Miracle-dz/UniFAR-FTUs huggingface dataset:
Successful Therapy Reduction and Intensification for Childhood Acute Lymphoblastic Leukemia Based on Minimal Residual Disease Monitoring: Study ALL10 From the Dutch Childhood Oncology Group.

PURPOSE Outcome of childhood acute lymphoblastic leukemia (ALL) improved greatly by intensifying chemotherapy for all patients. Minimal residual disease (MRD) levels during the first months predict outcome and may select patients for therapy reduction or intensification. METHODS Patients 1 to 18 years old with ALL were stratified on the basis of MRD levels after the first and second course of chemotherapy. Thereafter, therapy was substantially reduced in patients with undetectable MRD (standard risk) and intensified in patients with intermediate (medium risk) and high (high risk) levels of MRD. Seven hundred seventy-eight consecutive patients were enrolled. The method of analysis was intention-to-treat. Outcome was compared with historical controls. RESULTS In MRD-based standard-risk patients, the 5-year event-free survival (EFS) rate was 93% (SE 2%), the 5-year survival rate was 99% (SE 1%), and the 5-year cumulative incidence of relapse rate was 6% (SE 2%). The safety upper limit of number of observation years was reached and therapy reduction was declared safe.MRD-based medium-risk patients had a significantly higher 5-year EFS rate (88%, SE 2%) with therapy intensification (including 30 weeks of asparaginase exposure and dexamethasone/vincristine pulses) compared with historical controls (76%, SE 6%). Intensive chemotherapy and stem cell transplantation in MRD-based high-risk patients resulted in a significantly better 5-year EFS rate (78%, SE 8% v 16%, SE 8% in controls). Overall outcome improved significantly (5-year EFS rate 87%, 5-year survival rate 92%, and 5-year cumulative incidence of relapse rate 8%) compared with preceding Dutch Childhood Oncology Group protocols. CONCLUSION Chemotherapy was substantially reduced safely in one-quarter of children with ALL who were selected on the basis of undetectable MRD levels, without jeopardizing the survival rate. Outcomes of patients with intermediate and high levels of MRD improved with therapy intensification.
Scaling Peer-to-Peer Video-on-Demand systems using helpers

The throughput of Peer-to-Peer (P2P) Video-on-Demand (VoD) systems is typically capped by the users' aggregate upload bandwidth [1]. The drastic increase in the popularity of VoD and the demand of higher quality content has thus placed substantial burden on the content servers. We investigate a novel P2P VoD architecture that leverages idle internet resources, which we call helpers, to provide a scalable solution to P2P VoD systems. Helpers are volatile in nature, and can be individually unreliable. However, we investigate the statistical aggregation of a large number of helpers to guarantee quality of service. Since helpers do not come with “free” preloaded content, trade-offs between how much a helper should download and how much it can aid the system need to be explored. In this paper, the optimal steady-state design parameters are derived to maximize the helpers' upload bandwidth utilization. Packet level simulations have verified the efficiency of the system. In a typical scenario of 240 users and a required theoretical minimum of 120 helpers with an average upload bandwidth of 256 kbps, a streaming rate of 384 kbps can be sustained with ≪ 2% relative server load. Results also show that the system is robust to helper churn.
The Associations between Regional Gray Matter Structural Changes and Changes of Cognitive Performance in Control Groups of Intervention Studies

In intervention studies of cognitive training, the challenging cognitive tests, which were used as outcome measures, are generally completed in more than a few hours. Here, utilizing the control groups' data from three 1-week intervention studies in which young healthy adult subjects underwent a wide range of cognitive tests and T1-weighted magnetic resonance imaging (MRI) before and after the intervention period, we investigated how regional gray matter (GM) density (rGMD) of the subjects changed through voxel-based morphometry (VBM). Statistically significant increases in rGMD were observed in the anatomical cluster that mainly spread around the bilateral dorsal anterior cingulate cortex (dACC) and the right superior frontal gyrus (rSFG). Moreover, mean rGMD within this cluster changes were significantly and positively correlated with performance changes in the Stroop task, and tended to positively correlate with performance changes in a divergent thinking task. Affected regions are considered to be associated with performance monitoring (dACC) and manipulation of the maintained information including generating associations (rSFG), and both are relevant to the cognitive functions measured in the cognitive tests. Thus, the results suggest that even in the groups of the typical “control group” in intervention studies including those of the passive one, experimental or non-experimental factors can result in an increase in the regional GM structure and form the association between such neural changes and improvements related to these cognitive tests. These results suggest caution toward the experimental study designs without control groups.
Advances in the treatment of type 2 diabetes: impact of dulaglutide

The purpose of this review is to provide a review of current data of the most recently approved glucagon-like peptide (GLP)-1-receptor agonist, dulaglutide, in the treatment of type 2 diabetes. To complete this, a PubMed search was performed to identify manuscripts published from 1947 to July 2015. The search terms “Trulicity”, “dulaglutide”, and “LY2189265” were utilized, and publications were included if they evaluated the pharmacology, pharmacokinetics, efficacy, safety, or patient-reported outcomes of dulaglutide. Dulaglutide is a GLP-1 receptor agonist that mimics endogenous GLP-1, the hormone produced in response to food intake. Modifications have been made to the molecule to delay breakdown and allow for once-weekly dosing. Dulaglutide has been studied as monotherapy and in combination with several agents, including metformin, glimepiride, pioglitazone, and insulin lispro. Dulaglutide has demonstrated superior efficacy compared to placebo, metformin, insulin glargine, sitagliptin, and twice-daily exenatide. It was found to be noninferior to liraglutide. The most common adverse effects in clinical studies were gastrointestinal-related adverse events, and patient satisfaction was high with the use of dulaglutide. Dulaglutide is an appealing option for the treatment of type 2 diabetes, based on its once-weekly dosing, A1c lowering comparable to liraglutide, weight reduction comparable to exenatide, and a similar adverse-effect profile to other GLP-1 receptor agonists.
An Automatic Approach for Radial Lens Distortion Correction From a Single Image

Radial lens distortion correction is a fundamental task in photogrammetry and computer vision disciplines, mainly when metric and quality results are required. Radial lens distortion estimation plays an essential role in several photogrammetric tasks such as: registration of sensors, 3-D reconstruction, and mapping of textures. This paper presents an iterative numerical approach for the automatic estimation and correction of radial lens distortion using only a single image. To this end, several geometric constraints (rectilinear elements and vanishing points) are considered. The reported experimental tests indicate that within certain limits, results from a single image can stand the comparison with those from multiple image bundle adjustment.
Persistent Changes in Circulating and Intestinal γδ T Cell Subsets, Invariant Natural Killer T Cells and Mucosal-Associated Invariant T Cells in Children and Adults with Coeliac Disease

Coeliac disease is a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals. The only current therapy is a lifelong gluten free diet. While much work has focused on the gliadin-specific adaptive immune response in coeliac disease, little is understood about the involvement of the innate immune system. Here we used multi-colour flow cytometry to determine the number and frequency of γδ T cells (Vδ1, Vδ2 and Vδ3 subsets), natural killer cells, CD56+ T cells, invariant NKT cells, and mucosal associated invariant T cells, in blood and duodenum from adults and children with coeliac disease and healthy matched controls. All circulating innate lymphocyte populations were significantly decreased in adult, but not paediatric coeliac donors, when compared with healthy controls. Within the normal small intestine, we noted that Vδ3 cells were the most abundant γδ T cell type in the adult epithelium and lamina propria, and in the paediatric lamina propria. In contrast, patients with coeliac disease showed skewing toward a predominant Vδ1 profile, observed for both adult and paediatric coeliac disease cohorts, particularly within the gut epithelium. This was concurrent with decreases in all other gut lymphocyte subsets, suggesting a specific involvement of Vδ1 cells in coeliac disease pathogenesis. Further analysis showed that γδ T cells isolated from the coeliac gut display an activated, effector memory phenotype, and retain the ability to rapidly respond to in vitro stimulation. A profound loss of CD56 expression in all lymphocyte populations was noted in the coeliac gut. These findings demonstrate a sustained aberrant innate lymphocyte profile in coeliac disease patients of all ages, persisting even after elimination of gluten from the diet. This may lead to impaired immunity, and could potentially account for the increased incidence of autoimmune co-morbidity.
The survival and rejection of epithelium in experimental corneal transplants.

