Miracle-dz/UniFAR-FTUs huggingface dataset:
Association of a gene expression profile from whole blood with disease activity in systemic lupus erythaematosus

Objective: To determine whether peripheral blood gene expression of patients with systemic lupus erythaematosus (SLE) correlates with disease activity measured using the SLE Disease Activity Index 2000 (SLEDAI-2K). Methods: RNA was isolated from peripheral blood of 269 patients with SLE and profiled on a custom microarray. Hierarchical clustering and a heat map were used to categorise samples into major clusters based on gene expression pattern. Correlates, including demographic and disease-related characteristics such as SLEDAI-2K score, of the major sample clusters were compared using multivariate regression models. Results: A set of 31 interferon (IFN)-regulated genes were seen to be driving the separations of samples into two clusters, one characterised by a relatively high IFN-regulated gene signature (n = 150) and the other by a relatively low IFN-regulated gene signature (n = 119). Disease activity measured using the SLEDAI-2K was significantly correlated with the high IFN gene signature. In multivariate regression analysis the immunological component of the SLEDAI-2K was a significant correlate of the high IFN gene signature as was presence of antibodies to U1RNP. There were no discernable correlates of the 156 non-IFN regulated genes profiled on the custom array. Conclusion: Peripheral blood gene expression profiling (GEP) in SLE allows patients to be categorised into two groups based on a high or low IFN gene signature. Disease activity measured using the SLEDAI-2K is correlated with the high IFN gene signature, indicating that GEP may be a useful biomarker of disease activity in SLE.
Therapeutic drug monitoring of A77 1726, the active metabolite of leflunomide: serum concentrations predict response to treatment in patients with rheumatoid arthritis

Background: Leflunomide is the prodrug of the disease modifying antirheumatic metabolite A77 1726. More than 50% of patients withdraw from leflunomide treatment within one year, mainly because of adverse drug reactions. Therapeutic drug monitoring of A77 1726 may be useful in predicting the efficacy of leflunomide treatment. Objective: To study the relation between A77 1726 steady state serum concentrations and disease activity using the 28 joint (DAS28) response. Methods: Outpatients with rheumatoid arthritis on a stable leflunomide dose for >4 months were included. DAS28 score and adverse drug reactions were recorded. Blood samples were taken for determination of A77 1726 concentrations. The primary end point was the relation of serum A77 1726 concentrations with DAS28 response category Results: Serum A77 1726 concentrations were determined in 52 patients. A receiver operating characteristic (ROC) curve showed an area under the curve (AUC) of 0.73 (95% confidence interval, 0.54 to 0.93) (p<0.05). The sensitivity exceeded 99% at concentrations below 16 mg/l. DAS28 values at the point of sampling showed no relation with A77 1726 concentrations (AUC of the ROC curve = 0.50 (0.33 to 0.67) (NS)). Conclusions: A77 1726 steady state serum concentrations show a relation with DAS28 response. Determination of serum A77 1726 concentrations in patients with insufficient response to treatment may help when decisions have to be made about continuation of treatment or dose adjustment.
Penerapan 2 SLS GMM-AB pada Persamaan Simultan Data Panel Dinamis untuk Pemodelan Pertumbuhan Ekonomi Indonesia sebagai Islamic Country

Indonesia is an islamic country that still has problems in economics such as unemployment and poverty. Stability and economic growth are expected to overcome these problems. Two-way relationship between unemployment and economic growth can be summarized in a system of simultaneous equation. Two directions relationship of mutual influence can be summarizedin a system of simultaneous equations. Economic variables are dynamic; the value is influenced by value of variable itself in the past and also the value of other variables. In a dynamic panel data model there is a lag of the dependent variable that causes the OLS estimates can be biased and inconsistent. Arellano-Bond GMM with optimal weight produces parameter estimate which is unbiased, consistent, and efficient. From this study we can conclude that there is a simultaneous relationship between economic growth and unemployment. If economic growth increases 1%, it will cause the unemployment decrease to 0.956% in short-term and 0.988% in shortterm. On the other hand, if unemployment increases 1%, it will cause a slowdown in economics to 0.465% and 0.615% for the long term
Fossil Fuel Price Shocks and CO2 Emissions: The Case of Spain

