Miracle-dz/UniFAR-FTUs huggingface dataset:
Association between disease activity and risk of serious infections in subjects with rheumatoid arthritis treated with etanercept or disease-modifying anti-rheumatic drugs.

OBJECTIVES To determine the risk of serious infection in patients with rheumatoid arthritis (RA) receiving etanercept (ETN) or disease-modifying anti-rheumatic drugs (DMARDs) and to identify factors that predict a higher risk. METHODS Five-year data from the British Society of Rheumatology Biologics Register (BSRBR), a prospective observational study of patients with active RA treated with ETN, were used. These data were compared with a cohort of patients receiving DMARDs with active RA. RESULTS Total follow-up was 19,964 patient-years (py; ETN, 14,381 py; DMARDs, 5583 py). Over the study period, 651 first-recorded serious infections were reported (ETN, 469 [39.9 per 1000 py]; DMARDs, 182 [35.0 per 1000 py]). Overall the risk of serious infection was similar for the 2 treatments; however, in the first 6 months of treatment the hazard ratio (HR) was higher in the ETN than the DMARD group (1.979; p=0.015). A linear association was observed between the serious infection rate and disease-activity score in 28 joints (DAS28) in patients from each treatment group and overall (DAS28 <4, 27.1 per 1000 py; DAS28 ≥8, 64.4 per 1000 py; 7.5% increase in serious infection for each unit increase of DAS28 score at baseline). In a time-dependent analysis, a DAS28 change of 1 unit during follow-up predicted a 27% increase in serious infection rates. CONCLUSIONS No significant increase in the risk of serious infection was observed with ETN versus DMARDs over the 5-year study; a linear relationship existed between the serious infection rate and disease activity, as measured by DAS28.
Impact of venous drainage on regeneration of the anterior segment of right living‐related liver grafts

Abstract: The effect of additional venous reconstruction on morphologic and functional regeneration of the anterior segment of right‐lobe liver grafts was compared among three groups according to graft type: right liver graft without the middle hepatic vein (MHV) or MHV tributaries (n = 7), with MHV tributaries (n = 25) and with the MHV (n = 10). Whole graft volume (GV) and anterior segment volume (ASV) were estimated from CT scans and post‐operative laboratory data and daily ascitic fluid volume were examined. Peak GV in each group was reached two or three wk after surgery. The ASV/GV ratios of the grafts with the MHV or MHV tributaries were higher than those of grafts without additional venous reconstruction. However, the asparate aminotransferase and ascitic fluid volume values in the group that received grafts with MHV tributaries were higher than in the group that received grafts with the MHV in the same period. Although rapid enlargement of the anterior segment of right‐lobe grafts with MHV tributaries occurred in the early post‐operative period, complete functional liver regeneration may not occur even after additional tributary reconstruction. These results suggest that the selection of right‐lobe grafts with the MHV is more beneficial for recipients, as long as donor safety is protected and that as many MHV tributaries as possible should be reconstructed in right‐lobe grafts without MHV.
Towards consumer-driven meat supply chains: opportunities and challenges for differentiation by taste

Abstract This paper investigates the state of pork supply as to its neglect of developing innovations and mechanisms for delivering superior eating quality to consumers. We explore reasons behind pork supply chains’ predominant focus on mass production combined with traceability and food safety, while only little attention has been given to potentially lucrative niche markets focused on intrinsic quality cues. Using established analytical frameworks of hedonic pricing and transactions costs economics we discuss alternative strategies for the segregation and promotion of intrinsic sensory differentiated pork. Growing empirical evidence in the literature underpins the importance of eating experience in delivering utility to consumers and in stabilizing declining demand trends in major markets. Building on current consumer behavioral literature and organizational developments in meat supply chains in Europe and Australia, we critically discuss opportunities to overcome this supposedly suboptimal situation.
Radiopharmaceutical chemistry of targeted radiotherapeutics, Part 2: radiolytic effects of 211At alpha-particles influence N-succinimidyl 3-211AT-astatobenzoate synthesis.

UNLABELLED A variety of promising targeted radiotherapeutics labeled with alpha-emitters have been developed. Clinical investigation of these radiopharmaceuticals requires the production of high activity levels, which can be hindered by alpha-particle-mediated radiolytic effects on labeling chemistry. The purpose of this study was to investigate the effects of radiation dose on the synthesis of N-succinimidyl 3-(211)At-astatobenzoate (SAB), a compound used in our clinical trials for labeling antibodies with alpha-particle-emitting (211)At. METHODS Yields for the synthesis of SAB as a function of the radiation dose received by the reaction medium were determined. The variables studied included the radiohalogenation precursors N-succinimidyl 3-(tri-n-butylstannyl)benzoate (BuSTB) and N-succinimidyl 3-(trimethylstannyl)benzoate (MeSTB); the solvents chloroform, benzene, and methanol; and the addition of acetic acid and the oxidant N-chlorosuccinimide. The (211)At product spectra were determined from high-performance liquid chromatograms and then plotted against radiation dose. RESULTS SAB production declined rapidly with increasing dose, consistent with the documented radiolytic decomposition of BuSTB and MeSTB in chloroform. Even though these tin precursors were not appreciably degraded in benzene, SAB could not be produced in this solvent; instead, highly lipophilic (211)At-labeled species were generated in nearly quantitative yields. Although a dose-dependent decline in SAB yield also was observed in methanol, both in the presence and in the absence of an oxidant, the results were better than those obtained with the other solvents. An unexpected observation was that SAB could be obtained at a yield of greater than 30% when the reaction was run in methanol without the addition of acetic acid or an oxidant; these 2 components previously were considered essential for astatodestannylation. CONCLUSION Radiolytic factors can play an important role in the synthesis of clinical-level activities of (211)At-labeled radiopharmaceuticals, necessitating the development of reaction conditions different from those that are used successfully at lower activity levels.
Screening mammography in older women: a review.

IMPORTANCE Guidelines recommend individualizing screening mammography decisions for women aged 75 years and older. However, little pragmatic guidance is available to help counsel patients. OBJECTIVE To provide an evidence-based approach for individualizing decision-making about screening mammography in older women. EVIDENCE ACQUISITION We searched PubMed for English-language studies in peer-reviewed journals published from January 1, 1990, to February 1, 2014, to identify risk factors for late-life breast cancer in women aged 65 years and older and to quantify the benefits and harms of screening mammography for women aged 75 years and older. FINDINGS Age is the major risk factor for developing and dying from breast cancer. Breast cancer risk factors that reflect hormonal exposures in the distant past, such as age at first birth or age at menarche, are less predictive of late-life breast cancer than factors indicating recent hormonal exposures such as high bone mass or obesity. Randomized trials of the benefits of screening mammography did not include women older than 74 years. Thus it is not known if screening mammography benefits older women. Observational studies favor extending screening mammography to older women who have a life expectancy of more than 10 years. Modeling studies estimate 2 fewer breast cancer deaths/1000 women who in their 70s continue biennial screening for 10 years instead of stopping screening at age 69. Potential harms of continued screening over 10 years include false-positive mammograms in approximately 200/1000 women screened and overdiagnosis (ie, finding breast cancer that would not have clinically surfaced otherwise) in approximately 13/1000 women screened. Providing information about life expectancy along with potential benefits and harms of screening may help older women's decision-making about screening mammography. CONCLUSIONS AND RELEVANCE For women with less than a 10-year life expectancy, recommendations to stop screening mammography should emphasize increased potential harms from screening and highlight health promotion measures likely to be beneficial over the short term. For women with a life expectancy of more than 10 years, deciding whether potential benefits of screening outweigh harms becomes a value judgment for patients, requiring a realistic understanding of screening outcomes.
The GTPase Rac Regulates the Proliferation and Invasion of Fibroblast-Like Synoviocytes from Rheumatoid Arthritis Patients

Fibroblast-like synoviocytes (FLS) isolated from joints of rheumatoid arthritis (RA) patients display proliferative and invasive properties reminiscent of those of malignant tumor cells. Rac small GTPases play an important role in tumor cell proliferation and invasion. We therefore investigated the potential role of Rac proteins in the proliferative and invasive behavior of RA-FLS. We showed that inhibiting Rac activity with the Rac-specific small molecule inhibitor NSC23766 causes a strong inhibition of RA-FLS proliferation, without affecting cell survival. Rac inhibition also results in a strong reduction in RA-FLS invasion through reconstituted extracellular matrix and a less marked inhibition of two-dimensional migration as measured by monolayer wound healing. We also showed that small interfering RNA-mediated depletion of Rac1 inhibits RA-FLS proliferation and invasion to a similar extent as NSC23766. These results demonstrate for the first time that Rac proteins play an important role in the aggressive behavior of FLS isolated from RA patients. In addition, we observed that inhibiting Rac proteins prevents JNK activation and that the JNK inhibitor SP600125 strongly inhibits RA-FLS invasion, suggesting that Rac-mediated JNK activation contributes to the role of Rac proteins in the invasive behavior of RA-FLS. In conclusion, Rac-controlled signaling pathways may present a new source of drug targets for therapeutic intervention in RA.
Effects of alcohol misuse on gambling patterns in youth.

OBJECTIVE Gambling and alcohol misuse are prevalent among youth and may be part of a common problem behavior syndrome. It was hypothesized that alcohol misuse would predict a pattern of increased youth gambling or a pattern of stable high gambling after controlling for key sociodemographic, socialization and individual factors. METHOD Data were analyzed from two longitudinal studies of youth living in a western New York metropolitan area. Respondents' gambling at two times over the course of 12-18 months was classified into one of five gambling pattern groups, representing flat-low, increasing, flat-medium, flat-high and decreasing levels of gambling. RESULTS Alcohol misuse among males predicted increasing gambling over time or a pattern of stability of high rates of gambling even after controlling for socioeconomic status, race, age, impulsivity and parental monitoring in the family study. Higher parental monitoring and lower alcohol misuse were significant in predicting a decreasing pattern of gambling among males in the male delinquency study. For females in the family study, alcohol misuse predicted an increasing pattern of gambling only when other factors such as high impulsivity or low parental monitoring were present. CONCLUSIONS An understanding of adolescent gambling must take into account a variety of demographic, socialization and individual factors, as well as the co-occurrence of alcohol misuse.
Endothelin-1–Induced Arrhythmogenic Ca2+ Signaling Is Abolished in Atrial Myocytes of Inositol-1,4,5-Trisphosphate(IP3)–Receptor Type 2–Deficient Mice

Recent studies have suggested that inositol-1,4,5-trisphosphate-receptor (IP3R)–mediated Ca2+ release plays an important role in the modulation of excitation–contraction coupling (ECC) in atrial tissue and the generation of arrhythmias, specifically chronic atrial fibrillation (AF). IP3R type-2 (IP3R2) is the predominant IP3R isoform expressed in atrial myocytes. To determine the role of IP3R2 in atrial arrhythmogenesis and ECC, we generated IP3R2-deficient mice. Our results revealed that endothelin-1 (ET-1) stimulation of wild-type (WT) atrial myocytes caused an increase in basal [Ca2+]i, an enhancement of action potential (AP)-induced [Ca2+]i transients, an improvement of the efficacy of ECC (increased fractional SR Ca2+ release), and the occurrence of spontaneous arrhythmogenic Ca2+ release events as the result of activation of IP3R-dependent Ca2+ release. In contrast, ET-1 did not alter diastolic [Ca2+]i or cause spontaneous Ca2+ release events in IP3R2-deficient atrial myocytes. Under basal conditions the spatio-temporal properties (amplitude, rise-time, decay kinetics, and spatial spread) of [Ca2+]i transients and fractional SR Ca2+ release were not different in WT and IP3R2-deficient atrial myocytes. WT and IP3R2-deficient atrial myocytes also showed a significant and very similar increase in the amplitude of AP-dependent [Ca2+]i transients and Ca2+ spark frequency in response to isoproterenol stimulation, suggesting that both cell types maintained a strong inotropic reserve. No compensatory changes in Ca2+ regulatory protein expression (IP3R1, IP3R3, RyR2, NCX, SERCA2) or morphology of the atria could be detected between WT and IP3R2-deficient mice. These results show that lack of IP3R2 abolishes the positive inotropic effect of neurohumoral stimulation with ET-1 and protects from its arrhythmogenic effects.
Is Accounting an Applied Discipline? An Institutional Theory Assessment of Its Labor Market

This paper recasts the debate over whether accounting research is relevant to accounting practice by asking the more fundamental question of whether modern academic accounting is an applied discipline. Using an institutional theory template, we argue that academic accounting only purports to be an applied discipline relative to the professional practice of accounting. We study the human capital of personnel inflows into academic accounting in terms of practice work experience. We conclude that pre-academia practice experience is counterproductive to academic success in terms of research productivity and movement in academic labor markets. Implications pertaining to the broadly based schism between “town and gown” in accounting are drawn.
Association Between Corneal Endothelial Cell Density and Topical Glaucoma Medication Use in an Eye Bank Donor Population

Purpose: To evaluate the association between corneal endothelial cell density (ECD) and donor topical glaucoma medication use in an eye bank database. Methods: Raw eye bank data included 19,159 donors over the period July 2007 to May 2015. Free-text, donor medication lists were retrospectively searched for glaucoma medication. Exclusion criteria were age less than 40 years, history of eye surgery, endothelial trauma, guttae, and cell densities <1000 or >3300/mm2. Analysis of covariance was used to test differences in cell density between groups while adjusting for age. Linear regression was used to test the correlation of independent interval variables while adjusting for age. Results: Twelve thousand one hundred fifty-seven donors were included in the final analysis; 134 were on topical glaucoma medication. The mean ECD for donors not on glaucoma medication and pooled donors on glaucoma medication was 2561 ± 348 and 2516 ± 320 cells/mm2, respectively (P = 0.42). Subgroup analysis by medication class resulted in nonstatistically significant differences between ECDs of nonmedicated donors and donors on alpha agonists (P = 0.76), beta blockers (P = 0.90), carbonic anhydrase inhibitors (P = 0.13), cholinergics (P = 0.37), and prostaglandin analogs (P = 0.62). The number of glaucoma medication classes used by donors was not a statistically significant predictor of endothelial density (P = 0.298). Conclusions: Donors on topical glaucoma medication do not have ECDs statistically significantly lower than donors not on medication.
Large-scale classification of P-glycoprotein inhibitors using SMILES-based descriptors

Abstract P-glycoprotein (Pgp) inhibition has been considered as an effective strategy towards combating multidrug-resistant cancers. Owing to the substrate promiscuity of Pgp, the classification of its interacting ligands is not an easy task and is an ongoing issue of debate. Chemical structures can be represented by the simplified molecular input line entry system (SMILES) in the form of linear string of symbols. In this study, the SMILES notations of 2254 Pgp inhibitors including 1341 active, and 913 inactive compounds were used for the construction of a SMILE-based classification model using CORrelation And Logic (CORAL) software. The model provided an acceptable predictive performance as observed from statistical parameters consisting of accuracy, sensitivity and specificity that afforded values greater than 70% and MCC value greater than 0.6 for training, calibration and validation sets. In addition, the CORAL method highlighted chemical features that may contribute to increased and decreased Pgp inhibitory activities. This study highlights the potential of CORAL software for rapid screening of prospective compounds from a large chemical space and provides information that could aid in the design and development of potential Pgp inhibitors.
Heat Shock Cognate Protein 70 Is Involved in Rotavirus Cell Entry

