Miracle-dz/UniFAR-FTUs huggingface dataset:
Aspergillus PCR: One Step Closer to Standardization

ABSTRACT PCR has been used as an aid in the diagnosis of invasive aspergillosis for almost 2 decades. A lack of standardization has limited both its acceptance as a diagnostic tool and multicenter clinical evaluations, preventing its inclusion in disease-defining criteria. In 2006, the European Aspergillus PCR Initiative was formed. The aim of the initiative was to provide optimal standardized protocols for the widespread clinical evaluation of the Aspergillus PCR to determine its diagnostic role and allow inclusion in disease diagnosis criteria. Quality control panels were developed and circulated to centers for evaluation of the existing methodology before recommendations based on the initial results were proposed for further panels. The centers were anonymously classified as “compliant” or “noncompliant,” according to whether they had followed the proposed recommendations before the performance parameters were determined and meta-regression analysis was performed. Most PCR amplification systems provided similar detection thresholds, although positivity was a function of the fungal burden. When PCR amplification was combined with DNA extraction, 50% of the centers failed to achieve the same level of detection. Meta-regression analysis showed positive correlations between sensitivity and extraction protocols incorporating the proposed recommendations and the use of bead beating, white cell lysis buffer, and an internal control PCR. The use of elution volumes above 100 μl showed a negative correlation with sensitivity. The efficiency of the Aspergillus PCR is limited by the extraction procedure and not by PCR amplification. For PCR testing of whole blood, it is essential that large blood volumes (≥3 ml) be efficiently lysed before bead beating to disrupt the fungal cell and performance of an internal control PCR to exclude false negativity. DNA should be eluted in volumes of <100 μl.
Keeping it in the family? People with learning disabilities and families employing their own care and support workers

This article focuses on people with learning disabilities and their families who employ care or support workers using public (government) and/or private (self and family) funds. Such consumer-directed support takes place in England through personal budgets and direct payments. Research and material relevant to these employment relationships were explored in a scoping review undertaken by the authors in 2010. The review identified a small number of studies that involved people with learning disabilities as respondents, although more relied on family carers as proxy respondents. The findings from these studies covered recruitment and administration, employment of family members, training needs, the nature and content of employment relationships, and ending employment. The review observed that employment relationships, practices, and dynamics are surprisingly little explored in the literature and generally unobserved. The article concludes with specific messages from the review for family carers, for people with learning disabilities and for care and support workers.
Convex analysis based minimum-volume enclosing simplex algorithm for hyperspectral unmixing

Hyperspectral unmixing aims at identifying the hidden spectral signatures (or endmembers) and their corresponding proportions (or abundances) from an observed hyperspectral scene. Many existing approaches to hyperspectral unmixing rely on the pure-pixel assumption, which may be violated for highly mixed data. A heuristic unmixing criterion without requiring the pure-pixel assumption has been reported by Craig: The endmember estimates are determined by the vertices of a minimum-volume simplex enclosing all the observed pixels. In this paper, using convex analysis, we show that the hyperspectral unmixing by Craig's criterion can be formulated as an optimization problem of finding a minimum-volume enclosing simplex (MVES). An algorithm that cyclically solves the MVES problem via linear programs (LPs) is also proposed. Some Monte Carlo simulations are provided to demonstrate the efficacy of the proposed MVES algorithm.
Rehabilitation for Shoulder Instability – Current Approaches

Background: The shoulder relies predominantly on dynamic muscular control to provide stability. Successful treatment is highly dependent upon the correct clinical diagnosis, identification of anatomical structural defects and abnormal movement patterns so that rehabilitation programs can be designed accordingly and individualised to the patient. Method: A systematic outline is provided to guide the clinician on how to identify muscular insufficiencies both local to the shoulder joint and global muscles that can influence shoulder instability. Management is based on expert experience and current literature. Results: The Stanmore classification helps to correctly diagnose the type of instability and prioritise management. Symptom modification tests can help to guide management, however assessing individual muscle groups local to glenohumeral control is also recommended. Conclusion: Physical and psychosocial factors can influence motor control in the presence of pain and injury. A multi-disciplinary approach is required to avoid recurrence of symptoms with rehabilitation focusing on kinetic chain, scapular and gleno-humeral control.
Markers of fibroblast-rich tumor stroma and perivascular cells in serous ovarian cancer: Inter- and intra-patient heterogeneity and impact on survival

Inter- and intra-patient variations in tumor microenvironment of serous ovarian cancer are largely unexplored. We aimed to explore potential co-regulation of tumor stroma characteristics, analyze their concordance in primary and metastatic lesions, and study their impact on survival. A tissue microarray (TMA) with 186 tumors and 91 matched metastases was subjected to immunohistochemistry double staining with endothelial cell marker CD34 and fibroblast and pericyte markers α-SMA, PDGFβR and desmin. Images were digitally analyzed to yield “metrics” related to vasculature and stroma features. Intra-case analyses showed that PDGFβR in perivascular cells and fibroblasts were strongly correlated. Similar findings were observed concerning α-SMA. Most stroma characteristics showed large variations in intra-case comparisons of primary tumors and metastasis. Large PDGFβR-positive stroma fraction and high PDGFβFR positive perivascular intensity were both significantly associated with shorter survival in uni- and multi-variate analyses (HR 1.7, 95% CI 1.1-2.5; HR 1.7, 95% CI 1.1-2.8). In conclusion, we found PDGFβR- and α-SMA-expression to be largely independent of each other but concordantly activated in perivascular cells and in fibroblasts within the primary tumor. Stromal characteristics differed between primary tumors and metastases. PDGFβR in perivascular cells and in fibroblasts may be novel prognostic markers in serous ovarian cancer.
Edge-weighting Hyperlink-Induced Topic Search (E-HITS) Algorithm

Link analysis method in general and Hyperlink-Induced Topic Search (HITS) algorithm in particular is used for analyzing graph in many important contexts, including ranking search results based on the hyperlink structure of the World Wide Web and privacy analysis of social networks with the purpose of identifying the role of each object (node) of graph by computing node weight. Similar to almost link analysis algorithms, HITS method consider all edges identically in each computation. However, we find that value of edges in real cases are not identical in analyzing and depend on the relationships/associations in content of two endings. Therefore, in HITS, edge weight should be also computed so that be suitable with value of corresponding relationship/association. Benefiting from the edge weighting, we can treat the problems of "invaluable edges" and their relevant nodes (normally as "rubbishes") in analysis. With this motivation, an improvement HITS (E-HITS) is proposed in this paper. In proposed method, we analyze the meaning of edge, corresponding relationship/association and its characteristics (especially as "group-based") as basis for edge-weight calculation, in which, the calculation is only based on the available hub and authority parameters on graph. Experiments on simulation graphs as well as on real web-graph data show evidently that along with edge weighting, our proposed method can remove the impacts of invaluable edges as well as rubbish nodes in analysis, give the result more positively and objectively than the original HITS method.
Distant Supervision for Entity Linking

Entity linking is an indispensable operation of populating knowledge repositories for information extraction. It studies on aligning a textual entity mention to its corresponding disambiguated entry in a knowledge repository. In this paper, we propose a new paradigm named distantly supervised entity linking (DSEL), in the sense that the disambiguated entities that belong to a huge knowledge repository (Freebase) are automatically aligned to the corresponding descriptive webpages (Wiki pages). In this way, a large scale of weakly labeled data can be generated without manual annotation and fed to a classifier for linking more newly discovered entities. Compared with traditional paradigms based on solo knowledge base, DSEL benefits more via jointly leveraging the respective advantages of Freebase and Wikipedia. Specifically, the proposed paradigm facilitates bridging the disambiguated labels (Freebase) of entities and their textual descriptions (Wikipedia) for Web-scale entities. Experiments conducted on a dataset of 140,000 items and 60,000 features achieve a baseline F1-measure of 0.517. Furthermore, we analyze the feature performance and improve the F1-measure to 0.545.
TorsinA in PC12 cells: Localization in the endoplasmic reticulum and response to stress

Most cases of early‐onset torsion dystonia are caused by deletion of GAG in the coding region of the DYT1 gene encoding torsinA. This autosomal dominant neurologic disorder is characterized by abnormal movements, believed to originate from neuronal dysfunction in the basal ganglia of the human brain. The torsins (torsinA and torsinB) are members of the “ATPases associated with a variety of cellular activities” (AAA+) superfamily of proteins that mediate chaperone and other functions involved in conformational modeling of proteins, protection from stress, and targeting of proteins to cellular organelles. In this study, the intracellular localization and levels of endogenous torsin were evaluated in rat pheochromocytoma PC12 cells following differentiation and stress. TorsinA, apparent MW 37 kDa, cofractionates with markers for the microsomal/endoplasmic reticulum (ER) compartment and appears to reside primarily within the ER lumen based on protease resistance. TorsinA immunoreactivity colocalizes with the lumenal ER protein protein disulfide isomerase (PDI) and extends throughout neurites. Levels of torsinA did not increase notably in response to nerve growth factor‐induced differentiation. None of the stress conditions tested, including heat shock and the unfolded protein response, affected torsinA, except for oxidative stress, which resulted in an increase in the apparent MW of torsinA and redistribution to protrusions from the cell surface. These findings are consistent with a relatively rapid covalent modification of torsinA in response to oxidative stress causing a change in state. Mutant torsinA may interfere with and/or compromise ER functions, especially in dopaminergic neurons, which have high levels of torsinA and are intrinsically vulnerable to oxidative stress. © 2003 Wiley‐Liss, Inc.
Filling a glass of water: Continuously decoding the speed of 3D hand movements from EEG signals

We present a new system for the continuous decoding of hand movement speed in three-dimensional (3D) space from EEG signals. We recorded experimental data of five subjects during mimicking the natural task of filling a glass of water. The proposed system uses filter bank common spatial patterns and linear regression to estimate the speed of hand movements from artifact cleaned EEG signals. Average Pearson correlations between the speed trajectories predicted from EEG and the speed trajectories measured using a high-precision motion tracking system are r=0.41 for the x-axis, r=0.36 for the y-axis, r=0.48 for the z-axis, and r=0.17 for absolute speed in 3D space.
cAMP-Mediated Mechanisms for Pain Sensitization during Opioid Withdrawal

Chronic opioid-induced drug dependence and withdrawal syndrome after opioid cessation remain a severe obstacle in clinical treatment of chronic pain and opioid drug addiction. One of the key symptoms during opioid withdrawal is a state of sensitized pain. The most significant molecular adaptation induced by chronic opioids in the brain is upregulation of the cAMP-signaling pathway. Although the cAMP system is known to have multiple effects on central neuron functions, how its upregulation mediates behavioral opioid dependence and withdrawal-induced pain in vivo remains unclear. In this study, we demonstrate that withdrawal from chronic morphine significantly upregulates the mRNA level of adenylyl cyclase (AC) VI and VIII isoforms and immunoreactivity of ACV/VI in the nucleus raphe magnus (NRM), a brainstem site critically involved in opioid modulation of pain. In cellular studies of NRM neurons containing μ-opioid receptors, we show that morphine withdrawal significantly increases glutamate synaptic transmission via a presynaptic mechanism mediated by an upregulated cAMP pathway. Morphine withdrawal also enhances the hyperpolarization-activated current in these neurons by increased intracellular cAMP. Both of the withdrawal-induced cAMP actions increase the excitability of these μ-receptor-containing neurons, which are thought to facilitate spinal pain transmission. Furthermore, in morphine-dependent rats in vivo, blocking the cAMP pathway significantly reduces withdrawal-induced pain sensitization. These results illustrate neurobiological mechanisms for the cAMP-mediated withdrawal pain and provide potential therapeutic targets for the treatment of opioid dependence and withdrawal-related problems.
Maintenance support for web sites: a case study

This paper reports on results gathered during a case study using a Web maintenance tool called Perlbot. The main objective of the study is to observe the history of modifications made on various Web documents. Based on selected metrics, we collect data with respect to how such sites are maintained and evolve. The data gathered support our hypothesis that there is a worldwide tendency to accumulate large numbers of stale documents over long periods of time. Moreover, our quantitative results reveal inconsistent Web maintenance activities spanning over various international sites.
Sestrin2 Suppresses Classically Activated Macrophages-Mediated Inflammatory Response in Myocardial Infarction through Inhibition of mTORC1 Signaling

Myocardial infarction (MI) triggers an intense inflammatory response that is essential for dead tissue clearance but also detrimental to cardiac repair. Macrophages are active and critical players in the inflammatory response after MI. Understanding the molecular mechanisms by which macrophage-mediated inflammatory response is regulated is important for designing new therapeutic interventions for MI. In the current study, we examined the role of Sestrin2, which is a stress-inducible protein that regulate metabolic homeostasis, in the regulation of inflammatory response of cardiac macrophages after MI. We found that cardiac macrophages upregulated Sestrin2 expression in a mouse MI model. Using a lentiviral transduction system to overexpress Sestrin2 in polarized M1 and M2 macrophages, we revealed that Sestrin2 predominantly functioned on M1 rather than M2 macrophages. Sestrin2 overexpression suppressed inflammatory response of M1 macrophages both in vitro and in vivo. Furthermore, in the mouse MI model with selective depletion of endogenous macrophages and adoptive transfer of exogenous Sestrin2-overexpressing macrophages, the anti-inflammatory and repair-promoting effect of Sestrin2-overexpressing macrophages was demonstrated. Furthermore, Sestrin2 significantly inhibited mTORC1 signaling in M1 macrophages. Taken together, our study indicates the importance of Sestrin2 for suppression of M1 macrophage-mediated cardiac inflammation after MI.
Intraspinal steroids: history, efficacy, accidentality, and controversy with review of United States Food and Drug Administration reports

This review, covering a timespan of almost a century, attempts to answer five pressing questions: (1) Are intraspinal steroid therapies effective for back pain or radicular syndromes? (2) Do epidural injections remain confined to the epidural space? (3) Are presently prescribed steroid formulations neurotoxic? (4) What are the risks of epidural steroid injection? (5) What information should be given to patients in obtaining informed consent for these procedures? ### REMOTE HISTORY #### Early cocaine and “pressure injections” In 1901 there were reports of cocaine injection via the sacral hiatus for sciatica.1-3 De Pasquier and Leri2 used lumbar intrathecal injections containing 5 mg cocaine that produced “toxic cocaine accidents . to the bulbar and cerebral centers. ” They attempted without success to prevent flow of cocaine intracranially “by the use of a band of rubber gently tightened around the neck. ” Then they tried sacral epidural injections and claimed success. In 1925, Viner4also employed the sacral route, using procaine in normal saline, Ringer's solution, or “liquid petrolatum. ” Evans5reported treating 40 patients with “idiopathic sciatica” by sacral hiatus injection of normal saline and procaine hydrochloride. In attempts to relieve “mechanical stretching” of nerve roots, he found that the volume of injectate (100 ml or more with and without local anaesthetic) was the most important factor. Sciatica was relieved completely in 24 patients and “considerable benefit” occurred in six In these uncontrolled trials, the nature of the pathological process and the duration of pain relief were not specified.4 5 #### Articular steroid injection—the harbinger of intraspinal therapy Compound E (cortisone) was discovered in 1936.6 7 In 1950 Hench et al 8 9 reported that it produced transient improvement of “rheumatoid arthritis, rheumatic fever, and certain other conditions. ” Then Hollander10 reported the intra-articular effects of a longer acting steroid, Compound F (hydrocortisone), warning that “ . it should be emphasised that its …
A Meta-Analysis of Microarray Gene Expression in Mouse Stem Cells: Redefining Stemness

