Miracle-dz/UniFAR-FTUs huggingface dataset:
The prevalence of pineal cyst in patients with cerebral palsy.

PURPOSE Pineal cysts are common incidental findings during magnetic resonance imaging (MRI) examinations. The etiology of pineal cyst development is still unclear. We aimed to determine whether there is an association between periventricular leukomalacia and pineal cyst prevalence. METHODS Clinical and MRI data of 201 patients with periventricular leukomalacia (110 female, 91 male; mean age, 6 years; range, 2-18 years) and 687 control patients (355 female, 332 male; mean age, 6 years¸ range, 2-18 years) who did not have any evidence of periventricular leukomalacia were independently evaluated by two radiologists for presence or absence of pineal cyst. RESULTS Pineal cysts were detected in 32.3% of the study group (65/201) and 8.4% of the control group (58/687) (P < 0.001). Patients with periventricular leukomalacia were more likely to have a pineal cyst. In terms of pineal cyst detection on MRI, interobserver reliability was high between the two radiologists. CONCLUSION The prevalence of pineal cysts is higher in patients with periventricular leukomalacia. We suggest that an ischemic process may have a role in the etiopathogenesis of pineal cyst development.
Drug therapy for anxiety in palliative care.

BACKGROUND Anxiety is common among patients with advanced disease. It can be a natural response to impending death, but may also result from an underlying anxiety disorder, pain, or other untreated or poorly managed symptoms. OBJECTIVES The primary objective of this review was to identify and evaluate studies examining medications used to treat patients suffering from anxiety during the terminal phases of disease. SEARCH STRATEGY We searched the following sources: MEDLINE (1966 to July 2003), EMBASE (1980 to July 2003), CINAHL (1982 to July 2003), PsycLit (1974 to July 2003), PsycInfo (1990 to July 2003), and the Cochrane Library (Issue 2, 2003) for literature pertaining to this topic published in any language using a detailed search strategy. SELECTION CRITERIA Prospective, randomized trials with or without blinding involving the use of pharmacological agents for the treatment of anxiety at the end of life were sought. DATA COLLECTION AND ANALYSIS Six potential studies were identified by the search strategy but none met the criteria for inclusion in this review. Two of these studies assessed the effectiveness of alprazolam in patients with a diagnosis of cancer, but who would not be considered in the end-stage of life. MAIN RESULTS No data were available to enable an assessment to be made of the effectiveness of drugs to treat anxiety in palliative care patients. REVIEWER'S CONCLUSIONS There remains insufficient evidence to draw a conclusion about the effectiveness of pharmacotherapy for anxiety in terminally ill patients. To date no studies were found that met the inclusion criteria for this review. Prospective controlled clinical trials are necessary in order to establish the benefits and harms of pharmacotherapy for the treatment of anxiety in palliative care.
Trk‐dependent ADAM17 activation facilitates neurotrophin survival signaling

Signaling by TrkA and TrkB receptor tyrosine kinase is required for peripheral neuron survival. TrkA and TrkB signaling is facilitated by the p75 neurotrophin receptor (p75NTR), a member of the tumor necrosis factor (TNF) receptor superfam‐ily, through mechanisms that remain obscure. Here, we demonstrate that TrkA and TrkB induces MEK‐dependent phosphorylation of the transmembrane cysteine protease ADAM17 (a disintegrin and metal‐loprotease 17) at the intracellular residue threonine 735. Phosphorylation at this site activates ADAM17 and causes cleavage of p75NTR and production of the receptors’ intracellular domain (p75NTRICD) in PC12 cells and in primary cerebellar granule neurons. We show that Trk‐induced ADAM17 phosphorylation and generation of the p75NTR is required for neurotrophin‐induced Erk and Akt activation and for neurotrophin‐dependent survival signaling. Survival of PC12 cells maintained in 10 ng/ml nerve growth factor drops by 47% in cells depleted of ADAM17; this survival deficit is resolved if the p75NTR is overexpressed in the ADAM17 depleted cells. These studies identify a novel signaling circuit in which Trk activates ADAM17‐dependent p75NTRICD production to feedback to sustain Trk signaling and Trk‐dependent survival. —Kommaddi, R. P., Thomas, R. , Ceni, C, Daigneault, K. , Barker, P. A. Trk‐dependent ADAM17 activation facilitates neurotrophin survival signaling. FASEB J. 25, 2061‐2070 (2011). www.fasebj. org
Duplicate Gene Divergence by Changes in MicroRNA Binding Sites in Arabidopsis and Brassica

Gene duplication provides large numbers of new genes that can lead to the evolution of new functions. Duplicated genes can diverge by changes in sequences, expression patterns, and functions. MicroRNAs play an important role in the regulation of gene expression in many eukaryotes. After duplication, two paralogs may diverge in their microRNA binding sites, which might impact their expression and function. Little is known about conservation and divergence of microRNA binding sites in duplicated genes in plants. We analyzed microRNA binding sites in duplicated genes in Arabidopsis thaliana and Brassica rapa. We found that duplicates are more often targeted by microRNAs than singletons. The vast majority of duplicated genes in A. thaliana with microRNA binding sites show divergence in those sites between paralogs. Analysis of microRNA binding sites in genes derived from the ancient whole-genome triplication in B. rapa also revealed extensive divergence. Paralog pairs with divergent microRNA binding sites show more divergence in expression patterns compared with paralog pairs with the same microRNA binding sites in Arabidopsis. Close to half of the cases of binding site divergence are caused by microRNAs that are specific to the Arabidopsis genus, indicating evolutionarily recent gain of binding sites after target gene duplication. We also show rapid evolution of microRNA binding sites in a jacalin gene family. Our analyses reveal a dynamic process of changes in microRNA binding sites after gene duplication in Arabidopsis and highlight the role of microRNA regulation in the divergence and contrasting evolutionary fates of duplicated genes.
Optimum Internet Gateway Selection in Ad Hoc Networks

Wireless ad hoc networks are connected to the fixed Internet by means of Internet gateways. Whenever a node within the ad hoc network wishes to communicate with a host in the Internet, it selects a default Internet gateway to relay its traffic from the ad hoc network to the Internet. In this paper, we formulate the problem of selecting the best Internet gateway as a mixed integer linear program minimizing the maximum node utilization in the wireless network. By simulations, we show that the performance that can be achieved by solving this optimization problem is significantly higher than what is achieved by standard gateway selection algorithms based on hop count or gateway load. In particular, these heuristic algorithms fail to adapt to the offered traffic and available capacity in the network.
Allosteric MEK1/2 Inhibitors for the Treatment of Cancer: an Overview

The RAS-RAF-MEK-ERK mitogen activated protein kinase (MAPK) pathway is a driver behind key cellular processes such as gene transcription, cellular proliferation, survival and motility and is aberrantly activated/dysregulated in many cancers. Mutations in RAS or RAF and/or increased signaling by receptor tyrosine kinases (RTK) associated with the cascade are frequently observed in many tumor settings and are linked to the dysregulation and aberrant activation of this pathway. MEK is a central component of this highly important cascade and has a unique allosteric pocket adjacent to its ATP binding site. As such, there has been an intense pursuit of allosteric small molecule inhibitors of this kinase. This pursuit, to date, has resulted in the advancement of 16 compounds to clinical trials and the approval of trametinib (Mekinist®) for the treatment of melanoma. In this brief review we provide an overview of the RAF-RAS-MEK-ERK cascade, its cancer implications and brief account of the allosteric MEK inhibitors that reached the clinic.
Modeling and Evaluating the Resilience of Critical Electrical Power Infrastructure to Extreme Weather Events

Electrical power systems have been traditionally designed to be reliable during normal conditions and abnormal but foreseeable contingencies. However, withstanding unexpected and less frequent severe situations still remains a significant challenge. As a critical infrastructure and in the face of climate change, power systems are more and more expected to be resilient to high-impact low-probability events determined by extreme weather phenomena. However, resilience is an emerging concept, and, as such, it has not yet been adequately explored in spite of its growing interest. On these bases, this paper provides a conceptual framework for gaining insights into the resilience of power systems, with focus on the impact of severe weather events. As quantifying the effect of weather requires a stochastic approach for capturing its random nature and impact on the different system components, a novel sequential Monte-Carlo-based time-series simulation model is introduced to assess power system resilience. The concept of fragility curves is used for applying weather- and time-dependent failure probabilities to system's components. The resilience of the critical power infrastructure is modeled and assessed within a context of system-of-systems that also include human response as a key dimension. This is illustrated using the IEEE 6-bus test system.
Advances in Brief Forced Expression of NESH Suppresses Motility and Metastatic Dissemination of Malignant Cells 1

To characterize the function of a novel Src homology 3 (SH3) adapter protein termed NESH, we have established transfectants stably expressing NESH. We observed that every clone of NESH transfectants caused a marked reduction in motility, although the clones exhibited no significant differences in intrinsic cell growth compared with the control cells in vitro. The NESH transfectants also exhibited significant reduction in tumor metastatic potential in vivo. We found that NESH expression is frequently lost in invasive cancer cell lines despite its ubiquitous expression in normal tissues. The SH3 domain of NESH seems to interact with p21-activated kinase (PAK), which is involved in regulation of cell motility. Furthermore, a significant decrease in PAK phosphorylation at Thr was found in NESH transfectants. Taken together, these results suggest that NESH inhibits ectopic metastasis of tumor cells as well as cell migration through interaction with intracellular molecules such as PAK that are essential for cell motility.
Enhanced secretion through the Shigella flexneri Mxi‐Spa translocon leads to assembly of extracellular proteins into macromolecular structures

Genes required for entry of Shigella flexneri into epithelial cells in vitro are clustered in two adjacent loci, one of which encodes secretory proteins, the IpaA–D proteins, and the other their dedicated secretion apparatus, the Mxi–Spa translocon. Ipa secretion, which is induced upon contact of bacteria with epithelial cells, is prevented during growth in vitro. Here, we show that ipaB and ipaD mutations lead to enhanced secretion of a set of about 15 proteins. These extracellular proteins and some Ipas associate in organized structures consisting of extended sheets. Growth of the wild‐type strain in the presence of Congo red is shown to induce protein secretion through the Mxi–Spa translocon. Cultures grown to stationary phase in the presence of Congo red contain extracellular filaments whose composition and morphology are similar to those produced by the hyper‐secreting ipaB and ipaD mutants.
MHC-I modulation due to changes in tumor cell metabolism regulates tumor sensitivity to CTL and NK cells

Tumor cells have a tendency to use glucose fermentation to obtain energy instead of mitochondrial oxidative phosphorylation (OXPHOS). We demonstrated that this phenotype correlated with loss of ERK5 expression and with reduced MHC class I expression. Consequently, tumor cells could evade cytotoxic T lymphocyte (CTL)-mediated immune surveillance, but also increase their sensitivity to natural killer (NK) cells. These outcomes were evaluated using two cellular models: leukemic EL4 cells and L929 transformed fibroblasts and their derived ρ° cell lines, which lack mitochondrial DNA. We have also used a L929 cell sub-line that spontaneously lost matrix attachment (L929dt), reminiscent of metastasis generation, that also downregulated MHC-I and ERK5 expression. MHC-I expression is lower in ρ° cells than in the parental cell lines, but they were equally sensitive to CTL. On the contrary, ρ° cells were more sensitive to activated NK cells than parental cells. On the other hand, L929dt cells were resistant to CTL and NK cells, showed reduced viability when forced to perform OXPHOS, and surviving cells increased MHC-I expression and became sensitive to CTL. The present results suggest that when the reduction in MHC-I levels in tumor cells due to glycolytic metabolism is partial, the increase in sensitivity to NK cells seems to predominate. However, when tumor cells completely lose MHC-I expression, the combination of treatments that increase OXPHOS with CTL-mediated immunotherapy could be a promising therapeutic approach.
Relationships Between Neighborhood Social Capital and The Occurrence of Outdoor Falls in Canadian Older Adults: A Multilevel Analysis

Objective: The aim of this study was to examine whether neighborhood-level social capital is a risk factor for falls outside of the home in older adults. Methods: Health questionnaires were completed by community-dwelling Canadians aged +65 years living in Kingston (Ontario) and St-Hyacinthe (Quebec), supplemented by neighborhood-level census data. Multilevel logistic regression models with random intercepts were fit. Variations in the occurrence of falls across neighborhoods were quantified by median odds ratio and 80% interval odds ratio. Results: Between-neighborhood differences explained 7% of the variance in the occurrence of falls; this variance decreased to 2% after adjustment for neighborhood-level variables. In the fully adjusted models, higher levels of social capital increased the odds of falls by almost 2 times: (odds ratio [OR] = 2.10, 95% confidence interval [CI] = [1.19, 3.71]). Discussion: Living in neighborhoods with higher levels of social capital was associated with higher risk of falling in older adults, possibly through more involvement in social activities.
3-Functions Meta-Learner Algorithm: a Mixture of Experts Technique to Improve Regression Models

This paper presents a new method for multiple regressor combination called 3-Functions Meta-Learner. The proposed technique improves the prediction performance of a given regressor by generating two additional regressors and an internal model that learns the weight of each output. The suggested model is able to explain the data in terms of its membership to three weak regression models and preserves the interpretability level of the original model. The experimental results suggest that the 3-Functions MetaLearning algorithm outperforms Bagging and AdaBoots.R2 when the initial regressor is a weak and stable learner.
Elongation and clustering of glycosomes in Trypanosoma brucei overexpressing the glycosomal Pex11p

Kinetoplastid protozoa confine large parts of glycolysis within glycosomes, which are microbodies related to peroxisomes. We cloned the gene encoding the second most abundant integral membrane protein of Trypanosoma brucei glycosomes. The 24 kDa protein is very basic and hydrophobic, with two predicted transmembrane domains. It is targeted to peroxisomes when expressed in mammalian cells and yeast. The protein is a functional homologue of Pex11p from Saccharomyces cerevisiae: pex11Δ mutants, which are defective in peroxisome proliferation, can be complemented by the trypanosome gene. Sequence conservation is significant in the N‐ and C‐terminal domains of all putative Pex11p homologues known, from trypanosomes, yeasts and mammals. Several lines of evidence indicate that these domains are oriented towards the cytosol. TbPex11p can form homodimers, like its yeast counterpart. The TbPEX11 gene is essential in trypanosomes. Inducible overexpression of the protein in T.brucei bloodstream forms causes growth arrest, the globular glycosomes being transformed to clusters of long tubules filling significant proportions of the cytoplasm. Reduced expression results in trypanosomes with fewer, but larger, organelles.
Location-based Mobile Games

In the recent years location-based services have become more and more popular due to advanced mobile devices that make the use of these services very convenient. With the rise of location-based services location-based games will also gain popularity and become more wide spread. This seminar paper describes game patterns and new game types that are possible with location based games. It also examines different techniques to determine the geolocation of players, and it analyses the changes to the game experiences known from traditional video games. Ultimately this paper gives an overview of the current state of the art concerning location-based games and discusses several issues and possibilities concerning the implementation of one.
Use of human aortic extracellular matrix as a scaffold for construction of a patient-specific tissue engineered vascular patch

Synthetic or biologic materials are usually used to repair vascular malformation in congenital heart defects; however, non-autologous materials show both mismatch compliance and antigenicity, as well as a lack of recellularization on its surface. Here, we constructed a tissue-engineered vascular patch (TEVP) using decellularized extracellular matrix (ECM) scaffold obtained from excised human aorta during surgery, which was seeded with patient-derived bone marrow CD34-positive (CD34+) progenitor cells. While cellular components were removed, the decellularized ECM scaffold retained native ECM composition, similar mechanical performance to undecellularized aortic tissue, and supported the adhesion, survival and proliferation of CD34+ progenitor cells. Interestingly, after in vitro seeding of decellularized aortic ECM scaffold for 21 d, CD34+ progenitor cells differentiated into mature vascular endothelial cells without addition of any growth factors, as confirmed by the increased levels of endothelial surface markers (CD31, Von Willebrand factor (VWF), VE-cadherin and ICAM-2) and upregulated gene levels (CD31, VWF and eNOS) concurrently with decreased expression of stem cell markers (CD133 and CD34), thus, resulting in surface endothelialization of decellularized ECM scaffold. Consequently, the patient-specific TEVP constructed in this study holds great potential for clinical use in pediatric patients with vascular malformation.
Globally minimal contours and surfaces for image segmentation

This thesis develops a new geometric optimisation framework that can provide significant improvements over both traditional active contour and graph-based approaches to image segmentation. It combines active contour and graph-based methods to produce powerful image segmentation methods sharing their strengths: continuity and reliability. We begin by reviewing the relevant literature in image segmentation and in geometric optimisation. This includes the role of image derivatives in segmentation, active contour methods such as snakes and level sets, and graph-based methods such as shortest paths and minimum cuts. We also discuss hybrid methods which combine the best properties of active contours and graph-based methods. Finally we introduce a previously unsolved problem that is central to this thesis: the computation of globally minimal surfaces in continuous spaces. We then investigate the recursive computation of derivatives in finite and discrete images. Previous approaches to recursive filtering are reviewed including convolution and Fourier methods. A matrix viewpoint is put forward which deals naturally with image boundaries. We give an efficient decomposition and solution for this matrix formulation. It is proven to exist for stable filters and shown both in theory and practice to have good accuracy in finite precision implementations. We demonstrate its application to the fast computation of image derivatives at arbitrary scales. Next we consider in detail the segmentation of planar images by optimal curves. First we give a simple technique for object segmentation by a minimal convex polygon. We then extend this technique to continuous curves, convoluted boundaries, and oriented metrics. Experiments demonstrate that the optimality of these techniques produces significantly more accurate and robust segmentations than standard active contour methods. An
A Psychopathological Comparison between Delusional Disorder and Schizophrenia

Objective: To contribute to a better differential clinical categorisation of delusional disorder (DD) versus schizophrenia (SZ) and to add and complete evidence from previous clinical studies of DD compared to schizophrenia. Methods: A cross-sectional study using a clinical sample of 275 patients (132 patients with DD) was studied. Patients were consecutively attending public clinics located in urban and rural areas in both Andalusia and Catalonia (Spain). All participants met DSM-IV diagnostic criteria for either DD or SZ. Data were gathered on sociodemographics, illness duration, Barona-Index estimation of intelligence quotient (IQ), and global functioning, along with a thorough psychopathological assessment using the Positive and Negative Syndrome Scale (PANSS). Comparisons between both groups were calculated using χ2, Student t, and multivariate analysis of covariance tests. Results: Patients with DD were older (mean [SD], 50.3 [14.6] years vs. 36.6 [11.1] years; t = 8.597; P ≤ 0.0001), were more frequently married (45.4% vs. 10.8%; χ2 = 38.569; P ≤ 0.0001), and had a higher mean estimated premorbid IQ (111.4 vs. 105.4; t = 2.609; P ≤ 0.01). On the other hand, SZ patients were predominantly male (71.4% vs. 48.9%; χ2 = 14.433; P ≤ 0.0001) and had greater work-related disability than DD patients (20.5% vs. 50.3%; χ2 = 19.564; P ≤ 0.001). Overall, the DD group showed a less severe PANSS psychopathology than SZ group. Thus, total mean (SD) PANSS scores for schizophrenia and delusional disorder, respectively, were 76.2 (22.4) versus 54.1 (18.4) (t = –8.762; P ≤ 0.0001). Moreover, patients with DD showed a better global functioning than those with SZ (62.7 [13.2] vs. 51.9 [16.9]; F = 44.114; P ≤ 0.0001). Conclusions: DD is a milder and distinct disorder compared to SZ in terms of psychopathology and global functionality.