Evidence is presented that the epithelium on a donor corneal allograft is neither sloughed off rapidly in the immediate postoperative period, nor is it even slowly replaced by recipient epithelium in the technically successful corneal transplant. Specific immunologic rejection of the surviving epithelium of a graft may take place long after transplantation, and is characterized by a linear defect consisting of dying epithelial cells and inflammatory cells, stainable by topical methylene blue or fluorescein, which defect migrates slowly across the entire surface of the graft until all donor epithelium has been destroyed.
Effects of a weighted vest on attention to task and self-stimulatory behaviors in preschoolers with pervasive developmental disorders.

OBJECTIVE This study examined the effectiveness of using a weighted vest for increasing attention to a fine motor task and decreasing self-stimulatory behaviors in preschool children with pervasive developmental disorders (PDD). METHOD Using an ABA single-subject design, the duration of attention to task and self-stimulatory behaviors and the number of distractions were measured in five preschool children with PDD over a period of 6 weeks. RESULTS During the intervention phase, all participants displayed a decrease in the number of distractions and an increase in the duration of focused attention while wearing the weighted vest. All but 1 participant demonstrated a decrease in the duration of self-stimulatory behaviors while wearing a weighted vest; however, the type of self-stimulatory behaviors changed and became less self-abusive for this child while she wore the vest. During the intervention withdrawal phase, 3 participants experienced an increase in the duration of self-stimulatory behaviors, and all participants experienced an increase in the number of distractions and a decrease in the duration of focused attention. The increase or decrease, however, never returned to baseline levels for these behaviors. CONCLUSION The findings suggest that for these 5 children with PDD, the use of a weighted vest resulted in an increase in attention to task and decrease in self-stimulatory behaviors. The most consistent improvement observed was the decreased number of distractions. Additional research is necessary to build consensus about the effectiveness of wearing a weighted vest to increase attention to task and decrease self-stimulatory behaviors for children with PDD.
FRP strengthening of masonry arches: analysis of local mechanisms and global behaviour

In the last two decades, FRP (Fibre-Reinforced Polymers) composite materials have been adopted for strengthening and repair of both modern and historic masonry constructions (buildings, bridges, towers) and structural components (walls, arches and vaults, piers and columns). Strengthening of masonry brick arches and vaults with FRP laminates can contribute significantly in the improvement of their structural capacity at a limit state, by activating local mechanisms both at material and interface levels, but also modifies the collapse mechanisms of the original structures, as the reinforcement prevents the typical brittle failure due to the formation of hinge-mechanisms. Despite the increasing number of specific studies on FRP reinforcement of masonry structures, investigations are still limited if compared to reinforced concrete applications. Moreover, few codes and recommendations are currently available. Starting from these points, the present work deals with experimental investigations on three local mechanisms involved by the collapse of FRP-reinforced masonry arches: the interface behaviour in the case of stresses normal to the surface (FRP detachment observed in structures with intrados reinforcement) has been investigated through the execution of a large number of combined tests on solid clay bricks (flexural, compressive, splitting and pull-off tests) aimed at experimentally calibrate possible correlations among the corresponding strength parameters and to observed possible influences of the fibres type and the presence of primer on the pull-off behaviour; the bond behaviour has been investigated by performing ten Double-lap Shear Tests on solid clay bricks, aimed at calibrating fracture energy value and bond-slip law for both carbon FRP and glass FRP reinforcement (moreover, a simple exponential-based bond-slip law has been proposed); the mixed-mode behaviour (fourteen tested samples) has been investigated by adapting a test setup developed for FRP applications on reinforced concrete, known as V-shape Peel Test, to clay substrate, in order to reproduce on a local scale the conditions related to the shear sliding failure of arches with extrados reinforcement. Finally, several case studies, concerning real-scale or scaled brick masonry arches and vaults reinforced at their intrados or extrados, have been collected from literature in order to compare the experimental results to the available interpretative models of the global behaviour of the structure at failure.
Perimetric measurements with flicker-defined form stimulation in comparison with conventional perimetry and retinal nerve fiber measurements.

