Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of the Combination of Lisinopril and Hydrochlorothiazide on the Bioequivalence of Tablet Formulations

Summary The aim of the present studies, performed in two different groups of volunteers, was to compare the bioavailability of 20 mg Lisinopril tablets (Sinopryl® as test and an orignator product as reference formulation; study 1) and lisinopril/hydrochlorothiazide (20 mg/12.5 mg) (CAS 83915-83-7/CAS 58-93-5) combined formulations (Sinoretik® as test and an originator product as reference formulation; study 2). Each study was conducted according to an open, randomized, single-dose, two-period cross-over design in healthy volunteers with a wash-out period from 7 to 14 days. Blood samples were taken up to 72 h in both studies, the plasma was separated. Concentrations of lisinopril and hydrochlorothiazide were determined by HPLC-MS-MS method. In the first study, the 90 % confidence interval for intra-individual ratios of AUC0–t and Cmax of lisinopril were between 0.85 and 1.12 (AUC0–t) and between 0.87 and 1.17 (Cmax), and thus within the acceptance ranges. In the second study, i.e. after administration of combined lisinopril/hydrochlorothiazide formulations, the 90 % confidence interval for intra-individual ratios of AUC0–inf and Cmax of lisinopril were between 0.83 and 1.22 (AUC0–inf) and between 0.80 and 1.25 (Cmax). The 90 % confidence interval for intra-individual ratios of AUC0–inf and Cmax of hydrochlorothiazide were between 0.92 and 1.04 (AUC0–inf) and between 0.88 and 1.08 (Cmax). All the above values were within the acceptance ranges for bioequivalence studies. In the light of the present studies it can be concluded that lisinopril as well as lisinopril/hydrochlorothiazide test formulations are bioe-quivalent to the respective reference formulations.
The Effect of Curcumin and Tocotrienol on the Development of Eye Disease

There is growing evidence that inflammation may be one of the causative factors of many chronic diseases especially which is related to eyes such as cataract,age-related macular degeneration and uveitis. Several cytokines such as IL-1,IL-6, RANKL, OPG, and M-CSF were implicated in the pathogenesis of chronic diseases. Anticytokine therapy using cytokine antagonists such as IL-receptor antagonist and TNF-binding protein was able to suppress the activity of the respective cytokines and prevent bone loss. Few animal studies have shown that vitamin E in the forms of palm-derived tocotrienol and α-tocopherol may prevent chronic eye disease in rat models by suppressing IL-1 and IL-6. Free radicals are known to activate transcription factor NFκB which leads to the production of bone resorbing cytokines. Tocotrienol, a potent antioxidant, may be able to neutralize free radicals before they could activate NFκB, therefore suppressing cytokine production and inflammatory reaction. Curcumin is widely reported to have potent anti-oxidative, anti-inflammatory and anticarcinogenic effects. The anti-inflammatory action of curcumin seems to be closely related to inhibition of TNF-α and other inflammatory cytokines production and suppression of NF-κB activation by blocking phosphorylation of inhibitory factor I-kappa B kinase (IκB) Tocotrienol and curcuminhave also been shown to inhibit COX-2, the enzyme involved in inflammatory reactions of the these studied, tocotrienol seemed to be better than tocopherols in terms of its ability to suppress inflammation induced by cytokines.
Discretized Opinion Dynamics of the Deffuant Model on Scale-Free Networks

The consensus model of Deffuant et al is simplified by allowing for many discrete instead of infinitely many continuous opinions, on a directed Barabasi-Albert network. A simple scaling law is observed. We then introduce noise and also use a more realistic network and compare the results. Finally, we look at a multi-layer model representing various age levels, and we include advertising effects.
Maternal–fetal cellular trafficking: clinical implications and consequences

Purpose of review Maternal–fetal cellular trafficking (MFCT) is the bidirectional passage of cells between mother and fetus during pregnancy. This results in the presence of fetal cells in the maternal circulation, known as fetal microchimerism, and maternal cells in the fetal circulation, known as maternal microchimerism. The biologic role of this transplacental cellular trafficking during pregnancy is not known, although it has been implicated in development of the fetal immune system, tolerance mechanisms during pregnancy, tissue repair in autoimmune disease and cancer, and immune surveillance. Recent findings Clinical utility of MFCT has been identified in prenatal testing for aneuploidies and prediction of pregnancy complications. Additionally, this transplacental passage of cells has been implicated in the delicate balance between immunologic priming and tolerance, which can influence the occurrence of autoimmune disease and transplantation outcomes. Ongoing studies are evaluating the utility of microchimerism in predicting the risk of graft rejection in transplantation. Summary In this review, we will discuss the clinical implications of MFCT in pregnancy, fetal surgery, autoimmune disease, transplantation, and cancer.
Identifying gaps in flaring Herbig Ae/Be disks using spatially resolved mid-infrared imaging - Are all group I disks transitional?

Context. The evolution of young massive protoplanetary disks toward planetary systems is expected to correspond to structural changes in observational appearance, which includes the formation of gaps and the depletion of dust and gas. Aims. A special group of disks around Herbig Ae/Be stars do not show prominent silicate emission features, although they still bear signs of flaring disks, the presence of gas, and small grains. We focus our attention on four key Herbig Ae/Be stars to understand the structural properties responsible for the absence of silicate feature emission. Methods. We investigate Q- and N-band images taken with Subaru/COMICS, Gemini South/T-ReCS and VLT/VISIR. We perform radiative transfer modeling to examine the radial distribution of dust and PAHs. Our solutions require a separation of inner- and outerdisks by a large gap. From this we characterize the radial density structure of dust and PAHs in the disk. Results. The inner edge of the outer disk has a high surface brightness and a typical temperature between 100‐150 K and therefore dominates the emission in the Q-band. All four disks are characterized by large gaps. We derive radii of the inner edge of the outer disk of 34 +4 , 23 +3 , 30 +5 and 63 +4 AU for HD 97048, HD 169142, HD 135344 B and Oph IRS 48 respectively. For HD 97048 this is the first detection of a disk gap. The large gaps deplete the entire population of silicate particles with temperatures suitable for prominent midinfrared feature emission, while small carbonaceous grains and PAHs can still show prominent emission at mid-infrared wavelengths. The continuum emission in the N-band is not due to emission in the wings of PAHs. This continuum emission can be due to VSGs or to thermal emission from the inner disk. We find that PAH emission is not always dominated by PAHs on the surface of the outer disk. Conclusions. The absence of silicate emission features is due to the presence of large gaps in the critical temperature regime. Many, if not all Herbig disks with Spectral Energy Distribution (SED) classification ‘group I’ are disks with large gaps and can be characterized as (pre-) transitional. An evolutionary path from the observed group I to the observed group II sources seems no longer likely. Instead, both might derive from a common ancestor.
New strategies for clinical trials in patients with sepsis and septic shock

ObjectiveThe difficulty in identifying new treatment modalities that significantly reduce the mortality and morbidity rates associated with sepsis has highlighted the need to reevaluate the approach to clinical trial design. The United Kingdom Medical Research Council convened an International Working Party to address these issues. Data SourcesThe subject areas that were to be the focus of discussion were identified by the co-chairs, and group leaders were nominated. Preconference reading material was circulated to group members. Study Selection and Data Extraction Small-group discussion fed into an iterative process of feedback from plenary sessions, followed by the formulation of recommendations. Finally, each working group prepared a summary of its recommendations and these are reported herein. Data SynthesisThere were five key recommendations. First, investigators should no longer rely solely on the American College of Chest Physicians/Society of Critical Care Medicine definitions of sepsis or sepsis syndrome as the basis of trial entry. Entry criteria should be based on three principles: a) All patients should have infection; b) there should be evidence of a pathologic process that represents a biologically plausible target for the proposed intervention, for example, an abnormal circulating level of a biological marker pertinent to the study drug; and c) patients should fall into an appropriate category of severity (usually severe sepsis). Second, investigators should use a scoring system for organ dysfunctions that has been validated and that can be incorporated into all sepsis studies; agreement on the use of a single system would simplify comparisons between studies. Third, the primary outcome measure generally should be mortality rates, but under appropriate circumstances major morbidities could be considered as primary end points. Regardless of choice of the duration to primary end point, patients should be followed for ≥90 days. Fourth, sample size needs to be based on a realistic assessment of achievable effect size based on knowledge of the at-risk population. Fifth, subgroups should be few in number and should be defined a priori on the basis of variables present before randomization. ConclusionsImportant changes in several aspects of trial design may improve the quality of clinical studies in sepsis and maximize the chance of identifying effective therapeutic agents.
The Medicare Electronic Health Record Incentive Program: provider performance on core and menu measures.

OBJECTIVE To measure performance by eligible health care providers on CMS's meaningful use measures. DATA SOURCE Medicare Electronic Health Record Incentive Program Eligible Professionals Public Use File (PUF), which contains data on meaningful use attestations by 237,267 eligible providers through May 31, 2013. STUDY DESIGN Cross-sectional analysis of the 15 core and 10 menu measures pertaining to use of EHR functions reported in the PUF. PRINCIPAL FINDINGS Providers in the dataset performed strongly on all core measures, with the most frequent response for each of the 15 measures being 90-100 percent compliance, even when the threshold for a particular measure was lower (e.g., 30 percent). PCPs had higher scores than specialists for computerized order entry, maintaining an active medication list, and documenting vital signs, while specialists had higher scores for maintaining a problem list, recording patient demographics and smoking status, and for providing patients with an after-visit summary. In fact, 90.2 percent of eligible providers claimed at least one exclusion, and half claimed two or more. CONCLUSIONS Providers are successfully attesting to CMS's requirements, and often exceeding the thresholds required by CMS; however, some troubling patterns in exclusions are present. CMS should raise program requirements in future years.
Penalized contrast estimation in functional linear models with circular data

Our aim is to estimate the unknown slope function in the functional linear model when the response Y is real and the random function X is a second-order stationary and periodic process. We obtain our estimator by minimizing a standard (and very simple) mean-square contrast on linear finite dimensional spaces spanned by trigonometric bases. Our approach provides a penalization procedure which allows to automatically select the adequate dimension, in a non-asymptotic point of view. In fact, we can show that our penalized estimator reaches the optimal (minimax) rate of convergence in the sense of the prediction error. We complete the theoretical results by a simulation study and a real example that illustrates how the procedure works in practice.
Inference on subsets of parameters in GMM without assuming identification

We construct bounds on the limiting distributions of the identification robust GMM statistics for testing hypothezes that are specified on subsets of the parameters. The upper bounds correspond with the limiting distribution that result when the unrestricted parameters are well identified. It therefore leads to more powerful tests than those that result from using projection arguments on tests on all the parameters. The upper bound only applies when the unrestricted parameters are estimated using the continuous updating estimator. The critical values that result from the upper bound lead to conservative tests when the unrestricted parameters are not well-identified. The identification robust GMM statistics resemble identification statistics when we evaluate them at a value of the hypothesized parameter that is distant from the true one. The power of these statistics is therefore governed by the least identified parameter so a weakly identified parameter implies that the power for tests on any of the parameters is low.
A comparison of cytopathology caused by myxoviruses. I. The relation of the infectious process to cytopathology.

Summary A comparison of cytopathology in HeLa and L cells caused by Newcastle disease virus (NDV), PR8-influenza virus and mumps virus demonstrated that all viruses produced cytopathic effects (CPE) in both cell lines but mumps virus, which failed to lyse L cells. A high virus/cell ratio was required for production of CPE by PR8 virus in HeLa cells and for PR8 virus and NDV in L cells. Replication of infectious virus could be demonstrated only for NDV and mumps virus in HeLa cells, but noninfectious hemagglutinins were produced in both cell lines after infection with high multiplicities of NDV or PR8 virus. The production of these noninfectious hemagglutinins by individual cells was demonstrated by a modification of the hemadsorption technique. The specificity of the cytopathic action of these myxoviruses was indicated by the facts that the CPE were dependent on adsorption of the viruses to the cells and that when the cell surface was altered by RDE that the viral CPE were prevented. Cellular receptors involved in the viral CPE appeared to be identical for all three viruses since RDE was uniformly effective for all three viruses, and saturation of cells with one virus prevented the adsorption of a second virus. The CPE of these viruses on HeLa and L cells were shown to involve two stages, the first of which was dissociable by RDE which prevented the CPE. Following this initial stage at 37°C, the initial virus-cell complex proceeded rapidly to a stage which was not affected by RDE or specific antibody since the cells were lysed on further incubation.
Procalcitonin N-Terminal Peptide Causes Catabolic Effects via the Hypothalamus and Prostaglandin-Dependent Pathways

