Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacology of HIV integrase inhibitors

Purpose of reviewThe purpose of this study is to review recent and relevant pharmacology data for three HIV integrase inhibitors: raltegravir (marketed), dolutegravir, and elvitegravir (both in phase III drug development). Recent findingsData from January 2011 to April 2012 were evaluated. These data better characterized integrase inhibitor pharmacokinetics, assessed dosing regimens, and investigated previously undescribed drug–drug interactions. Due to formulation challenges, raltegravir inter-patient and intra-patient pharmacokinetic variability is high. Twice-daily 400 mg dosing has been shown to be clinically superior to 800 mg once-daily dosing. A pediatric formulation of raltegravir with less variable pharmacokinetics and greater bioavailability was US Food and Drug Administration (US FDA)-approved in December 2011. Cobicistat-boosted elvitegravir, and the second-generation integrase inhibitor dolutegravir, have lower pharmacokinetic variability and are dosed once daily. Dolutegravir drug interactions are similar to raltegravir, whereas boosted elvitegravir participates in additional CYP3A-mediated interactions. SummaryRaltegravir's potent antiretroviral activity has resulted in widespread use in both treatment-naïve and experienced patients. Dolutegravir and cobicistat-boosted elvitegravir have some pharmacokinetic advantages. Pharmacokinetic data in special populations (pregnancy, pediatrics) to optimize dosing are still required.
Beyond Food Deserts

Given the emerging focus on improving food environments and food systems through planning, this article investigates racial disparities in neighborhood food environments. An empirical case of Erie County, New York tests the hypothesis that people belonging to different racial groups have access to different neighborhood food destinations. Using multiple methods—Gini coefficients and Poisson regression—we show that contrary to studies elsewhere in the country there are no food deserts in Erie County. However, like other studies, we find an absence of supermarkets in neighborhoods of color when compared to white neighborhoods. Nonetheless, our study reveals an extensive network of small grocery stores in neighborhoods of color. Rather than soliciting supermarkets, supporting small, high-quality grocery stores may be a more efficient strategy for ensuring access to healthful foods in minority neighborhoods.
The pressor action of 2,5‐dimethoxy‐4‐methylamphetamine in rats

The hallucinogen, 2,5-dimethoxy-4-methylamphetamine (DOM or STP) increases the systolic blood pressure and exerts other autonomic effects in man (Snyder, Faillace & Hollister, 1967). The effects of STP on biogenic amines in animal brains have also been studied. In rats, it caused an increase of the level of 5-hydroxytryptamine (5-HT) with a concomitant decrease of that of 5-hydroxyindoleacetic acid (5-HIAA) (Freedman, Gottlieb & Lovell, 1970), and a decrease in 5-HT turnover (Andh, Corrodi, Fuxe & Meek, personal communication). Increases in the concentration of 5-HT and, even more profoundly, that of noradrenaline were also observed in young chickens (Wallach, Friedman & Gershon, 1972); however, no marked changes of either 5-HT or noradrenaline concentrations resulted from the administration of STP to mice (Idanpaan-Heikkila & McIsaac, 1970). In view of the above findings which have demonstrated the influence of STP on neurotransmitters, possibly also on their receptors, we undertook to study effects of STP on the blood pressure of animals. Male Sprague-Dawley rats, 300 to 380 g, were anaesthetized by intraperitoneal injection of 50 mg/kg of pentobarbitone sodium in saline. Arterial pressure was recorded from a polyethylene cannula placed in the left common carotid artery and connected to a Linear-Core pressure transducer (Model P-1000) and a E & M physiograph (Type DNP4A). Injections of drugs were made through a polyethylene cannula in the right jugular vein. Pithed rats were prepared according to the method of Gillespie & Muir (1967). Reserpine (5 mg/kg) was injected intraperitoneally to animals 6 h before the measurement of blood pressure. Where artificial respiration was needed, a Harvard rodent respirator (Model 680) was used; output (400 ml/kg)/min. STP exhibited a potent pressor action in rats (Table 1). The increase of systolic pressure was greater than that of the diastolic pressure. The effect was transient: after a dose of 50 pg/kg via the jugular vein a peak was reached within 15 s, and the blood pressure returned to normal in 30min. When STP was given to man, the systolic pressure was also increased; however, in contrast to the observation in rats, the diastolic pressure was unaffected.
Deep learning combined with de-noising data for network intrusion detection

