Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic Variants of Arachidonate 5-Lipoxygenase–Activating Protein, and Risk of Incident Myocardial Infarction and Ischemic Stroke: A Nested Case-Control Approach

Background and Purpose— Recent findings have implicated specific gene polymorphisms of arachidonate 5-lipoxygenase–activating protein (ALOX5AP), and 2 at-risk haplotypes (HapA, HapB) in myocardial infarction and stroke. To date, no prospective data are available. Methods— We evaluated 10 specific Icelandic ALOX5AP gene variants among 600 male participants with incident atherothrombotic events (myocardial infarction [MI] or ischemic stroke) and among 600 age- and smoking-matched male participants, all white, who remained free of reported cardiovascular disease during follow-up within the Physicians' Health Study cohort. Results— Overall allele, genotype, and haplotype distributions were similar between cases and controls. Single-marker conditional logistic regression analysis adjusted for potential risk factors found no association with risk of atherothrombotic events. Further investigation using a haplotype-based approach showed similar null findings with MI (HapA: odds ratio [OR]=1.18, 95% CI, 0.76 to 1.85; P=0.46; HapB: odds ratio=0.62, 95% CI, 0.36 to 1.07; P=0.08), and with ischemic stroke (HapA: odds ratio=1.11, 95% CI, 0.65 to 1.89; P=0.71; HapB: odds ratio=0.82, 95% CI, 0.47 to 1.42; P=0.47). Conclusions— We found no evidence for an association of the specific Icelandic ALOX5P gene variants/at-risk haplotypes tested with risk of incident MI nor ischemic stroke in this prospective, non-Icelandic study.
Levetiracetam and Felbamate Interact Both Pharmacodynamically and Pharmacokinetically: An Isobolographic Analysis in the Mouse Maximal Electroshock Model

Summary: Purpose: Polytherapy with two or more antiepileptic drugs (AEDs) is generally required for approximately 30% of patients with epilepsy, who do not respond satisfactorily to monotherapy. The potential usefulness of AED combinations, producing synergistic anticonvulsant efficacy and minimal adverse effects, is therefore of significant importance. The present study sought to ascertain the potential usefulness of levetiracetam (LEV) and felbamate (FBM) in combination in the mouse maximal electroshock (MES)‐induced seizure model.
An Unusual Signal Peptide Extension Inhibits the Binding of Bacterial Presecretory Proteins to the Signal Recognition Particle, Trigger Factor, and the SecYEG Complex*

Considerable evidence indicates that the Escherichia coli signal recognition particle (SRP) selectively targets proteins that contain highly hydrophobic signal peptides to the SecYEG complex cotranslationally. Presecretory proteins that contain only moderately hydrophobic signal peptides typically interact with trigger factor (TF) and are targeted post-translationally. Here we describe a striking exception to this rule that has emerged from the analysis of an unusual 55-amino acid signal peptide associated with the E. coli autotransporter EspP. The EspP signal peptide consists of a C-terminal domain that resembles a classical signal peptide plus an N-terminal extension that is conserved in other autotransporter signal peptides. Although a previous study showed that proteins containing the C-terminal domain of the EspP signal peptide are targeted cotranslationally by SRP, we found that proteins containing the full-length signal peptide were targeted post-translationally via a novel TF-independent mechanism. Mutation of an invariant asparagine residue in the N-terminal extension, however, restored cotranslational targeting. Remarkably, proteins containing extremely hydrophobic derivatives of the EspP signal peptide were also targeted post-translationally. These and other results suggest that the N-terminal extension alters the accessibility of the signal peptide to SRP and TF and promotes post-translational export by reducing the efficiency of the interaction between the signal peptide and the SecYEG complex. Based on data, we propose that the N-terminal extension mediates an interaction with an unidentified cytoplasmic factor or induces the formation of an unusual signal peptide conformation prior to the onset of protein translocation.
ACID-BASE, BLOOD GAS, AND PHYSIOLOGIC PARAMETERS DURING LAPAROSCOPY IN THE HEAD-DOWN POSITION IN WHITE-TAILED DEER (ODOCOILEUS VIRGINIANUS)

