Miracle-dz/UniFAR-FTUs huggingface dataset:
Vancomycin MIC plus Heteroresistance and Outcome of Methicillin-Resistant Staphylococcus aureus Bacteremia: Trends over 11 Years

ABSTRACT Vancomycin MICs (V-MIC) and the frequency of heteroresistant vancomycin-intermediate Staphylococcus aureus (hVISA) isolates are increasing among methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) isolates, but their relevance remains uncertain. We compared the V-MIC (Etest) and the frequency of hVISA (Etest macromethod) for all MRSA blood isolates saved over an 11-year span and correlated the results with the clinical outcome. We tested 489 isolates: 61, 55, 187, and 186 isolates recovered in 1996-1997, 2000, 2002-2003, and 2005-2006, respectively. The V-MICs were ≤1, 1.5, 2, and 3 μg/ml for 74 (15.1%), 355 (72.6%), 50 (10.2%), and 10 (2.1%) isolates, respectively. We detected hVISA in 0/74, 48/355 (13.5%), 15/50 (30.0%), and 8/10 (80.0%) isolates with V-MICs of ≤1, 1.5, 2, and 3 μg/ml, respectively (P < 0.001). The V-MIC distribution and the hVISA frequency were stable over the 11-year period. Most patients (89.0%) received vancomycin. The mortality rate (evaluated with 285 patients for whose isolates the trough V-MIC was ≥10 μg/ml) was comparable for patients whose isolates had V-MICs of ≤1 and 1.5 μg/ml (19.4% and 27.0%, respectively; P = 0.2) but higher for patients whose isolates had V-MICs of ≥2 μg/ml (47.6%; P = 0.03). However, the impact of V-MIC and hVISA status on mortality or persistent (≥7 days) bacteremia was not substantiated by multivariate analysis. Staphylococcal chromosome cassette mec (SCCmec) typing of 261 isolates (including all hVISA isolates) revealed that 93.0% of the hVISA isolates were SCCmec type II. These findings demonstrate that the V-MIC distribution and hVISA frequencies were stable over an 11-year span. A V-MIC of ≥2 μg/ml was associated with a higher rate of mortality by univariate analysis, but the relevance of the V-MIC and the presence of hVISA remain uncertain. A multicenter prospective randomized study by the use of standardized methods is needed to evaluate the relevance of hVISA and determine the optimal treatment of patients whose isolates have V-MICs of ≥2.0 μg/ml.
Paid and Unpaid Work, and Its Relation to Low Back and Neck/Shoulder Disorders Among Women

ABSTRACT The aim of the present study was to estimate the influence of total work hours, paid work in the labor market and unpaid work in the family domain, on care-seeking for low back and neck/shoulder disorders in the female population. The exposure assessments considered a typical working day during the previous twelve months and were assessed by interviews and questionnaires; 704 cases and 984 referents were examined. The cases had sought professional care during the study period; the referents were randomly selected from the same source population. There was no increased relative risk for care-seeking for low back and neck/shoulder disorders for gainfully employed women compared to those not employed, or for full-time compared to part-time working women. At least 60 hours per week of paid work, or at least 40 hours per week of unpaid work, separately, indicated an increased relative risk for care-seeking. The present results did not strengthen the hypothesis that a high amount of hours of work is an independent risk factor for musculoskeletal disorders.
Antigenic and phenotypic variations of Haemophilus influenzae type b lipopolysaccharide and their relationship to virulence

