Templetonmeyer7773

Macroautophagy/autophagy induction by caloric restriction mimetics (CRMs) is a strategy to stimulate anticancer immune responses of immunogenic cell death (ICD)-inducing chemotherapeutics. We designed a phenotypic screening campaign in which we identified pharmacological agents that have CRM properties (i.e., non-cytotoxic induction of autophagic flux that reduces cytoplasmic protein acetylation) and simultaneously act as ICD amplifiers (i.e. with the capacity to enhance the release of adenosine triphosphate, ATP, from stressed and dying cancer cells). This approach led to the identification of thiostrepton, a natural cyclic oligopeptide antibiotic, as an agent that enhances chemotherapy-induced anticancer immune responses in vivo, in immunocompetent mice bearing syngeneic tumors. Interestingly, both the pro-autophagic and the anticancer effects of thiostrepton rely on the activation of TFEB (transcription factor EB) and TFE3 (transcription factor E3). In summary, thiostrepton represents a novel CRM and ICD amplifier that may be useful for cancer therapy.This study was conducted to assess the nasopharyngeal (NP) carriage and acute otitis media (AOM) occurrence in Korean children who received pneumococcal conjugate vaccines (PCVs). The longitudinal study was conducted through four consecutive visits. At each visit, NP aspirates were obtained and subjects were asked to visit if AOM occurred. A total of 305 subjects were enrolled and received PCV13 (n = 182) or PCV10 (n = 123). In the PCV13 group, the NP carriage of Streptococcus pneumoniae at each visit was 2.7%, 14.8%, 18.7%, and 15.9%, respectively. Non-typeable Haemophilus influenzae (NTHi) was 3.3%, 2.7%, 2.7%, and 5.5%, and that of Moraxella catarrhalis was 1.1%, 9.3%, 4.9%, and 0.5%. In the PCV10 group, the NP carriage of S. pneumoniae at each visit was 3.3%, 7.3%, 6.5%, and 4.1%, respectively. That of NTHi was 2.4%, 4.1%, 1.6%, and 0.8%, and that of M. catarrhalis was 4.1%, 0.8%, 0.8%, and 0.0%. EGFR signaling pathway AOM occurrence in the PCV13 group observed after the primary dose and before booster dose was 20.9%, occurrence after booster dose was 11.0%, and the incidence of two or more AOM was 11.0%. In the PCV10 group, AOM occurrence was 9.8%, 7.3%, respectively, and the incidence of two or more AOM was 2.4%. The predominant S. pneumoniae isolated were non-vaccine type (10A, 15A, and 15B). In this study, AOM occurrence was lower in the PCV10 group than in the PCV13 group. This seems to be related to ecological changes that lead to differences in NP carriage, especially S. pneumoniae and NTHi.RATIONALE AND OBJECTIVES We expanded upon a previous pooled case-control analysis on diesel engine exhaust and lung cancer by including 3 additional studies and quantitative exposure assessment to evaluate lung cancer and subtype risks associated with occupational exposure to diesel exhaust, characterized by elemental carbon (EC) concentrations. METHODS We used a quantitative EC job-exposure matrix for exposure assessment. Unconditional logistic regression models were used to calculate lung cancer odds ratios (ORs) and 95% confidence intervals (CI) associated with various metrics of EC exposure. Lung cancer excess lifetime risks (ELR) were calculated using life-tables accounting for all-cause mortality. Additional stratified analyses by smoking history and lung cancer subtypes were performed in men. RESULTS Our study included 16,901 cases and 20,965 controls. In men, exposure-response between EC and lung cancer was observed ORs ranged from 1.09 (95% CI 1.00, 1.18) to 1.41 (95% CI 1.30, 1.52) for the lowest and highest cumulative exposure groups, respectively. EC-exposed men had elevated risks in all lung cancer subtypes investigated; associations were strongest for squamous and small cell carcinomas and weaker for adenocarcinoma. EC-lung cancer exposure-response was observed in men regardless of smoking history, including among never smokers. ELR associated with 45 years of EC exposure at 50, 20, and 1 μg/m3 were 3.0%, 0.99%, and, 0.04%, respectively, for both sexes combined. CONCLUSION We observed a consistent exposure-response relationship between EC exposure and lung cancer in men. Reduction of workplace EC levels to background environmental levels will further reduce lung cancer ELR in exposed workers.RATIONALE AND OBJECTIVES Respirable crystalline silica is a lung carcinogen with millions of exposed workers globally. We aimed to address current knowledge gaps in lung cancer risks associated with low levels of occupational silica exposure and the joint effects of smoking and silica exposure on lung cancer risks. METHODS Subjects from 14 case-control studies from Europe and Canada with detailed smoking and occupational histories were pooled. A quantitative job-exposure matrix was used to estimate silica exposure by occupation, time period, and geographical region. Logistic regression models were used to estimate exposure-disease associations and the joint effects of silica exposure and smoking on risk of lung cancer. Stratified analyses by smoking history and cancer subtypes were also performed. MEASUREMENTS AND MAIN RESULTS Our study included 16,901 cases and 20,965 controls. Lung cancer odds ratios ranged from 1.15 (95% CI 1.04, 1.27) to 1.45 (95% CI 1.31, 1.60) for groups with the lowest and highest cumulative exposure, respectively. Increasing cumulative silica exposure was associated (p-trend less then 0.01) with increasing lung cancer risks in non-silicotics, and in current, former, and never smokers. Increasing exposure was also associated (p-trend≤0.01) with increasing risks of lung adenocarcinoma, squamous cell carcinoma, and small cell carcinoma. Super-multiplicative interaction of silica exposure and smoking was observed on overall lung cancer risks; super-additive effects were observed in risks of lung cancer and all three included subtypes. CONCLUSIONS Silica exposure is associated with lung cancer at low exposure levels. Exposure-response relationship was robust and present regardless of smoking, silicosis status, and cancer subtype.The amount of online messages that are personalized based on people's characteristics and interests is growing. Due to technological advancements, it has become possible to personalize messages across media in real time. However, little is known about people's perceptions of these different personalization techniques, while this can have important implications for message effectiveness and the privacy debate. A survey with U.S. adults (N = 1,008) showed that in the context of real-time personalization, all personalization techniques are seen as unacceptable and they are all associated with perceptions of surveillance. This applies to all generations, but younger generations are more likely to accept and to perceive less surveillance than older generations. Furthermore, we found that, of all predictors, perceived surveillance and attitudes toward personalization were the strongest predictors of acceptance of all personalization techniques. The results advance theory by differentiating between personalization techniques and introducing privacy cynicism and mobile device dependency as factors that positively relate to acceptance of personalization techniques.