Abstract The objective of this project was to evaluate the acid-base, blood gas, and physiologic parameters of white-tailed deer (Odocoileus virginianus) during laparoscopy in the head-down position. Eleven white-tailed does were captured and then immobilized with xylazine (6 mg/kg i.m.) and ketamine (7 mg/kg i.m.). The deer were intubated orotracheally and maintained with isoflurane in oxygen. The deer were positioned in dorsal recumbency and positive pressure ventilated. Heart rate (HR), arterial blood pressure, end-tidal carbon dioxide concentration (FE/CO2), and CO2 insufflation pressure were recorded every 5 min. Respiratory parameters, plasma electrolytes, and peak inspiratory pressure were measured immediately before tilting deer in the head-down position (45–55°), 5 min after tilting, and immediately before the end of the procedure (while tilted). Butorphanol (0.05 mg/kg i.m.) was administered at the end of the procedure and yohimbine (0.2 mg/kg i.v.) administered before release. The deer weighed 52 kg (28–70 kg) [median (minimum—maximum)]. The peak inspiratory pressure in dorsal recumbency while still horizontal was 25 cm H2O (16–28 cm H2O), which increased to 29 cm H2O (18–46 cm H2O) after tilting (P = 0.02). PaO2, PaCO2, FE/CO2, and pH did not change after tilting in the head-down position or after insufflation. HR did not change during the anesthetic period. Mean arterial pressure did not change after tilting or abdominal insufflation, but decreased by the end of the anesthetic period (approximately 1 hr). Time from intubation to extubation was 117 min (72–170 min) (n = 5) and surgery time was 31 min (17–60 min; n = 10). We conclude that captured white-tailed deer have minimal derangements to acid-base, blood gas, or physiologic parameters during laparoscopy in the head-down position with abdominal insufflation, and thus this procedure may be performed safely in ventilated white-tailed deer.
Effects of regular treatment with combination of salmeterol/fluticasone propionate and salmeterol alone in cough variant asthma

Abstract Objective: Cough variant asthma (CVA) is an important cause of chronic cough, and pathophysiological features of the disease appear to be similar to typical asthma. Because CVA is recognized as a precursor of asthma, early intervention with long-term anti-inflammatory agents may be recommended. However, the role of combination therapy with inhaled corticosteroid and β2-agonist in the treatment of CVA has not been elucidated. To evaluate the effectiveness of the combination therapy, we investigated the clinical impact of regular treatment with salmeterol/fliticasone propionate combination (SFC) and inhaled salmeterol (SAL) alone in patients with CVA. Methods: The study was a randomized, controlled, parallel-group multi-center trial. Forty-three CVA patients were assigned to SFC (50/100 µg once daily) or SAL (50 µg twice daily) for 12 weeks. Then, these medications were stopped for the next 24 weeks. Main outcome measures were cough symptoms, pulmonary function and airway inflammation. Results: Treatment with each of SFC and SAL significantly decreased cough scores and increased FEV1 and PEF, where the efficacy was more pronounced with SFC than SAL. SFC also decreased sputum eosinophil counts and eosinophil cationic protein contents, whereas SAL had no effect. After discontinuation of the treatment, cough scores increased, pulmonary function and eosinophilic airway inflammation were aggravated and returned to the baseline levels. Conclusions: Maintenance therapy with SFC provides further improvements in cough symptoms, pulmonary function and airway inflammation, and discontinuation of the therapy causes worsening of the disease, indicating that stopping or interrupting anti-inflammatory therapy may not be advisable in patients with CVA.
Weight-based discrimination and medication adherence among low-income African Americans with hypertension: how much of the association is mediated by self-efficacy?

OBJECTIVES Much of the excessive morbidity and mortality from cardiovascular disease among African Americans results from low adherence to anti-hypertensive medications. Therefore, we examined the association between weight-based discrimination and medication adherence. METHODS We used cross-sectional data from low-income African Americans with hypertension. Ordinal logistic regression estimated the odds of medication non-adherence in relation to weight-based discrimination adjusted for age, sex, education, income, and weight. RESULTS Of all participants (n = 780), the mean (SD) age was 53.7 (9.9) years and the mean (SD) weight was 210.1 (52.8) lbs. Reports of weight-based discrimination were frequent (28.2%). Weight-based discrimination (but not weight itself) was associated with medication non-adherence (OR: 1.94; 95% CI: 1.41-2.67). A substantial portion 38.9% (95% CI: 19.0%-79.0%) of the association between weight-based discrimination and medication non-adherence was mediated by medication self-efficacy. CONCLUSION Self-efficacy is a potential explanatory factor for the association between reported weight-based discrimination and medication non-adherence. Future research should develop and test interventions to prevent weight-based discrimination at the societal, provider, and institutional levels.
Expression of MUC1 and MUC2 mucin gene products in human ovarian carcinomas.

BACKGROUND Aberrations in expression of mucin glycoproteins have been observed during malignant transformation of human ovarian epithelium. To date, several secretory mucin genes designated the MUC gene family have been identified, of which MUC1 encodes a mammary-type and MUC2 an intestinal-type epithelial mucin. However, information on the expression and potential value of MUC1 and MUC2 mucins in ovarian cancer is limited. METHODS This study investigated immunohistochemical expressions of MUC1 and MUC2 mucins in 23 benign and 45 malignant human ovarian tumors to assess their clinicopathological relevance. RESULTS All benign serous tumors and also associated normal-appearing epithelia expressed MUC1 mucin on the cell surfaces. Benign mucinous tumors occasionally expressed MUC1 and MUC2 mucins. Most serous carcinomas (19/21; 90%) expressed MUC1 but not MUC2 mucin. Of the 16 mucinous carcinomas, 10 (62%) and five (31%) expressed MUC1 and MUC2 mucins, respectively. Four of the five clear cell and the three endometroid type carcinomas expressed MUC-1 but not MUC-2 mucin. A significant association was found between a high expression of MUC1 and histological grade (P = 0.005) and also disease stage (P = 0.001). CONCLUSION These results suggest that a high expression of MUC1 may contribute to a poor prognosis in ovarian carcinoma.
Analysis of hepatic T lymphocyte and immunoglobulin deposits in patients with primary biliary cirrhosis

The histological findings in patients with primary biiary cirrhosis have been well‐defined and are often used in the clinical staging of disease. However, it has only been with the development of reagents that phenotypically characterize the lymphoid infiltrate that attempts have been made to correlate pathophysiology with immune effector populations. Indeed, the inflammatory hepatic lesions in primary biliary cirrhosis have been described as containing CD4‐positive and CD8‐positive T cells. Less clear, however, have been the T cell receptors in these lesions. Further, the data on immunoglobulin deposits in hepatic lesions have been less well‐defined; this deficit may be a result of the quality of polyspecific sera and difficulties in background. To address these issues, we have used a battery of well‐defined monospecific and polyspecific reagents to phenotypically define the occurrence of lymphoid cells in the livers of patients undergoing transplantation. Furthermore, we have defined these same markers on T cell lines derived from liver, regional lymph node and peripheral blood. The predominant cell type in the mononuclear infiltrate is the CD3+, CD4+ T lymphocyte bearing the T cell receptor αβ. T cell lines from the same patients demonstrate similar findings. Of special importance, however, was the detection of CD20+ B cells and Ig+ cells in the lymphoid infiltrate. Indeed, we also readily demonstrated the presence of immunoglobulin on the surface of biliary epithelium. These data suggest that mechanisms involved in the pathophysiology of primary biliary cirrhosis may include both T cell and antibody mechanisms. The results also underscore the need to develop a functional, and not just a phenotypical, assay of the inflammatory infiltrate. (HEPATOLOGY 1990;12:306–313).
Reliability Optimization Using Fault Tree Analysis in the Grid Connected Mode of Microgrid