Haemophilus influenzae type b (Hib) strains NO100 and COL10 were found to produce bacteremia in infant rats at a much lower frequency than other Hib strains previously tested. These relatively avirulent strains were the only Hib strains among 200 clinical isolates examined to date which failed to react with two Hib lipopolysaccharide (LPS)-specific monoclonal antibodies (MAbs). LPS analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that strains NO100 and COL10 possessed LPS which migrated faster than the LPS of Hib strains that reacted with one of the two or with both of these MAbs. These observations suggested that the relative lack of virulence of strains NO100 and COL10 might be related to their unusual LPS phenotype. To determine whether alteration of LPS structure would affect the virulence of these strains, we identified and isolated isogenic LPS antigenic variants of strains NO100 and COL10 using the LPS-specific MAbs 4C4 and 5G8 in a colony blot radioimmunoassay. Antigenic variation of LPS was found to occur spontaneously in these two strains at a relatively high frequency in terms of both acquisition and loss of MAb reactivity (ca. 0.2 to 16.7%). LPS antigenic variants of strains NO100 and COL10 reactive with both MAbs 4C4 and 5G8 (4C4+ 5G8+) were more virulent in the infant rat model than their respective 4C4- 5G8- parental strains (P less than 0.01). An antigenic variant of COL10 reactive with only MAb 4C4 (4C4+ 5G8-) was also significantly more virulent than its 4C4- 5G8- parent. These LPS antigenic variants with increased virulence synthesized altered LPS molecules which possessed apparent molecular weights higher than those of the LPS of the parental strains. Increased resistance of strain NO100 to the bactericidal activity of normal infant rat serum was associated with changes in LPS structure, while strain COL10 and its LPS variants were all uniformly resistant to serum bactericidal activity. Our results demonstrate that (i) spontaneous antigenic and phenotypic variation of LPS occurs at a relatively high frequency in some strains of Hib; (ii) the higher-molecular-weight type of LPS is associated with the full expression of Hib virulence; (iii) LPS phenotype may not correlate with Hib serum resistance; and (iv) serum resistance of Hib is not an accurate indicator of virulence.
Animal models in tuberculosis research – where is the beef?

Introduction: Tuberculosis (TB) is a major global health problem, and new drugs and vaccines are urgently needed. As clinical trials in humans require tremendous resources, preclinical drug and vaccine development largely relies on valid animal models that recapitulate the pathology of human disease and the immune responses of the host as closely as possible. Areas covered: This review describes the animal models used in TB research, the most widely used being mice, guinea pigs and nonhuman primates. In addition, rabbits and cattle provide models with a disease pathology resembling that of humans. Invertebrate models, including the fruit fly and the Dictyostelium amoeba, have also been used to study mycobacterial infections. Recently, the zebrafish has emerged as a promising model for studying mycobacterial infections. The zebrafish model also facilitates the large-scale screening of drug and vaccine candidates. Expert opinion: Animal models are needed for TB research and provide valuable information on the mechanisms of the disease and on ways of preventing it. However, the data obtained in animal studies need to be carefully interpreted and evaluated before making assumptions concerning humans. With an increasing understanding of disease mechanisms, animal models can be further improved to best serve research goals.
Transiciones tipo yo-yo y trayectorias fallidas: hacia las políticas integradas de transición para los jóvenes europeos

El articulo proporciona un marco teorico para entender los cambios estructurales y biograficos que han llevado a una desestandarizacion de las transiciones de los jovenes. Los conceptos centrales en este capitulo, ilustrados por la metafora de las transiciones tipo "yo-yo", son "jovenes adultos" y "trayectorias fallidas". Mediante un analisis comparativo, los efectos no deseados de las politicas de integracion dirigidas a jovenes adultos se explican por unas estructuras institucionales y procedimientos que permanecen inspirados por los supuestos de biografias normalizadas en funcion del genero y la posibilidad de lograr el pleno empleo. Estos autores fijan el contexto politico de los textos que publicamos en este numero e introducen la perspectiva de las Politicas Integradas de Transicion, las cuales parten de la base de las biografias individuales y son coordinadas de manera transversal. En los articulos siguientes, los demas autores adoptan tambien esta perspectiva.
Universal image steganalytic method based on binary similarity measures

This paper is focused on comparison of two steganalytic methods that are able to detect embedding of secret message using popular and novel steganographic algorithms in JPEG images. First one is based on binary similarity measures and second method exploits 66 or 274 statistical features in transform domain from cover and stego images. The tested universal model was trained using novel steganographic method previously proposed by the same authors. Subsequently, the obtained statistical parameters from cover and stego images are used for training of model that is applied on detection of secret message in testing phase. The aim of this paper was to examine the accuracy detection (ACR) of these novel universal steganalytic models for popular steganographic tools in static images and also to compare time consumption in process of extraction parameters and training of model.
The roles of temperature, pH and mosquito factors as triggers of male and female gametogenesis of Plasmodium berghei in vitro

