Miracle-dz/UniFAR-FTUs huggingface dataset:
Treating refractory dermatomyositis or polymyositis with adrenocorticotropic hormone gel: a retrospective case series

Background Effective and tolerable treatment options for patients with dermatomyositis and polymyositis are limited. This retrospective case review describes treatment with adrenocorticotropic hormone (ACTH) gel in five patients who experienced a disease exacerbation and either failed or were unable to tolerate the side effects of previous therapy with steroids, intravenous immunoglobulins, and steroid-sparing drugs. Methods Patients received ACTH gel subcutaneous injections of 80 U (1 mL) twice weekly (four patients) or once weekly (one patient) over the course of 12 weeks for short-term treatment of symptom exacerbations. Manual muscle testing using the Medical Research Council scale was assessed at baseline and at 3 months. Results Improvement was seen in all patients, including improved muscle strength, decreased pain, and resolution of skin involvement. All patients tolerated the treatment well, and no significant side effects occurred. Conclusion The treatment of dermatomyositis and polymyositis is an approved use for ACTH gel, and these anecdotal reports would suggest consideration of ACTH gel as a therapeutic option. Further investigation is warranted.
Trial-by-Trial Coupling of Concurrent Electroencephalogram and Functional Magnetic Resonance Imaging Identifies the Dynamics of Performance Monitoring

Goal-directed behavior requires the continuous monitoring and dynamic adjustment of ongoing actions. Here, we report a direct coupling between the event-related electroencephalogram (EEG), functional magnetic resonance imaging (fMRI), and behavioral measures of performance monitoring in humans. By applying independent component analysis to EEG signals recorded simultaneously with fMRI, we found the single-trial error-related negativity of the EEG to be systematically related to behavior in the subsequent trial, thereby reflecting immediate behavioral adjustments of a cognitive performance monitoring system. Moreover, this trial-by-trial EEG measure of performance monitoring predicted the fMRI activity in the rostral cingulate zone, a brain region thought to play a key role in processing of response errors. We conclude that investigations of the dynamic coupling between EEG and fMRI provide a powerful approach for the study of higher order brain functions.
Variation in Brain Organization and Cerebellar Foliation in Chondrichthyans: Sharks and Holocephalans

The widespread variation in brain size and complexity that is evident in sharks and holocephalans is related to both phylogeny and ecology. Relative brain size (expressed as encephalization quotients) and the relative development of the five major brain areas (the telencephalon, diencephalon, mesencephalon, cerebellum, and medulla) was assessed for over 40 species from 20 families that represent a range of different lifestyles and occupy a number of habitats. In addition, an index (1–5) quantifying structural complexity of the cerebellum was created based on length, number, and depth of folds. Although the variation in brain size, morphology, and complexity is due in part to phylogeny, as basal groups have smaller brains, less structural hypertrophy, and lower foliation indices, there is also substantial variation within and across clades that does not reflect phylogenetic relationships. Ecological correlations, with the relative development of different brain areas as well as the complexity of the cerebellar corpus, are supported by cluster analysis and are suggestive of a range of ‘cerebrotypes’. These correlations suggest that relative brain development reflects the dimensionality of the environment and/or agile prey capture in addition to phylogeny.
ATF3 Gene

ATF3 gene, which encodes a member of the activating transcription factor/cAMP responsive element binding protein (ATF/CREB) family of transcription factors, is induced by many physiological stresses. As a step toward understanding the induction mechanisms, we isolated the human ATF3 gene and analyzed its genome organization and 5′-flanking region. We found that the human ATF3 mRNA is derived from four exons distributed over 15 kilobases. Sequence analysis of the 5′-flanking region revealed a consensus TATA box and a number of transcription factor binding sites including the AP-1, ATF/CRE, NF-κB, E2F, and Myc/Max binding sites. As another approach to understanding the mechanisms by which the ATF3 gene is induced by stress signals, we studied the regulation of the ATF3 gene in tissue culture cells by anisomycin, an approach that has been used to study the stress responses in tissue culture cells. We showed that anisomycin at a low concentration activates the ATF3 promoter and stabilizes the ATF3 mRNA. Significantly, co-transfection of DNAs expressing ATF2 and c-Jun activates the ATF3 promoter. A possible mechanism implicating the C-Jun NH-terminal kinase/stress-activated protein kinase (JNK/SAPK) stress-inducible signaling pathway in the induction of the ATF3 gene is discussed.
Analysis and synthesis: multi-agent systems in the social sciences

