the consequence that the addition of the CK2β, in the presence of polylysine and low concentrations of substrate protein, can cause a 242‐fold stimulation of the activity of CK2α. Other polycationic compounds such as polyarginine and spermine do not inhibit the phosphorylation of casein by CK2α, indicating that the effect is specific for lysine‐rich peptides. Since there is evidence that there may be free CK2α subunits in the nuclei of cells, where there is abundant histone H1, the inhibition of CK2α by this lysine‐rich protein may have physiological relevance. J. Cell. Biochem. 89: 348–355, 2003. © 2003 Wiley‐Liss, Inc.
Collagen Metabolism Biomarkers and Health Related Quality of Life in Pulmonary Arterial Hypertension.

OBJECTIVES The goal of this study was to investigate the association between collagen metabolism biomarkers and health related quality of life (HRQoL) in PAH patients. METHODS We prospectively enrolled 68 stable idiopathic, anorexigen-associated, and hereditary PAH subjects and 37 healthy controls. Serum samples were analyzed for N-terminal propeptide of type III procollagen (PIIINP), c-terminal telopeptide of collagen type I (CITP), matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1). The Minnesota Living with Heart Failure (MLWHF), Euro QoL-5D (EQ-5D), Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) and Short Form (SF-36) general health survey were administered at the time of blood draw. General linear models, as well as logistic regression models were used to assess associations between variables. RESULTS CITP, PIIINP, MMP9, and TIMP1 levels, and all HRQoL domains were significantly different between controls and PAH patients (p<0.001 for each). Interestingly, PIIINP levels were significantly associated with MLWHF physical (coef=1.63, and p=0.02), SF-36 physical (coef=-2.93, p=0.004), and EQ-5D aggregate (coef=0.34, p=0.001) scores. Several of the CAMPHOR scores strongly linearly associated with PIIINP. The odds of obtaining a walk distance ≥330 meters decrease by 38% per unit increase in PIIINP (OR=0.62; 95% CI=0.43, 0.90) and a PIIINP cutoff of 5.53 μg/L provided 81% sensitivity and 82% specificity. CONCLUSIONS PIIINP is a good predictor of disease severity, and is strongly related to HRQoL scores in PAH patients. These relationships suggest PIIINP as a promising tool for PAH clinicians to determine or confirm the level of disease severity.
Immobilization of Laccase for Oxidative Coupling of Trans-Resveratrol and Its Derivatives

Trametes villosa Laccase (TVL) was immobilized through physical adsorption on SBA-15 mesoporous silica and the immobilized TVL was used in the oxidative coupling of trans-resveratrol. Higher loading and activity of the immobilized enzyme on SBA-15 were obtained when compared with the free enzyme. The effects of reaction conditions, such as buffer type, pH, temperature and substrate concentration were investigated, and the optimum conditions were screened and resulted in enzyme activity of up to 10.3 μmol/g·h. Furthermore, the oxidative couplings of the derivatives of trans-resveratrol were also catalyzed by immobilized TVL. The immobilized TVL was recyclable and could maintain 78% of its initial activity after reusing it four times.
Plastid-produced interorgannellar stress signal MEcPP potentiates induction of the unfolded protein response in endoplasmic reticulum

Significance A defining characteristic of living organisms is dynamic alignment of cellular responses to stress through activation of signal transduction pathways essential for fine-tuning of interorgannellar communication. Uncovering these communication signals is one of the prime challenges of biology. We have identified a chloroplast-produced retrograde signal, methylerythritol cyclodiphosphate (MEcPP), as a trigger of unfolded protein response (UPR) required for restoration of protein-folding homeostasis in the endoplasmic reticulum (ER). Increased levels of MEcPP via genetic manipulation or exogenous application potentiate expression of a sub-set of UPR genes, and alter plant’s resistance to the ER stress inducing agent. These findings provide a link between a plastidial retrograde signal and transcriptional reprogramming of ER genes critical for readjustment of protein-folding capacity in stressed cells. Cellular homeostasis in response to internal and external stimuli requires a tightly coordinated interorgannellar communication network. We recently identified methylerythritol cyclodiphosphate (MEcPP) as a novel stress-specific retrograde signaling metabolite that accumulates in response to environmental perturbations to relay information from plastids to the nucleus. We now demonstrate, using a combination of transcriptome and proteome profiling approaches, that mutant plants (ceh1) with high endogenous levels of MEcPP display increased transcript and protein levels for a subset of the core unfolded protein response (UPR) genes. The UPR is an adaptive cellular response conserved throughout eukaryotes to stress conditions that perturb the endoplasmic reticulum (ER) homeostasis. Our results suggest that MEcPP directly triggers the UPR. Exogenous treatment with MEcPP induces the rapid and transient induction of both the unspliced and spliced forms of the UPR gene bZIP60. Moreover, compared with the parent background (P), ceh1 mutants are less sensitive to the ER-stress-inducing agent tunicamycin (Tm). P and ceh1 plants treated with Tm display similar UPR transcript profiles, suggesting that although MEcPP accumulation causes partial induction of selected UPR genes, full induction is triggered by accumulation of misfolded proteins. This finding refines our perspective of interorgannellar communication by providing a link between a plastidial retrograde signaling molecule and its targeted ensemble of UPR components in ER.
The Bumpy Road to Universal Access: An Actor-Network Analysis of a U.S. Municipal Broadband Internet Initiative