Background While much progress has been made in understanding stem cell (SC) function, a complete description of the molecular mechanisms regulating SCs is not yet established. This lack of knowledge is a major barrier holding back the discovery of therapeutic uses of SCs. We investigated the value of a novel meta-analysis of microarray gene expression in mouse SCs to aid the elucidation of regulatory mechanisms common to SCs and particular SC types. Methodology/Principal Findings We added value to previously published microarray gene expression data by characterizing the promoter type likely to regulate transcription. Promoters of up-regulated genes in SCs were characterized in terms of alternative promoter (AP) usage and CpG-richness, with the aim of correlating features known to affect transcriptional control with SC function. We found that SCs have a higher proportion of up-regulated genes using CpG-rich promoters compared with the negative controls. Comparing subsets of SC type with the controls a slightly different story unfolds. The differences between the proliferating adult SCs and the embryonic SCs versus the negative controls are statistically significant. Whilst the difference between the quiescent adult SCs compared with the negative controls is not. On examination of AP usage, no difference was observed between SCs and the controls. However, comparing the subsets of SC type with the controls, the quiescent adult SCs are found to up-regulate a larger proportion of genes that have APs compared to the controls and the converse is true for the proliferating adult SCs and the embryonic SCs. Conclusions/Significance These findings suggest that looking at features associated with control of transcription is a promising future approach for characterizing “stemness” and that further investigations of stemness could benefit from separate considerations of different SC states. For example, “proliferating-stemness” is shown here, in terms of promoter usage, to be distinct from “quiescent-stemness”.
QGRS-H Predictor: a web server for predicting homologous quadruplex forming G-rich sequence motifs in nucleotide sequences

Naturally occurring G-quadruplex structural motifs, formed by guanine-rich nucleic acids, have been reported in telomeric, promoter and transcribed regions of mammalian genomes. G-quadruplex structures have received significant attention because of growing evidence for their role in important biological processes, human disease and as therapeutic targets. Lately, there has been much interest in the potential roles of RNA G-quadruplexes as cis-regulatory elements of post-transcriptional gene expression. Large-scale computational genomics studies on G-quadruplexes have difficulty validating their predictions without laborious testing in ‘wet’ labs. We have developed a bioinformatics tool, QGRS-H Predictor that can map and analyze conserved putative Quadruplex forming 'G'-Rich Sequences (QGRS) in mRNAs, ncRNAs and other nucleotide sequences, e.g. promoter, telomeric and gene flanking regions. Identifying conserved regulatory motifs helps validate computations and enhances accuracy of predictions. The QGRS-H Predictor is particularly useful for mapping homologous G-quadruplex forming sequences as cis-regulatory elements in the context of 5′- and 3′-untranslated regions, and CDS sections of aligned mRNA sequences. QGRS-H Predictor features highly interactive graphic representation of the data. It is a unique and user-friendly application that provides many options for defining and studying G-quadruplexes. The QGRS-H Predictor can be freely accessed at: http://quadruplex.ramapo. edu/qgrs/app/start.
Studying Attraction Power in Proxemics-Based Visual Concepts for Large Public Interactive Displays

A key challenge in designing interfaces for large interactive displays deployed in public settings is to draw (and keep) a passerby's attention. Proxemic interactions--a design approach that applies human spatial behavior to guide system behavior in response to a user's proximity to a display--has been proposed for attracting and engaging potential users. Yet, the effectiveness of this approach has not been evaluated. Moreover, little research exists in the broader literature on the relative efficacy of possible visual design strategies to attract and engage large display users. We conducted a study to the effectiveness of promising visual concepts applied in a proxemic interactions framework: content motion and user shadows. While both visual concepts were more effective than a control condition at capturing attention, the inclusion of user's shadow was found to have stronger attraction power than content motion alone. In contrast, they were found to be ineffective for communicating possible user interactions in the display, limiting their potential to facilitate further system use.