Abstract Although they flow from a common source, the uses of multi-agent systems (or ‘agent-based computational systems’––ACE) vary between the social sciences and computer science. The distinction can be broadly summarized as analysis versus synthesis, or explanation versus design. I compare and contrast these uses, and discuss sufficiency and necessity in simulations in general and in multi-agent systems in particular, with a computer science audience in mind.
Interruptive Events and Team Knowledge Acquisition

Interruptions have commonly been viewed as negative and as something for managers to control or limit. In this paper, I explore the relationship between interruptions and acquisition of routines-a form of knowledge-by teams. Recent research suggests that interruptions may play an important role in changing organizational routines, and as such may influence knowledge transfer activities. Results suggest that interruptions influence knowledge transfer effort, and both knowledge transfer effort and interruptions are positively related to the acquisition of new work routines. I conclude with implications for research and practice.
Mechanics of Thin Carbon Fiber Composites with a Silicone Matrix

This thesis presents an experimental, numerical and analytical study of the behavior of thin fiber composites with a silicone matrix. The main difference with respect to traditional composites with epoxy matrix is the fact that the soft matrix allows the fibers to microbuckle without breaking. This process acts as a stress relief mechanism during folding, and allows the material to reach very high curvatures, which makes them particularly interesting as components of space deployable structures. The goal of this study is to characterize the behavior and understand the mechanics of this type of composite. Experimental testing of the bending behavior of unidirectional composites with a silicone matrix shows a highly non-linear moment vs. curvature relationship, as well as strain softening under cyclic loading. These effects are not usually observed in composites with an epoxy matrix. In the case of tension in the direction transverse to the fibers, the behavior shows again non-linearity and strain softening, as well as an initial stiffness much higher than what would be expected based on the traditional estimates for fiber composites. The micro mechanics of the material have been studied with a finite element model. It uses solid elements and a random fiber arrangement produced with a reconstruction process based on micrographs of the material cross section. The simulations capture the macroscopic non-linear response, as well as the fiber microbuckling, and show how microbuckling reduces the strain in the fibers. The model shows good agreement for the bending stiffness of specimens with low fiber volume fraction, but it overestimates the effect of the matrix for more densely packed fibers. This is due to the high matrix strain that derives from the assumption of perfect bonding between fiber and matrix. In the case of tension transverse to the fibers, the model shows a much better agreement with experiments than traditional composite theory, and shows that the reason for the observed high stiffness is the incompressibility of the matrix. In order to capture the strain softening due to fiber debonding, cohesive elements have been introduced between the fibers and the matrix. This allows the model to capture quantitatively the non-linear behavior in the case of loading transverse to the fibers, and the damage due to cyclic loading. A single set of parameters for the cohesive elements produce good agreement with the experimental results for very different values of the fiber volume fraction, and could also be used in the analysis of more complicated loading cases, such as bending or biaxial tension. In addition to the simulations, a homogenized analytical model has also been created. It extends previous analysis of composites with a soft matrix to the case of very thin composites. It provides a good qualitative description of the material behavior, and it helps understand the mechanics that take place within the material, such as the equilibrium of energy terms leading to a finite wave length, as opposed to microbuckling under compression.
Human motion analysis and action recognition

The goal of human activity recognition systems is to build a system that can automatically infer a range of predefined activities, such as running, handclapping, etc, from recorded video sequences. Such a computerized system would be of great use for a variety of applications ranging from video surveillance for security to human-machine interaction. Typically, pattern recognition is the key component of such a system, where the goal is to classify, or more specifically "recognize" the data, based on a priori knowledge or statistical information extracted from the patterns. In this study, we presented a comparison of several well-known pattern recognition techniques for a human activity recognition system. We used Motion History Images (MHI) to describe these activities in a qualitative way and computed Hu moments, a widely used and well-known feature set to describe 2D or 3D shape, for further processing. Several feature extraction and classification methods were compared using different combinations and the results were analyzed. These methods are Principle Component Analysis and Linear Discriminant Analysis. Then we tested features with Support Vector Machines and K Nearest Neighbours classifiers.
Women and Men Who Have Served in Afghanistan/Iraq: Coming Home

The experience of war changes people – some will acknowledge that the changes are positive and some will feel the opposite or a combination, but that it changes a person cannot be disputed. For those who return, the experience of reintegration to civilian life or as a respite before redeployment can present numerous challenges. The research presented in this article reports the findings on interviews with over 800 service members who had returned from either Afghanistan or Iraq. The Post Deployment Reintegration Scale was used to refine the areas that respondents identified as positive or negative in their reintegration experience. Implications for practice with returning service members are noted.
Improving Peripherally Inserted Central Catheter (PICC) care on a Trauma and Orthopaedics ward

Abstract Peripherally Inserted Central Catheter (PICC) blockage rate was audited over a two month period on the Trauma & Orthopaedics ward at our District General Hospital. A 70% (five out of seven) PICC blockage rate was observed. High blockage rates lead to potential treatment complications, delays in delivery of treatment, increase in costs, and reduction in patient satisfaction. The factors contributing to the significant blockage rate include, long and contradictory PICC care guidelines, no information sheets in the patient notes, lack of training and awareness about care of, and flushing of, PICC lines, and lack of accountability for PICC flushing. Our project aimed to achieve a greater rate of PICC patency. We produced one succinct and comprehensive PICC care guideline, carried out staff training sessions, introduced a sticker reminding staff to flush the PICC line after use, and introduced a prescription of weekly heparin saline and PRN saline flushes (for monitoring and accountability). We used questionnaires to assess competency of hospital staff pre-teaching (doctors 6%, nurses 0%), and post-teaching (doctors 70%, nurses 38%). Blockage rate data post-intervention is pending. Education improved awareness of guidelines amongst staff and we anticipate that the proposed interventions will translate into reduced blockage rates, improving patient outcomes and reducing costs.
Cyclic AMP responsive element-binding protein promotes renal cell carcinoma proliferation probably via the expression of spindle and kinetochore-associated protein 2

Emerging evidence shows that the aberrantly expressed cyclic AMP responsive element-binding protein (CREB) is associated with tumor development and progression in several cancers. Spindle and kinetochore-associated protein 2 (SKA2) is essential for regulating the progress of mitosis. In this study, we evaluate in vitro and in vivo the functional relationship between CREB and SKA2 in renal cell carcinoma (RCC). Suppressing and replenishing CREB levels were used to manipulate SKA2 expression, observing the effects on RCC cell lines. Computational prediction and ChIP assay identified that CREB targeted ska2 by binding its CRE sequence in the human genome. Overexpression of CREB reversed the inhibited cell growth following siSKA2 treatment, and reduced the number of cells holding in mitosis. Decreased expression of CREB suppressed RCC cell growth and xenograft tumor formation, accompanied by reduced expression of SKA2. In RCC tumor samples from patients, mRNA for SKA2 were plotted near those of CREB in each sample, with significantly increased immunohistochemical staining of higher SKA2 and CREB in the higher TNM stages. The study adds evidence that CREB, a tumor oncogene, promotes RCC proliferation. It probably achieves this by increasing SKA2 expression.
High Glucose Predisposes Gene Expression and ERK Phosphorylation to Apoptosis and Impaired Glucose-Stimulated Insulin Secretion via the Cytoskeleton

