The relationship between body mass index (BMI) and sedentary behavior is mediated by negative peer interaction in boys

To determine if self-reported negative social interaction mediates the relationship between sedentary behavior and body mass index (BMI) percentile in boys. Twelve overweight/obese (≥85th BMI percentile) and 14 non-overweight (\u3c85th BMI percentile) boys (10.5 ± 1.5 years old) completed surveys assessing overt peer victimization and relational victimization. Children were individually given access to a gymnasium with physical activity equipment and sedentary alternatives for 30 minutes. Children could play with the equipment in any pattern they wished and the amount of time allocated to sedentary activities (sitting time) was recorded. Overt and relational victimization were moderately and positively associated with BMI percentile (r ≥ 0.40, p ≤ 0.04) and sitting time (r ≥ 0.40, p ≤ 0.05) and sitting time was positively associated with BMI percentile (r = 0.4, p = 0.05). After controlling for overt and relational victimization the correlation between sitting time and BMI percentile was non-significant (r ≤ 0.28, p ≥ 0.18). The positive relationship between BMI percentile and sedentary behavior was mediated by measures of negative social interaction

The Acute Effects of the COVID-19 Pandemic on Physical Activity and Sedentary Behavior in University Students and Employees

International Journal of Exercise Science 13(5): 1326-1339, 2020. The COVID-19 pandemic has closed non-essential businesses which may alter individuals’ leisure behaviors. Consequently, physical activity and sedentary behavior may be negatively impacted as many fitness and recreational centers have been closed. This study aimed to examine the impact of the pandemic on physical activity and sedentary behavior in a sample of university students and employees before and after the university cancelled face-to-face classes and closed campus. Participants (N = 398) completed the validated Godin physical activity questionnaire and the International Physical Activity Questionnaire which assessed physical activity and sedentary behavior pre- and post-cancellation of face-to-face classes. Participants were also separated in the groups (low, moderate, high physical activity) based upon a tertile split of pre-pandemic total physical activity. Physical activity group by time ANOVAs were used to assess potential changes in total physical activity and sedentary behavior. Post-cancellation sedentary behavior was greater (F (1, 388) = 9.2, p = 0.003, partial η2 = 0.032) than pre-cancellation. Physical activity group moderated (F (2, 395) = 22.0, p \u3c 0.001, partial η2 ≥ 0.10) changes in total physical activity from pre- to post cancellation. The high activity group decreased physical activity whereas the moderate and low activity groups increased physical activity (t ≥ 2.4, p ≤ 0.02, Cohen’s d = 0.23). While the university closure increased sedentary behavior across the sample, it only decreased physical activity in participants who were the most active pre-cancellation. Pandemic-related closure of facilities designed for physical activity may disproportionately impact active individuals

In Pursuit of Prehistoric Caribou on Thandlät, Southern Yukon

In 1997, the first author noted a large concentration of caribou (Rangifer sp.) fecal pellets and a caribou antler on a permanent snow patch in the Kusawa Lake area of southern Yukon. Caribou are completely absent from this area today. Coring of the snow patch revealed continuous deposits of fecal pellets to depths of at least 160 cm. The proximal portion of a wooden dart or arrow shaft fragment recovered on the edge of the snow patch represents one of the few organic examples of mid-Holocene hunting technology ever found in Canada. An age of 2450 BP ± 50 years was obtained for the fecal material from approximately 1.6 m below the surface of the snow patch, and the dart was dated at 4360 BP ± 50 years. These dates indicate that aboriginal Yukon hunters have been harvesting caribou at this location for at least 4000 years. The Thandlät site offers a rare opportunity to explore a number of questions regarding the prehistoric ecology of large caribou populations, the implications of climate change for caribou populations, and human use of high-elevation hunting sites.En 1997, le premier auteur a découvert une concentration élevée de boulettes fécales (Rangifer sp.) et des bois de caribou sur une congère dans la région du lac Kusawa, dans le sud du Yukon. Il n'y a plus de caribous dans cette région. Le carottage de la congère a révélé des dépôts de boulettes jusqu'à une profondeur de 160 cm. Un fragment de dard ou de la flèche en bois trouvé sur le bord de la congère représente une des rares découvertes au Canada relatives à ce type d'arme. Il a été déterminé que les matières fécales prélevées dans la congère, à environ 1,6 m de profondeur, sont âgées de 2450 BP ± 50 ans, et que le dard aurait 4360 BP ± 50 ans. Ces dates montrent que les Autochtones du Yukon chassaient déjà le caribou à cet endroit il y a 4000 ans. Le site Thandlät est un des rares endroits où l'on peut observer divers aspects préhistoriques des grandes populations de caribou, des effets des changements climatiques sur les populations de caribous et des activités de chasse à grande altitude

Increased Physical Activity and Reduced Pain with Spinal Cord Stimulation: a 12-Month Study

International Journal of Exercise Science 13(3): 1583-1594, 2020. The purpose of this study was to assess changes in pain and physical activity after replacing a traditional spinal cord stimulation (SCS) implantable pulse generator with a next generation SCS in patients for whom traditional SCS was no longer providing adequate relief of low back and/or leg pain. Subjects (n = 19) who reported that they were no longer receiving adequate relief from traditional SCS were implanted with a next generation SCS. Eighteen additional patients who were receiving relief from traditional SCS were also followed as a control. Both groups (next generation, traditional) were assessed for low-back and limb pain (visual analog scale) and daily physical activity (wearable accelerometer) at baseline and three, six, nine and 12 months following the SCS implant. Relative to baseline, next generation SCS subjects exhibited reductions (p ≤ 0.05 for all) in low-back pain (average reduction of 22%) at every time point, in leg pain (average reduction of 23%) at every time point except six months and increased physical activity (average increase of 57%) at three, six and nine months. As expected, there were no changes in pain or physical activity in the traditional SCS subjects (p ≥ 0.1). In conclusion, pain decreased, and physical activity increased in patients receiving a next generation SCS. Physical activity may serve as an objectively measured marker of pain

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

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice