Human Papillomavirus (HPV) Vaccination Status Among University Freshmen in Hawai‘i

Purpose/Background: The HPV vaccine provides immunity against nine HPV strains that cause cancer and genital warts. It is recommended for 11 to 12 year olds, and catch-up immunization is recommended for females 13 to 26 years old and males 13 to 21 years old. College students represent an important population for HPV vaccination due to their increased risk for HPV infection. Despite the benefits of the HPV vaccine, its coverage rates are low in Hawaii. Hawai‘i is the home of two large universities on two islands that are representative of Hawai‘i’s populations, including Native Hawaiians, Filipinos, and Pacific Islanders. The purpose of this study was to assess the current HPV and HPV vaccine knowledge, barriers and beliefs among incoming Freshmen university students at University of Hawai‘i at Mānoa and University of Hawai‘i at Hilo. Materials & Methods: In 2016, 200 University of Hawai‘i at Mānoa (UHM) and University of Hawai‘i at Hilo (UHH) Freshmen students responded to a survey that assessed their knowledge and awareness of HPV, the HPV vaccine, their current vaccination status, and barriers and motivators to vaccination. Descriptive statistics were used to summarize each survey variable first for all students and then separately for each campus. Results: Overall 76% of Freshmen from both campuses heard of the HPV vaccine and 54% reported hearing it from their health care provider. Only 28% UHM and 23% UHH Freshmen students have received partial (1-2 shots) or completed doses of the HPV vaccine. For those who received the vaccine, 45% reported that they were told by their parent and 43% were told by their doctor. For the 147 students who did not receive the vaccine, 28% reported that they are still not sure to get it and 20% need more information. Their main reasons for not receiving the HPV vaccine were: their doctor did not mention the vaccine to him/her (44%), he/she never knew about the vaccine (18%), and they don\u27t know enough about the vaccine (17%). Discussion/Conclusion: Although the HPV vaccine has been available for 13 years, young adults remain unvaccinated. Freshmen students reported that they are informed about the vaccine, but were not vaccinated because of the lack of parental and/or healthcare provider recommendation. With no active education campaigns in Hawaii promoting the HPV vaccine at college campuses, a first step to increasing vaccination rates is to develop a health education campaign to inform students of the HPV vaccine and its availability at campus clinics and neighboring pharmacies

Typhoid fever in Fiji: a reversible plague?

Le pays des îles Fidji, avec une population d\u27environ 870 000 personnes, fait face à une charge croissante de plusieurs maladies transmissibles, y compris l\u27infection bactérienne de la fièvre typhoïde. Les données de surveillance indiquent que la fièvre typhoïde est devenue de plus en plus fréquente dans les zones rurales de Fidji et est plus fréquente chez les jeunes adultes. La transmission des organismes qui causent la fièvre typhoïde est facilitée par la contamination fécale des aliments ou de l\u27eau et peut être influencée par les pratiques comportementales locales dans les îles Fidji. Le Ministère fidjien de la Santé, avec le soutien de l\u27aide australienne, a organisé une réunion en août 2012 afin d’élaborer des stratégies complètes de lutte et de prévention de la fièvre typhoïde à Fidji. Les spécialistes internationaux et locaux ont été invités à partager les données pertinentes et discuter des options de lutte contre la typhoïde. Les recommandations qui en ont résulté sont axées sur l’établissement d\u27une vision plus claire de l’épidémiologie de la fièvre typhoïde à Fidji et l\u27exploration de la contribution de potentielles voies de transmission. En outre, le comité a suggéré des étapes telles que l\u27assurance que les doses recommandées de ciprofloxacine soient appropriées afin de réduire le risque possible de rechute et de réinfection dans les cas cliniques, l\u27encouragement d\u27une hygiène correcte des mains pour les manipulateurs d\u27aliments et de boissons, le travail en collaboration avec les agences de l\u27eau et de l\u27assainissement afin d\u27analyser les pratiques actuelles d\u27assainissement et la considération d\u27une politique de vaccination ciblant les populations épidémiologiquement concernées

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

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

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

Using a Human Challenge Model of Infection to Measure Vaccine Efficacy: A Randomised, Controlled Trial Comparing the Typhoid Vaccines M01ZH09 with Placebo and Ty21a