Developmentally arrested malarial gametocytes undergo gamete formation in the mosquito midgut immediately after ingestion of the infected bloodmeal. In the rodent malaria parasite Plasmodium berghei male gametogenesis (exflagellation) can be induced in vitro by a temperature decrease (from 39°C in the vertebrate host to 20°C) and a concomitant pH increase (from 7·3 in mouse blood to 8·0). We report the presence of additional Gametocyte Activating Factor(s) (GAF) present in Anopheles stephensi tissue extracts, which induce both male and female gametogenesis at the otherwise non-permissive pH of 7·3 in vitro but are unable to overcome the low temperature requirement. All constituent cellular events of microgametogenesis studied here are induced by the same triggers in vitro. A temperature decrease is also required for exflagellation in the mosquito midgut. The possible role of GAF as a second obligatory natural trigger of gametogenesis is discussed.
Mechanical loss characterization at cryogenic temperature of a tungsten wire: An automated measurement system

The paper describes an automated measurement system for mechanical loss characterization of wires at cryogenic temperature. The important role of these measurements for the design of the Kamioka Gravitational Wave Detector (KAGRA) is highlighted. The experimental setup used to perform the measurements are presented and discussed. Furthermore, preliminary results obtained for a tungsten wire in term of quality factor are reported.
Infrared photostimulation of the crista ampullaris

Non‐technical summary It has been shown previously that application of short pulses of optical energy at infrared wavelengths can evoke action potentials in neurons and mechanical contraction in cardiac muscle cells. Optical stimuli are particularly attractive because of the ability to deliver focused energy through tissue without physical contact or electrical charge injection. Here we demonstrate efficacy of pulsed infrared radiation to stimulate balance organs of the inner ear, specifically to modulate the pattern of neural signals transmitted from the angular motion sensing semicircular canals to the brain. The ability to control action potentials demonstrates the potential of pulsed optical stimuli for basic science investigations and future therapeutic applications.
A Criterion-Based Role-Based Multilayer Access Control Model for Multimedia Applications

This paper presents a criterion-based role-based multilayer access control model in which a number of security criterion expressions are embedded into every object to specify the security attributes of its sub objects. Meanwhile, a security criterion subset is combined with each operation to reflect the relevant keys of the embedded security criterion expressions in the corresponding object, and another security criterion subset is associated with each user to specify the user's security features. The desired multilayer access control is achieved by evaluating the embedded security criterion expressions by using the common elements of the security criterion subsets associated with the related operation and the related user. The proposed model, which is an extension of traditional role-based access control (REAC) model, efficiently supports both the multilayer access control and non-multilayer access control. In addition to the advantages of traditional RBAC, the model is simple in logic and efficient in performance
Contrasting Two Frameworks for ROC Analysis of Ordinal Ratings

Background. Statistical evaluation of medical imaging tests used for diagnostic and prognostic purposes often employs receiver operating characteristic (ROC) curves. Two methods for ROC analysis are popular. The ordinal regression method is the standard approach used when evaluating tests with ordinal values. The direct ROC modeling method is a more recently developed approach, motivated by applications to tests with continuous values. Objective. The authors compare the methods in terms of model formulations, interpretations of estimated parameters, the ranges of scientific questions that can be addressed with them, their computational algorithms, and the efficiencies with which they use data. Results. The authors show that a strong relationship exists between the methods by demonstrating that they fit the same models when only a single test is evaluated. The ordinal regression models are typically alternative parameterizations of the direct ROC models and vice versa. The direct method has two major advantages over the ordinal regression method: 1) estimated parameters relate directly to ROC curves, facilitating interpretations of covariate effects on ROC performance, and 2) comparisons between tests can be done directly in this framework. Comparisons can be made while accommodating covariate effects and even between tests that have values on different scales, such as between a continuous biomarker test and an ordinal valued imaging test. The ordinal regression method provides slightly more precise parameter estimates from data in our simulated data models. Conclusion. Although the ordinal regression method is slightly more efficient, the direct ROC modeling method has important advantages in regard to interpretation, and it offers a framework to address a broader range of scientific questions, including the facility to compare tests.
Mitogen-induced genes are subject to multiple pathways of regulation in the initial stages of T-cell activation