ABSTRACT This paper focuses on the impact of oil, natural gas and coal price shocks on the Spanish business cycle from 1969 to 2013. It uses Bayesian procedures to estimate a Dynamic Stochastic General Equilibrium (DSGE) model for a small open economy. The paper shows that natural gas and coal shocks are relevant sources of macroeconomic disruption in addition to oil price shocks. The three fossil fuel prices have an impact on the economic activity and explain the evolution of the energy mix. However, we find that oil price shocks have a significantly larger impact on economic volatility. Finally, we assess the impact of hydrocarbon price shocks on carbon emissions given that different price shocks result in a different fossil fuel mix and, thus, in different CO2 emissions.
Toll‐like receptor stimulation as a third signal required for activation of human naive B cells

According to the current model, naive B cell activation is dependent on the sequential integration of two signals: B cell receptor (BCR) cross‐linking by antigen, followed by cognate interaction with helper T cells through an immunological synapse. Using an improved method to purify human naive B cells we found that BCR stimulation and T cell help induced initial cell division but were not sufficient to promote survival and differentiation thus leading to abortive proliferation of naive B cells. Extensive B cell proliferation, isotypic switch and differentiation to immunoglobulin (Ig)‐secreting cells was induced by addition of microbial products that trigger any of the Toll‐like receptors (TLR) that are up‐regulated in naive B cells upon BCR triggering. TLR agonists acted directly on B cells and were required irrespective of the nature of the T helper cells present. Supernatants of dendritic cells (DC) stimulated by DC‐specific TLR agonists were also capable of enhancing B cell responses although to a much lower and variable extent. These results indicate that human naive B cell activation is critically dependent on innate stimuli acting optimally on TLR expressed by B cells. The coupling of BCR stimulation to TLR expression endows the human system with a high degree of specificity since it allows focusing of innate signals only on antigen‐stimulated B cells.
Critical linkages between quality management practices and performance from Indian IT enabled service SMEs

The purpose of this paper is to critically investigate the relationship among quality management (QM) practices with their direct and indirect effects on performance outcome by means of conceptual extension and generalisation. The paper uses factor analysis and structural equation modelling which has been tested using cross-sectional data collected from IT enabled small and medium service firms in India. The analysis shows the interdependency of QM practices and the importance of a systematic approach for managing QM practices. The findings from this study indicate that the nature of the interrelationships between these core QM practices is unique to the Indian context. The unique contribution of this study has been in terms of its model-building approach towards designing a linkage model showing interdependencies among critical QM practices with its direct and indirect effects on performance outcome. Such a holistic framework with plausible interaction effects has not been studied earlier in the Indian context with sector-specific relevance to IT enabled service SMEs. Further the paper recommends suggestions for improvement along with managerial implications and future scope of study.
Seizure frequency and sex steroids in women with partial epilepsy on antiepileptic therapy

Purpose: Neuroactive sex steroids influence neuron excitability, which is enhanced by estradiol (E2) and decreased by progesterone (Pg). In epilepsy, the production, metabolism, biologic availability, and activity of sex hormones may be affected by seizures themselves or by antiepileptic drugs (AEDs). This cross‐sectional observational study was aimed at evaluating the relationships between sex steroids, seizure frequency, and other clinical parameters in women with partial epilepsy (PE) on AED treatments.
Entrepreneurial orientation and export performance: the mediating effect of organisational resources and dynamic capabilities

This study analyses the relationships among entrepreneurial orientation, organisational resources, dynamic capabilities, and export performance. Specifically, we propose that entrepreneurial orientation enhances the attraction of financial, informational and relational resources thus affecting export performance through dynamic capabilities. This model is empirically tested with data from 265 managers of exporting companies in Portugal. Results validate ten out of eleven direct relationships of the model and confirm the mediating effect of organisational resources and dynamic capabilities on export performance. Entrepreneurial orientation contributes to the attraction of relational and informational resources, relational resources boost the development of informational and financial resources, and these three types of organisational resources directly affect the development of dynamic capabilities and export performance. In what concerns the managerial implications, managers, public policy makers, and researchers aiming to contribute to firms' competitiveness and performance must clearly understand how resources affect the development of differentiated dynamic capabilities.
MDGs to SDGs – new goals, same gaps: the continued absence of urban food security in the post-2015 global development agenda