Background Typhoid persists as a major cause of global morbidity. While several licensed vaccines to prevent typhoid are available, they are of only moderate efficacy and unsuitable for use in children less than two years of age. Development of new efficacious vaccines is complicated by the human host-restriction of Salmonella enterica serovar Typhi (S. Typhi) and lack of clear correlates of protection. In this study, we aimed to evaluate the protective efficacy of a single dose of the oral vaccine candidate, M01ZH09, in susceptible volunteers by direct typhoid challenge. Methods and Findings We performed a randomised, double-blind, placebo-controlled trial in healthy adult participants at a single centre in Oxford (UK). Participants were allocated to receive one dose of double-blinded M01ZH09 or placebo or 3-doses of open-label Ty21a. Twenty-eight days after vaccination, participants were challenged with 104CFU S. Typhi Quailes strain. The efficacy of M01ZH09 compared with placebo (primary outcome) was assessed as the percentage of participants reaching pre-defined endpoints constituting typhoid diagnosis (fever and/or bacteraemia) during the 14 days after challenge. Ninety-nine participants were randomised to receive M01ZH09 (n = 33), placebo (n = 33) or 3-doses of Ty21a (n = 33). After challenge, typhoid was diagnosed in 18/31 (58.1% [95% CI 39.1 to 75.5]) M01ZH09, 20/30 (66.7% [47.2 to 87.2]) placebo, and 13/30 (43.3% [25.5 to 62.6]) Ty21a vaccine recipients. Vaccine efficacy (VE) for one dose of M01ZH09 was 13% [95% CI -29 to 41] and 35% [-5 to 60] for 3-doses of Ty21a. Retrospective multivariable analyses demonstrated that pre-existing anti-Vi antibody significantly reduced susceptibility to infection after challenge; a 1 log increase in anti-Vi IgG resulting in a 71% decrease in the hazard ratio of typhoid diagnosis ([95% CI 30 to 88%], p = 0.006) during the 14 day challenge period. Limitations to the study included the requirement to limit the challenge period prior to treatment to 2 weeks, the intensity of the study procedures and the high challenge dose used resulting in a stringent model. Conclusions Despite successfully demonstrating the use of a human challenge study to directly evaluate vaccine efficacy, a single-dose M01ZH09 failed to demonstrate significant protection after challenge with virulent Salmonella Typhi in this model. Anti-Vi antibody detected prior to vaccination played a major role in outcome after challenge

Interferon-driven alterations of the host’s amino acid metabolism in the pathogenesis of typhoid fever

Enteric fever, caused by Salmonella enterica serovar Typhi, is an important public health problem in resource-limited settings and, despite decades of research, human responses to the infection are poorly understood. In 41 healthy adults experimentally infected with wild-type S. Typhi, we detected significant cytokine responses within 12 h of bacterial ingestion. These early responses did not correlate with subsequent clinical disease outcomes and likely indicate initial host–pathogen interactions in the gut mucosa. In participants developing enteric fever after oral infection, marked transcriptional and cytokine responses during acute disease reflected dominant type I/II interferon signatures, which were significantly associated with bacteremia. Using a murine and macrophage infection model, we validated the pivotal role of this response in the expression of proteins of the host tryptophan metabolism during Salmonella infection. Corresponding alterations in tryptophan catabolites with immunomodulatory properties in serum of participants with typhoid fever confirmed the activity of this pathway, and implicate a central role of host tryptophan metabolism in the pathogenesis of typhoid fever

HIV-1 Populations in Semen Arise through Multiple Mechanisms

HIV-1 is present in anatomical compartments and bodily fluids. Most transmissions occur through sexual acts, making virus in semen the proximal source in male donors. We find three distinct relationships in comparing viral RNA populations between blood and semen in men with chronic HIV-1 infection, and we propose that the viral populations in semen arise by multiple mechanisms including: direct import of virus, oligoclonal amplification within the seminal tract, or compartmentalization. In addition, we find significant enrichment of six out of nineteen cytokines and chemokines in semen of both HIV-infected and uninfected men, and another seven further enriched in infected individuals. The enrichment of cytokines involved in innate immunity in the seminal tract, complemented with chemokines in infected men, creates an environment conducive to T cell activation and viral replication. These studies define different relationships between virus in blood and semen that can significantly alter the composition of the viral population at the source that is most proximal to the transmitted virus

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms