Miracle-dz/UniFAR-FTUs huggingface dataset:
Delinking CARD9 and IL-17: CARD9 Protects against Candida tropicalis Infection through a TNF-α–Dependent, IL-17–Independent Mechanism

Candida is the third most common cause of bloodstream infections in hospitalized patients. Immunity to C. albicans, the most frequent species to be isolated in candidiasis, involves a well-characterized Dectin-1/caspase-associated recruitment domain adaptor 9 (CARD9)/IL-17 signaling axis. Infections caused by non-albicans Candida species are on the rise, but surprisingly little is known about immunity to these pathogens. In this study, we evaluated a systemic infection model of C. tropicalis, a clinically relevant, but poorly understood, non-albicans Candida. Mice lacking CARD9 were profoundly susceptible to C. tropicalis, displaying elevated fungal burdens in visceral organs and increased mortality compared with wild-type (WT) controls. Unlike C. albicans, IL-17 responses were induced normally in CARD9−/− mice following C. tropicalis infection. Moreover, there was no difference in susceptibility to C. tropicalis infection between WT and IL-23p19−/−, IL-17RA−/−, or Act1−/− mice. However, TNF-α expression was markedly impaired in CARD9−/− mice. Consistently, WT mice depleted of TNF-α were more susceptible to C. tropicalis, and CARD9-deficient neutrophils and monocytes failed to produce TNF-α following stimulation with C. tropicalis Ags. Both neutrophils and monocytes were necessary for defense against C. tropicalis, because their depletion in WT mice enhanced susceptibility to C. tropicalis. Disease in CARD9−/− mice was not due to defective neutrophil or monocyte recruitment to infected kidneys. However, TNF-α treatment of neutrophils in vitro enhanced their ability to kill C. tropicalis. Thus, protection against systemic C. tropicalis infection requires CARD9 and TNF-α, but not IL-17, signaling. Moreover, CARD9-dependent production of TNF-α enhances the candidacidal capacity of neutrophils, limiting fungal disease during disseminated C. tropicalis infection.
Simplified electrocardiogram sampling maintains high diagnostic capability for atrial fibrillation: implications for opportunistic atrial fibrillation screening in primary care.

AIMS Atrial fibrillation (AF) is a major cause of morbidity, mortality, and health resource consumption. However, as many patients with chronic AF are asymptomatic, rapid, accurate opportunistic screening is needed in primary care to detect AF. Conventional electrocardiogram (ECG) technology is too clumsy and time consuming for mass opportunistic screening, thus technology that allows easy, rapid, yet accurate AF screening is required. To address this requirement a prototype hand-held electrode assembly was developed. We hypothesized that a 6-lead frontal-plane ECG acquired from this apparatus in a seated, clothed patient would be as accurate at detecting AF as conventional 12-lead ECG in the undressed, supine patient (the 'gold standard'). METHODS AND RESULTS Electrocardiograms were obtained from 78 patients with AF and 79 with sinus rhythm (SR). All had a conventional 12-lead ECG, a 6-lead ECG from conventionally positioned limb electrodes, a supine 6-lead recording using the prototype recorder placed on the lower thorax/upper abdomen, and a 6-lead prototype recording in the seated patient, the latter with loosened clothing only. Electrocardiograms were randomly and blindly assessed by two cardiologists for (i) diagnosis of AF vs. SR and (ii) tracing quality (subjectively assessed as good, adequate, or bad). Compared with conventional 12-lead ECG recordings, all 'new' recording methods performed satisfactorily with sensitivities ≥90% (90-99%), specificities ≥94% (94-100%), positive predictive values ≥94% (94-100%), negative predictive values ≥90% (90-99%), and accuracies ≥93% (93-99%). Tracing quality was higher in conventional 12-lead recordings (71 and 80% were assessed as good by the two observers) compared with conventional 6-lead (57 and 59%), supine prototype (41 and 31%), and sitting prototype (39 and 19%). CONCLUSIONS Despite inferior electrocardiographic quality a 6-lead frontal plane ECG acquired by a simple prototype hand-held electrode assembly allowed reliable differentiation of AF from SR compared with standard 12-lead ECG.
Energetics of ambulation with spring-loaded crutches

Habitual users of underarm crutches may suffer severe shoulder and wrist pain. Our aim is to investigate the effect of using spring-loaded crutches on mechanical efficiency by comparing its performance with standard crutches through a biomechanical approach. In our experiments, seven male subjects were instructed to walk around a track on crutches for 5 minutes under 4 controlled conditions. The externally-loaded and segmental work involved with the motions was computed based on ground reaction forces and centre of motion trajectories. Simultaneously, portable gas analysis machinery was used to collect the metabolic parameters of subjects to work out mechanical efficiency, the ratio of mechanical to metabolic work. It was found that the mechanical efficiency was significantly higher when subjects walked with spring-loaded crutches than when they walked with standard crutches.
Demand Analysis of Water Resources Based on Pulse Process of Complex System

In this paper, we examine the demand for fresh water of China in 2025 from the complex system modeling perspective and we develop an efficient, economical and practical water strategy to meet the demand for fresh water in 2025.Different from previous research, this study focus on studying several factors that can influence the demand for fresh water, and their interplay within the complex large-scale system. We construct the Directed Graph Model and the Impulse Process Model to study the complex system in a qualitatively way. After that, on the basis of qualitative study, we study the whole system quantitatively by using the Leontief Inverse Matrix. And draw an effective, feasible, and cost-efficient water strategy, namely, adjusting the relation between seawater desalination and the water protection.
Reduced virulence of Candida albicans mutants affected in multidrug resistance

Disruption of a multidrug resistance gene (CaMDR1) in Candida albicans resulted in mutant strains that colonized mouse kidneys to very high levels but were markedly reduced in their virulence. No obvious differences in several properties related to colonization and dissemination were noted among MDR+ or mdr- strains. These results suggest that specific fungal efflux pumps play a role in fungal pathogenicity.
Automated detection of inconsistent phraseology translation

Abstract We investigate the extent to which the detection of phraseological (in)consistency in the translation process can be automated. We describe the acquisition of a large corpus of Belgian legal documents consisting of French arrests translated into Dutch. We apply the sentence alignment tool GMA to the corpus, and extract phraseological unit candidates from the sentence pairs through the term candidate extraction tool TermCalc and the word alignment data produced by the GIZA++ tool. The candidates are compared to a reference set from a manual study of an MA student at Lessius/ KULeuven. They appear to cover only 33% of the bilingual phraseological unit pairs and only four French units with more than one Dutch equivalent. This indicates the need for devising techniques specifically aimed at detecting multiple equivalence, hence potential phraseological inconsistency.
Indicators for Measuring the Success of Video Usage in Public Services: The Case of Education

Despite the fact that governments continue to push the use of Information and Communication Technology (ICT) in public service provision, their adoption rate has not always been as high as expected. In this research, we focus on indicators that could lead to the adoption of video-to-video communication in education. With this aim we organized three focus groups with teachers from Ireland and Greece and one interview with the principal head teacher from an Irish primary school with the aim of understanding the most important criteria necessary for the adoption of video-to-video communication for collaborative education in primary and secondary schools. The paper presents the technical (network and application) and user (user experience and pedagogical) criteria that were identified through these focus groups.
The Analysis of Ordered Categorical Data : An Overview and a Survey of Recent Developments

This article reviews methodologies used for analyzing ordered categorical (ordinal) response variables. We begin by surveying models for data with a single ordinal response variable. We also survey recently proposed strategies for modeling ordinal response variables when the data have some type of clustering or when repeated measurement occurs at various occasions for each subject, such as in longitudinal studies. Primary models in that case include marginal models and cluster-specific (conditional) models for which effects apply conditionally at the cluster level. Related discussion refers to multi-level and transitional models. The main emphasis is on maximum likelihood inference, although we indicate certain models (e.g., marginal models, multi-level models) for which this can be computationally difficult. The Bayesian approach has also received considerable attention for categorical data in the past decade, and we survey recent Bayesian approaches to modeling ordinal response variables. Alternative, non-model-based, approaches are also available for certain types of inference.
Development of Inpatient Risk Stratification Models of Acute Kidney Injury for Use in Electronic Health Records

Objective. Patients with hospital-acquired acute kidney injury (AKI) are at risk for increased mortality and further medical complications. Evaluating these patients with a prediction tool easily implemented within an electronic health record (EHR) would identify high-risk patients prior to the development of AKI and could prevent iatrogenically induced episodes of AKI and improve clinical management. Methods. The authors used structured clinical data acquired from an EHR to identify patients with normal kidney function for admissions from 1 August 1999 to 31 July 2003. Using administrative, computerized provider order entry and laboratory test data, they developed a 3-level risk stratification model to predict each of 2 severity levels of in-hospital AKI as defined by RIFLE criteria. The severity levels were defined as 150% or 200% of baseline serum creatinine. Model discrimination and calibration were evaluated using 10-fold cross-validation. Results. Cross-validation of the models resulted in area under the receiver operating characteristic (AUC) curves of 0.75 (150% elevation) and 0.78 (200% elevation). Both models were adequately calibrated as measured by the Hosmer-Lemeshow goodness-of-fit test chi-squared values of 9.7 (P = 0.29) and 12.7 (P = 0.12), respectively. Conclusions. The authors generated risk prediction models for hospital-acquired AKI using only commonly available electronic data. The models identify patients at high risk for AKI who might benefit from early intervention or increased monitoring.
Toward Learning the Causal Layer of the Spatial Semantic Hierarchy using SOMs

The Spatial Semantic Hierarchy (SSH) is a multi-level representation of the cognitive map used for navigation in largescale space. We propose a method for learning a portion of this representation, specifically, the representation of views in the causal level of the SSH using self-organizing neural networks (SOMs). We describe the criteria that a good view representation should meet, and why SOMs are a promising view representation. Our preliminary experimental results indicate that SOMs show promise as a view representation, though there are still some problems to be resolved.
Checkpoint Inhibition: Programmed Cell Death 1 and Programmed Cell Death 1 Ligand Inhibitors in Hodgkin Lymphoma

AbstractHodgkin lymphoma (HL) is a lymphoid malignancy characterized by a reactive immune infiltrate surrounding relatively few malignant cells. In this scenario, active immune evasion seems to play a central role in allowing tumor progression. Immune checkpoint inhibitor pathways are normal mechanisms of T-cell regulation that suppress immune effector function following an antigenic challenge. Hodgkin lymphoma cells are able to escape immune surveillance by co-opting these mechanisms. The programmed cell death 1 (PD-1) pathway in particular is exploited in HL as the malignant Hodgkin and Reed-Sternberg cells express on their surface cognate ligands (PD-L1/L2) for the PD-1 receptor and thereby dampen the T-cell–mediated antitumoral response. Monoclonal antibodies that interact with and disrupt the PD-1:PD-L1/L2 axis have now been developed and tested in early-phase clinical trials in patients with advanced HL with encouraging results. The remarkable clinical activity of PD-1 inhibitors in HL highlights the importance of immune checkpoint pathways as therapeutic targets in HL. In this review, we discuss the rationale for targeting PD-1 and PD-L1 in the treatment of HL. We will evaluate the published clinical data on the different agents and highlight the safety profile of this class of agents. We discuss the available evidence on the use of biomarkers as predictors of response to checkpoint blockade and summarize the areas under active investigation in the use of PD-1/PD-L1 inhibitors for the treatment of HL.
Interventional Management of Stroke III Trial: establishing the foundation

