9 research outputs found

    A Visual Modeling Method for Spatiotemporal and Multidimensional Features in Epidemiological Analysis: Applied COVID-19 Aggregated Datasets

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    The visual modeling method enables flexible interactions with rich graphical depictions of data and supports the exploration of the complexities of epidemiological analysis. However, most epidemiology visualizations do not support the combined analysis of objective factors that might influence the transmission situation, resulting in a lack of quantitative and qualitative evidence. To address this issue, we have developed a portrait-based visual modeling method called +msRNAer. This method considers the spatiotemporal features of virus transmission patterns and the multidimensional features of objective risk factors in communities, enabling portrait-based exploration and comparison in epidemiological analysis. We applied +msRNAer to aggregate COVID-19-related datasets in New South Wales, Australia, which combined COVID-19 case number trends, geo-information, intervention events, and expert-supervised risk factors extracted from LGA-based censuses. We perfected the +msRNAer workflow with collaborative views and evaluated its feasibility, effectiveness, and usefulness through one user study and three subject-driven case studies. Positive feedback from experts indicates that +msRNAer provides a general understanding of analyzing comprehension that not only compares relationships between cases in time-varying and risk factors through portraits but also supports navigation in fundamental geographical, timeline, and other factor comparisons. By adopting interactions, experts discovered functional and practical implications for potential patterns of long-standing community factors against the vulnerability faced by the pandemic. Experts confirmed that +msRNAer is expected to deliver visual modeling benefits with spatiotemporal and multidimensional features in other epidemiological analysis scenarios

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

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    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

    31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

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    Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

    Nanoscience and Nanotechnology Cross Borders

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    The recent ExecutiveOrder by President Trump attempting to ban temporarily the citizens of seven countries (Iran, Iraq, Libya, Somalia, Sudan, Syria, and Yemen) from entering the United States is having significant consequences within the country and around the world. The Order poses a threat to the health and vitality of science, barring students and scientists from these countries from traveling to the United States to study or to attend conferences. In preventing those members of the international scientific community from traveling beyond U.S. borders without guaranteed safe return, the Executive Order demeans them; in so doing, it demeans us all. Universities and research communities are especially impacted, as major universities have students and often faculty holding passports from one of these seven countries. This temporary ban would affect refugees fleeing war-torn areas, challenging the long-standing notion that the United States is a safe haven for those fleeing persecution and war in addition to being a magnet for talent from every corner of the world. The pages of this journal reflect the geographic, ethnic, and cultural diversity that underpins great science. The ban impacts domestic and global scientific efforts and communities. Science succeeds through the cooperation between collections of individuals and teams around the world discovering and learning from each other. To ensure rapid scientific progress, open communication and exchange between scientists are essential. As scientists, engineers, and clinicians, we have benefited from open interactions and collaborations with visitors and students from all parts of the world as well as through scientific publications and discussions at scientific meetings