Miracle-dz/UniFAR-FTUs huggingface dataset:
Is the Recommended Dose of Efavirenz Optimal in Young West African Human Immunodeficiency Virus-Infected Children?

ABSTRACT We aimed in this study to describe efavirenz concentration-time courses in treatment-naïve children after once-daily administration to study the effects of age and body weight on efavirenz pharmacokinetics and to test relationships between doses, plasma concentrations, and efficacy. For this purpose, efavirenz concentrations in 48 children were measured after 2 weeks of didanosine-lamivudine-efavirenz treatment, and samples were available for 9/48 children between months 2 and 5 of treatment. Efavirenz concentrations in 200 plasma specimens were measured using a validated high-performance liquid chromatography method. A population pharmacokinetic model was developed with NONMEM. The influence of individual characteristics was tested using a likelihood ratio test. The estimated minimal and maximal concentrations of efavirenz in plasma (Cmin and Cmax, respectively) and the area under the concentration-time curve (AUC) were correlated to the decrease in human immunodeficiency virus type 1 RNA levels after 3 months of treatment. The threshold Cmin (and AUC) that improved efficacy was determined. The target minimal concentration of 4 mg/liter was considered for toxicity. An optimized dosing schedule that would place the highest percentage of children in the interval of effective and nontoxic concentrations was simulated. The pharmacokinetics of efavirenz was best described by a one-compartment model with first-order absorption and elimination. The mean apparent clearance and volume of distribution for efavirenz were 0.211 liter/h/kg and 4.48 liters/kg, respectively. Clearance decreased significantly with age. When the recommended doses were given to 46 of the 48 children, 19% (44% of children weighing less than 15 kg) had Cmins below 1 mg/liter. A significantly higher percentage of children with Cmins of >1.1 mg/liter or AUCs of >51 mg/liter·h than of children with lower values had viral load decreases greater than 2 log10 copies/ml after 3 months of treatment. Therefore, to optimize the percentage of children with Cmins between 1.1 and 4 mg/liter, children should receive the following once-daily efavirenz doses: 25 mg/kg of body weight from 2 to 6 years, 15 mg/kg from 6 to 10 years, and 10 mg/kg from 10 to 15 years. These assumptions should be prospectively confirmed.
Influence of gangliosides on primary and metastatic neoplastic growth in human and murine cells.

The influence of gangliosides on tumor growth and frequency of metastasis in vivo as well as on growth and motility of neoplastic cells in vitro was tested utilizing human and rodent cell populations. In mice receiving injections of a ganglioside mixture twice daily the tumor volume, the number of spontaneous metastases per animal, and the number of mice with metastasis was approximately double that of controls. Preincubation of neoplastic cells with the ganglioside mixture doubled the number of metastatic foci in the lungs of mice receiving the cells by i.v. injection. Addition of a ganglioside mixture to the culture medium enhanced motility of neoplastic cells about 3-fold. This finding was similar to that observed for capillary endothelium. The presence of gangliosides in the culture media for a 48-h incubation period about doubled the number of neoplastic cells as compared to controls; the same was observed for capillary endothelium. The data are interpreted to indicate that gangliosides improve growth and mobilization of capillary endothelium and neoplastic cells. Both events may concur in enhancing tumor growth in vivo, the first by improving angiogenesis, the second by direct action on the neoplastic cell population.
In-hospital and long-term prognosis of elderly patients requiring endotracheal intubation for life-threatening presentation of cardiogenic pulmonary edema

