High-Throughput Antigen Microarray Identifies Longitudinal Prognostic Autoantibody for Chemoimmunotherapy in Advanced Non-Small Cell Lung Cancer.

Chemoimmunotherapy has evolved as a standard treatment for advanced non-small cell lung cancer (aNSCLC). However, inevitable drug resistance has limited its efficacy, highlighting the urgent need for biomarkers of chemoimmunotherapy. A three-phase strategy to discover, verify, and validate longitudinal predictive autoantibodies (AAbs) for aNSCLC before and after chemoimmunotherapy was employed. A total of 528 plasma samples from 267 aNSCLC patients before and after anti-PD1 immunotherapy were collected, plus 30 independent formalin-fixed paraffin-embedded samples. Candidate AAbs were firstly selected using a HuProt high-density microarray containing 21,000 proteins in the discovery phase, followed by validation using an aNSCLC-focused microarray. Longitudinal predictive AAbs were chosen for ELISA based on responders versus non-responders comparison and progression-free survival (PFS) survival analysis. Prognostic markers were also validated using immunohistochemistry and publicly available immunotherapy datasets. We identified and validated a panel of two AAbs (MAX and DHX29) as pre-treatment biomarkers and another panel of two AAbs (MAX and TAPBP) as on-treatment predictive markers in aNSCLC patients undergoing chemoimmunotherapy. All three AAbs exhibited a positive correlation with early responses and PFS (p < 0.05). The kinetics of MAX AAb showed an increasing trend in responders (p < 0.05) and a tendency to initially increase and then decrease in non-responders (p < 0.05). Importantly, MAX protein and mRNA levels effectively discriminated PFS (p < 0.05) in aNSCLC patients treated with immunotherapy. Our results present a longitudinal analysis of changes in prognostic AAbs in aNSCLC patients undergoing chemoimmunotherapy.

Multi-omics analysis and response prediction of PD-1 monoclonal antibody containing regimens in patients with relapsed/refractory diffuse large B-cell lymphoma.

Patients with relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) show varied responses to PD-1 monoclonal antibody (mAb) containing regimens. The mechanisms and predictive biomarkers for the efficacy of this regimen are unclear. This study retrospectively collected r/r DLBCL patients who received PD-1 mAb and rituximab regimens as salvage therapy. Clinical and genomic features were collected, and mechanisms were explored by multiplex immunofluorescence and digital spatial profiling. An artificial neural network (ANN) model was constructed to predict the response. Between October 16th, 2018 and May 4th, 2023, 50 r/r DLBCL patients were collected, 29 were response patients and 21 were non-response patients. CREBBP (p = 0.029) and TP53 (p = 0.015) alterations were statistically higher in non-response patients. Patients with PD-L1 CPS ≥ 5 were correlated with a longer overall survival (OS) than those with PD-L1 CPS < 5 (median OS: not reached vs. 9.7 months, hazard ratio [HR]: 3.8, 95% confidence interval [CI] 0.64-22.44, p = 0.016). Immune-related pathways were activated in response patients. The proportion and spatial organization of tumor-infiltrating immune cells affect the response. PD-L1 CPS level, age, and alterations of TP53, MYD88, CREBBP, EP300, GNA13 were used to build an ANN predictive model that showed high prediction efficiency (training set area under curve [AUC] of 0.97 and test set AUC of 0.94). The proportion and spatial distribution of tumor-infiltrating immune cells may be related to the function of immune-related pathways, thereby influencing the efficacy of PD-1 mAb containing regimens. The ANN predictive model showed potential value in predicting the responses of r/r DLBCL patients received PD-1 mAb and rituximab regimens.

Efficacy of dolutegravir + lamivudine q.d. with food in people with TB/HIV using a rifampicin-based regimen: A retrospective observational case series.

OBJECTIVES: Dolutegravir + lamivudine (DTG + 3TC) is a first-line regimen for people with HIV. However, there are still concerns about its efficacy in people with tuberculosis (TB)/HIV due to the lack of available evidence and drug-drug interaction with rifampicin. METHODS: A single-centre retrospective observational case series was conducted in Guangxi Zhuang Autonomous Region, China. We included all people with TB/HIV on combined use of once-daily (q.d.) dosing DTG + 3TC and rifampicin (RIF)-containing anti-TB regimens between 2020 and 2022. HIV-RNA, CD4 cell counts were collected and analysed. RESULTS: In all, 21 people with HIV (PWH) were included in this study. All the PWH were treatment-naïve and told to take DTG + 3TC q.d. with food. The median age was 53 years, and 71.43% were male. A total of 71.43% PWH had baseline viral load (VL) > 100 000 copies/mL, and 33.33% had baseline VL greater than 500 000 copies/mL. Only one PWH had CD4 cell count greater than 200 cells/µL, and the median CD4 count was 20 cells/µL. A total of 16 PWH started DTG + 3TC after initiation of the RIF-based anti-TB regimen, and the other five PWH initiated DTG + 3TC before the treatment of TB. All the PWH had at least 24 weeks of follow-up visits and all of the TB treatments were successful. A total of 20 PWH (95.24%) achieved viral suppression (VL <50 copies/mL). All detected viral loads between weeks 24 and 48 were less than 200 copies/mL. Among the PWH who started DTG + 3TC after the initiation of RIF-based anti-TB regimen, all achieved viral suppression by week 24 except the non-suppressed PWH. CD4 counts were greatly improved after antiretroviral treatment: the median CD4 counts were raised from 20 to 171 cells/µL at week 48. No serious adverse events were reported. CONCLUSIONS: This case series preliminarily validates the efficacy of DTG + 3TC q.d. with food when combined with RIF-based anti-TB regimens in people with TB/HIV.