In a microgrid, PTC Wind Solutions is used to implement the optimization of reliability with the help of Fault Tree Analysis (FTA). The reliability of each energy source along with the non-critical load is calculated. To interpret the fault tree results, the quantitative and qualitative analysis are calculated. Then the importance measures like Risk Achievement Worth, Risk Reduction Worth, Criticality Importance and Fussel - Vesely Importance are used to calculate the sensitivity and uncertainty of fault tree results. The components which are sensitive and at high risk are calculated from the results. Using the logic gates in the PTC Windchill Solutions, the entire fault tree for a non-critical load outage is built and studied. From the results, the unreliability and unavailability of the fault tree are used to calculate there liability and availability of non-critical load outage. From the Fault Tree Analysis, the unavailability and unreliability of non critical load outage are calculated which illustrates the values of availability and reliability. From the fault tree analysis, the unavailability and unreliability of non-critical load outage are calculated as 0.01228, which illustrates that the availability and reliability as 98.77%. Minimal cut sets of circuit breaker across the non-critical load, Point of Common Coupling at the maingrid, and a transformer are calculated from the Qualitative Analysis. The top event probability evaluation of a non -- critical load is performed using the Quantitative analysis which indicates the system failure probability. The calculation of Importance measures -- Risk Achievement Worth, Risk Reduction Worth, Criticality Importance, Fussel - Vesely Importance is performed. Thus, the reliability and availability of non-critical load is obtained using the PTC Windchill Solutions. The top event occurrence is caused by the basic and intermediate events of a fault trees. The components at high riskare calculated using the importance measures. Therefore, from the Qualitative and Quantitative analysis the components which are at high risk and sensitive are obtained and maintained well to optimize the reliability.
Chronic pulmonary aspergillosis as a cause of smear-negative TB and/or TB treatment failure in Nigerians.

OBJECTIVE To evaluate chronic pulmonary aspergillosis (CPA) as an alternative diagnosis of smear-negative tuberculosis (TB) and treatment failure in TB patients in Nigeria. METHODS We conducted a cross-sectional multicentre survey in human immunodeficiency virus (HIV) positive and negative adult patients at the end of their TB treatment in clinics in Lagos and Ilorin states. All were assessed using clinical examination, chest X-ray (CXR) and aspergillus immunoglobulin G (IgG) serology, and some for sputum fungal culture. CPA was defined as a positive Aspergillus fumigatus IgG titre with compatible CXR or a positive sputum culture of Aspergillus with a visible fungal ball on CXR with symptoms of underlying lung disease. RESULTS Of 208 patients recruited between June 2014 and May 2015, 153 (73.6%) were HIV-positive. The mean age was 39.8 years, 124 (59.6%) were female and 39 (18.8%) were unable to work. The median CD4 count was 169.5 cells/ml (range 4-593) in HIV-infected patients with positive Aspergillus IgG. Overall, 109 (52.4%) had documented TB, 140 (67.3%) had a productive cough and 50 had haemoptysis. CPA prevalence was 8.7%; 10 (6.5%) had HIV infection and 8 (14.5%) were HIV-negative (Fisher's exact P = 0.092). CONCLUSION CPA is a neglected disease in Nigeria, and most cases match the World Health Organization diagnostic criteria for smear-negative TB.
Real-time Dose Adjustment of Cyclophosphamide in a Preparative Regimen for Hematopoietic Cell Transplant: A Bayesian Pharmacokinetic Approach

Purpose: Dose-related toxicity of cyclophosphamide may be reduced and therapeutic efficacy may be improved by pharmacokinetic sampling and dose adjustment to achieve a target area under the curve (AUC) for two of its metabolites, hydroxycyclophosphamide (HCY) and carboxyethylphosphoramide mustard (CEPM). To facilitate real-time dose adjustment, we developed open-source code within the statistical software R that incorporates individual data into a population pharmacokinetic model. Experimental Design: Dosage prediction performance was compared to that obtained with nonlinear mixed-effects modeling using NONMEM in 20 cancer patients receiving cyclophosphamide. Bayesian estimation of individual pharmacokinetic parameters was accomplished from limited (i.e., five samples over 0-16 hours) sampling of plasma HCY and CEPM after the initial cyclophosphamide dose. Conditional on individual pharmacokinetics, simulations of the AUC of both HCY and CEPM were provided for a range of second doses (i.e., 0-100 mg/kg cyclophosphamide). Results: The results compared favorably with NONMEM and returned accurate predictions for AUCs of HCY and CEPM with comparable mean absolute prediction error and root mean square prediction error. With our method, the mean absolute prediction error and root mean square prediction error of AUC CEPM were 11.0% and 12.8% and AUC HCY were 31.7% and 44.8%, respectively. Conclusions: We developed dose adjustment software that potentially can be used to adjust cyclophosphamide dosing in a clinical setting, thus expanding the opportunity for pharmacokinetic individualization of cyclophosphamide. The software is simple to use (requiring no programming experience), reads individual patient data directly from an Excel spreadsheet, and runs in less than 5 minutes on a desktop PC.
Humoral-mediated recognition of 'phagocyte-resistant' beads by lymph node macrophages of poloxamine-treated rats.

