Miracle-dz/UniFAR-FTUs huggingface dataset:
Hedgehog-mediated epithelial-to-mesenchymal transition and fibrogenic repair in nonalcoholic fatty liver disease.

BACKGROUND & AIMS Repair responses define the ultimate outcomes of liver disease. This study evaluated the hypothesis that fibrogenic repair in nonalcoholic fatty liver disease (NAFLD) is mediated by Hedgehog (Hh) pathway activation and consequent induction of epithelial-to-mesenchymal transitions (EMT) in ductular-type progenitors. METHODS Immature ductular cells were exposed to Sonic hedgehog (Shh) in the presence or absence of the Hh inhibitor cyclopamine to determine whether Hh-pathway activation directly modulates EMT in liver progenitors. Potential biologic correlates of progenitor cell EMT were assessed using mice fed methionine-choline-deficient + ethionine (MCDE) diets with or without cyclopamine. The effects of increased Hh signaling on EMT and fibrogenic repair during diet-induced NAFLD were also compared in wild-type (WT) and Patched haplo-insufficient (Ptc(+/-)) mice. Finally, evidence of Hh-pathway activation and EMT was examined in liver sections from patients with NAFLD. RESULTS In cultured progenitors, Shh repressed expression of epithelial genes and EMT inhibitors but induced genes that are expressed by myofibroblasts. Cyclopamine reversed these effects. In mouse NAFLD models, Hh-pathway activation, EMT, expansion of myofibroblastic populations, and liver fibrosis occurred. Cyclopamine inhibited Hh-pathway activation and induction of EMT. Ptc(+/-) mice, which have an overactive Hh pathway, exhibited sustained overinduction of Hh target genes and more EMT, myofibroblast accumulation, and fibrosis than WT mice. Numbers of Shh-producing cells and Hh-responsive ductular cells that expressed EMT markers increased in parallel with liver fibrosis in patients with NAFLD. CONCLUSIONS Hh-mediated EMT in ductular cells contributes to the pathogenesis of cirrhosis in NAFLD.
Evaluation of rK39 Rapid Diagnostic Tests for Canine Visceral Leishmaniasis: Longitudinal Study and Meta-Analysis

Background There is a need for sensitive and specific rapid diagnostic tests (RDT) for canine visceral leishmaniasis. The aims of this study were to evaluate the diagnostic performance of immunochromatographic dipstick RDTs using rK39 antigen for canine visceral leishmaniasis by (i) investigating the sensitivity of RDTs to detect infection, disease and infectiousness in a longitudinal cohort study of natural infection in Brazil, and (ii) using meta-analysis to estimate the sensitivity and specificity of RDTs from published studies. Methodology We used a rK39 RDT (Kalazar Detect Canine Rapid Test; Inbios) to test sera collected from 54 sentinel dogs exposed to natural infection in an endemic area of Brazil. Dogs were sampled bimonthly for up to 27 months, and rK39 results compared to those of crude antigen ELISA, PCR, clinical status and infectiousness to sandflies. We then searched MEDLINE and Web of Knowledge (1993–2011) for original studies evaluating the performance of rK39 RDTs in dogs. Meta-analysis of sensitivity and specificity was performed using bivariate mixed effects models. Principal Findings The sensitivity of the rK39 RDT in Brazil to detect infection, disease and infectiousness was 46%, 77% and 78% respectively. Sensitivity increased with time since infection, antibody titre, parasite load, clinical score and infectiousness. Sixteen studies met the inclusion criteria for meta-analysis. The combined sensitivity of rK39 RDTs was 86.7% (95% CI: 76.9–92.8%) to detect clinical disease and 59.3% (37.9–77.6%) to detect infection. Combined specificity was 98.7% (89.5–99.9%). Both sensitivity and specificity varied considerably between studies. Conclusion The diagnostic performance of rK39 RDTs is reasonable for confirmation of infection in suspected clinical cases, but the sensitivity to detect infected dogs is too low for large-scale epidemiological studies and operational control programmes.
Descriptive analysis of objectively assessed physical activity among talented soccer players: a study of three Norwegian professional football clubs