Proposal of a revised 3-tier "2 mm" risk classification model for postoperative pancreatic fistula in robotic pancreatoduodenectomy.

BACKGROUND: The recent International Study Group for Pancreatic Surgery (ISGPS) risk classification for postoperative pancreatic fistula (grade B/C) was developed based on data from open and mixed minimally invasive pancreatoduodenectomy. The ISGPS risk classification model has not been validated specifically for POPF after robotic pancreatoduodenectomy (RPD). METHODS: We calculated the rate of POPF (ISGPS 2016 definition, grade B/C) by analyzing consecutive patients after RPD by surgeons after their learning curves (80 RPDs per surgeon). The validation of the ISGPS 4-tier and the simplified 3-tier risk classification was conducted using the area under the receiver operating curve (AUC). RESULTS: From 2019 to 2023, 187 patients after RPD were included. Neither the ISGPS 4-tier nor the simplified 3-tier classification model showed robust discrimination (AUC: 0.696 and 0.685, respectively). Moreover, both risk classifications failed to differentiate the rates of POPF and major complications among subgroups. Multivariate analysis suggested that soft pancreatic texture and pancreatic duct ≤ 2 mm were independent risk factors for POPF after RPD. After adjusting the duct size's cutoff from 3 to 2 mm, the revised 4-tier "2 mm" classification model showed no significant difference between risk categories B and C (6.7% vs. 9.4%, P = 0.063). The revised 3-tier "2 mm" classification model stratified patients into A (n = 54), B (n = 68), and C (n = 65) groups, with corresponding POPF rates of 0.0%, 8.8%, and 23.1% (P < 0.001), and major complication rates of 5.6, 14.7, and 24.6% (P = 0.014), respectively. Compared to the simplified 3-tier classification model, the revised 3-tier "2 mm" classification model showed improved discrimination (AUC: 0.753 vs. 0.685, P = 0.034) and clinical utility. CONCLUSIONS: The current ISGPS 4-tier and the simplified 3-tier classification models lacked sufficient discrimination in patients after RPD. We propose a revised 3-tier "2 mm" risk classification model for RPD with a robust discrimination, which requires further international validation with prospectively obtained data.

The application of 5E rehabilitation management mode in the nursing of patients with aortic dissection complicated by obstructive sleep apnea.

OBJECTIVE: This study was designed to explore the effect of 5E rehabilitation mode (encouragement, education, exercise, employment, and evaluation) in patients with aortic dissection (AD) complicated by obstructive sleep apnea (OSA). METHODS: Patients with Stanford type B AD (TBAD) complicated by OSA were admitted to Guangdong Provincial People's Hospital from January 2019 to December 2020. They were randomly divided into an experimental group and a control group. After discharge, patients in the control group were given routine nursing and follow-up education, whereas patients in the experimental group were given 5E rehabilitation management mode-based nursing and follow-up education. Upon the nursing intervention, the differences in polysomnography (PSG) parameters, medication adherence, quality of life, blood pressure, and heart rate of patients between the two groups were compared. Logistic regression analysis was performed to evaluate the risk factors for the occurrence of adverse aortic events. RESULTS: A total of 89 patients were enrolled, 49 in the experimental group and 40 in the control group. After the intervention, the control of heart rate, systolic blood pressure, medication adherence, PSG parameters, and quality of life scores in the experimental group were significantly better than those in the control group (P<0.05). The incidence of adverse aortic events including aortic rupture and progressive aortic dilation in the experimental group was significantly lower than that in the control group (P < 0.05). Logistic regression analysis revealed that acute TBAD [odds ratio (OR) = 15.069; 95%confidence interval (CI), 1.738-130.652; P=0.014], history of chronic kidney disease (OR=10.342; 95%CI, 1.056-101.287; P=0.045), and apnea hypopnea index (AHI) ≥ 30 (OR=2.880; 95%CI, 1.081-9.51; P=0.036) were adverse factors affecting adverse aortic events; while 5E rehabilitation management mode (OR=0.063; 95%CI, 0.008-0.513; P=0.010) was a favorable factor for occurrence of adverse aortic events. CONCLUSION: The findings suggest that continuous nursing based on information carrier 5E rehabilitation management significantly enhanced medication adherence, improved patients' overall quality of life, and decreased the incidence of adverse aortic events in patients TBAD patients and OSA.

