114 research outputs found

    High Healthcare Utilization at the Onset of Medically Unexplained Symptoms

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    Objective: Patients with medically unexplained syndromes (MUS) often do not receive appropriate healthcare. A critical time for effective healthcare is the inception of MUS. The current study examined data from a prospective longitudinal study of Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans to understand the relationship of increasing physical symptom burden to healthcare utilization. Methods: Data was examined from a prospective study of OEF/OIF veterans assessed before and one year after deployment (n=335). Physical symptom burden was measured with the Patient Health Questionnaire (PHQ-15). Analyses were conducted with polynomial regression and response surface analysis (RSA). Results: Increases in physical symptom burden predicted greater healthcare utilization one year after deployment: primary care practitioner (slope = -0.26, F=4.07, p=0.04), specialist (slope = -.43, t=8.67, p=0.003), allied health therapy (e.g., physical therapy) (slope = -.41, t=5.71, p=0.02) and mental health (slope = -.32, F=4.04, p=0.05). There were no significant difference in utilization between those with consistently high levels and those with increases in physical symptom burden. Conclusion: This is the first prospective study to examine, and show, a relationship between onset of clinically significant physical symptoms and greater healthcare utilization. Our data suggest that patients with increasing physical symptom burden have the same level of healthcare as patients with chronic physical symptom burden. Needed next steps are to better understand the quality of care at inception and determine how to intervene so that recommended approaches to care are provided from the onset

    Binge Eating and Weight-Related Quality of Life in Obese Adolescents

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    Limited data exist regarding the association between binge eating and quality of life (QOL) in obese adolescent girls and boys. We, therefore, studied binge eating and QOL in 158 obese (BMI ≥ 95th percentile) adolescents (14.5 ± 1.4 years, 68.0% female, 59% African-American) prior to weight-loss treatment. Youth completed an interview to assess binge eating and a questionnaire measure of QOL. Controlling for body composition, binge eating youth (n = 35), overall, reported poorer QOL in domains of health, mobility, and self-esteem compared to those without binge eating (ps < 0.05). Also, girls, overall, reported poorer QOL than boys in activities of daily-living, mobility, self-esteem, and social/interpersonal functioning (ps < 0.05). Girls with binge eating reported the greatest impairments in activities of daily living, mobility, self-esteem, social/interpersonal functioning, and work/school QOL (ps < 0.05). Among treatment-seeking obese adolescents, binge eating appears to be a marker of QOL impairment, especially among girls. Prospective and treatment designs are needed to explore the directional relationship between binge eating and QOL and their impact on weight outcomes

    Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

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

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    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

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    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

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    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

    Plasma and dietary carotenoid, retinol and tocopherol levels and the risk of gastric adenocarcinomas in the European prospective investigation into cancer and nutrition

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    Despite declining incidence rates, gastric cancer (GC) is a major cause of death worldwide. Its aetiology may involve dietary antioxidant micronutrients such as carotenoids and tocopherols. The objective of this study was to determine the association of plasma levels of seven common carotenoids, their total plasma concentration, retinol and α- and γ-tocopherol, with the risk of gastric adenocarcinoma in a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 countries. A secondary objective was to determine the association of total sum of carotenoids, retinol and α-tocopherol on GCs by anatomical subsite (cardia/noncardia) and histological subtype (diffuse/intestinal). Analytes were measured by high-performance liquid chromatography in prediagnostic plasma from 244 GC cases and 645 controls matched by age, gender, study centre and date of blood donation. Conditional logistic regression models adjusted by body mass index, total energy intake, smoking and Helicobacter pylori infection status were used to estimate relative cancer risks. After an average 3.2 years of follow-up, a negative association with GC risk was observed in the highest vs the lowest quartiles of plasma β-cryptoxanthin (odds ratio (OR)=0.53, 95% confidence intervals (CI)=0.30–0.94, Ptrend=0.006), zeaxanthin (OR=0.39, 95% CI=0.22–0.69, Ptrend=0.005), retinol (OR=0.55, 95% CI=0.33–0.93, Ptrend=0.005) and lipid-unadjusted α-tocopherol (OR=0.59, 95% CI=0.37–0.94, Ptrend=0.022). For all analytes, no heterogeneity of risk estimates or significant associations were observed by anatomical subsite. In the diffuse histological subtype, an inverse association was observed with the highest vs lowest quartile of lipid-unadjusted α-tocopherol (OR=0.26, 95% CI=0.11–0.65, Ptrend=0.003). These results show that higher plasma concentrations of some carotenoids, retinol and α-tocopherol are associated with reduced risk of GC

    Future research directions on the "elusive" white shark

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    White sharks, Carcharodon carcharias, are often described as elusive, with little information available due to the logistical difficulties of studying large marine predators that make long-distance migrations across ocean basins. Increased understanding of aggregation patterns, combined with recent advances in technology have, however, facilitated a new breadth of studies revealing fresh insights into the biology and ecology of white sharks. Although we may no longer be able to refer to the white shark as a little-known, elusive species, there remain numerous key questions that warrant investigation and research focus. Although white sharks have separate populations, they seemingly share similar biological and ecological traits across their global distribution. Yet, white shark’s behavior and migratory patterns can widely differ, which makes formalizing similarities across its distribution challenging. Prioritization of research questions is important to maximize limited resources because white sharks are naturally low in abundance and play important regulatory roles in the ecosystem. Here, we consulted 43 white shark experts to identify these issues. The questions listed and developed here provide a global road map for future research on white sharks to advance progress toward key goals that are informed by the needs of the research community and resource managers
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