The delivery of a mitogenic signal to T cells via any one of several cell surface molecules elicits a variety of intracellular responses, some or all of which regulate subsequent gene expression events. The expression of nine novel mitogen-induced genes in response to various T-cell-activating agents was examined to evaluate the diversity of pathways which regulate such genes. The relative contribution of distinct secondary signals, individually or together, to mitogen-stimulated gene induction and the capability of individual genes to respond to the sometimes divergent signals generated from different cell surface structures is addressed. The activation of T cells with mitogenic monoclonal antibodies directed against the CD2 or CD3 cell surface molecules, or with phytohemagglutinin, induced all nine genes. Thus, stimulation by fully mitogenic agents regardless of cell surface-binding specificity correlated with the expression of all of the genes studied. However, heterogeneous patterns of gene expression, encompassing five regulatory classes, were revealed by the use of phorbol 12-myristate 13-acetate, calcium ionophore, and anti-CD28 monoclonal antibody, agents which mediated only a subset of intracellular events and thus an incomplete mitogenic signal. Interleukin-2 and two novel lymphokines represented one regulatory class that appeared to require unique transcriptional activation signals relative to the other mitogen-induced genes. As demonstrated in the accompanying paper (P. F. Zipfel, S. G. Irving, K. Kelly, and U. Siebenlist, Mol. Cell. Biol. 9:1041-1048, 1989), the immediate transcriptional response of T cells to mitogenic stimulation is quite complex, involving numerous genes beyond those which have been previously described. Furthermore, the discrimination of several regulatory phenotypes among these nine genes suggests that a multiplicity of signaling pathways extends from the cell surface to the level of transcription.
A HECT Domain E3 Enzyme Assembles Novel Polyubiquitin Chains*

Although polyubiquitin chains linked through Lys29 of ubiquitin have been implicated in the targeting of certain substrates to proteasomes, the signaling properties of these chains are poorly understood. We previously described a ubiquitin-protein isopeptide ligase (E3) from erythroid cells that assembles polyubiquitin chains through either Lys29 or Lys48 of ubiquitin (Mastrandrea, L. D., You, J., Niles, E. G., and Pickart, C. M. (1999)J. Biol. Chem. 274, 27299–27306). Here we describe the purification of this E3 based on its affinity for a linear fusion of ubiquitin to the ubiquitin-conjugating enzyme UbcH5A. Among five major polypeptides in the affinity column eluate, the activity of interest was assigned to the product of a previously cloned human cDNA known as KIAA10 (Nomura, N., Miyajima, N., Sazuka, T., Tanaka, A., Kawarabayasi, Y., Sato, S., Nagase, T., Seki, N., Ishikawa, K., and Tabata, S. (1994) DNA Res. 1, 27–35). The KIAA10 protein is a member of the HECT (homologous to E6-APcarboxyl terminus) domain family of E3s. These E3s share a conserved C-terminal (HECT) domain that functions in the catalysis of ubiquitination, while their divergent N-terminal domains function in cognate substrate binding (Huibregtse, J. M., Scheffner, M., Beaudenon, S., and Howley, P. M. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 2563–2567). Recombinant KIAA10 catalyzed the assembly of both Lys29- and Lys48-linked polyubiquitin chains. Surprisingly, the C-terminal 428 residues of KIAA10 were both necessary and sufficient for this activity, suggesting that the ability to assemble polyubiquitin chains may be a general property of HECT domains. The N-terminal domain of KIAA10 interacted in vitro with purified 26 S proteasomes and with the isolated S2/Rpn1 subunit of the proteasome's 19 S regulatory complex, suggesting that the N-terminal domains of HECT E3s may function in proteasome binding as well as substrate binding.
Molecular subtypes identified by gene expression profiling in early stage endometrioid endometrial adenocarcinoma

