The Vehicle, 1965, Vol. 7

Vol. 7 Table of Contents CommentaryElaine Lancepage 3 Lost Island and The Unseen SeaDaun Alan Leggpage 5 ElegyWilliam Mosierpage 6 AwayDavid Dixpage 7 DulceyRoberta Mathewspage 8 Alarum Tuam JonneDavid Walkerpage 11 Little BrotherSteve Gibbspage 13 River RunningDaun Alan Leggpage 15 PortraitRobert D. Thomaspage 16 The RockRoger Lewis Hudsonpage 17 Jarman HospitalElaine Lancepage 18 Of Domes and DiamondsDwight Ashbypage 19 Friday NightRoger J. Barrypage 20 MurderHelen Coxpage 23 Vigil SongDaun Alan Leggpage 24 Had You But Been the OneDavid Helmpage 25 To A Useless WeaponDarlene Brewerpage 25 Out of the NightPat Hartpage 26 La MortAdrian Beardpage 28 Mrs. Milton\u27s LamentBob Millerpage 30 Cockle CoveSusan McCabepage 31 Loss of VirtueJim Rinnertpage 32 The KeepsakeDwight Ashbypage 33 The RuinsRoger Lewis Hudsonpage 35 Ante Major OdysseyDaun Alan Leggpage 38 ReligionAnthony Barrettepage 39 All JoyJim Rinnertpage 40 SesameElaine Lancepage 40 CenterpieceDwight Ashbypage 41 A Great White WaveJohn Rhodespage 42 QueryElaine Lancepage 44 PistachioRita Salyerspage 45 FacadeKathleen McCormackpage 46 Winter Wisp AwaySteve Gibbspage 46 ScenarioDavid Dixpage 47 Damn-GodSteve Gibbspage 48 AccidentElaine Lancepage 48https://thekeep.eiu.edu/vehicle/1013/thumbnail.jp

A high concentration of genistein down-regulates activin A, Smad3 and other TGF-β pathway genes in human uterine leiomyoma cells

Previously, we found that high doses of genistein show an inhibitory effect on uterine leiomyoma (UtLM) cell proliferation. In this study, using microarray analysis and Ingenuity Pathways Analysis™, we identified genes (up- or down-regulated, ≥ 1.5 fold, P ≤ 0.001), functions and signaling pathways that were altered following treatment with an inhibitory concentration of genistein (50 µg/ml) in UtLM cells. Downregulation of TGF-β signaling pathway genes, activin A, activin B, Smad3, TGF-β2 and genes related to cell cycle regulation, with the exception of the upregulation of the CDK inhibitor P15, were identified and validated by real-time RT-PCR studies. Western blot analysis further demonstrated decreased protein expression of activin A and Smad3 in genistein-treated UtLM cells. Moreover, we found that activin A stimulated the growth of UtLM cells, and the inhibitory effect of genistein was partially abrogated in the presence of activin A. Overexpression of activin A and Smad3 were found in tissue samples of leiomyoma compared to matched myometrium, supporting the contribution of activin A and Smad3 in promoting the growth of UtLM cells. Taken together, these results suggest that down-regulation of activin A and Smad3, both members of the TGF-β pathway, may offer a mechanistic explanation for the inhibitory effect of a high-dose of genistein on UtLM cells, and might be potential therapeutic targets for treatment of clinical cases of uterine leiomyomas

THE VAXED PROJECT: An Assessment of Immunization Education in Canadian Health Professional Programs

<p>Abstract</p> <p>Background</p> <p>Knowledge & attitudes of healthcare providers (HCP) have significant impact on frequency with which vaccines are offered & accepted but many HCP are ill equipped to make informed recommendations about vaccine merits & risks. We performed an assessment of the educational needs of trainees regarding immunization and used the information thus ascertained to develop multi-faceted, evaluable, educational tools which can be integrated into formal education curricula.</p> <p>Methods</p> <p>(i) A questionnaire was sent to all Canadian nursing, medical & pharmacy schools to assess immunization-related curriculum content (ii) A 77-item web-based, validated questionnaire was emailed to final-year students in medicine, nursing, & pharmacy at two universities in Nova Scotia, Canada to assess knowledge, attitudes, & behaviors reflecting current immunization curriculum.</p> <p>Results</p> <p>The curriculum review yielded responses from 18%, 48%, & 56% of medical, nursing, & pharmacy schools, respectively. Time spent on immunization content varied substantially between & within disciplines from <1 to >50 hrs. Most schools reported some content regarding vaccine preventable diseases, immunization practice & clinical skills but there was considerable variability and fewer schools had learning objectives or formal evaluation in these areas. 74% of respondents didn't feel comfortable discussing vaccine side effects with parents/patients & only 21% felt they received adequate teaching regarding immunization during training.</p> <p>Conclusions</p> <p>Important gaps were identified in the knowledge of graduating nursing, medical, & pharmacy trainees regarding vaccine indications/contraindications, adverse events & safety. The national curriculum review revealed wide variability in immunization curriculum content & evaluation. There is clearly a need for educators to assess current curricula and adapt existing educational resources such as the Immunization Competencies for Health Professionals in Canada.</p

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

Brain Research to Ameliorate Impaired Neurodevelopment - Home-based Intervention Trial (BRAIN-HIT)

<p>Abstract</p> <p>Background</p> <p>This randomized controlled trial aims to evaluate the effects of an early developmental intervention program on the development of young children in low- and low-middle-income countries who are at risk for neurodevelopmental disability because of birth asphyxia. A group of children without perinatal complications are evaluated in the same protocol to compare the effects of early developmental intervention in healthy infants in the same communities. Birth asphyxia is the leading specific cause of neonatal mortality in low- and low-middle-income countries and is also the main cause of neonatal and long-term morbidity including mental retardation, cerebral palsy, and other neurodevelopmental disorders. Mortality and morbidity from birth asphyxia disproportionately affect more infants in low- and low-middle-income countries, particularly those from the lowest socioeconomic groups. There is evidence that relatively inexpensive programs of early developmental intervention, delivered during home visit by parent trainers, are capable of improving neurodevelopment in infants following brain insult due to birth asphyxia.</p> <p>Methods/Design</p> <p>This trial is a block-randomized controlled trial that has enrolled 174 children with birth asphyxia and 257 without perinatal complications, comparing early developmental intervention plus health and safety counseling to the control intervention receiving health and safety counseling only, in sites in India, Pakistan, and Zambia. The interventions are delivered in home visits every two weeks by parent trainers from 2 weeks after birth until age 36 months. The primary outcome of the trial is cognitive development, and secondary outcomes include social-emotional and motor development. Child, parent, and family characteristics and number of home visits completed are evaluated as moderating factors.</p> <p>Discussion</p> <p>The trial is supervised by a trial steering committee, and an independent data monitoring committee monitors the trial. Findings from this trial have the potential to inform about strategies for reducing neurodevelopmental disabilities in at-risk young children in low and middle income countries.</p> <p>Trial Registration</p> <p>Clinicaltrials.gov NCT00639184</p

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