PURPOSE We compared the results of flicker-defined form (FDF) perimetry with standard automated perimetry (SAP) and retinal nerve fiber layer (RNFL) thickness measurements using spectral domain optical coherence tomography (OCT). METHODS A total of 64 healthy subjects, 45 ocular hypertensive patients, and 97 "early" open-angle glaucoma (OAG) patients participated in this study. Definition of glaucoma was based exclusively on glaucomatous optic disc appearance. All subjects underwent FDF perimetry, SAP, and peripapillary measurements of the RNFL thickness. The FDF perimetry and SAP were performed at identical test locations (G1 protocol). Exclusion criteria were subjects younger than 34 years, SAP mean defect (SAP MD) > 5 dB, eye diseases other than glaucoma, or nonreliable FDF measurements. The correlations between the perimetric data on one hand and RNFL thicknesses on the other hand were analyzed statistically. RESULTS The age-corrected sensitivity values and the local results from the controls were used to determine FDF mean defect (FDF MD). The FDF perimetry and SAP showed high concordance in this cohort of experienced patients (MD values, R = -0.69, P < 0.001). Of a total of 42 OAG patients with abnormal SAP MD, 38 also displayed abnormal FDF MD. However, FDF MD was abnormal in 28 of 55 OAG patients with normal SAP MD. The FDF MD was significantly (R = -0.61, P < 0.001) correlated with RNFL thickness with a (nonsignificantly) larger correlation coefficient than conventional SAP MD (R = -0.48, P < 0.001). CONCLUSIONS The FDF perimetry is able to uncover functional changes concurrent with the changes in RNFL thickness. The FDF perimetry may be an efficient functional test to detect early glaucomatous nerve atrophy. (ClinicalTrials.gov number, NCT00494923.).
Evaluation of DNA damage in an Ecuadorian population exposed to glyphosate

We analyzed the consequences of aerial spraying with glyphosate added to a surfactant solution in the northern part of Ecuador. A total of 24 exposed and 21 unexposed control individuals were investigated using the comet assay. The results showed a higher degree of DNA damage in the exposed group (comet length = 35.5 µm) compared to the control group (comet length = 25.94 µm). These results suggest that in the formulation used during aerial spraying glyphosate had a genotoxic effect on the exposed individuals.
Exploring day-to-day variability in EEG-based emotion classification

The research of electroencephalography (EEG)-based emotion classification has gained much popularity in the past few years. Researchers continue to seek an optimal machine learning-based pipeline to characterize the associations between complex spatio-spectral EEG dynamics and implicit emotional responses. However, toward a real-life application, addressing the inherent day-to-day variability in EEG signals is also of urgent importance, yet was less concerned in the literature. This study explored the day-to-day EEG variability and tested the feasibility of developing an emotion-classification pipeline that can account for such variability. The empirical results of this study showed that the use of a proper feature extraction, e.g., band-power asymmetries over the fronto-posterior regions, in conjunction with an effective artifact removal method, e.g., independent component analysis, could alleviate the impacts of inter-day variability and improve the classification performance.
Histone deacetylase 4 associates with extracellular signal-regulated kinases 1 and 2, and its cellular localization is regulated by oncogenic Ras.