ObjectiveWe studied the in-hospital course, long-term prognosis, and functional status of elderly patients with life-threatening cardiogenic pulmonary edema requiring mechanical ventilation. DesignSemiprospective evaluation. SettingTwelve intensive care units and one emergency prehospital medical department in university hospitals. PatientsPatients, aged >75 yrs, with life-threatening cardiogenic pulmonary edema requiring invasive airway management during the prehospital phase between January 1994 and January 1999 were included. InterventionNone. Measurements and Main Results A total of 79 patients were studied, of which 55 were included in the prospective phase and 24 during the retrospective phase. The age range was 75–99 yrs, with a mean age of 82.4 ± 5.9. The male/female ratio was 35:44. The in-hospital mortality was 26.6%. The mean follow-up time for all 58 survivors was 23 months (range, 2–56 months). Among those discharged, survival at 1 yr was 69%. At 3 months after hospital discharge, 49 (87%) patients lived at home, 46 (82%) were able to bathe themselves, 35 (62%) could walk at least one block, and 34 (61%) could climb one flight of stairs. ConclusionsMortality after severe pulmonary edema requiring endotracheal intubation in a very elderly cohort has a predictably high mortality, although not related directly to the degree of presenting respiratory compromise. However, approximately 50% of the overall cohort returned to relatively good functional status, despite advanced age and a severely compromised presentation. Aggressive airway management appears, therefore, justified in this select group of patients.
Risk factors for eating disorders in adolescents A Spanish community-based longitudinal study

L. Beato-Fernández ( ) Carretera de Valdepeñas, 5 Portal 3, 4° B 13004 – Ciudad Real, Spain ■ Abstract Objective The aim of this study was to identify psychopathological, social and family variables that, measured at the age of 13, might predict the development of eating disorders 2 years later, using a standardized interview and controlling the effect of initially abnormal eating behavior. Method At age 13 and 15, 1076 adolescents completed questionnaires for the screening of psychiatric morbidity, abnormal eating attitudes and family dysfunction. Probable cases of eating disorders [159] and 150 controls were assessed with standardized interviews (SCAN). Results Controlling the effect of previous eating psychopathology, pathological body dissatisfaction, measured with the Body Shape Questionnaire (BSQ), and a negative perception of parental attitudes were predictors of eating disorders 2 years later. Self-esteem was a protective factor for body dissatisfaction. Conclusions Preventive actions should focus on self-esteem as a protective factor for body dissatisfaction, a strong predictor for eating disorders. The significance of family perception should be explored more in detail in future research.
Pregnane X receptor-mediated induction of Cyp3a by black cohosh

Black cohosh (BC) has been widely applied for the treatment of menopausal symptoms. However, increasing concerns about herb–drug interactions demand the need for studies on the influence of BC on cytochrome 450. Cyp3a11 in liver was induced by 7-fold in wild-type mice treated with 500 mg/kg black cohosh for 28 days compared with the control group as assessed by quantitative real-time PCR; no difference was found in small intestine and kidney, suggesting that up-regulation of Cyp3a11 by black cohosh was liver-specific. Western blot, activity assays, and pharmacokinetic analyses established dose- and time-dependent induction of Cyp3a11. To determine the mechanism of Cyp3a11 induction, including the role of pregnane X receptor (PXR) in vivo and in vitro, respectively, in Pxr-null, PXR-humanized, and double transgenic CYP3A4/hPXR mice, cell-based luciferase assays were employed revealing that mouse PXR played a direct role in the induction of Cyp3a11; human PXR was not activated by black cohosh. Overall, these findings demonstrate that induction of Cyp3a11 is liver-specific and involved only mouse PXR, not the human counterpart. Thus, the incidence of herb–drug interaction in patients administered black cohosh may not be mediated by human PXR and CYP3A4.
Reverse triage: more than just another method

Reverse triage is a way to rapidly create inpatient surge capacity by identifying hospitalized patients who do not require major medical assistance for at least 96 h and who only have a small risk for serious complications resulting from early discharge. Electronic searches were conducted in the MEDLINE, TRIP, Cochrane Library, CINAHL, EMBASE, Web of Science, and SCOPUS databases to identify relevant publications published from 2004 to 2014. The reference lists of all relevant articles were screened for additional relevant studies that might have been missed in the primary searches. There will always be small individual differences in the reverse triage decision process, influencing the potential effect on surge capacity, but at most, 10–20% of hospital total bed capacity can be made available within a few hours. Reverse triage could be a response to Emergency Department (ED) crowding, as it gives priority to ED patients with urgent needs over inpatients who can be discharged with little to no health risks. The early discharge of inpatients entails negative consequences. They often return to the ED for further assessment, treatment, and even readmission. When time to a medical referral or bed is less than 4–6 h, 100 additional lives per annum are predicted to be potentially saved. The results of our systematic review identified only a small number of publications addressing reverse triage, indicating that reverse triage and surge capacity are relatively new subjects of research within the medical field. Not all research questions could be fully answered.
Path planning for autonomous mobile robots with mobility and threat information

Autonomous navigation is a basic feature for unmanned vehicle systems. For successful autonomous navigation, safety and mobility should be considered for path planning. For safety, a path should be planned to avoid threat, and for mobility, it should be planned by considering landscape and robot dynamics. This path can be obtained by applying the threat and mobility information to calculate the cost of path planning. In this paper we consider the case where threat property is provided as an indirect form of information which requires processing to represent in the cost function, but mobility property is given in a direct form. Thus, we should generate the threat map from the threat information for path planning. Using the threat information, we generate the threat map for the cost of path planning and perform path planning based on these mobility and threat maps. From the path planning results, we confirmed that our cost formulations are valid and the generated path satisfies the safety and mobility.
Low predictive value of traditional risk factors in identifying women at risk for gestational diabetes

Background. There is no worldwide agreement on the best way to screen for gestational diabetes mellitus (GDM), and different diagnostic methods have been developed in order to identify women at risk. The aim of this study was to evaluate the prevalence and predictive value of the traditional risk indicators for GDM in a large group of Caucasian women. Methods. We evaluated the frequency distribution of age, body mass index (BMI), prior macrosomia, prior GDM, and family history of diabetes of 1,414 pregnant women with GDM and 1,011 healthy pregnant women. Results. The distribution of risk factors in both groups was different and significantly higher in GDM women. The cut‐off value for age was 28years, and 23kg/m2 for BMI. The accumulation of two or more risk factors was frequent in GDM, but not in healthy women. By multiple logistic regression, there were significant interactions between independent variables of interest and GDM (OR: 3.19; p<0.001; sensitivity: 57.9%, specificity: 69.8%). The strongest predictors were prior GDM (OR: 4.35; 95% CI: 2.42–7.82) and a family history of diabetes (OR: 3.03; 95% CI: 2.47–3.72); less predictive were age (OR: 1.69; 95% CI: 1.44–1.99), BMI (OR: 1.50; 95% CI: 1.28–1.77), and prior macrosomia (OR: 1.64; 95% CI: 1.19–2.26). Conclusions. Selective screening based on traditional risk factors for GDM had relatively low sensitivity, and identified <60% of Caucasian women at risk. The cut‐off value for BMI as a risk indicator (23kg/m2) was lower than that proposed by guidelines about screening for GDM.
Experimental design and analysis of activators regenerated by electron transfer-atom transfer radical polymerization experimental conditions for grafting sodium styrene sulfonate from titanium substrates.

A 24 factorial design was used to optimize the activators regenerated by electron transfer-atom transfer radical polymerization (ARGET-ATRP) grafting of sodium styrene sulfonate (NaSS) films from trichlorosilane/10-undecen-1-yl 2-bromo-2-methylpropionate (ester ClSi) functionalized titanium substrates. The process variables explored were: (1) ATRP initiator surface functionalization reaction time; (2) grafting reaction time; (3) CuBr2 concentration; and (4) reducing agent (vitamin C) concentration. All samples were characterized using x-ray photoelectron spectroscopy (XPS). Two statistical methods were used to analyze the results: (1) analysis of variance with [Formula: see text], using average [Formula: see text] XPS atomic percent as the response; and (2) principal component analysis using a peak list compiled from all the XPS composition results. Through this analysis combined with follow-up studies, the following conclusions are reached: (1) ATRP-initiator surface functionalization reaction times have no discernable effect on NaSS film quality; (2) minimum (≤24 h for this system) grafting reaction times should be used on titanium substrates since NaSS film quality decreased and variability increased with increasing reaction times; (3) minimum (≤0.5 mg cm-2 for this system) CuBr2 concentrations should be used to graft thicker NaSS films; and (4) no deleterious effects were detected with increasing vitamin C concentration.
Do the flags related to immature granulocytes reported by the Sysmex XE-5000 warrant a microscopic slide review?

