Miracle-dz/UniFAR-FTUs huggingface dataset:
Anti-pseudomonal beta-lactams for the initial, empirical, treatment of febrile neutropenia: comparison of beta-lactams.

BACKGROUND Several beta-lactams are recommended as single agents for the treatment of febrile neutropenia. OBJECTIVES To compare the effectiveness of different anti-pseudomonal beta-lactams as single agents in the treatment of febrile neutropenia. To compare the development of bacterial resistance, bacterial and fungal superinfections during or following treatment with the different beta-lactams. SEARCH STRATEGY We searched the Cochane Register of Controlled Trials (CENTRAL), Issue 3, 2010. MEDLINE, EMBASE, LILACS, FDA drug applications, conference proceedings and ongoing clinical trial databases up to August 2010. References of included studies were scanned. SELECTION CRITERIA Randomised controlled trials (RCTs) comparing an antipseudomonal beta-lactam to another antipseudomonal beta-lactam antibiotic, both given alone or with the addition of the same glycopeptide to both study arms, for the initial treatment of fever and neutropenia among cancer patients. DATA COLLECTION AND ANALYSIS Two review authors applied inclusion criteria and extracted the data independently. Missing data were sought. Risk ratios (RR) were calculated with 95% confidence intervals (CI), and pooled using the fixed effect model. The primary outcome was all-cause mortality. Risk of bias was assessed using a domain-based evaluation and its effect of results was assessed through sensitivity analyses. MAIN RESULTS Forty-four trials were included. The antibiotics assessed were cefepime, ceftazidime, piperacillin-tazobactam, imipenem and meropenem. Adequate allocation concealment and generation were reported in about half of the trials and only two trials were double-blinded. The risk for all-cause mortality was significantly higher with cefepime compared to other beta-lactams (RR 1.39, 95% CI 1.04 to 1.86, 21 trials, 3471 participants), without heterogeneity and with higher RRs in trials at low risk for bias. There were no differences in secondary outcomes but for a non-significantly higher rate of bacterial superinfections with cefepime. Mortality was significantly lower with piperacillin-tazobactam compared to other antibiotics (RR 0.56, 95% CI 0.34 to 0.92, 8 trials, 1314 participants), without heterogeneity. Carbapenems resulted in similar all-cause mortality and a lower rate of clinical failure and antibiotic modifications as compared to other antibiotics, but a higher rate of diarrhea caused by Clostridium difficile. AUTHORS' CONCLUSIONS Current evidence supports the use of piperacillin-tazobactam in locations where antibiotic resistance profiles do not mandate empirical use of carbapenems. Carbapenems result in a higher rate of antibiotic-associated and Clostridium difficile-associated diarrhea. There is a high level of evidence that all-cause mortality is higher with cefepime compared to other beta-lactams and it should not be used as monotherapy for patients with febrile neutropenia.
Living with inflammatory bowel disease: A Crohn's and Colitis Canada survey.

BACKGROUND Despite improvements in therapies for inflammatory bowel diseases (IBDs), patient quality of life continues to be significantly impacted. OBJECTIVE To assess the impact of IBD on patients and families with regard to leisure, relationships, mental well-being and financial security, and to evaluate the quality and availability of IBD information. METHODS An online survey was advertised on the Crohn's and Colitis Canada website, and at gastroenterology clinics at the University of Alberta Hospital (Edmonton, Alberta) and University of Calgary Hospital (Calgary, Alberta). RESULTS The survey was completed by 281 IBD patients and 32 family members. Among respondents with IBD, 64% reported a significant or major impact on leisure activities, 52% a significant or major impact on interpersonal relationships, 40% a significant or major impact on financial security, and 28% a significant or major impact on planning to start a family. Patient information needs emphasized understanding disease progression (84%) and extraintestinal symptoms (82%). There was a strong interest in support systems such as health care insurance (70%) and alternative therapies (66%). The most common source of information for patients was their gastroenterologist (70%); however, most (70%) patients preferred to obtain their information from the Crohn's and Colitis Canada website. CONCLUSIONS The impact of IBD on interpersonal relationships and leisure activities was significant among IBD patients and their families. Understanding the disease, but also alternative treatment options, was of high interest. Currently, there is a discrepancy between interest in information topics and their availability. Respondents reported a strong desire to obtain information regarding disease progression, especially extraintestinal symptoms.
SCD5‐induced oleic acid production reduces melanoma malignancy by intracellular retention of SPARC and cathepsin B