Anomaly-based Network Intrusion Detection Systems (NIDSs) are a common security defense for modern networks. The success of their operation depends upon vast quantities of training data. However, one major limitation is the inability of NIDS to be reliably trained using imbalanced datasets. Network observations are naturally imbalanced, yet without substantial data pre-processing, NIDS accuracy can be significantly reduced. With the diversity and dynamicity of modern network traffic, there are concerns that the current reliance upon un-natural balanced datasets cannot remain feasible in modern networks. This paper details our de-noising method, which when combined with deep learning techniques can address these concerns and offer accuracy improvements of between 1.5% and 4.5%. Promising results have been obtained from our model thus far, demonstrating improvements over existing approaches and the strong potential for use in modern NIDSs.
Analysis of Drosophila 26 S Proteasome Using RNA Interference*

We have utilized double-stranded RNA interference (RNAi) to examine the effects of reduced expression of individual subunits of the 26 S proteasome in Drosophila S2 cells. RNAi significantly decreased mRNA and protein levels of targeted subunits of both the core 20 S proteasome and the PA700 regulatory complex. Cells deficient in any of several 26 S proteasome subunits (e.g. dβ5, dRpt1, dRpt2, dRpt5, dRpn2, and dRpn12) displayed decreased proteasome activity (as judged by hydrolysis of succinyl-Leu-Leu-Val-Tyr-aminomethylcoumarin), increased apoptosis, decreased cell proliferation without a specific block of the cell cycle, and accumulation of ubiquitinated cellular proteins. RNAi of many individual 26 S proteasome subunits promoted increased expression of many non-targeted subunits. This effect was not mimicked by chemical proteasome inhibitors such as lactacystin. Reduced expression of most targeted subunits disrupted the assembly of the 26 S proteasome. RNAi of six of eight targeted PA700 subunits disrupted that structure and caused accumulation of increased levels of uncapped 20 S proteasome. Notable exceptions included RNAi of dRpn10, a polyubiquitin binding subunit, and dUCH37, a ubiquitin isopeptidase. dRpn10-deficient cells showed a significant increase in succinyl-Leu-Leu-Val-Tyr-aminomethylcoumarin hydrolyzing activity of the 26 S proteasomes but accumulated polyubiquitinated proteins. dβ5-Deficient cells had a phenotype similar to that of most PA700-deficient cells but also accumulated low molecular mass complexes containing subunits of the 20 S proteasome, probably representing unassembled precursors of the 20 S proteasomes. Cells deficient in several of the 26 S proteasome subunits were more resistant to otherwise toxic concentrations of various proteasome inhibitors. Our data suggest that those cells adapted to grow in conditions of impaired ubiquitin and proteasome-dependent protein degradation.
Direct estimation of the area under the receiver operating characteristic curve in the presence of verification bias

The area under a receiver operating characteristic (ROC) curve (AUC) is a commonly used index for summarizing the ability of a continuous diagnostic test to discriminate between healthy and diseased subjects. If all subjects have their true disease status verified, one can directly estimate the AUC nonparametrically using the Wilcoxon statistic. In some studies, verification of the true disease status is performed only for a subset of subjects, possibly depending on the result of the diagnostic test and other characteristics of the subjects. Because estimators of the AUC based only on verified subjects are typically biased, it is common to estimate the AUC from a bias‐corrected ROC curve. The variance of the estimator, however, does not have a closed‐form expression and thus resampling techniques are used to obtain an estimate. In this paper, we develop a new method for directly estimating the AUC in the setting of verification bias based on U‐statistics and inverse probability weighting (IPW). Closed‐form expressions for the estimator and its variance are derived. We also show that the new estimator is equivalent to the empirical AUC derived from the bias‐corrected ROC curve arising from the IPW approach. Copyright © 2008 John Wiley & Sons, Ltd.
Unplanned extubation in critically ill adults: clinical review.