Hunger and food insecurity have held prominent positions in the framing of both the Millennium Development Goals and the succeeding Sustainable Development Goals (SDGs). This paper argues, however, that the food goal proposed within the SDGs is flawed in its approach towards achieving food security through its neglect of the urbanization of food insecurity in Africa and of the nutrition transition. The paper argues that these misalignments reflect a limited appreciation of the nature of food and nutrition insecurity in Africa and one that serves the interest of particular sets of development agendas.
Vulvar Vestibulitis Syndrome: An Exploratory Case-Control Study

Objective: To assess the prevalence of genital bacterial infection among women with vulvar vestibulitis syndrome and to evaluate the association of several potential risk factors with the occurrence of the syndrome. Methods: Fifty-seven women referred for dyspareunia who satisfied Friedrich's criteria and had symptoms for at least 6 months were recruited as cases. Controls included 173 patients without dyspareunia seen at a private clinic. Cases and controls were aged 18-35 years and were not pregnant. Results: Among cases, the prevalences were low for genital infection with gonorrhea (0%), Chlamydia (0%), Trichomonas(0%), Mycoplasma (0%), Gardnerella (14%), and Candida(8.8%). Ureaplasma was detected in the Bartholin glands of ten affected women (17.5%). Human papillomavirus DNA was detected in only three cases (5.3%) based on polymerase chain reaction assays on vestibular biopsies. The relative risk (RR) of the syndrome was related to some aspects of sexual and reproductive history. In particular, the RR in women who had used oral contraceptives (OCs) early (before age 17) reached 11.0 (95% confidence interval [CI] 1.3-97.1) relative to those who had never used OCs. Women who had first intercourse at age 15 or earlier had a 3.3-fold increase in RR (95% CI 1.4-8.0) compared to those who had first intercourse at age 16 or later. Conclusion: Our data provide little support for the idea that infection causes the vulvar vestibulitis syndrome. Hormonal factors such as early OC use may be involved in the etiology of this condition.
Knowledge, Practice, and Associated Factors of Home-Based Management of Diarrhea among Caregivers of Children Attending Under-Five Clinic in Fagita Lekoma District, Awi Zone, Amhara Regional State, Northwest Ethiopia, 2016

Introduction In Ethiopia, it is the second cause for clinical presentation among under five-year child population. Objective The main aim of this study was to assess knowledge, practice, and associated factors of home-based management of diarrhea among caregivers of children attending the under-five clinic. Methods Institution based quantitative cross-sectional study was carried out from March 1, 2016, to April 22, 2016. Results Two hundred eight (56.2%) of them had good knowledge and one hundred thirty-nine (37.6%) of them had the good practice of home management of diarrhea, specifically, primary education (AOR: 5.384, 95% CI: 2.008, 14.438), secondary and above education (AOR: 11.769, 95% CI: 3.527, 39.275), daily laborer (AOR: 0.208, 95% CI: 0.054, 0.810), and no information about diarrhea (AOR: 0.139, 95% CI: 0.054, 0.354). Moreover, age range of 25–35 (AOR: 4.091, 95% CI: 1.741, 9.616) and 36–45 (AOR: 3.639, 95% CI: 1.155, 11.460), being single (AOR: 0.111, 95% CI: 0.013, 0.938), being divorced (AOR: 0.120, 95% CI: 0.024, 0.598), illiteracy (AOR: 0.052, 95% CI: 0.017, 0.518), primary education (AOR: 0.143, CI: 0.046, 0.440), and no information about diarrhea (AOR: 0.197, 95% CI: 0.057, 0.685) were significantly associated variables with the outcome variables in multivariate regression. Conclusion Caregivers had slightly adequate knowledge but poor practice.
Fasting and postprandial glucose, insulin, leptin, and ghrelin values in preterm babies and their mothers: relationships among their levels, fetal growth, and neonatal anthropometry