A proper balance between saturated and unsaturated fatty acids (FAs) is required for maintaining cell homeostasis. The increased demand of FAs to assemble the plasma membranes of continuously dividing cancer cells might unbalance this ratio and critically affect tumour outgrowth. We unveiled the role of the stearoyl‐CoA desaturase SCD5 in converting saturated FAs into mono‐unsaturated FAs during melanoma progression. SCD5 is down‐regulated in advanced melanoma and its restored expression significantly reduced melanoma malignancy, both in vitro and in vivo, through a mechanism governing the secretion of extracellular matrix proteins, such as secreted protein acidic and rich in cysteine (SPARC) and collagen IV and of their proteases, such as cathepsin B. Enforced expression of SCD5 or supplementation of its enzymatic product, oleic acid, reduced the intracellular pH (pHe > pHi) and, in turn, vesicular trafficking across plasma membranes as well as melanoma dissemination. This intracellular acidification appears also to depend on SCD5‐induced reduction of the C2 subunit of the vacuolar H+‐ATPase, a proton pump whose inhibition changes the secretion profile of cancer cells. Our data support a role for SCD5 and its enzymatic product, oleic acid, in protection against malignancy, offering an explanation for the beneficial Mediterranean diet. Furthermore, SCD5 appears to functionally connect tumour cells and the surrounding stroma toward modification of the tumour microenvironment, with consequences on tumour spread and resistance to treatment. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
miR-20b Inhibits T Cell Proliferation and Activation via NFAT Signaling Pathway in Thymoma-Associated Myasthenia Gravis

Purpose. We examined the role of miR-20b in development of thymoma-associated myasthenia gravis, especially in T cell proliferation and activation. Materials and Methods. Using qRT-PCR, we assessed expression levels of miR-20b and its target genes in cultured cells and patient samples and examined the proliferation of cultured cells, using MTT cell proliferation assays and flow cytometry based cell cycle analysis. Activation of T cells was determined by both flow cytometry and qRT-PCR of activation-specific marker genes. Results. Expression of miR-20b was downregulated in samples of thymoma tissues and serum from patients with thymoma-associated myasthenia gravis. In addition, T cell proliferation and activation were inhibited by ectopic overexpression of miR-20b, which led to increased T cell proliferation and activation. NFAT5 and CAMTA1 were identified as targets of miR-20b. Expression levels of NFAT5 and CAMTA1 were inhibited by miR-20b expression in cultured cells, and the expression levels of miR-20b and NFAT5/CAMTA1 were inversely correlated in patients with thymoma-associated myasthenia gravis. Conclusion. miR-20b acts as a tumor suppressor in the development of thymoma and thymoma-associated myasthenia gravis. The tumor suppressive function of miR-20b in thymoma could be due to its inhibition of NFAT signaling by repression of NFAT5 and CAMTA1 expression.
Cell Guidance by 3D-Gradients in Hydrogel Matrices: Importance for Biomedical Applications

Concentration gradients of soluble and matrix-bound guidance cues in the extracellular matrix direct cell growth in native tissues and are of great interest for design of biomedical scaffolds and on implant surfaces. The focus of this review is to demonstrate the importance of gradient guidance for cells as it would be desirable to direct cell growth onto/into biomedical devices. Many studies have been described that illustrate the production and characterization of surface gradients, but three dimensional (3D)-gradients that direct cellular behavior are not well investigated. Hydrogels are considered as synthetic replacements for native extracellular matrices as they share key functions such as 2D- or 3D-solid support, fibrous structure, gas- and nutrition permeability and allow storage and release of biologically active molecules. Therefore this review focuses on current studies that try to implement soluble or covalently-attached gradients of growth factors, cytokines or adhesion sequences into 3D-hydrogel matrices in order to control cell growth, orientation and migration towards a target. Such gradient architectures are especially desirable for wound healing purposes, where defined cell populations need to be recruited from the blood stream and out of the adjacent tissue, in critical bone defects, for vascular implants or neuronal guidance structures where defined cell populations should be guided by appropriate signals to reach their proper positions or target tissues in order to accomplish functional repair.
Mining representative actions for actor identification

Previous works on actor identification mainly focused on static features based on face identification and costume detection, without considering the abundant dynamic information contained in videos. In this paper, we propose a novel method to mine representative actions of each actor, and show the remarkable power of such actions for actor identification task. Videos are firstly divided into shots and represented by BoW based on spatial-temporal features. Then we integrate the prototype theory with SVM to rank the shots and obtain the representative actions. Our method for actor identification combines representative actions with actors' appearance. We validate the method on episodes of the TV series "The Big Bang Theory". The experimental results show that the representative actions are consistent with human judgements and can greatly improve the matching performance as complementary to existing handcrafted static features for actor identification.
A Meta-Analysis Exploring the Relationship Between Psychopathy and Instrumental Versus Reactive Violence