Background Talented football players are expected to overcome large training and match loads, indicating a high weekly level of physical activity (PA). Aims With the use of accelerometers, the aim of this study was to objectively describe the players’ total time spent in moderate-to-vigorous PA (MVPA), vigorous PA (VPA) and very vigorous PA (VVPA) per day in 1 week. Since high-intensity PA has been highlighted as important in terms of overall PA load, we also included 2 and 4 min bouts of VPA. Methods Data were collected in three junior teams in professional football clubs in March (club 1: 2014, club 2: 2012 and club 3: 2011). A one-way analysis of variance was applied to analyse differences between the three respective clubs. Results The players averaged 77.2–86.2 min in MVPA, 14.9–18.5 min in VPA and 1.0–3.1 in VVPA per day. While there were no differences in total time spent in MVPA and VPA per day, VVPA was significantly higher in club 1 (p<0.01) compared with clubs 2 and 3. Moreover, when using the VPA bouts, club 3 (p<0.01) achieved significantly more time in this intensity compared with clubs 1 and 2. Conclusion This study acknowledges the importance of including both club-related and non-club-related PA when analysing talented football players’ PA level. We suggest that future studies examining players’ PA with accelerometers should emphasise time spent in high-intensity PA and how this is associated with physical overload, psychological burnout and risk of injury.
Interleukin-6 Deficiency Attenuates Retinal Ganglion Cell Axonopathy and Glaucoma-Related Vision Loss

The pleotropic cytokine interleukin-6 (IL-6) is implicated in retinal ganglion cell (RGC) survival and degeneration, including that associated with glaucoma. IL-6 protects RGCs from pressure-induced apoptosis in vitro. However, it is unknown how IL-6 impacts glaucomatous degeneration in vivo. To study how IL-6 influences glaucomatous RGC axonopathy, accompanying glial reactivity, and resultant deficits in visual function, we performed neural tracing, histological, and neurobehavioral assessments in wildtype (B6;129SF2/J; WT) and IL-6 knock-out mice (B6;129S2-IL6tm1kopf/J; IL-6-/-) after 8 weeks of unilateral or bilateral microbead-induced glaucoma (microbead occlusion model). IOP increased by 20% following microbead injection in both genotypes (p < 0.05). However, deficits in wound healing at the site of corneal injection were noted. In WT mice, elevated IOP produced degenerating axon profiles and decreased axon density in the optic nerve by 15% (p < 0.01). In IL-6-/- mice, axon density in the optic nerve did not differ between microbead- and saline-injected mice (p > 0.05) and degenerating axon profiles were minimal. Preservation of RGC axons was reflected in visual function, where visual acuity decreased significantly in a time-dependent manner with microbead-induced IOP elevation in WT (p < 0.001), but not IL-6-/- mice (p > 0.05). Despite this preservation of RGC axons and visual acuity, both microbead-injected WT and IL-6-/- mice exhibited a 50% decrease in anterograde CTB transport to the superior colliculus, as compared to saline-injected controls (p < 0.01). Assessment of glial reactivity revealed no genotype- or IOP-dependent changes in retinal astrocytes. IOP elevation decreased microglia density and percent retinal area covered in WT mice (p < 0.05), while IL-6-/- mice exhibited only a decrease in density (p < 0.05). Together, our findings indicate that two defining features of RGC axonopathy—axon transport deficits and structural degeneration of axons—likely occur via independent mechanisms. Our data suggest that IL-6 is part of a mechanism that specifically leads to structural degeneration of axons. Furthermore, its absence is sufficient to prevent both structural degeneration of the optic nerve and vision loss. Overall, our work supports the proposition that functional deficits in axon transport represent a therapeutic window for RGC axonopathy and identify IL-6 signaling as a strong target for such a therapeutic.
Virtual machine management for Tele-Lab "IT-security" server

Tele-Lab "IT-security" Server is a new concept for practical security education. The Tele-lab server builds a virtual security laboratory using lightweight virtual machines and features a pure Web user interface. Thus, students can easily exercise security over the Internet. Running such a security laboratory on the Internet is difficult. Its infrastructure is subject to misuse and crash due to the nature of security tasks. The management of virtual machines is a crucial component which enables running the Tele-Lab server on the Internet. It effectively saves resources and improves security and reliability of the virtual laboratory. This paper briefly reviews the architecture of the Tele-Lab "IT-security" server, describes its virtual machine management in detail, and presents some experiential and experimental results.
Amplification of c-myc in Hepatocellular Carcinoma: Correlation with Clinicopathologic Features, Proliferative Activity and p53 Overexpression

Expression of the proto-oncogene c-myc has been implicated in liver regeneration and hepatocarcinogenesis. The biologic significance of c-myc gene amplification in human hepatocellular carcinoma, however, is unconfirmed. We correlated c-myc gene amplification with clinicopathologic features, proliferative activity, and p53 expression in 42 resected tumors. c-myc amplification in tumor tissue was determined using a differential polymerase chain reaction, a useful procedure for the evaluation of gene amplification in archival formalin-fixed paraffin-embedded tissues, in comparison with a dopamine D2 receptor gene. Proliferative activity was estimated by numbers of argyrophilic nucleolar organizer regions and immunohistochemical nuclear labeling rates using a monoclonal antibody against Ki-67. The c-myc gene was amplified in 14 of 42 tumors (33.3%). Amplification of c-myc was more frequent in younger patients and in larger tumors, and less differentiated tumors. No correlation was noted with α-fetoprotein level or viral hepatitis state. The amplification showed positive correlation with both proliferative activity and p53 overexpression. Disease-free survival in patients showing c-myc amplification was significantly shorter than in those without amplification. These results suggest that c-myc amplification is an indicator of malignant potential and poor prognosis in hepatocellular carcinoma. c-myc amplification and p53 alteration may be coparticipating events in the progression of these tumors.
An Extensive Comparison of Quantitative Trait Loci Mapping Methods

Background: The choices of study design and statistical approach for mapping a quantitative trait (QT) are of great importance. Larger sibships and a study design based upon phenotypically extreme siblings can be expected to have a greater statistical power. On the other hand, selected samples and/or deviation from normality can influence the robustness and power. Unfortunately, the effects of violation of multivariate normality assumptions and/or selected samples are only known for a limited number of methods. Some recommendations are available in the literature, but an extensive comparison of robustness and power under several different conditions is lacking. Methods: We compared eight freely available and commonly applied QT mapping methods in a Monte-Carlo simulation study under 36 different models and study designs (three genetic models, three selection schemes, two family structures and the possible effect of deviation from normality). Results: Empirical type I error fractions and empirical power are presented and explained as a whole and for each method separately, followed by a thorough discussion. Conclusions: The results from this extensive comparison could serve as a valuable source for the choice of the study design and the statistical approach for mapping a QT.
Using hierarchical histogram representation for the EM clustering algorithm enhancement

This paper is devoted to EM clustering improvement using hierarchical multivariate histogram for probability density representation. We propose to store and operate with the image histogram by means of a special tree data structure. This allows to speed up computations in the case of multivariate input. We also answer the questions of the algorithm initialization and offer an initialization rule, which exploits the proposed histogram-tree structure. We have tested our algorithm modification and initialization rule using remote sensing images. Obtained results have confirmed that the modified algorithm is faster and the initialization rule provides better clustering in comparison with the traditional EM algorithm implementation.
Ultrasound Biomicroscopy for Longitudinal Studies of Carotid Plaque Development in Mice: Validation with Histological Endpoints

Atherosclerosis is responsible for the death of thousands of Americans each year. The carotid constriction model of plaque development has recently been presented as a model for unstable plaque formation in mice. In this study we 1) validate ultrasound biomicroscopy (UBM) for the determination of carotid plaque size, percent stenosis, and plaque development in live animals, 2) determine the sensitivity of UBM in detecting changes in blood flow induced by carotid constriction and 3) test whether plaque formation can be predicted from blood flow parameters measured by UBM. Carotid plaques were induced by surgical constriction in Apo E−/− mice. Arteries were imaged bi-weekly by UBM, at which time PW-Doppler measurements of proximal blood flow, as well as plaque length and percent stenosis were determined. Histology was performed 9 weeks post surgery. When compared to whole mount post-mortem measurements, UBM accurately reported carotid plaque length. Percent stenosis, based on transverse B-mode UBM measurements, correlated well with that calculated from histological sections. PW-Doppler revealed that constriction reduced maximum systolic velocity (vmax) and duration of the systolic velocity peak (ts/tt). Pre-plaque (2 week post-surgery) PW-Doppler parameters (vmax and ts/tt) were correlated with plaque length at 9 weeks, and were predictive of plaque formation. Correlation of initiating PW-Doppler parameters (vmax and ts/tt) with resulting plaque length established the degree of flow disturbance required for subsequent plaque development and demonstrated its power for predicting plaque development.
Improving digital handoff in shared tabletop workspaces

Handoff of objects and tools occurs frequently and naturally in face-to-face work; in tabletop groupware, however, digital handoff is often awkward. In this paper, we investigate ways of improving support for digital handoff in tabletop systems. We first observed how handoff works at a physical table, and then compared the performance of tangible and standard transfer techniques on digital tables. Based on our observations, we developed a new technique called force-field handoff that allows objects to drift between pointers that are approaching one another. We tested force-field handoff in an experiment, and found that it is significantly faster than current digital handoff; no difference was found with tangible handoff. In addition, force-field handoff was preferred by the majority of participants.
Stable clinical prediction using graph support vector machines

The stability matters in clinical prediction models because it makes the model to be interpretable and generalizable. It is paramount for high dimensional data, which employ sparse models with feature selection ability. We propose a new method to stabilize sparse support vector machines using intrinsic graph structure of the electronic medical records. The graph structure is exploited using the Jaccard similarity among features. Our method employs a convex function to penalize the pairwise l∞-norm of connected feature coefficients in the graph. We apply the alternating direction method of multipliers to solve the proposed formulation. Our experiments are conducted on a synthetic and three real-world hospital datasets. We show that our proposed method is more stable than the state-of-the-art feature selection and classification techniques in terms of three stability measures namely, Jaccard similarity measure, Spearman's rank correlation coefficient and Kuncheva index. We further show that our method has resulted in better classification performance compared to the baselines.
Measurement of In Vivo Three-Dimensional Corneal Cell Density and Size Using Two-Photon Imaging in C57BL/6 Mice

ABSTRACT Purpose: To measure the cell size and cell density in five layers of the central cornea in the widely used inbred C57BL/6 mouse strain using in vivo three-dimensional (3D) two-photon (2PH) imaging. Methods: Corneas were scanned using a 2PH laser scanning fluorescence microscope after staining with plasma membrane stain and Hoechst 33342. Good quality 3D images were selected for the cell density and cell size analysis. Cell density was determined by counting the cell nuclei in a predefined cube of 3D images. Cell size measurements, including cell surface area, cell volume, nuclear surface area and nuclear volume, were automatically quantified using the Imaris software. The cell and nuclear surface-area-to-volume ratio (S:V ratio) and the cell nuclear-cytoplasmic ratio (N:C ratio) were calculated. Results: The highest cell density was observed in the basal epithelium and the lowest in the posterior stroma. The highest cell surface area was found in the anterior stroma, and the highest cell volume was observed in the superficial epithelium. The lowest cell surface area and cell volume were both found in the basal epithelium. The highest S:V ratio was observed in the basal epithelium and the lowest in the superficial epithelium. The highest cell nuclear surface area and volume were both observed in the superficial epithelium and the lowest in the basal epithelium. The highest cell nuclear S:V ratio was observed in the basal epithelium and the lowest in the superficial epithelium. The highest N:C ratio was found in the basal epithelial cells and the lowest in the posterior keratocytes. Conclusions: We are the first to quantify the cell density and size parameters, including cell surface area and volume, cell nuclear surface area and volume, and the S:V ratio, in the five layers of the central cornea. These data provide important cell morphology features for the study of corneal physiology, pathology and disease in mice, particularly in C57BL/6 mice.
Stem Cell-Derived Models of Neural Crest Are Essential to Understand Melanoma Progression and Therapy Resistance

During development, neural crest (NC) cells are early precursors of several lineages including melanocytes. Along their differentiation from multipotent cells to mature melanocytes, NC cells will go through successive steps which require either proliferative or motile capacities. For example, they will undergo Epithelial to Mesenchymal Transition (EMT) in order the separate from the neural tube and migrate to their final location in the epidermis (Larribere and Utikal, 2013; Skrypek et al., 2017). The differentiated melanocytes are the cells of origin of melanoma tumors which progress through several stages such as radial growth phase, vertical growth phase, metastasis formation, and often resistance to current therapies. Interestingly, depending on the stage of the disease, melanoma tumor cells share phenotypes with NC cells (proliferative, motile, EMT). These phenotypes are tightly controlled by specific signaling pathways and transcription factors (TFs) which tend to be reactivated during the onset of melanoma. In this review, we summarize first the main TFs which control these common phenotypes. Then, we focus on the existing strategies used to generate human NCs. Finally we discuss how identification and regulation of NC-associated genes provide an additional approach to improving current melanoma targeted therapies.
Where Should I Go? City Recommendation Based on User Communities

Recommender systems play a key role in the decision making process of users in Web systems. In tourism, it is widely used to recommend hotels, tourist attractions, accommodations, etc. In this paper, we present a personalized neighborhood-based method to recommend cities. This is a fundamental problem whose solution support other tourism recommendations. Our recommendation approach takes into account information of two different layers, namely, an upper layer composed by cities and a lower layer composed by attractions of each city. It consists of first building a social network among users, where the edges are weighted by the similarity of interests between pairs of users, and then using this network as a component of a collaborative filtering strategy to recommend cities. We evaluate our method using a large dataset collected from Trip Advisor. Our experimental results show that our approach, despite being simple, outperforms the precision achieved by a state-of-the-art baseline approach for implicit feedback (WRMF), which exploits only the overall popularity of cities. We also show that the use of a secondary layer (attraction) contributes to improve the effectiveness of our approach.
A Feasibility and Acceptability Trial of Social Cognitive Therapy in Early Psychosis Delivered Through a Virtual World: The VEEP Study

Background Addressing specific social cognitive difficulties is an important target in early psychosis and may help address poor functional outcomes. However, structured interventions using standard therapy settings including groups suffer from difficulties in recruitment and retention. Aims To address these issues, we aimed to modify an existing group social cognitive intervention entitled ‘Social Cognition and Interaction Training' (SCIT) to be delivered through a virtual world environment (Second Life ©). Methods A single arm nonrandomized proof-of-concept trial of SCIT-VR was conducted. Five groups of three to five individuals per group were recruited over 6 months. Eight sessions of SCIT-VR therapy were delivered through the virtual world platform Second Life© over a 5-week intervention window. Feasibility was examined using recruitment rates and retention. Acceptability was examined using qualitative methods. Secondary outcomes including social cognitive indices, functioning, and anxiety were measured pre- and postintervention. Results The SCIT-VR therapy delivered was feasible (36% consent rate and 73.3% intervention completion rate), acceptable (high overall postsession satisfaction scores) and safe (no serious adverse events), and had high levels of participant satisfaction. Users found the environment immersive. Prepost changes were found in emotion recognition scores and levels of anxiety. There were no signs of clinical deterioration on any of the secondary measures. Conclusion This proof-of-concept pilot trial suggested that delivering SCIT-VR through a virtual world is feasible and acceptable. There were some changes in prepost outcome measures that suggest the intervention has face validity. There is sufficient evidence to support a larger powered randomized controlled trial. Clinical Trial Registration ISRCTN, identifier 41443166