AIMS AND OBJECTIVES To investigate and synthesize the evidence on the incidence and consequences of unplanned extubation (UE) in intensive care unit (ICU) patients, and on risk factors for UE. BACKGROUND ICU patients generally spend considerable time being intubated via the endotracheal route. Non-planned endotracheal tube removal, either deliberate or accidental, may pose significant safety risks for them. As UE is among the most studied critical incidents in the ICU, evaluation and summary of existing findings could provide important implications for clinical practice. SEARCH STRATEGIES, INCLUSION AND EXCLUSION CRITERIA: Observational studies published between 1990 and 2012 in English-language journals indexed by Cumulative Index for Nursing and Allied Health Literature (CINAHL), PubMed, Web of Science and the Cochrane Library were searched for studies on UE of critically ill adults. Thirty-three articles were considered eligible for inclusion. CONCLUSIONS UE incidence varies considerably among reports, with self-extubation representing the majority of cases. Agitation, especially when combined with inadequate sedation, and decreased patient surveillance are the major risk factors for UE. Inexperienced personnel and improper tube fixation may also be important, while physical restraint use remains controversial. UE can be followed by serious complications, mainly aspiration, laryngeal oedema and increased risk for pneumonia. Need for re-intubation is a major determinant of patient outcomes. Implementation of educational or quality improvement programs is expected to advance personnel's knowledge about risk factors for UE, promote skills on safe, standardized procedures for patient care and increase compliance with them. RELEVANCE TO CLINICAL PRACTICE Identifying risk factors for UE and minimizing UE incidence through appropriate preventive strategies are prerequisites for improving nursing care quality and patient safety in the ICU.
Deep Venous Thrombosis and Lupus Anticoagulant

Summary Background. A definite evidence in favour of an association of deep-vein thrombosis (DVT) with lupus anticoagulant (LA) in patients free from systemic lupus erythematosus is still lacking. Methods. In a case-control study, LA was determined in 176 consecutive outpatients who underwent phlebography because of the first episode of clinically suspected DVT of lower limbs. The association between DVT and LA was described using odds ratios (OR). Results. Contrast venography confirmed the clinical suspicion in 59 patients (33.5%). LA was detected in 5 of the 59 patients with DVT (8.5%), and in none of the 117 subjects with normal venogram (P = 0.007). The OR for having an acute DVT in patients with LA was 10.7 (95% CI: 1.2-94.2). Conclusions. LA is significantly associated with DVT in symptomatic patients. Further studies are needed to establish the clinical implications of this association.
Chest ultrasound in acute respiratory distress syndrome

Purpose of reviewThis review discusses the role of chest ultrasound in diagnosis and management of acute respiratory distress syndrome (ARDS) and the most recent technical progresses in this field. Recent findingsClinically, suspected ARDS can be easily confirmed by lung ultrasonography through the recognition of a typical pattern characterized by B-lines, spared areas, pleural line thickening, and subpleural consolidations. A visual score based on number and thickness of B-lines permits a semiquantitative evaluation of the amount of extravascular lung water and lung density. Recently, a quantitative lung ultrasound method has been proposed. The heart may be also involved in ARDS either primarily or by the application of positive pressure ventilation. The incidence of acute cor pulmonale during ARDS is, even if under protective ventilation, not negligible. The use of echocardiography combined with lung ultrasound is important for early detection of cor pulmonale, identification of the best ventilator strategy to preserve heart-to-lung interaction, and prediction of weaning success. SummaryAn ultrasound-integrated approach combining lung ultrasound and echocardiography should be recommended as a suitable technique to manage ARDS during diagnosis, mechanical ventilation setting, and weaning.
Pregnenolone, Dehydroepiandrosterone, and Schizophrenia: Alterations and Clinical Trials

Neurosteroids, such as pregnenolone (PREG), dehydroepiandrosterone (DHEA), and their sulfates (PREGS and DHEAS) are reported to have a modulatory effect on neuronal excitability and synaptic plasticity. They also have many other functions associated with neuroprotection, response to stress, mood regulation, and cognitive performance. Furthermore, these neurosteroids have been linked to, and their levels are altered in, neuropsychiatric disorders. This review highlights what is currently known about the metabolism and mode of action of PREG and DHEA, as well as about alterations of these neurosteroids in schizophrenia. This review also provides substantial information about clinical trials with DHEA and PREG augmentation with of antipsychotic agents in schizophrenia.
Variable Dimension Complexes Part II: A Unified Approach to Some Combinatorial Lemmas in Topology

