Radiocarbon Evidence for Contrasting Soil Carbon Dynamics in a Andisol and Non-Andisol Pasture Soil Comparison

Symposium Pape

Effort Perception

Research addressing children's perceptions of exercise effort (their ‘perceived exertion’) has appeared steadily in the scientific literature over the last 30 years. Accepting that the established Borg adult rating of perceived exertion (RPE) scale was not appropriate for children, investigators set about developing child-specific scales which employed numbers, words and/or images that were more familiar and understandable. Numerous studies have examined the validity and reliability of such scales as the CERT, PCERT and OMNI amongst children aged 5 to 16, across different modes of exercise (cycling, running, stepping, resistance exercise), protocols (intermittent vs. continuous, incremental vs. non-incremental) and paradigms (estimation vs. production). Such laboratory-based research has enabled the general conclusion that children can, especially with practice, use effort perception scales to differentiate between exercise intensity levels, and to self-regulate their exercise output to match various levels indicated on them. However, inconsistencies in the methodological approaches adopted diminish the certainty of some of the interpretations made by researchers. In addition, though often mentioned, the would-be application of effort perception in physical education and activity/health promotion contexts has been relatively ignored. Accordingly, the scope for research in this applied domain is now considerable

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

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

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

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

Differentiated Perceived Exertion and Self-Regulated Wheelchair Exercise

OBJECTIVE. To investigate the utility of the differentiated rating of perceived exertion (RPE) for the self-regulation of submaximal wheelchair propulsion in novice users. DESIGN. Each participant completed a submaximal incremental test and a graded test to exhaustion to determine peak oxygen consumption (Vo2peak) on a wheelchair ergometer. On a separate day, two 12-minute intermittent bouts consisting of three 4-minute stages were completed at individualized imposed power outputs equating to light (40% Vo 2peak) and moderate (60% Vo2peak) intensity exercise. On a third occasion, participants were assigned to either the overall group or the peripheral group and were required to self-regulate 12-minute intermittent exercise according to either overall RPE or peripheral RPE reported during the corresponding imposed intensity trial. SETTING. Laboratory facilities at a university. PARTICIPANTS. Preliminary population of able-bodied participants with no prior experience of wheelchair propulsion (N=18). INTERVENTIONS. Not applicable. MAIN OUTCOME MEASURES. Differences in oxygen consumption (V̇o2), heart rate, blood lactate concentration, and power output between the imposed and self-regulated exercise trials. RESULTS. No difference was found in physiological responses between the moderate-intensity imposed and RPE-regulated trials in the peripheral group, whereas a significant (P<.05) underproduction in V̇o2 (1.76±.31 vs 1.59±.25L/min) and blood lactate concentration (2.8±0.90 vs 2.21±.83mmol/L) was seen in the overall group. In contrast, a significant (P<.05) overproduction was seen in the peripheral group at a light exercise intensity, whereas no difference was found between all variables during the light-intensity imposed and RPE-regulated trials in the overall group. CONCLUSIONS. Peripheral RPE enabled a more precise self-regulation during moderate-intensity wheelchair exercise in novice users. In contrast, overall RPE provided a more accurate stimulus when performing light-intensity propulsion

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