ABSTRACT In this work, we have identified the heat shock cognate protein (hsc70) as a receptor candidate for rotaviruses. hsc70 was shown to be present on the surface of MA104 cells, and antibodies to this protein blocked rotavirus infectivity, while not affecting the infectivity of reovirus and poliovirus. Preincubation of the hsc70 protein with the viruses also inhibited their infectivity. Triple-layered particles (mature virions), but not double-layered particles, bound hsc70 in a solid-phase assay, and this interaction was blocked by monoclonal antibodies to the virus surface proteins VP4 and VP7. Rotaviruses were shown to interact with hsc70 at a postattachment step, since antibodies to hsc70 and the protein itself did not inhibit the virus attachment to cells. We propose that the functional rotavirus receptor is a complex of several cell surface molecules that include, among others, hsc70.
Adaptation of the Two Sources of Code and One-Hot Encoding Method for Designing a Model of Microprogram Control Unit with Output Identification

This article presents a proposal for a model of a microprogram control unit (CMCU) with output identification adapted for implementation in complex programmable logic devices (CPLD) equipped with integrated memory modules [1]. An approach which applies two sources of code and one-hot encoding has been used in a base CMCU model with output identification [2] [3]. The article depicts a complete example of processing for the proposed CMCU model. Furthermore, it also discusses the advantages and disadvantages of the approach in question and presents the results of the experiments conducted on a real CPLD system.
Optimal linear combination of biomarkers for multi‐category diagnosis

The receiver operating characteristic (ROC) curve and the area under the ROC curve have been popularly employed in evaluating the diagnosis accuracy for diseases with binary outcome categories and have been naturally used as the utility measures for finding the ‘optimal’ linear combination of multiple biomarkers, in the hope to improve the diagnostic accuracy based on each single biomarker. For diseases with more than two outcome categories, the ROC manifold and the hypervolume under the ROC manifold (HUM) have been analogously proposed as diagnostic accuracy measures. However, finding optimal combinations of biomarkers based on the HUM criterion is less easily feasible in computation, especially when the number of disease categories is more than three and the number of biomarkers is large. In this study, we propose two new indices for evaluating the diagnostic accuracy for multi‐category diagnosis, which are related to the lower and upper bounds of HUM, and involve only diagnostic accuracies for comparing adjacent pairs of outcome categories. We then propose finding the optimal linear combinations of biomarkers for multi‐category diagnosis using the new indices as the criterion functions. Simulations and real data examples show that the optimal linear combinations identified by the new proposal perform quite well in diagnostic accuracy and can be much more efficient in computation than the HUM‐based method. Copyright © 2015 John Wiley & Sons, Ltd.
Immunoelectron microscopic localization of snRNPs

Small nuclear ribonucleoprotein particles (snRNPs) were identified in nuclear sonicates of Novikoff hepatoma ascites cells and in intact Novikoff hepatoma and PtK2 cells by immunofluorescence and immunoelectron microscopy. Auto‐antibodies (anti‐Sm and anti‐RNP) obtained from patients with systemic lupus erythematosus an autoimmune disease, were used to localize snRNP particles. The Sm antibody is specific for U1, U2, U4, U5 and U6 containing snRNPs. The RNP antibody is specific for only U1 containing snRNPs. Isolated particles, 120 +/‐ 10 A in diameter, were found to be associated with ferritin‐conjugated goat anti‐human antibodies coupled to Sm antibodies. In addition, these particles (snRNPs) were occasionally associated with larger particles measuring 230 +/‐ 10 A in diameter which are presumed to be hnRNP particles. Double label immunofluorescence and immunoelectron microscopy have shown Sm and RNP antibodies to colocalize in PtK2 cells. However, the perinucleolar chromatin and juxtanuclear envelope chromatin was devoid of RNP immunostaining. Therefore, U1 containing snRNPs do not appear to be in these regions. The Sm antibody localizes in a nuclear network including the perinucleolar chromatin and juxtanuclear envelope chromatin. Cells treated with the drug DRB (5,6‐dichloro‐1‐beta‐D‐ribofuranosylbenzimidazole), which inhibits hnRNA synthesis, show an altered pattern of Sm immunostaining. Such cells contain large clusters of snRNPs which do not extend to the perinucleolar chromatin or perinuclear lamina chromatin. Nuclear matrix preparations maintain an snRNP nuclear network as visualized by Sm immunofluorescence. It is notable that the size and density of the immunostained particles in the nuclear network during interphase, is similar to that of interchromatinic granules.