Part II of this study uses the path-following theory of labelled V-complexes developed in Part I to provide constructive algorithmic proofs of a variety of combinatorial lemmas in topology. We demonstrate two new dual lemmas on the n-dimensional cube, and use a generalized Sperner lemma to prove a generalization of the Knaster–Kuratowski–Mazurkiewicz covering lemma on the simplex. We also show that Tucker's lemma can be derived directly from the Borsuk–Ulam theorem. We report the interrelationships between these results, Brouwer's fixed point theorem, and the existence of stationary points on the simplex.
Ticks and tickborne diseases: raising awareness of the risks

Commercial vaccines based on the tick gut protein Bm86 have been successful in controlling the onehost tick Rhipicephalus (Boophilus) microplus and provide heterologous protection against certain other non-target ixodid tick species. This cross protection, however, does not extend to the three-host tick R. appendiculatus, the vector of the protozoan parasite Theileria parva. When transmitted to cattle, T. parva causes the often fatal disease East Coast fever. Here, we used insect cell-expressed recombinant versions of the R. appendiculatus homologs of Bm86, named Ra86, to vaccinate cattle. We measured multiple fitness characteristics for ticks that were fed on cattle Ra86-vaccinated or unvaccinated. The Ra86 vaccination of cattle significantly decreased the molting success of nymphal ticks to the adult stage. Modeling simulations based on our empirical data suggest that repeated vaccinations using Ra86 could reduce tick populations over successive generations. Vaccination with Ra86 could thus form a component of integrated control strategies for R. appendiculatus leading to a reduction in use of environmentally damaging acaricides. © 2012 Elsevier GmbH. All rights reserved.
Nuclear Power and Resource Efficiency—A Proposal for a Revised Primary Energy Factor

Measuring resource efficiency can be achieved using different methods, of which primary energy demand is commonly used. The primary energy factor (PEF) is a figure describing how much energy from primary resources is being used per unit of energy delivered. The PEF for nuclear power is typically 3, which refers to thermal energy released from fission in relation to electricity generated. Fuel losses are not accounted for. However; nuclear waste represents an energy loss, as current plans for nuclear waste management mostly include final disposal. Based on a literature review and mathematical calculations of the power-to-fuel ratio for nuclear power, PEF values for the open nuclear fuel cycle (NFC) option of nuclear power and different power mixes are calculated. These calculations indicate that a more correct PEF for nuclear power would be 60 (range 32–88); for electricity in Sweden (41% nuclear power) PEF would change from 1.8 to 25.5, and the average PEF for electricity in the European Union (EU) would change from 2.5 to 18. The results illustrate the poor resource efficiency of nuclear power, which paves the way for the fourth generation of nuclear power and illustrates the policy implication of using PEFs which are inconsistent with current waste management plans.
Fiber Lasers of Prof. Okhotnikov: Review of the Main Achievements and Breakthrough Technologies

This review is dedicated to the scientific work of Professor Oleg G. Okhotnikov (April 8, 1951 to April 8, 2016), an inspired scientist who has made a significant contribution to the development of fiber lasers. Prof. Okhotnikov published more than 280 journal articles, 100 conference papers, and numerous patents, many of which represented pioneering work in the area of fiber lasers. This article highlights the most valuable scientific and technological breakthroughs in fiber lasers achieved by Prof. Okhotnikov and his research groups.
A novel Elephant Herding Optimization based PID controller design for Load frequency control in power system

This paper presented a new approach known as Elephant Herding Optimization for designing a load frequency controller for single-area non-reheat power system to damping the oscillations of the frequency response in the power system. Elephant Herding Optimization Algorithm is employed to search the parameters of the PID controllers. The PID controller tuned using Elephant Herding Optimization (EHO) techniques. The proposed controller is simulated in MATLAB/SIMULINK for a single area power system with step change in load demand. The proposed method based PID controller improves the performances of the power system in terms of time specifications such as undershoot, overshoot and settling time. The performance is compared with the PID controllers in literature and found to be superior in performance.
Role of endothelin receptor subtypes in the in vivo regulation of renal function.