Chronic high glucose (HG) inflicts glucotoxicity on vulnerable cell types such as pancreatic β cells and contributes to insulin resistance and impaired insulin secretion in diabetic patients. To identify HG-induced cellular aberrations that are candidate mediators of glucotoxicity in pancreatic β cells, we analyzed gene expression in ERoSHK6, a mouse insulin-secreting cell line after chronic HG exposure (six-day exposure to 33.3 mM glucose). Chronic HG exposure which reduced glucose-stimulated insulin secretion (GSIS) increased transcript levels of 185 genes that clustered primarily in 5 processes namely cellular growth and proliferation; cell death; cellular assembly and organization; cell morphology; and cell-to-cell signaling and interaction. The former two were validated by increased apoptosis of ERoSHK6 cells after chronic HG exposure and reaffirmed the vulnerability of β cells to glucotoxicity. The three remaining processes were partially substantiated by changes in cellular morphology and structure, and instigated an investigation of the cytoskeleton and cell-cell adhesion. These studies revealed a depolymerized actin cytoskeleton that lacked actin stress fibers anchored at vinculin-containing focal adhesion sites as well as loss of E-cadherin-mediated cell-cell adherence after exposure to chronic HG, and were concomitant with constitutive ERK1/2 phosphorylation that was refractory to serum and glucose deprivation. Although inhibition of ERK phosphorylation by PD98059 promoted actin polymerization, it increased apoptosis and GSIS impairment. These findings suggest that ERK phosphorylation is a proximate regulator of cellular processes targeted by chronic HG-induced gene expression and that dynamic actin polymerization and depolymerization is important in β cell survival and function. Therefore, chronic HG alters gene expression and signal transduction to predispose the cytoskeleton towards apoptosis and GSIS impairment.
Cytokine Responses of Intestinal Epithelial-Like Caco-2 Cells to Non-Pathogenic and Opportunistic Pathogenic Yeasts in the Presence of Butyric Acid

Candida albicans, Saccharomyces cerevisiae and their cell wall components, zymosan and glucan, have been shown to stimulate interleukin-8 (IL-8/CXCL-8) production by intestinal epithelial cell-like Caco-2 cells pre-cultured with 10 mM butyric acid. We examined in this study whether these yeasts also altered the production of other cytokines and cyclooxygenases (COXs) by Caco-2 cells. Culturing Caco-2 cells with 10 mM butyric acid and 15% FBS for 4 days enhanced the basal levels of mRNA encoding IL-6, IL-8, IL-18, monocyte chemoattractant protein (MCP)-1, stem cell factor, transforming growth factor (TGF)-β1, TGF-β3, tumor necrosis factor (TNF)-α, COX-1, and COX-2, but not of granulocyte-macrophage colony-stimulating factor (GM-CSF) and TGF-β2. The inclusion of live S. cerevisiae or C. albicans further enhanced the production of IL-8, but not of the other cytokines and COXs. The non-pathogenic yeasts, C. kefyr, C. utilis, C. versatilis, Kluyveromyces lactis, K. marxianus, Schizosaccharomyces pombe and Zygosaccharomyces rouxii, used for the production of fermented foods and probiotics, and the opportunistic pathogens, C. glabrata, C. krusei, C. parapsilosis and C. tropicalis, isolated from human tissue samples also enhanced IL-8 secretion by Caco-2 cells.
Multiple Immunosuppressive Effects of CpG-c41 on Intracellular TLR-Mediated Inflammation

A growing body of literature suggests that most chronic autoimmune diseases are associated with inappropriate inflammation mediated by Toll-like receptor (TLR) 3, TLR7/8, or TLR9. Therefore, research into blocking TLR activation to treat these disorders has become a hot topic. Here, we report the immunomodulatory properties of a nonstimulatory CpG-containing oligodeoxynucleotide (CpG-ODN), CpG-c41, which had previously only been known as a TLR9 antagonist. In this study, we found that both in vitro and in vivo CpG-c41 decreased levels of various proinflammatory factors that were induced by single activation or coactivation of intracellular TLRs, but not membrane-bound TLRs, no matter what downstream signal pathways the TLRs depend on. Moreover, CpG-c41 attenuated excessive inflammation in the imiquimod-induced psoriasis-like mouse model of skin inflammation by suppressing immune cell infiltration and release of inflammatory factors. We also found evidence that the immunosuppressive effects of CpG-c41 on other intracellular TLRs are mediated by a TLR9-independent mechanism. These results suggest that CpG-c41 acts as an upstream of signaling cascades, perhaps on the processes of ligand internalization and transfer. Taken together, these results suggest that CpG-c41 disrupts various aspects of intracellular TLR activation and provides a deeper insight into the regulation of innate immunity.
Dynamic Maintenance of Wavelet-Based Histograms

In this paper, we introduce an e cient method for the dynamic maintenance of wavelet-based histograms (and other transform-based histograms). Previous work has shown that wavelet-based histograms provide more accurate selectivity estimation than traditional histograms, such as equi-depth histograms. But since wavelet-based histograms are built by a nontrivial mathematical procedure, namely, wavelet transform decomposition, it is hard to maintain the accuracy of the histogram when the underlying data distribution changes over time. In particular, simple techniques, such as split and merge, which works well for equi-depth histograms, and updating a xed set of wavelet coe cients, are not suitable here. We propose a novel approach based upon probabilistic counting and sampling to maintain waveletbased histograms with very little online time and space costs. The accuracy of our method is robust to changing data distributions, and we get a considerable improvement over previous methods for updating transform-based histograms. A very nice feature of our method is that it can be extended naturally to maintain multidimensional wavelet-based histograms, while traditional multidimensional histograms can be less accurate and prohibitively expensive to build and maintain.
Time Dependence in Relativistic Collisionless Shocks: Theory of the Variable “Wisps” in the Crab Nebula

We describe results from time-dependent numerical modeling of the collisionless reverse shock terminating the pulsar wind in the Crab Nebula. We treat the upstream relativistic wind as composed of ions and electron-positron plasma embedded in a toroidal magnetic field, flowing radially outward from the pulsar in a sector around the rotational equator. The relativistic cyclotron instability of the ion gyrational orbit downstream of the leading shock in the electron-positron pairs launches outward-propagating magnetosonic waves. Because of the fresh supply of ions crossing the shock, this time-dependent process achieves a limit cycle, in which the waves are launched with periodicity on the order of the ion Larmor time. Compressions in the magnetic field and pair density associated with these waves, as well as their propagation speed, semiquantitatively reproduce the behavior of the wisp and ring features described in recent observations obtained using the Hubble Space Telescope and the Chandra X-Ray Observatory. By selecting the parameters of the ion orbits to fit the spatial separation of the wisps, we predict the period of time variability of the wisps that is consistent with the data. When coupled with a mechanism for nonthermal acceleration of the pairs, the compressions in the magnetic field and plasma density associated with the optical wisp structure naturally account for the location of X-ray features in the Crab. We also discuss the origin of the high-energy ions and their acceleration in the equatorial current sheet of the pulsar wind.
Recruited mast cells in the tumor microenvironment enhance bladder cancer metastasis via modulation of ERβ/CCL2/CCR2 EMT/MMP9 signals

Early clinical studies suggested that infiltrating mast cells could be associated with a poor outcome in bladder cancer (BCa) patients. The mechanisms of how mast cells influence the BCa progression, however, are unclear. Using the human clinical BCa sample survey and in vitro co-culture systems, we found BCa cells could recruit more mast cells than the surrounding non-malignant urothelial cells. The consequences of this better recruitment of mast cells toward BCa cells could then enhance BCa cell invasion. Mechanism dissection revealed that the enhanced BCa cell invasion could function via up-regulation of the estrogen receptor beta (ERβ) in both mast cells and BCa cells, which resulted in the increased CCL2/CCR2/EMT/MMP9 signals. Using the pre-clinical mouse BCa model, we further validated the mast cell-promoted BCa invasion. Interruption of the newly identified ERβ/CCL2/CCR2/EMT/MMP9 pathway via either ERβ-siRNA, ERβ antagonist PHTPP, or CCR2 antagonist can effectively reverse the mast cell-enhanced BCa cells invasion. Together, our finding could lead to the development of an alternative new therapeutic approach to better treat BCa metastasis.