Structural Characterization, and Antioxidant, Hypoglycemic and Immunomodulatory Activity of Exopolysaccharide from Sanghuangporus sanghuang JM-1.

Sanghuang as a medicinal fungus in China has a history of more than 2000 years, and is known as the "forest gold". Most notably, the polysaccharides of Sanghuangporus sp. have attracted widespread attention due to their significant bioactivity in recent years. At present, extensive studies are being carried out on the extraction methods, structural characterization, and activity evaluation of polysaccharides. Here, we aimed to evaluate the structure and bioactivity of LEPS-1, an exopolysaccharide derived from the S. sanghuang JM-1 strain. The structure was elucidated by chromatography/spectral methods and hydrolyzation, and the solubility, the antioxidant activity, hypoglycemic activity and immunomodulatory activity were investigated. Results showed that LEPS-1 contained a →2)-α-Manp(1→6)-α-Galp(1→[2)-α-Manp(1→]n→2,6)-α-Manp(1→6,2)-α-Manp(1→3)-α-Manp(1→ backbone substituted at the O-6 and O-2 positions with side chains. These two branching fragments were ß-Manp(1→. The molecular weight of LEPS-1 is 36.131 kDa. The results of biological activity analysis suggested that LEPS-1 was easily soluble in water, with reducing capability and DPPH radical scavenging capability. Furthermore, the IC50 values of LEPS-1 against α-amylase and α-glucosidase were 0.96 mg/mL and 1.92 mg/mL. LEPS-1 stimulated RAW264.7 cells to release NO, TNF-α and IL-6 with no cytotoxicity, showing potent potential for immunomodulatory activity. These findings describe a potential natural exopolysaccharide with medicinal value and a basis for the development of S. sanghuang exopolysaccharides.

Identification of an antigen-presenting cells/T/NK cells-related gene signature to predict prognosis and CTSL to predict immunotherapeutic response for lung adenocarcinoma: an integrated analysis of bulk and single-cell RNA sequencing.

BACKGROUND: Antigen-presenting cells (APC)/T/NK cells are key immune cells that play crucial roles in fighting against malignancies including lung adenocarcinoma (LUAD). In this study, we aimed to identify an APC/T/NK cells-related gene signature (ATNKGS) and potential immune cell-related genes (IRGs) to realize risk stratification, prognosis, and immunotherapeutic response prediction for LUAD patients. METHODS: Based on the univariate Cox regression and the LASSO Cox regression results of 196 APC/T/NK cells-related genes collected from three pathways in the KEGG database, we determined the final genes and established the ATNKGS-related risk model. The single-cell RNA sequencing data were applied for key IRGs identification and investigate their value in immunotherapeutic response prediction. Several GEO datasets and an external immunotherapy cohort from Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, were applied for validation. RESULTS: In this study, nine independent public datasets including 1108 patients were enrolled. An ATNKGS containing 16 genes for predicting overall survival of LUAD patients was constructed with robust prognostic capability. The ATNKGS high risk group was related to significantly worse OS outcomes than those in the low-risk group, which were verified in TCGA and four GEO datatsets. A nomogram combining the ATNKGS risk score with clinical TNM stage achieved the optimal prediction performance. The single-cell RNA sequencing analysis revealed CTSL as an IRG of macrophage and monocyte. Moreover, though CTSL was an indicator for poor prognosis of LUAD patients, CTSL high expression group was associated with higher ESTIMATEScore, immune checkpoints expression, and lower TIDE score. Several immunotherapeutic cohorts have confirmed the response-predicting significance of CTSL in patients receiving immune checkpoint inhibitor (ICI) treatment. CONCLUSIONS: Our study provided an insight into the significant role of APC/T/NK cells-related genes in survival risk stratification and CTSL in response prediction of immunotherapy in patients with LUAD.

Incidence, survival comparison, and novel prognostic evaluation approaches for stage iii-iv pulmonary large cell neuroendocrine carcinoma and small cell lung cancer.