The in vivo properties and biological behaviour of ‘ longcirculating’ or ‘phagocyte-resistant ’ particles is of particular interest for the development of synthetic vehicles for targeting cells beyond the reticuloendothelial system (RES). Coating of model polystyrene beads (60 nm) with co-polymer non-ionic surfactant poloxamine-908 counteracts recognition and clearance by macrophages of the RES after parenteral administration [1]. Recently we suggested possible interactions of parenterally applied non-ionic surfactants with elements of the RES [2,3]. An unexpected observation was a dramatic reduction in the half-life of poloxamine-908-coated nanobeads after intravenous pretreatment of rats with a small quantity of the coating agent (i.e. poloxamine-908) [3]. Detailed histological and ultrastructural studies suggested that in poloxamine-treated rats, resident Kupffer cells as well as certain subpopulations of splenic red-pulp macrophages were responsible for the clearance of surfactant-coated particles by a mechanism independent of blood opsonization processes [3]. Since intravenously injected copolymer non-ionic surfactants can gain access into interstitial fluid and lymph [4], experiments were designed to examine the fate of subcutaneously injected poloxamine-coated beads in animals pretreated with an endotoxin-free solution of poloxamine-908. Groups of three to four male Wistar rats, body weight 150310 g, were injected subcutaneously in the dorsal surface of the left footpad with either "#&I-labelled uncoated or poloxamine-coated nanospheres (0.1 mg of polystyrene nanospheres in 100 μl) [5]. A second group of animals was injected intravenously with poloxamine908, 18.5 mg}kg body weight [1.0% (w}v)], via the tail vein on days 0 and 14 before nanosphere administration [3]. In certain cases, nanospheres were preincubated in 50% (v}v) rat serum for 15 min before interstitial administration. Finally, rats were killed at 2 h post
Validation of a historical physical activity questionnaire in middle-aged women.

BACKGROUND Historical physical activity (PA) questionnaires assess relationships between past PA and chronic diseases. The 4-Corner's Historical Physical Activity Questionnaire (HPAQ) was validated in 78 middle-age women. METHODS In 1996 and 1998, women kept PA records (PAR) for four consecutive days while wearing Caltrac accelerometers. In 2001, the same women recalled their past PA levels using the HPAQ. PA levels from the HPAQ were compared to PARs and the Caltrac. Race-adjusted Spearman correlations determined validity. RESULTS Low to modest correlations existed between PA (min/wk and MET-min/wk) from the HPAQ and PARs for moderate (r = 0.16 and 0.14, respectively), vigorous PA (r = 0.26 and 0.27, respectively; P < 0.05) and moderate-vigorous PA (r = 0.20 and 0.17, respectively). Moderate and moderate-vigorous, but not vigorous PA was positively related to energy expenditure expressed as kilocalories (r = 0.23, P < 0.05 and 0.22, -0.03, respectively) or PA volume (MET-min/wk) (r = 0.29, 0.29, P < 0.05 and 0.10, respectively). CONCLUSION The HPAQ can produce valid estimates of women's past moderate and vigorous PA levels.
A Very Fast Trace-Driven Simulation Platform for Chip-Multiprocessors Architectural Explorations

Simulation is the main tool for computer architects and parallel application developers for developing new architectures and parallel algorithms on many-core machines. Simulating a many-core architecture represent a challenge to software simulators even with parallelization of these SW on multi-cores. Field Programmable Gate Arrays offer an excellent implementation platform due to inherent parallelism. Existing FPGA-based simulators however, are mostly execution-driven which consumes too many FPGA resources. Hence, they still trade-off accuracy with simulation speed as SW simulators do. In this work, an application-level trace-driven FPGA-based many-core simulator is presented. A parameterized Verilog template was developed that can generate any number of simulator tiles. The input trace has an architecturally agnostic format that is directly interpreted by the FPGA-based timing model to re-construct the execution events of the original application with accurate timing. This allows fitting a large number of simulation tiles on a single FPGA without sacrificing simulation speed or accuracy. Experimental results show that the simulator's average accuracy is ∼14 percent with simulation speeds ranging from 100’s of MIPs to over 2,200 MIPS for a 16-core target architecture. Hence, with accuracy similar to SW simulators, its speed is higher than all other FPGA-based simulators.