Histone deacetylase 4 (HDAC4) is a member of a family of enzymes that catalyze the removal of acetyl groups from core histones, resulting in a compact chromatin structure that is generally associated with repressed gene transcription. Protein phosphorylation has been implicated in the regulation of the corepressor activity of the deacetylase. Here we report that serine/threonine kinases are found in association with HDAC4 and phosphorylate HDAC4 in vitro, and HDAC4 is phosphorylated in cells. The extracellular signal-regulated kinases 1 and 2 (ERK1/2), also known as p44(MAPK) and p42(MAPK), respectively, are two of the kinases associated with HDAC4. ERK1/2 are components of the Ras-mitogen-activated protein kinase (MAPK) signal transduction pathway. Activation of the Ras-MAPK pathway by expression of oncogenic Ras or constitutively active MAPK/ERK kinase 1 results in an increased percentage of cells (from approximately 10% to approximately 70%) that express HDAC4 in the nucleus in C2C12 myoblast cells. In cells transfected with oncogenic Ras, nuclear HDAC4 is associated with kinase activity. Our results provide evidence that protein kinase activity is present in a protein complex with HDAC4 and directly links the Ras-MAPK signal transduction pathway to a mechanism for chromatin remodeling (i.e., histone deacetylation).
Sparse Distributed Representation of Odors in a Large-scale Olfactory Bulb Circuit

In the olfactory bulb, lateral inhibition mediated by granule cells has been suggested to modulate the timing of mitral cell firing, thereby shaping the representation of input odorants. Current experimental techniques, however, do not enable a clear study of how the mitral-granule cell network sculpts odor inputs to represent odor information spatially and temporally. To address this critical step in the neural basis of odor recognition, we built a biophysical network model of mitral and granule cells, corresponding to 1/100th of the real system in the rat, and used direct experimental imaging data of glomeruli activated by various odors. The model allows the systematic investigation and generation of testable hypotheses of the functional mechanisms underlying odor representation in the olfactory bulb circuit. Specifically, we demonstrate that lateral inhibition emerges within the olfactory bulb network through recurrent dendrodendritic synapses when constrained by a range of balanced excitatory and inhibitory conductances. We find that the spatio-temporal dynamics of lateral inhibition plays a critical role in building the glomerular-related cell clusters observed in experiments, through the modulation of synaptic weights during odor training. Lateral inhibition also mediates the development of sparse and synchronized spiking patterns of mitral cells related to odor inputs within the network, with the frequency of these synchronized spiking patterns also modulated by the sniff cycle.
Occupational Exposure to Extremely Low-Frequency Magnetic Fields and Brain Tumor Risks in the INTEROCC Study

Background: Occupational exposure to extremely low-frequency magnetic fields (ELF) is a suspected risk factor for brain tumors, however the literature is inconsistent. Few studies have assessed whether ELF in different time windows of exposure may be associated with specific histologic types of brain tumors. This study examines the association between ELF and brain tumors in the large-scale INTEROCC study. Methods: Cases of adult primary glioma and meningioma were recruited in seven countries (Australia, Canada, France, Germany, Israel, New Zealand, and the United Kingdom) between 2000 and 2004. Estimates of mean workday ELF exposure based on a job exposure matrix were assigned. Estimates of cumulative exposure, average exposure, maximum exposure, and exposure duration were calculated for the lifetime, and 1 to 4, 5 to 9, and 10+ years before the diagnosis/reference date. Results: There were 3,761 included brain tumor cases (1,939 glioma and 1,822 meningioma) and 5,404 population controls. There was no association between lifetime cumulative ELF exposure and glioma or meningioma risk. However, there were positive associations between cumulative ELF 1 to 4 years before the diagnosis/reference date and glioma [odds ratio (OR) ≥ 90th percentile vs. < 25th percentile, 1.67; 95% confidence interval (CI), 1.36–2.07; PLinear trend < 0.0001], and, somewhat weaker associations with meningioma (OR ≥ 90th percentile vs. < 25th percentile, 1.23; 95% CI, 0.97–1.57; PLinear trend = 0.02). Conclusions: Results showed positive associations between ELF in the recent past and glioma. Impact: Occupational ELF exposure may play a role in the later stages (promotion and progression) of brain tumorigenesis. Cancer Epidemiol Biomarkers Prev; 23(9); 1863–72. ©2014 AACR.