Endothelin (ET) is a potent vasoconstrictor peptide of endothelial origin, which at low doses results in renal vasoconstriction and diuresis with variable actions on sodium excretion. The current study conducted in four groups of anesthetized dogs was designed to define the role of the ETA and ETB receptor subtypes in the renal actions of low-dose exogenous ET. Group 1 (n = 4) animals served as time controls. In group 2 (n = 6) a systemic ET-1 (5 ng.kg-1.min-1) infusion mediated renal vasoconstriction, antinatriuresis with increases in proximal fractional reabsorption of sodium, and diuresis with a decrease in urine osmolality. In group 3 (n = 6) intrarenal BQ-123 (4 micrograms.kg-1.min-1), a selective ETA antagonist, abolished the systemic ET-1-mediated changes in renal hemodynamics and unmasked a natriuretic action at the level of the proximal tubule. In contrast, the diuretic response of ET was not altered by BQ-123. In group 4 (n = 6) intrarenal sarafotoxin 6-c, a selective ETB receptor agonist, resulted in a diuretic response without a change in sodium excretion. These studies suggest that the ETA receptor contributes to the renal vasoconstriction, whereas the ETB receptor is largely responsible for the diuretic response during exogenous ET. This study also suggests that at low doses ET is natriuretic in vivo by decreasing proximal tubular reabsorption of sodium independent of ETA or ETB receptor activation.
The emerging cardio-inhibitory role of the Hippocampal Cholinergic Neurostimulating Peptide ( HCNP )

Department of Pharmaco-Biology, University of Calabria, 87030 Arcavacata di Rende (CS) Italy (T.A, M.C.C.); Department of Cell Biology, University of Calabria, 87030 Arcavacata di Rende (CS) Italy (T.A., M.C.C., B.T.); Inserm U575 “Physiopatologie du Système Nerveux” 67084 StrasbourgFrance (Y.G., M.-H. M.-B., D.A., T.A.) JPET Fast Forward. Published on April 11, 2006 as DOI:10.1124/jpet.106. 102103
Filling defects at CT colonography: pseudo- and diminutive lesions (the good), polyps (the bad), flat lesions, masses, and carcinomas (the ugly).

Numerous filling defects may be detected in the colon during interpretation of data sets obtained with computed tomographic (CT) colonography. A series of 230 patients were evaluated with thin-section multidetector row CT colonography immediately before conventional colonoscopy. In all cases, the interpreting radiologist and gastroenterologist reviewed the imaging findings as well as the results of histologic analysis of biopsy specimens to determine the causes of filling defects. In many cases, the cause of a filling defect can be confidently determined at CT colonography by using combinations of two- and three-dimensional images. However, lesions will occasionally be indeterminate because of overlapping features and will require further evaluation with endoscopy. With knowledge of the morphologic and attenuation characteristics of the various filling defects in the colon, one should be able to differentiate those filling defects detected at CT colonography that require no further evaluation from those that require endoscopic interrogation.
SOME PSYCHIATRIC ASPECTS OF ABORTION

The psychiatric elements found in or attributed to women who request and obtain abortions under regular medical auspices are presented as distilled from relevant literature and experience with several hundred unwillingly pregnant females. The confusion of the present situation prevailing in most states and consisting of a conglomerate of medical, legal, and sociocultural traditions and beliefs makes strictly professional judgments impossible. The importance of abortion as a stopgap for contraceptive failure in the broadest sense and hence as a significant family-planning measure with inherent benefits for the emotional health and welfare of all family members has been neglected. Abortion in itself is a safe, simple procedure without clinically significant psychiatric sequellae, but it becomes an emotionally traumatic experience because of the medicolegal obstacles which lead 1,000,000 or more women to seek illegal abortions in contrast to some 10,000 legal abortions performed annually. Psychiatric considerations must extend to the unhealthy consequences of unwanted pregnancy and motherhood and the attendant risks for the emotional development and personality of the unwanted offspring.