OBJECTIVES The Sysmex XE-5000 instruments (Sysmex, Kobe, Japan) count immature granulocytes (IGs) and use the "Imm Gran? " flag to signal unreliable results. This study investigated the usefulness of the "Imm Gran? " flag and the analytical and diagnostic performance of the IG measurements in a side-by-side evaluation. METHODS In total, 408 samples were analyzed on three XE-5000 instruments. The IG count and the "Imm Gran? " flag reports from all three instruments were used for reproducibility studies. The diagnostic performance of the automated IGs and the "Imm Gran? " flag were studied by comparing the XE-5000 results with the results of the manual differential. RESULTS The reproducibility of the "Imm Gran? " flagging between instruments was poor (қ, 0.75-0.80). The most significant contributor to the report of the "Imm Gran? " flag was bands, and the flag played a minor role in detecting blasts. The interinstrument reproducibility of the IG counts was high (intraclass correlation, 0.99). The IG count reported by XE-5000s was higher than the manual IG count (36%-55%), and the difference and the variability tended to increase with increasing levels of IGs. CONCLUSIONS The "Imm Gran? " flag has a poor analytical quality and gives no substantial information on the presence of blasts in the sample. We therefore suggest reporting the automated IG count without initial microscopic slide review.
Estimating real cell size distribution from cross-section microscopy imaging

MOTIVATION Microscopy imaging is an essential tool for medical diagnosis and molecular biology. It is particularly useful for extracting information about disease states, tissue heterogeneity and cell specific parameters such as cell type or cell size from biological specimens. However, the information obtained from the images is likely to be subjected to sampling and observational bias with respect to the underlying cell size/type distributions. RESULTS We present an algorithm, Estimate Tissue Cell Size/Type Distribution (EstiTiCS), for the adjustment of the underestimation of the number of small cells and the size of measured cells while accounting for the section thickness independent of the tissue type. We introduce the sources of bias under different tissue distributions and their effect on the measured values with simulation experiments. Furthermore, we demonstrate our method on histological sections of paraffin-embedded adipose tissue sample images from 57 people from a dietary intervention study. This data consists of measured cell size and its distribution over the dietary intervention period at four time points. Adjusting for the bias with EstiTiCS results in a closer fit to the true/expected adipocyte size distribution with earlier studies. Therefore, we conclude that our method is suitable as the final step in estimating the tissue wide cell type/size distribution from microscopy imaging pipeline. AVAILABILITY AND IMPLEMENTATION Source code and its documentation are available at https://github.com/michaelLenz/EstiTiCS The whole pipeline of our method is implemented in R and makes use of the 'nloptr' package. Adipose tissue data used for this study are available on request. CONTACT Michael.Lenz@Maastrichtuniversity.nl, Gokhan.Ertaylan@Maastrichtuniversity.nl.
Remelting of Highly Cross-linked Polyethylene Worn Under Laboratory Conditions