Background Early stage (FIGO stage I‐II) endometrioid endometrial adenocarcinoma (EEA) is very common in clinical practice. However, patients with the early stage EEA show various clinical behaviors due to biological heterogeneity. Hence, we aimed to discover distinct classes of tumors based on gene expression profiling, and analyze whether the molecular classification correlated with the histopathological stages or other clinical parameters. Methods Hierarchical clustering was performed for class discovery in 28 early stage EEA samples using a special cDNA microarray chip containing 492 genes designed for endometrial cancer. Correlations between clinicopathologic parameters and our classification were analyzed. And the significance analysis of microarrays (SAM) array was used to identify the signature genes according to the tumor grade and myometrial invasion. Results Three tumor subtypes (subtypes I, II and III) were identified by hierarchical clustering, each subtype had different clinicopathological factors, such as tumor grade, myometrial invasion status, and FIGO stage. Moreover, SAM analysis showed 34 up‐regulated genes in high grade tumors, and 38 up‐regulated genes and 1 down‐regulated in deep myometrial invasive tumors. The overlap genes between these two high‐risk factors were markedly up‐regulated in subtype I, but down‐regulated in subtype III. Conclusion We have identified novel molecular subtypes in early stage EEA. Differential gene signatures characterize each tumor subtype, which could be used for recognizing the tumor risk and providing a basis for further treatment stratification.
Age‐dependent changes in stratum corneum barrier function

The Stratum Corneum (SC) barrier function mainly depends on the SC structure at the tissue level, its composition, and the organization of intercellular lipidic cement at the molecular level. The goal of this study was to assess the age‐dependent changes of the SC barrier function and the associated physiological parameters.
A recommender model based on trust value and time decay: Improve the quality of product rating score in E-commerce platforms

Most of the existing products rating score algorithms do not take fake accounts and time decay of users' ratings into account when creating the list of recommendations. The trust values and the time decay of users' ratings to an item may improve the quality of product rating score in e-commerce platforms, especially when it is thought that nowadays the majority of customers read the reviews before making a purchase. In this paper, we first introduce the concept trust value of users by explaining its mathematical definition and redefine the product rating score based on users' trust relationship. Then we calculate the product rating score based on time decay by making the concept time decay clear. After that we execute both algorithms together in order to show their both effects on the quality of product rating score. Finally, we present experimentally effectiveness of three approaches on a large real dataset.
Deep resequencing of 17 glutamate system genes identifies rare variants in DISC1 and GRIN2B affecting risk of opioid dependence

The N‐methyl‐D‐aspartate (NMDA) glutamate receptors play important roles in the pathophysiology of substance dependence (SD), but no strong genetic evidence has associated common variants in NMDAR‐related genes to SD. We hypothesized that rare variants (RVs) with minor allele frequency <1% in the NMDAR‐related genes might exert large effects on SD risk. We sequenced 34 544 bp of coding and flanking intronic regions of 17 genes involved in the NMDA system in 760 subjects, all with co‐occurring alcohol dependence, cocaine dependence and opioid dependence (OD), and 760 healthy control subjects. One hundred percent of the target regions were sequenced at >1000× coverage. We identified 454 variants, including 380 RVs. Based on case‐control allele count differences, we genotyped 11 exonic RVs in 6751 additional subjects, and the 1520 subjects from the sequencing stage for validation. All alleles of the 11 RVs called in the sequencing stage were confirmed. We found a statistically significant association of the 11 RVs with OD in African Americans (P = 0.00080). Results from gene‐based association tests showed that the association signal derived mostly from DISC1 (P = 0.0010) and GRIN2B (P = 0.00085). DISC1 is a well‐validated schizophrenia risk gene. This is the first demonstration that RVs affect the risk of OD and the first demonstration of biological convergence of schizophrenia and OD risk—via DISC1.