UTILIZING SCRIBBLENAUTS TO INCREASE READING COMPREHENSION AND IMPROVE LITERACY SKILLS OF THIRD GRADE STUDENTS

The LEA’s problem of practice upon which this research was focused on improving academic achievement in the areas of reading comprehension, fluency and other literacy skills. In particular, the LEA is very concerned about third grade reading scores in the light of North Carolina legislation that implements a reading proficiency test to be taken by all third grade students. The focus of this research was to use "Scribblenauts Unlimited," a commercial-off-the-shelf video game to bolster the reading skills of third grade students in an elementary school located in a rural school district in eastern North Carolina. The research design of this action research study utilized pre - and post- assessment to measure the effectiveness of students’ involvement with “Scribblenauts Unlimited.� The intervention time-line consisted of sixteen weeks of intervention during which two sections of students alternated the roles of intervention and control groups at the eight-week mark. The intervention was implemented for one hour per week during student computer laboratory times. The one-hour per week exposure was divided into two thirty-minute sessions, one on each of two days each week. The quantitative data consisted of participant’s scores on the Reading 3D assessment. The qualitative data was gathered by means of video observations of selected small groups of students and, snapshot insights into individual participants’ learning experiences by means of experience sampling methodology. During each intervention time, a video camera was set up in the computer laboratory and focused on a small group of four or five participants. One or two of the members of the group on which the video camera was focused were invited to “think aloud� through excerpts of the edited videos. The aim was to capture the participants’ learning experience in their own words at what they seem to be key points of their learning trajectory. At the end of each eight-week intervention session, a survey designed to measure the extent to which participants experienced flow was administered to the participants in the intervention

Effect of a Commercially Available Low-Dose Capsaicin Supplement on Knee Extensor Contractile Function

International Journal of Exercise Science 13(2): 312-318, 2020. Capsaicin, the active pungent ingredient in chili peppers and various spicy foods, is demonstrated to influence a variety of physiological systems including skeletal muscle. The purpose of this study was to examine if a chewable capsaicin supplement (1.2 mg) could enhance isokinetic knee extensor contractile performance. Nine young, recreationally active individuals (5 females/4 males; 23.6 ± 1.5 yrs; 24.2 ± 3.3 kg/m2) participated in this randomized, single-blind crossover study. Following a familiarization session, participants completed two isokinetic knee extensor contractile function assessments, 45 minutes after ingesting either a capsaicin fruit gummy or eucaloric placebo, the order of which was randomized. Knee extensor peak torque (strength), summed torque (endurance) and fatigue index (fatigue) were compared between trials. Knee extensor peak torque was significantly greater (p \u3c 0.05; d= 0.80) in the capsaicin (126.0 ± 40.4 N⋅m-1) than the placebo (118.8 ± 41.3 N⋅m-1) trial. No significant differences (p \u3e 0.05) were found for summed torque (8012 ± 2771 vs. 7823 ± 2611 N⋅m-1; d= 0.45) or fatigue index (56.0 ± 17.1 vs. 48.7 ± 21.0 %; d= 0.46) between capsaicin and placebo trials, respectively. These findings, in a relatively modest and mixed-gender sample, suggest that pre-exercise capsaicin ingestion may benefit knee extensor muscle strength but does not appear to affect parameters of skeletal muscle endurance or fatigue

Recombinant tissue-type plasminogen activator versus a novel dosing regimen of urokinase in acute pulmonary embolism: a randomized controlled multicenter trial

AbstractThrombolysis of acute pulmonary embolism can be accomplished more rapidly and safely with 100 mg of recombinant human tissue-type plasminogen activator (rt-PA) (Activase) than with a conventional dose of urokinase (Abbokinase) given as a 4,400-U/kg bolus dose, followed by 4,400 U/kg per h for 24 h. To determine the effects of a more concentrated urokinase dose administered over a shorter time course, this trial enrolled 90 patients with baseline perfusion lung scans and angiographically documented pulmonary embolism. They were randomized to receive either 100 mg/2 h of rt-PA or a novel dosing regimen of urokinase: 3 million U/2 h with the initial 1 million U given as a bolus injection over 10 min. Both drugs were delivered through a peripheral vein.To assess efficacy after initiation of therapy, repeat pulmonary angiograms at 2 h were performed in 87 patients and then graded in a blinded manner by a panel of six investigators. Of the 42 patients allocated to rt-PA therapy, 79% showed angiographic improvement at 2 h, compared with 67% of the 45 patients randomized to urokinase therapy (95% confidence interval for the difference in these proportions [rt-PA minus urokinase] is −6.6% to 30.4%; p = 0.11). The mean change in perfusion lung scans between baseline and 24 h was similar for both treatments. Three patients (two treated with rt-PA and one with urokinase) had an intracranial hemorrhage, which was fatal in one.The results indicate that a 2-h regimen of rt-PA and a new dosing regimen of urokinase exhibit similar efficacy and safety for treatment of acute pulmonary embolism

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies

Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiation.

Cancer progression involves the gradual loss of a differentiated phenotype and acquisition of progenitor and stem-cell-like features. Here, we provide novel stemness indices for assessing the degree of oncogenic dedifferentiation. We used an innovative one-class logistic regression (OCLR) machine-learning algorithm to extract transcriptomic and epigenetic feature sets derived from non-transformed pluripotent stem cells and their differentiated progeny. Using OCLR, we were able to identify previously undiscovered biological mechanisms associated with the dedifferentiated oncogenic state. Analyses of the tumor microenvironment revealed unanticipated correlation of cancer stemness with immune checkpoint expression and infiltrating immune cells. We found that the dedifferentiated oncogenic phenotype was generally most prominent in metastatic tumors. Application of our stemness indices to single-cell data revealed patterns of intra-tumor molecular heterogeneity. Finally, the indices allowed for the identification of novel targets and possible targeted therapies aimed at tumor differentiation