Psychosocial Responses by Adolescent Male Victims to Peer Bullying

Bullying remains a pervasive problem in most schools throughout the nation. Peer-bullied victims report higher levels of depression, suicidal ideation, anxiety, and concerns regarding their safety in school. Reactions of victims to peer bullying have been extreme, as in the cases of the rampage school shooters. Primarily, current research has not focused on the high school adolescent, although most school shooters arise from that age group. The overall purpose of this study was to examine the psychosocial responses by adolescent male victims to peer bullying. Research questions addressed the frequency and severity of peer-victimization, distress, anxiety, and their perception of school violence. This quantitative analysis comprised a convenience sample of males in Grades 9 and 10 from six suburban Southern California high schools. Each participant completed the Reynolds Bullying Victimization Scales for Schools (RBVS). The RBVS includes three instruments; the Bully Victimization Scale (BVS), Bully Victimization Distress Scale (BVDS), and the School Violence Anxiety Scale (SVAS). Only those who self reported being victims on the BVS were analyzed as to their levels of distress, anxiety, and perception of school violence. In total, 1,697 students completed the RBVS; 43.1% ninth grade (n = 732), 43.8% tenth grade (n = 743), and 13.1% (n = 222) of ninth and tenth graders choosing not to declare their grade. Of the total respondents 1,487 participants completed the BVS, of which 25.5% (n = 379) reported being a victim of bullying within the past month. Of those, 57.2% reported being victimized by a peer five or more times within the past month. Victims consistently reported significantly higher scores on the BVDS when compared to their non-victim counterparts. Of victims, 70.5% reported severe anxiety and concern of school violence within the past month. African American teens consistently reported the highest scores of all races/ethnicities on all three instruments. Adolescent male victims of peer bullying experienced markedly elevated levels of distress and anxiety. They perceived their school environment to be unsafe and reported concern of possible school violence. Future study of adolescent peer victimization should consider examining race/ethnicity as a contributing factor in peer bullying

Transcriptional repressor ZEB2 promotes terminal differentiation of CD8⁺ effector and memory T cell populations during infection

ZEB2 is a multi-zinc-finger transcription factor known to play a significant role in early neurogenesis and in epithelial-mesenchymal transition-dependent tumor metastasis. Although the function of ZEB2 in T lymphocytes is unknown, activity of the closely related family member ZEB1 has been implicated in lymphocyte development. Here, we find that ZEB2 expression is up-regulated by activated T cells, specifically in the KLRG1(hi) effector CD8(+) T cell subset. Loss of ZEB2 expression results in a significant loss of antigen-specific CD8(+) T cells after primary and secondary infection with a severe impairment in the generation of the KLRG1(hi) effector memory cell population. We show that ZEB2, which can bind DNA at tandem, consensus E-box sites, regulates gene expression of several E-protein targets and may directly repress Il7r and Il2 in CD8(+) T cells responding to infection. Furthermore, we find that T-bet binds to highly conserved T-box sites in the Zeb2 gene and that T-bet and ZEB2 regulate similar gene expression programs in effector T cells, suggesting that T-bet acts upstream and through regulation of ZEB2. Collectively, we place ZEB2 in a larger transcriptional network that is responsible for the balance between terminal differentiation and formation of memory CD8(+) T cells

The Doctor and the Market: About the Influence of Market Reforms on the Professional Medical Ethics of Surgeons and General Practitioners in The Netherlands

To explore whether market reforms in a health care system affect medical professional ethics of hospital-based specialists on the one hand and physicians in independent practices on the other. Qualitative interviews with 27 surgeons and 28 general practitioners in The Netherlands, held 2–3 years after a major overhaul of the Dutch health care system involving several market reforms. Surgeons now regularly advertise their work (while this was forbidden in the past) and pay more attention to patients with relatively minor afflictions, thus deviating from codes of ethics that oblige physicians to treat each other as brothers and to treat patients according to medical need. Dutch GPs have abandoned their traditional reticence and their fear of medicalization. They now seem to treat more in accordance with patients’ preferences and less in accordance with medical need. Market reforms do affect medical professional principles, and it is doubtful whether these changes were intended when Dutch policy makers decided to introduce market elements in the health care system. Policy makers in other countries considering similar reforms should pay attention to these results

Examination of the association of sex and race/ethnicity with appearance concerns: A Scleroderma Patient-centered Intervention Network (SPIN) cohort study

Objective: Appearance concerns are common in systemic sclerosis (SSc) and have been linked to younger age and more severe disease. No study has examined their association with sex or race/ethnicity. Methods: SSc patients were sampled from the Scleroderma Patient-centered Intervention Network Cohort. Presence of appearance concerns was assessed with a single item, and medical and sociodemographic information were collected. Results: Of 644 patients, appearance concerns were present in 72%, including 421 of 565 women (75%), 42 of 79 men (53%), 392 of 550 patients who identified as White (71%), 35 of 41 who identified as Black (85%), and 36 of 53 who identified as another race/ethnicity (68%). In multivariate analysis, women had significantly greater odds of reporting appearance concerns than men (odds ratio (OR)=2.97, 95% confidence interval (CI)=1.78-4.95,

Quality of life in patients with various Barrett's esophagus associated health states

BACKGROUND: The management of Barrett's esophagus (BE), particularly high grade dysplasia (HGD), is an area of much debate and controversy. Surgical esophagectomy, intensive endoscopic surveillance and mucosal ablative techniques, especially photodynamic therapy (PDT), have been proposed as possible management strategies. The purpose of this study was to determine the health related quality of life associated with Barrett's esophagus and many of the pivotal health states associated with Barrett's HGD management. METHODS: 20 patients with Barrett's esophagus were enrolled in a pilot survey study at a large urban hospital. The utility of Barrett's esophagus without dysplasia (current health state) as well as various health states associated with HGD management (hypothetical states as the subject did not have HGD) were measured using a validated health utility instrument (Paper Standard Gamble). These specific health states were chosen for the study because they are considered pivotal in Barrett's HGD decision making. Information regarding Barrett's HGD was presented to the subject in a standardized format that was designed to be easily comprehendible. RESULTS: The average utility scores (0–1 with 0 = death and 1 = perfect health) for the various Barrett's esophagus associated states were: BE without dysplasia-0.95; Post-esophagectomy for HGD with dysphagia-0.92; Post-PDT for HGD with recurrence uncertainty-0.93; Post-PDT for HGD with recurrence uncertainty and dysphagia-0.91; Intensive endoscopic surveillance for HGD-0.90. CONCLUSION: We present the scores for utilities associated with Barrett's esophagus as well as various states associated with the management of HGD. The results of our study may be useful in advising patients and providers regarding expected outcomes of the various HGD management strategies as well as providing utility scores for future cost-effectiveness analyses

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