In the wake of the Interventional Management of Stroke (IMS) III independent data safety monitoring board's recommendation on 18 April 2012 to place the IMS III trial on hold due to prespecified planned interim analysis showing the very low likelihood of finding a significant difference between the two treatment arms, one might properly wonder, “What is next”? Restoration of blood flow after acute ischemic stroke (AIS) is associated with improved outcome and reduced mortality.1 2 Death and disability from AIS remains staggering despite the approval of intravenous thrombolysis with tissue plasminogen activator (IV-rtPA) over 15 years ago. The small population that benefits from IV-rtPA is, in part, limited to those patients treated within a narrow time window. Although cerebrovascular imaging is not consistently performed prior to administration of IV-rTPA, there is some evidence that the infusion is most effective in those patients who have small or distal vessel occlusions.3 The likelihood of recanalization with IV-rtPA declines considerably in occlusions of larger vessels such as the proximal middle cerebral artery and terminal internal carotid artery,3 and underscores the need for good AIS revascularization therapy (RT). The IMS I trial suggested that combination therapy with IV-rtPA and an intra-arterial (IA) approach was safe and may be clinically useful in AIS treatment.4 This was further supported by the IMS II trial, a single-arm pilot study showing preliminary estimates of efficacy and safety of combination IV and IA therapy.5 The IMS III trial subsequently became the pioneering phase III randomized multicenter open-label clinical trial that was designed to assess if the combined IV-rtPA and IA approach is superior to IV rt-PA alone when initiated within 3 h of AIS onset (http://clinicaltrials.gov/ct2/show/NCT00359424). 6 The randomization scheme was to enrol two-thirds in the combined arm and one-third in the IV-rtPA alone arm. …
Subspace clustering of dimensionality-reduced data

Subspace clustering refers to the problem of clustering unlabeled high-dimensional data points into a union of low-dimensional linear subspaces, assumed unknown. In practice one may have access to dimensionality-reduced observations of the data only, resulting, e.g., from “undersampling” due to complexity and speed constraints on the acquisition device. More pertinently, even if one has access to the high-dimensional data set it is often desirable to first project the data points into a lower-dimensional space and to perform the clustering task there; this reduces storage requirements and computational cost. The purpose of this paper is to quantify the impact of dimensionality-reduction through random projection on the performance of the sparse subspace clustering (SSC) and the thresholding based subspace clustering (TSC) algorithms. We find that for both algorithms dimensionality reduction down to the order of the subspace dimensions is possible without incurring significant performance degradation. The mathematical engine behind our theorems is a result quantifying how the affinities between subspaces change under random dimensionality reducing projections.
The Dimensional Structure of Asian American Acculturation: An Examination of Prototypes

This study investigated the dimensional structure of acculturation for three prototypic groups of Asian Americans: those who were more Asian identified, those who were more American identified, and those who were jointly Asian and American identified. Three-way multidimensional scaling revealed a two-dimensional structure in which the first dimension consisted of language and culture domains and the second dimension contained cultural identity and values domains. These findings are consistent with the theoretical literature that distinguishes between external and internal aspects of acculturation (e.g., Kwan & Sodowsky, 1997). The first dimension was salient for the American identified prototype group, the second dimension was salient for the Asian identified group, and both dimensions were salient for the Asian and American identified group. Implications of the dimensional structure are discussed with respect to the predominant models of acculturation and identity for Asian Americans (e.g., Berry, 1989; Sue & Sue, 2003; Suinn, Rickard-Figueroa, Lew, & Vigil, 1987), the role of sociocultural context, and Linville's (1987) theory of cognitive complexity. Recommendations are made for the assessment of acculturation among Asian Americans.
The Politics of Public Accountability: Implications for Centralized Music Education Policy Development and Implementation

This article addresses accountability issues that affect music education policy and implementation in the neoliberal education system. Using examples from education reform in Ontario, Canada, the author argues that two forms of accountability imbalances fostered by the neoliberal state—hierarchical answerability over communicative reason and top-down over bottom-up policymaking—allow the use of music curricula for political ends, to the detriment of curricular integrity and classroom delivery. The article also discusses how central governments that are responsible for developing standardized music curricula and allocating resources in an accountability vacuum may tacitly establish that "basic" subjects such as literacy, numeracy, and science are "more mandatory" than a mandated music curricula. The article concludes by recommending ways in which the centralized development of music education policy and resource allocation can be made more equitable both for those who encounter the curriculum at the local level and for the subject.
Distribution of Human-Specific Bacteroidales and Fecal Indicator Bacteria in an Urban Watershed Impacted by Sewage Pollution, Determined Using RNA- and DNA-Based Quantitative PCR Assays