The present meta-analysis explored the relationship between psychopathy and instrumental and reactive violence with a focus on factor and facet scores. A total of 53 studies (reporting on 55 unique samples, N = 8,753) from both published and unpublished sources were included. Results from random-effects analyses indicated moderate and significant relationships between psychopathy and both instrumental and reactive violence. There was some evidence that the Interpersonal facet was more important for instrumental violence, while Factor 2 (social deviance) was more important for reactive violence. The Lifestyle facet appeared important in explaining both violent outcomes. Effect sizes were significantly smaller for clinical rating scales compared with informant and self-report scales. Significant between-study variability was partly explained by mean age of the sample and type of outcome measure. The current findings do not support the conclusion that psychopathy is more related to instrumental violence as opposed to reactive violence.
Overlapping and Divergent Actions of Estrogen and the Neurotrophins on Cell Fate and p53-Dependent Signal Transduction in Conditionally Immortalized Cerebral Cortical Neuroblasts

The developing cerebral cortex undergoes overlapping periods of neurogenesis, suicide, and differentiation to generate the mature cortical plate. The following experiments examined the role of the gonadal hormone estrogen in comparison to the neurotrophins, in the regulation of p53-dependent cortical cell fate. To synchronize choices between neurogenesis, apoptosis, and neural differentiation, embryonic rat cerebral cortical neuroblasts were conditionally immortalized with the SV40 large T antigen containing the tsA58/U19 temperature-sensitive mutations. At the nonpermissive temperature, cessation of large T antigen expression was accompanied by induction of p53, as well as the p53-dependent proteins, wild-type p53-activated fragment-1/Cdk (cyclin-dependent kinase)-interacting protein-1 (p21/Waf1), Bcl (B-cell lymphoma)-associated protein (Bax), and murine double minute 2 (MDM2), that lead to cell cycle-arrest, suicide, and p53 inhibition, respectively. Simultaneously, neuroblasts exit cell cycle and die apoptotically or differentiate primarily into astrocytes and immature postmitotic neuroblasts. At the nonpermissive temperature, estrogen specifically induced an antagonist-independent increase in phosphorylated p53 expression, while increasing p21/Waf1 and decreasing Bax. Coincidentally, estrogen rapidly increased and then decreased MDM2 relative to controls, suggesting temporal modulation of p53 function. Both estrogen and neurotrophins prevented DNA fragmentation, a marker for apoptosis. However, estrogen also induced a transient increase in released lactate dehydrogenase, suggesting that estrogen simultaneously induced rapid cell death in a subpopulation of cells. In contrast to the neurotrophins, estrogen also increased cell proliferation. Both estrogen and the neurotrophins supported neuronal differentiation. However, in contrast to the neurotrophins, estrogen only supported the expression of a subset of oligodendrocytic markers. These results suggest that estrogen and the neurotrophins support overlapping and distinct aspects of differentiation in the developing cerebral cortex.
La gestion des émotions au travail : le cas des policiers d'élite

Police elite units involve significant emotional labor (Hochschild, 2003). For elite police officers, this emotional labor is necessary to carry out the mission, endangering their physical and/or mental health. Their emotional competencies allow them to do this emotional labor, and regulate their emotions during an intervention. This article put in relation emotional labor, emotional competencies, emotional regulation and social support, taking into account the emotional factor at work in the elite police units. This exploratory study includes three levels of analysis : the individual level, the collective and managerial level, and the level of institutional practices of Human Resources Management (HRM). How do the HRM practices of elite police units take into account the emotional competencies (Salovey and Mayer, 1990) allowing the hard emotional labor of the police officers ? Both the professionals' health and the intervention's quality depend on it. Some police officers in these units, most of them highly recognized and removed from service, were interviewed. All of them streamline the danger, consciously, to control their emotions and to condition themselves to be calm. This cognitive reappraisal (Gross, 1998) permits them to match up the displayed emotion with the really felt emotion : emotional labor appears to be an in-depth action. At the collective level, police officers insist on the beneficial role of various forms of social support. Finally, concerning the institutional practices of HRM, emotions are taken into account especially in recruitment. Managing emotions is developed further during daily training, in conditions close to the reality, then as part of training sessions specifically dedicated to the management of emotions. Managerial recommendations emerge beyond these two HRM practices : taking into account emotions at work in the careers and withdrawals management (absenteeism, job reassignments, job rotations and other withdrawals) and creating favorable conditions for social support. We note a few surprises and new tracks having sprung from this study : beyond the emotional competencies, " faith ", trainings, and the role of humor, will allow the professionals to regulate their emotions ; and an addiction to adrenaline could influence the career management. Key-words : emotions, emotional competencies, emotional labor, emotion regulation, social support, practices of human resources management.
From Betriebswirtschaftslehre to Human Relations: Turkish Management Literature before and after the Second World War