Recent evidence suggests that the free amino-terminal fragment of procalcitonin (N-PCT) plays a role in the central control of feeding behavior and energy homeostasis. However, little is known about the mechanisms through which N-PCT works. Here we report that intracerebroventricular administration of N-PCT to free-feeding male rats induced a significant decrease of longer-term food intake and body weight gain. Conversely, N-PCT increased body temperature. We also show that intracerebroventricular administration of N-PCT induced a marked neuronal activation in key thermoregulatory and feeding areas of the hypothalamus. We further show that N-PCT increases the responsiveness of proopiomelanocortin anorexigenic neurons in the arcuate nucleus of the hypothalamus, and that stimulation of the de novo synthesis of prostaglandins is crucial for the central effects induced by N-PCT. Results support the role of N-PCT to the central control of feeding behavior and suggest that N-PCT, acting probably through the eicosanoid cyclooxygenase pathway, may act as a signaling molecule in the hypothalamus by regulating the activity of anorexigenic neurons in the hypothalamus.
Researching Mental Health in Minority Ethnic Communities: Reflections on Recruitment

In this article we reflect on the recruitment of research participants to two related studies of experiences of mental health problems in Black and minority ethnic communities in the United Kingdom. A total of 65 people were recruited via three main strategies: the employment of bicultural recruiters, intensive information sharing about the studies, and work through local community groups. Three main issues seemed to affect recruitment: gatekeepers’ attitudes, the (non)payment of participants, and reciprocal arrangements with local community groups. The type of strategy employed resulted in recruits with differing characteristics (although our sample was too small to draw generalizable conclusions). We conclude that to ensure that research participation is accessible to all, researchers must employ flexible recruitment methods that permit adaptation to specific needs arising out of health status, level of involvement with services, culture, and socioeconomic status. Systematic research into this part of the research process is needed.
A Ty1 Reverse Transcriptase Active-Site Aspartate Mutation Blocks Transposition but Not Polymerization

ABSTRACT Reverse transcriptases (RTs) are found in a wide variety of mobile genetic elements including viruses, retrotransposons, and infectious organellar introns. An invariant triad of aspartates is thought to be required for the catalytic function of RTs. We generated RT mutants in the yeast retrotransposon Ty1, changing each of these active-site aspartates to asparagine or glutamate. All but one of the mutants lacked detectable polymerase activity. The novel exception, D211N, retained near wild-type in vitro polymerase activity within virus-like particles but failed to carry out in vivo transposition. For this mutant, minus-strand synthesis is impaired and formation of the plus-strand strong-stop intermediate is eliminated. Intragenic second-site suppressor mutations of the transposition defect map to the RNase H domain of the enzyme. Our results demonstrate that one of the three active-site aspartates in a retrotransposon RT is not catalytically critical. This implies a basic difference in the polymerase active-site geometry of Ty1 and human immunodeficiency virus RT and shows that subtle mutations in one domain can cause dramatic functional effects on a distant domain of the same enzyme.
Boundary integral equation methods for solving Laplace's equation with nonlinear boundary conditions

A nonlinear boundary value problem for Laplace's equation is solved numerically by using a reformulation as a nonlinear boundary integral equation. Two numerical methods are proposed and analyzed for discretizing the integral equation, both using product integration to approximate the singular integrals in the equation. The first method uses the product Simpson's rule, and the second is based on trigonometric interpolation. Iterative methods (including two-grid methods) for solving the resulting nonlinear systems are also discussed extensively. Numerical examples are included.
Path sensitization in critical path problem

Since the delay of a circuit is determined by the delay of its longest sensitizable paths (such paths are called critical paths), the problem of estimating the delay of a circuit is called critical path problem. One important aspect of the critical path problem is to decide whether a path is sensitizable. A framework which allows various previously proposed path sensitization criteria to be compared with each other in a unified way is presented. An exact path sensitization criterion and a looser path sensitization criterion based on the framework are also proposed. <<ETX>>
Identification of Cyclase-Associated Protein-2 as a Novel Biomarker for Early-Stage Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) is an aggressive deadly cancer with few therapeutic options mostly limited for early-stage HCC. Unfortunately, alphafetoprotein (AFP) has a limited performance, especially in early-stage HCC. Objectives: to investigate plasma levels of Cyclaseassociated protein-2 (CAP2) as a new biomarker and evaluate its role in detecting early-stage and AFP-negative HCC Egyptian patients. Methods: Plasma CAP2 and AFP levels in 150 HCC, 150 cirrhotic patients, 150 healthy controls. Correlation with tumor behavior, the area under the curve (AUC), sensitivity, specificity, and diagnostic accuracy were analyzed. Results: Plasma CAP2 and AFP levels were significantly elevated in HCC patients than liver cirrhosis and controls. Only plasma CAP2 levels significantly correlated with clinico-pathological characteristics of HCC (BCLC, histological and clinical stages) but not correlated with patient's age, gender, viral infection status or AFP levels. Compared to AFP, CAP2 had significantly higher AUC: 0.86 (0.79-0.93) vs. 0.75 (0.65-0.85), Sensitivity: 81.5% vs. 62% in all HCCs and significantly higher AUC: 0.80 (0.72-0.89) vs. 0.68 (0.58-0.79, Sensitivity: 80.5% vs. 43.1% in earlystage HCC. Moreover, the combined diagnostic value of both CAP2+AFP was statistically significantly better than either CAP2 or AFP alone. Also, CAP2 could predict 82.4% of AFP-negative HCCs [AUC: 0.85 (0.77-0.92)] and 73.5% of AFP-negative early-stage HCCs [AUC: 0.80 (0.72-0.88)]. Conclusion: Compared with AFP, CAP2 was significantly elevated in HCC patients with higher sensitivity and AUC especially for early-stage HCC. Moreover, CAP2 was significantly correlated with the clinico-pathological features of HCC. CAP2 could be a novel biomarker predicting early-stage, AFP-negative, and AFP-negative early-stage HCC patients.
Sunscreen use and increased duration of intentional sun exposure: Still a burning issue

Sunscreen use is often proposed for sun protection because of their ability to block UV‐induced sunburns (the sun protection factor – SPF). Among suntan seekers, however, risk of cutaneous melanoma may be increased because of extended sun exposure duration. We made a systematic review of the evidence linking sunscreen use to sun exposure duration. Five observational studies found that when sun exposure was associated with willingness to get a tan or to stay longer in the sun (i.e., intentional sun exposure), sunscreen use was associated with duration of sun exposure 13–39% longer. Paradoxically, sunburns tend to be more frequent among sunscreen users, probably because of greater natural sun sensitivity. When sun exposure was not intentional, sunscreen use did not increase time spent in the sun. Two European double‐blind randomized trials conducted among young sun seekers found daily sun exposure duration, especially sunbathing, 19–25% longer with use of SPF 30 than with use of SPF 10 sunscreens. One randomized trial in a holiday resort in France found a 3–13% increase in sun exposure duration with use of SPF 12 versus SPF 40 sunscreen. But, the SPF 12 groups used 3.6–4.2 more sunscreen than the SPF 40 group, and thus the actual SPF in the SPF 12 group was higher than in the SPF 40 groups. In conclusion, sunscreen use leads to longer duration of sun exposure when sun exposure is intentional, but not when sun exposure is non intentional. © 2007 Wiley‐Liss, Inc.