ABSTRACT The identification of fecal pollution sources is commonly carried out using DNA-based methods. However, there is evidence that DNA can be associated with dead cells or present as “naked DNA” in the environment. Furthermore, it has been shown that rRNA-targeted reverse transcription-quantitative PCR (RT-qPCR) assays can be more sensitive than rRNA gene-based qPCR assays since metabolically active cells usually contain higher numbers of ribosomes than quiescent cells. To this end, we compared the detection frequency of host-specific markers and fecal bacteria using RNA-based RT-qPCR and DNA-based qPCR methods for water samples collected in sites impacted by combined sewer overflows. As a group, fecal bacteria were more frequently detected in most sites using RNA-based methods. Specifically, 8, 87, and 85% of the samples positive for general enterococci, Enterococcus faecalis, and Enterococcus faecium markers, respectively, were detected using RT-qPCR, but not with the qPCR assay counterpart. On average, two human-specific Bacteroidales markers were not detected when using DNA in 12% of the samples, while they were positive for all samples when using RNA (cDNA) as the template. Moreover, signal intensity was up to three orders of magnitude higher in RT-qPCR assays than in qPCR assays. The human-specific Bacteroidales markers exhibited moderate correlation with conventional fecal indicators using RT-qPCR results, suggesting the persistence of nonhuman sources of fecal pollution or the presence of false-positive signals. In general, the results from this study suggest that RNA-based assays can increase the detection sensitivity of fecal bacteria in urban watersheds impacted with human fecal sources.
Evaluation of protective efficacy of three novel H3N2 canine influenza vaccines

Canine influenza virus (CIV) has the potential risk to spread in different areas and dog types. Thus, there is a growing need to develop an effective vaccine to control CIV disease. Here, we developed three vaccine candidates: 1) a recombinant pVAX1 vector expressing H3N2 CIV hemagglutinin (pVAX1-HA); 2) a live attenuated canine adenovirus type 2 expressing H3N2 CIV hemagglutinin (rCAV2-HA); and 3) an inactivated H3N2 CIV (A/canine/Guangdong/01/2006 (H3N2)). Mice received an initial intramuscular immunization that followed two booster injections at 2 and 4 weeks post-vaccination (wpv). The splenic lymphocytes were collected to assess the immune responses at 6 wpv. The protective efficacy was evaluated by challenging H3N2 CIV after vaccination (at 6 wpv). Our results demonstrated that all three vaccine candidates elicited cytokine and antibody responses in mice. The rCAV2-HA vaccine and the inactivated vaccine generated efficient protective efficacy in mice, whereas limited protection was provided by the pVAX1-HA DNA vaccine. Therefore, both the rCAV2-HA live recombinant virus and the inactivated CIV could be used as potential novel vaccines against H3N2CIV. This study provides guidance for choosing the most appropriate vaccine for the prevention and control of CIV disease.
Retinoic Acid Combined with Vitamin A Synergizes to Increase Retinyl Ester Storage in the Lungs of Newborn and Dexamethasone-Treated Neonatal Rats

Background: Retinyl esters (REs), the major storage form of vitamin A (retinol), provide substrates for the production of bioactive retinoids, including retinoic acid (RA), which are known to promote lung development and maturation. We previously showed that the nutrient-metabolite combination VARA (molar ratio 10 vitamin A to 1 RA), synergistically increased REs in the lungs of 1-week-old rats, compared to vitamin A or RA alone. Objectives: To test the hypotheses, first, that VARA is more effective in increasing lung RE than is vitamin A in newborn rats prior to alveolarization, and, second, that the effect of VARA is maintained during concurrent treatment with the glucocorticoid, dexamethasone (Dex). Methods: Newborn rats were treated with VARA, vitamin A alone, or oil (C) on postnatal days (P) 1–3, and RE in the lungs was quantified on P4, and again on P8 to assess retention. Additionally, neonatal rats were treated on P5–7 with VARA with and without Dex, and the lung and liver REs were quantified on P8. Results and Conclusions: Lung RE was nearly 8-fold higher in VARA compared to vitamin A-treated rats on P4 (p < 0.01) and 2.5-fold higher on P8. In neonates co-treated with Dex and VARA on P5–7, the elevation in lung RE on P8 by VARA was not antagonized by Dex, although Dex reduced growth. Lung morphology and development were not significantly altered. The VARA combination may significantly increase lung RE content even during concurrent Dex therapy. Because lung retinoids are important for lung maturation and repair, increasing lung RE may possibly have clinical benefit.