This article examines Turkish management literature from its beginnings in the mid-1930s up to the mid-1960s. The study traces and explores the impact of economic and political as well as institutional developments on the extent and changes in the reception that different management approaches have enjoyed in this formative period. Investigation of the management literature produced over the course of the 30-year time span shows that the business economics perspective that dominated pioneering work gave way after early 1950s to a Fayolist management process approach coupled with a human relations orientation. Taylorism attracted limited attention throughout the entire period. The article attempts to show that these findings can be traced to the shift from links with Germany and the German literature in early years to a strong American influence after the Second World War.
Saquinavir pharmacokinetics alone and in combination with ritonavir in HIV‐infected patients

Objective:The most important hepatic enzyme involved in the metabolism of protease inhibitors is cytochrome P450 3A4 (CYP3A4). Ritonavir (RIT) is a potent inhibitor of CYP3A4 and inhibits saquinavir (SQV) metabolism in healthy volunteers. In this study we investigated the kinetics of SQV when administered alone and in combination with RIT in HIV-infected patients. Design:SQV pharmacokinetics were determined in seven patients who had advanced HIV disease. Steady-state SQV profiles were obtained on two occasions following treatment with SQV 600 mg three times daily alone and when administered with RIT 300 mg twice daily. Methods:Blood samples were obtained at times 0, 1, 2, 4, 6 and 8 h post-dosing. Following centrifugation, separated plasma was heated at 58°C for at least 30 min to inactivate HIV and stored at −80°C until analysis using high performance liquid chromatography. Results:For patients treated with SQV alone there was a 12-fold variability in the area under the SQV concentration-time curve (AUC0–8h) ranging from 293 to 3446 ng•h/ml. When combined with RIT there was a marked increase in the maximum plasma concentration of SQV [median (range), 146 (57–702) versus 4795 (1420–15810) ng/ml; ∼95% confidence interval (CI), 2988–6819; P = 0.0006, Mann-Whitney U test]. The AUC0–8h for SQV was also significantly increased in the presence of RIT [median (range), 470 (293–3446) versus 27 458 (7357–108 001) ng•h/ml; ∼95% CI, 16 628–35 111; P= 0.0006]. Conclusions:For some patients, administration of SQV 600 mg three times daily results in very low SQV plasma levels and possibly little antiviral effect. Combination of SQV with RIT results in a significant drug interaction mediated by enzyme inhibition which exposes patients to very high SQV concentrations and potential toxicity. If combination therapy with SQV plus RIT is considered then the dose of SQV should be greatly reduced.
Efficient Algorithms for Online Game Playing and Universal Portfolio Management

A natural algorithmic scheme in online game playing is called ‘follow-the-leader’, first proposed by Hannan in the 1950’s. Simply stated, this method advocates the use of past history to make future predictions, by using the optimal strategy so far as the strategy for the next game iteration. Randomized variations on this method for the special case of linear payoff functions have been rigorously analyzed and have found numerous applications in machine learning and game theory. It was a long standing open problem whether the ‘follow the leader’ method attains any non-trivial regret guarantees for the case of concave regret functions. This question is significant since ’follow-the-leader’ is a natural deterministic method, easy to implement and computationally efficient. We introduce a new analysis technique and show that a deterministic variant of this method has optimal regret. This result is applicable to a variety of online optimization scenarios, including regret minimization for Lipschitz regret functions, universal portfolios management, online convex optimization and online utility maximization. For the well studied universal portfolio management problem, our algorithm combines optimal regret with computational efficiency. For the general setting, our algorithm achieves exponentially lower regret than previous algorithms. Our analysis shows a surprising connection between interior point methods and online optimization using follow-the-leader.
Interobserver Agreement in the Evaluation of Digitized Cervical Images

OBJECTIVE: To estimate the agreement among multiple expert colposcopists evaluating high-resolution digitized cervigrams taken from patients with a variety of human papillomavirus (HPV) infection states and previous cervigram interpretations. METHODS: Twenty expert colposcopists evaluated 939 digitized images of the uterine cervix obtained after the application of 5% acetic acid during the ASCUS-LSIL Triage Study. Twenty images selected to represent a broad range were graded by all the colposcopists. The remaining 919 pictures were distributed by stratified random sampling, such that each image was evaluated by two colposcopists, and each expert evaluated 112 images with similar distributions of cervigram diagnoses and HPV DNA test results. We evaluated interrater agreement among the pairs of colposcopists and confirmed the conclusions using the 20 images they all graded. RESULTS: Pairs of colposcopists agreed on the diagnosis for only 56.8% of images. Similar agreement was seen regarding number of visible lesions (of low-grade or greater). This variability in ratings remained when the images were stratified by final histologic diagnosis or HPV status. The results were confirmed by the presence of large variability in ratings (ranging in some cases from normal to cancer) for the 20 images graded by all colposcopists. CONCLUSION: Colposcopic diagnosis using static images is poorly reproducible and might reflect similar problems in clinical practice. Researchers should question the use of colposcopic images as a reference standard for teaching and evaluating the presence or severity of disease. LEVEL OF EVIDENCE: II