Abstract Objective: To investigate relationship between anthropometric values of premature babies with their’s glucose, insulin, leptin, and ghrelin at birth and on day 15. Methods: We analyzed fasting and postprandial glucose, insulin, leptin, and ghrelin levels at birth and on day 15 in babies born prematurely between 24 and 37 weeks, and who did not have serious problems aside from prematurity at birth. Results: Fasting glucose, insulin, leptin and ghrelin values of babies at birth and on day 15 were significantly lower than postprandial values (all p values p < 0.001). There were positive correlations between the mean insulin, leptin, and ghrelin levels with the gestational age, birth weight, body mass index, head circumference of babies at birth, and anthropometric values on day 15 (all r values > 0.400, all p values < 0.05). Fasting glucose, leptin, and ghrelin values of mothers birth were significantly lower than post-prandial values (all p values p < 0.05). Conclusions: The positive correlations between the insulin, leptin, and ghrelin values of babies at birth with gestational age and anthropometric values suggest that both hormones play important roles in fetal and neonatal growth and development.
Lower Leg Injury in Relation to Vehicle Front End

Objective: To set up a prescreening tool for vehicle front-end design, allowing numerically forecasting of the results of EC directive tests, with reference to pedestrian lower leg impact. Methods: A numerical legform model has been developed and certified according to EC directive. The frontal end of the vehicle has been simulated through a lumped-parameters model, having considered the predesign stage when the target overall behavior is being established. The stiffness behaviors of the bumper and of the spoiler have been estimated by means of more detailed numerical models. A parametric analysis has been performed to outline the effects of bumper and spoiler stiffness, bumper vertical height, and the longitudinal distance between the spoiler and the bumper. An analytical model has been introduced to predict tibial acceleration, knee shear displacement, and knee lateral bending, given the bumper and spoiler characteristics as input. Results:The parametric analysis has demonstrated that bumper stiffness, bumper profile height, and spoiler stiffness do have an impact on knee lateral bending, knee shear displacement, and peak tibial acceleration. Increasing bumper stiffness can result in higher knee bending, knee shear displacement, and peak tibial acceleration. Increasing bumper profile height produces lower knee bending and shear displacement. Increasing spoiler stiffness can determine higher knee shear displacement and peak tibial acceleration but lower knee bending. Spoiler stiffness and position have a strong correlation: higher bumper stiffness needs to be coupled to a moved forward spoiler position. The mechanical responses of the spoiler and of the bumper can be assumed to be linear: the softening behavior of the expanded polypropylene foam balances the hardening behavior of the fascia (due to contact area increase). The predictive model is well correlated to experimental findings (R 2 > 0.74) Conclusions: This simplified computer model can be used as a prescreening design tool to demonstrate general vehicle front-end design trade-offs and provide approximate results without physical testing.
Cystic Fibrosis Pathogens Activate Ca2+-dependent Mitogen-activated Protein Kinase Signaling Pathways in Airway Epithelial Cells*

Much of the pulmonary disease in cystic fibrosis is associated with polymorphonuclear leukocyte-dominated airway inflammation caused by bacterial infection. Respiratory epithelial cells express the polymorphonuclear chemokine interleukin-8 (IL-8) in response to ligation of asialylated glycolipid receptors, which are increased on damaged or regenerating cells and those with cystic fibrosis transmembrane conductance regulator mutations. Because both Pseudomonas aeruginosa andStaphylococcus aureus, the most common pathogens in cystic fibrosis, bind asialylated glycolipid receptors such as asialoGM1, we postulated that diverse bacteria can activate a common epithelial signaling pathway to elicit IL-8 expression. P. aeruginosa PAO1 but not pil mutants andS. aureus RN6390 but not the agr mutant RN6911 stimulated increases in [Ca2+] i in 1HAEo− airway epithelial cells. This response stimulated p38 and ERK1/2 mitogen-activated protein kinase (MAPK) signaling cascades resulting in NF-κB activation and IL-8 expression. Ligation of the asialoGM1 receptor or thapsigargin-elicited Ca2+ release activated this pathway, whereas P. aeruginosalipopolysaccharide did not. The rapid kinetics of epithelial activation precluded bacterial invasion of the epithelium. Recognition of asialylated glycolipid receptors on airway epithelial cells provides a common pathway for Gram-positive and Gram-negative organisms to initiate an epithelial inflammatory response.
Cerebrospinal fluid cleaved-tau protein and 9-hydroxyoctadecadienoic acid concentrations in pediatric patients with hydrocephalus

Objective: To ascertain if cerebrospinal fluid cleaved-tau protein and 9-hydroxyoctadecadienoic acid, reflecting potential biomarkers of overall neuronal injury and lipid peroxidation, respectively, are elevated in hydrocephalus patients compared with controls, and if cleaved-tau and 9-hydroxyoctadecadienoic acid levels correlate with each other. Design: Prospective clinical observational study. Setting: Tertiary-care children’s hospital. Patients: Children younger than or equal to 18 yrs who underwent ventriculoperitoneal shunt placement or revision surgery for intrinsic hydrocephalus. Measurements and Main Results: During the study period 12 patients with intrinsic hydrocephalus required ventriculoperitoneal shunt placement or revision. Cerebrospinal fluid cleaved-tau levels were significantly elevated in patients with hydrocephalus (44.7 ± 9.6 ng/mL, n = 11) compared with control patients (0.0 ± 0.0 ng/mL, n = 9; p < 0.0001). Cleaved-tau levels correlated with patient age (r = .609, p = 0.047) and duration of symptoms (r = .755, p = 0.007). No significant difference in cerebrospinal fluid 9-hydroxyoctadecadienoic acid levels between patients with hydrocephalus (24.6 ± 5.7, n = 8) and control patients (24.9 ± 9.3 ng/mL, n = 7) was detected (p = 0.25). There was also no statistically significant correlation between 9-hydroxyoctadecadienoic acid levels and duration of symptoms (r = .668, p = 0.07), nor was there a significant correlation between 9-hydroxyoctadecadienoic acid levels and patient age (r = −.011, p > 0.10). There was no significant relationship between 9-hydroxyoctadecadienoic acid levels and signs of elevated intracranial pressure, nor was there a correlation between 9-hydroxyoctadecadienoic acid levels and cleaved-tau levels. Conclusion: Children with hydrocephalus who have clinical signs of increased intracranial pressure and require ventriculoperitoneal shunt placement or revision exhibit markedly elevated cerebrospinal fluid cleaved-tau levels, suggesting evidence of axonal damage. However, this axonal injury does not seem to be associated with significant lipid peroxidation, at least as assessed by quantifying cerebrospinal fluid 9-hydroxyoctadecadienoic acid at a single, concurrent time point. The significant relationship between age and cerebrospinal fluid cleaved-tau levels suggest that brain injury associated with hydrocephalus may be more pronounced in older children.
Fallacies in the pathological confirmation of the diagnosis of Alzheimer’s disease

OBJECTIVE Necropsy confirmed clinical diagnostic accuracy for Alzheimer’s disease is claimed to exceed 90%. This figure contains two fallacies; it includes cases in which Alzheimer’s disease exists with other diseases affecting cognition and the studies that report these figures excluded cases without necropsy (verification bias). The effect of these errors is estimated. METHODS Data were taken from the University of Western Ontario Dementia Study, a registry of dementia cases with clinical and psychometric follow up to necropsy based in a university memory disorders clinic with secondary and tertiary referrals. Data were available on 307 patients; 200 (65%) had clinically diagnosed Alzheimer’s disease, 12 (4%) vascular dementia, 47 (15%) mixed dementia, and 48 (16%) had other diagnoses. One hundred and ninety two of 307 cases (63%) died and 122 of 192 fatalities (64%) had necropsies. The pathological material was interpreted in two ways, allowing and disallowing coexistent disease in making a diagnosis of Alzheimer’s disease. In cases without necropsy, progressive cognitive loss was used as a marker for degenerative dementia. The outcome measures of interest were the positive predictive value of a clinical diagnosis of Alzheimer’s disease allowing and disallowing coexistent diseases and with and without correction for cases that were not necropsied. RESULTS The clinical diagnoses differed significantly between the population who died and those who did not. In cases without necropsy, 22% had no dementia on follow up, concentrated in early cases and men, showing considerable scope for verification bias. The positive predictive value of a diagnosis of Alzheimer’s disease was 81% including coexistent diseases, falling to 44% when limited to pure cases. Combined, these factors reduce the positive predictive value to 38% for pure Alzheimer’s disease. CONCLUSIONS Correction for dual pathology and verification bias halves the positive predictive value of the clinical diagnosis of Alzheimer’s disease. Data derived from necropsy studies cannot be extrapolated to the whole population. This has important implications including uncertainty about diagnosis and prognosis and a dilution effect in therapeutic trials in Alzheimer’s disease.