Universal high-speed Internet access can productively transform a nation's economy. However, many municipalities in the United States have been left behind in terms of Internet penetration. Some municipal governments have tried to address this by launching initiatives that aim at offering citywide, universal broadband access. Unfortunately, most of these initiatives either have been discontinued or have ended in failure. Drawing on actor-network theory, we conducted a 3-year study to investigate the evolution of the Internet TV initiative in LaGrange, Georgia, in the United States. The results reveal distinct interpretations of the initiative by different actor groups (the government, the service providers, socioeconomically advantaged residents, and socioeconomically disadvantaged residents), at different stages of implementation, pointing to tensions among the various groups. These tensions reflect the structural problems embedded in the macro political, economic, and societal context. The findings offer insights for policymakers who intend to achieve universal broadband access.
Different patterns of atherosclerotic remodeling in the thoracic and abdominal aorta.

PURPOSE To investigate the relationship between the vascular diameter and the extent and histologic characteristics of atherosclerosis in the thoracic and abdominal aortas of patients who died of atherosclerotic disease. METHOD We measured the vascular diameter and evaluated the percentage atrophy of the medial layer of the thoracic and abdominal aortas of 19 patients who died due to atherosclerotic disease. The extent of plaques, calcification, ulceration, thrombosis, and the amount of fat in the plaques were evaluated semiquantitatively. RESULTS Atherosclerosis was more severe in the abdominal than the thoracic aorta as indicated by the higher sum of the macroscopic scores (P = .02) and the higher percentage atrophy of the medial layer (P < .001). The diameter of the thoracic, but not of the abdominal aorta, correlated with age (r = 0.56; P = .01), plaque score (r = 0.59; P = .008), calcification score (r = 0.749; P < .001), and fat score (r = 0.48; P = .04). Multiple linear regression showed that age (P = .06) and calcification score (P = .001) were the parameters with the strongest association to thoracic aorta diameter. CONCLUSION There are some differences regarding atherosclerosis in the thoracic compared to the abdominal aorta. Progressive thoracic aorta atherosclerosis is associated with fat deposition in the plaques, inducing arterial dilation. In the abdominal aorta, atherosclerosis can either have a similar evolution or be associated with less fat deposition in the arterial wall, which would result in more rigidity, hindering compensatory arterial enlargement.
Selective Expression of the MAPK Phosphatase Dusp9/MKP-4 in Mouse Plasmacytoid Dendritic Cells and Regulation of IFN-β Production

Plasmacytoid dendritic cells (pDCs) efficiently produce large amounts of type I IFN in response to TLR7 and TLR9 ligands, whereas conventional DCs (cDCs) predominantly secrete high levels of the cytokines IL-10 and IL-12. The molecular basis underlying this distinct phenotype is not well understood. In this study, we identified the MAPK phosphatase Dusp9/MKP-4 by transcriptome analysis as selectively expressed in pDCs, but not cDCs. We confirmed the constitutive expression of Dusp9 at the protein level in pDCs generated in vitro by culture with Flt3 ligand and ex vivo in sorted splenic pDCs. Dusp9 expression was low in B220− bone marrow precursors and was upregulated during pDC differentiation, concomitant with established pDC markers. Higher expression of Dusp9 in pDCs correlated with impaired phosphorylation of the MAPK ERK1/2 upon TLR9 stimulation. Notably, Dusp9 was not expressed at detectable levels in human pDCs, although these displayed similarly impaired activation of ERK1/2 MAPK compared with cDCs. Enforced retroviral expression of Dusp9 in mouse GM-CSF–induced cDCs increased the expression of TLR9-induced IL-12p40 and IFN-β, but not of IL-10. Conditional deletion of Dusp9 in pDCs was effectively achieved in Dusp9flox/flox; CD11c-Cre mice at the mRNA and protein levels. However, the lack of Dusp9 in pDC did not restore ERK1/2 activation after TLR9 stimulation and only weakly affected IFN-β and IL-12p40 production. Taken together, our results suggest that expression of Dusp9 is sufficient to impair ERK1/2 activation and enhance IFN-β expression. However, despite selective expression in pDCs, Dusp9 is not essential for high-level IFN-β production by these cells.