It has been suggested that apparent wear damage in highly cross-linked polyethylene acetabular liners can be removed with subsequent remelting of retrieved liners. To test this hypothesis, we remelted liners that had been previously tested under controlled laboratory conditions and that had experienced nonzero wear rates and visible wear damage. Five liner groups were examined: three with a range of irradiation doses without heat treatment, and two irradiated to 100 kGys, one with remelting, and the other annealing. All groups had been worn in a hip simulator under impingement conditions that produced nonzero wear rates and loss of machining marks. Each liner was cut into quadrants that were graded for wear damage before and after posttest remelting. Cross-linked liners not previously heat-treated lost all prior damage and all machining marks. Remelted liners and three of six annealed liners experienced only a slight return of machining marks at the interface of the burnished area and the remaining intact machining marks. Our experiments represent a severe wear case but demonstrate removal of material from the surface through measurable wear prevents the return of identifiable machining marks despite remelting.
Impaired placental autophagy in placental malaria

Background Placental malaria is a major cause of low birthweight, principally due to impaired fetal growth. Intervillositis, a local inflammatory response to placental malaria, is central to the pathogenesis of poor fetal growth as it impairs transplacental amino acid transport. Given the link between inflammation and autophagy, we investigated whether placental malaria-associated intervillositis increased placental autophagy as a potential mechanism in impaired fetal growth. Methods We examined placental biopsies collected after delivery from uninfected women (n = 17) and from women with Plasmodium falciparum infection with (n = 14) and without (n = 7) intervillositis. Western blotting and immunofluorescence staining coupled with advanced image analysis were used to quantify the expression of autophagic markers (LC3-II, LC3-I, Rab7, ATG4B and p62) and the density of autophagosomes (LC3-positive puncta) and lysosomes (LAMP1-positive puncta). Results Placental malaria with intervillositis was associated with higher LC3-II:LC3-I ratio, suggesting increased autophagosome formation. We found higher density of autophagosomes and lysosomes in the syncytiotrophoblast of malaria-infected placentas with intervillositis. However, there appear to be no biologically relevant increase in LC3B/LAMP1 colocalization and expression of Rab7, a molecule involved in autophagosome/lysosome fusion, was lower in placental malaria with intervillositis, indicating a block in the later stage of autophagy. ATG4B and p62 expression showed no significant difference across histological groups suggesting normal autophagosome maturation and loading of cargo proteins into autophagosomes. The density of autophagosomes and lysosomes in the syncytiotrophoblast was negatively correlated with placental amino acid uptake. Conclusions Placental malaria-associated intervillositis is associated with dysregulated autophagy that may impair transplacental amino acid transport, possibly contributing to poor fetal growth.
An Unscented Kalm an Filter-Based MultisensorTrack Fusion Algorithm

In this paper, an unscented Kalman filter (UKF)-based track fusion algorithm is developed for tracking targets in a nonlinear multisensor system. Employing the unscented Kalman filter and the measurements of the individual sensor in the multisensor system, the means and the variances of the states of a tracked target can be estimate. Based on these estimate results, an optimum state fusion scheme is obtained in terms of minimum mean square error (MMSE). The scheme can make the variance of the fused states smaller than that of the states estimated by UKF with any individual sensor in this multisensor system. Simulation results confirm the efficiency of the presented algorithm
Out of Africa? Locational determinants of South African cross-border mergers and acquisitions

ABSTRACT South Africa is the Africa’s biggest source of outward foreign direct investment. This study examines the principal locational motives of cross-border mergers and acquisitions CBMA by South African firms for the 1990–2014 period. The role of inter-country cultural and economic linkages is also studied. Firm-level data of South African merger and acquisition activities in 74 host countries are used to estimate a number of model specifications that control for host-country economic, geographical, cultural and institutional characteristics. Estimations are carried out using random-effects negative binomial panel model. Capturing the host-economy market and enhancing efficiency are found to be the two major motives driving South African corporations’ CBMA activities. Natural resources acquisition seems a less important motive, while strategic assets such as patents and technology do not appear to be attractive. The role of cultural and economic linkages between the home and the host country is found to be substantial. South African firms prefer investing in Africa, particularly in countries bordering South Africa. In light of the study’s findings, South African CBMA activities can be compared with those from other emerging economies.