9 research outputs found

    A Model of Social Explanations for a Conversational Movie Recommendation System

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    A critical aspect of any recommendation process is explaining the reasoning behind each recommendation. These explanations can not only improve users' experiences, but also change their perception of the recommendation quality. This work describes our human-centered design for our conversational movie recommendation agent, which explains its decisions as humans would. After exploring and analyzing a corpus of dyadic interactions, we developed a computational model of explanations. We then incorporated this model in the architecture of a conversational agent and evaluated the resulting system via a user experiment. Our results show that social explanations can improve the perceived quality of both the system and the interaction, regardless of the intrinsic quality of the recommendations

    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

    Autoimmune manifestations in patients with multiple myeloma and monoclonal gammopathy of undetermined significance

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    Background: Multiple myeloma (MM) and its precursor, monoclonal gammopathy of undetermined significance (MGUS), have been linked with several autoimmune conditions in the medical literature. Yet, significance of these associations is not well understood. Methods: Herein, we provide a comprehensive literature review on autoimmune disorders identified in patients with MM and MGUS. Most relevant papers were identified via searching the PubMed/Medline and EMBASE databases for articles published from inception until May 1, 2016. Findings: Scientific literature on autoimmune conditions in patients with MM and MGUS consists of several case series and a multitude of case reports. Our analysis suggests an increased prevalence of autoimmune conditions in patients with MM and monoclonal gammopathy of undetermined significance (MGUS), including various autoimmune hematologic and rheumatologic conditions among other entities. Conversely, persons with various autoimmune conditions tend to have a higher prevalence of MGUS and MM than the general population. Conclusions: Future research is required to explore further the link between MGUS/MM and autoimmune disorders. Inflammation in the setting of autoimmunity may serve as a trigger for MGUS and MM. In addition, a common genetic susceptibility for developing both an autoimmune disease and MM/MGUS might also exist. Autoimmune hematologic and rheumatologic diseases may pose important clinical problems for the MM patients. Therefore, a catalogue of these problems is important so that physicians are able to consider, identify and address them promptly

    Reactive thymic hyperplasia mimicking relapse in a child with post-treatment T-cell Non-Hodgkin's lymphoma: A case report and literature review

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    Background: Chemotherapy usually results in the premature shrinkage of thymic cells, often resulting in atrophy. However, in some children, the thymus has the potential to regenerate following the withdrawal of stimulus, resulting in an increase in thymic cells – called rebound/reactive thymic hyperplasia. This phenomenon often appears clinically and radiologically similar to lymphoma in the anterior mediastinum, leading to overtreatment. Case report: We report a 6-year-old boy with T-Lymphoblastic lymphoma (LL) who presented with mediastinal mass. He was treated with high risk ALL protocol and completed treatment uneventfully. Post-treatment PET-CT for routine assessment showed an anterior mediastinal mass with a SUVt of 4.64, highly suggestive of recurrence, however was finally diagnosed with thymic hyperplasia confirmed by biopsy. Conclusion: Pediatric hemato-oncologists and radiologists need to be aware of this phenomenon to avoid misdiagnosis and overtreatment. Relapse should always be confirmed by histopathological examination

    Pancreatic surgery outcomes: multicentre prospective snapshot study in 67 countries

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    Background: Pancreatic surgery remains associated with high morbidity rates. Although postoperative mortality appears to have improved with specialization, the outcomes reported in the literature reflect the activity of highly specialized centres. The aim of this study was to evaluate the outcomes following pancreatic surgery worldwide.Methods: This was an international, prospective, multicentre, cross-sectional snapshot study of consecutive patients undergoing pancreatic operations worldwide in a 3-month interval in 2021. The primary outcome was postoperative mortality within 90 days of surgery. Multivariable logistic regression was used to explore relationships with Human Development Index (HDI) and other parameters.Results: A total of 4223 patients from 67 countries were analysed. A complication of any severity was detected in 68.7 percent of patients (2901 of 4223). Major complication rates (Clavien-Dindo grade at least IIIa) were 24, 18, and 27 percent, and mortality rates were 10, 5, and 5 per cent in low-to-middle-, high-, and very high-HDI countries respectively. The 90-day postoperative mortality rate was 5.4 per cent (229 of 4223) overall, but was significantly higher in the low-to-middle-HDI group (adjusted OR 2.88, 95 per cent c.i. 1.80 to 4.48). The overall failure-to-rescue rate was 21 percent; however, it was 41 per cent in low-to-middle-compared with 19 per cent in very high-HDI countries.Conclusion: Excess mortality in low-to-middle-HDI countries could be attributable to failure to rescue of patients from severe complications. The authors call for a collaborative response from international and regional associations of pancreatic surgeons to address management related to death from postoperative complications to tackle the global disparities in the outcomes of pancreatic surgery (NCT04652271; ISRCTN95140761)
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