BACKGROUND: Pulmonary large cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer (SCLC) are two types of high-grade neuroendocrine carcinomas of the lung with poor prognosis. LCNEC has not been thoroughly studied due to its rarity, data are also lacking regarding the survival comparison and prognosis analysis of patients with locally advanced or metastatic LCNEC and SCLC. METHODS: Data of patients with LCNEC, SCLC, and other NSCLC who were diagnosed from 1975 to 2019 were extracted from the Surveillance, Epidemiology and End Results (SEER) database to estimate incidence. Those in stage III-IV and being diagnosed from 2010 to 2015 were utilized further to investigate their clinical characteristics and prognosis. Propensity score matching (PSM) analyses at a ratio of 1:2 was used to compare their survival outcomes. Nomograms of LCNEC and SCLC were established with internal validation, and the nomogram of SCLC was externally validated by 349 patients diagnosed in Cancer hospital, Chinese Academy of Medical Sciences & Peking Union Medical College from January 1, 2012 to December 31, 2018. RESULTS: The incidence of LCNEC has been increasing in recent decades, meanwhile that of SCLC and other types of NSCLC were decreasing. A total of 91,635 lung cancer patients, including 785 with LCNEC, 15,776 with SCLC, and 75,074 with other NSCLC were enrolled for further analysis. The survival of stage III-IV LCNEC resembles that of SCLC, and significantly worse than other types of NSCLC before and after PSM analysis. In pretreatment prognostic analysis, age, T stage, N stage, M stage, bone metastasis, liver metastasis, and brain metastasis were found to be associated with the survival of both LCNEC and SCLC, besides sex, bilaterality, and lung metastasis were additional prognostic factors for SCLC. Two nomograms and convenient online tools respectively for LCNEC and SCLC were established accordingly with favorable predicting accuracy of < 1-year, < 2-year, < 3-year survival probabilities. In external validation of the SCLC nomogram with a Chinese cohort, the AUCs of 1-year, 2-year and 3-year ROC were 0.652, 0.669, and 0.750, respectively. All the results of 1-, 2-, 3- year variable-dependent ROC curves verified the superior prognostic value of our nomograms for LCNEC and SCLC over the traditional T/N/M staging system. CONCLUSIONS: Based on large sample-based cohort, we compared the epidemiological trends and survival outcomes between locally advanced or metastatic LCNEC, SCLC, and other NSCLC. Furthermore, two prognostic evaluation approaches respectively for LCNEC and SCLC might present as practical tools for clinicians to predict the survival outcome of these patients and facilitate risk stratification.

Prognostic significance of baseline neutrophil-lymphocyte ratio in patients with non-small-cell lung cancer: a pooled analysis of open phase III clinical trial data.

Aim: This study aimed to assess survival and hematological prognostic indicators of patients with non-small-cell lung cancer (NSCLC). Material & methods: Through the Project Data Sphere portal, two phase III clinical trial datasets were downloaded to analyze survival outcomes and related risk factors. Results: The median progression-free survival and overall survival of 756 patients with stage III-IV NSCLC were 6.2 and 14.2 months, respectively. In multivariate Cox analysis, high baseline neutrophil-lymphocyte ratio (NLR; ≥3.8) was associated with worse progression-free survival (hazard ratio: 1.37; p = 0.0004) and overall survival (hazard ratio: 1.65; p < 0.0001). In addition, it exerted an unfavorable impact on survival across multiple subgroups. Conclusions: NLR, a powerful inflammatory and immunologic indicator, is an independent prognostic indicator in patients with advanced NSCLC.

Effects of a new fermented soya bean meal on growth performance, serum biochemistry profile, intestinal immune status and digestive enzyme activities in piglets.

BACKGROUND: Fermented soya bean meal (FSBM) is believed to have improved nutritional qualities compared with soya bean meal (SBM) and is also cheaper than soya protein concentration (SPC) and fish meal (FM). Therefore, the present study was conducted to compare the effects of FSBM replacing SBM, SPC and FM in diets on growth performance, serum biochemistry profile, short-chain fatty acid concentrations in digesta, intestinal mucosal enzyme activities, intestinal proinflammatory cytokine concentrations and morphology in weaned piglets. One hundred and twenty 28-day-old piglets (Duroc × Landrace × Yorkshire, body weight: 6.73 ± 1.14 kg) were randomly allocated to four treatment diets (six replicate pens with five piglets per pen) containing SBM, SPC, FM or FSBM as the protein source, respectively. RESULTS: Dietary FSBM supplementation improved average daily gain (p < 0.05), gain to feed ratio (p < 0.05), and digestibility of dry matter, gross energy, crude protein and organic matter (p < 0.05) in pigs compared with those fed SBM during 0-14 days and reduced diarrhoea rate (p < 0.05) compared with those fed SBM and FM during 0-14 days. Moreover, pigs fed FBSM had greater IgA and IgM contents and antioxidase activities than those provided SBM and SPC on day 14. In addition, the butyrate concentration in the cecum of pigs fed FSBM was greater than those fed the other diets (p < 0.05), and the trypsin activity in duodenum and jejunum of pigs provided FSBM was greater than those fed SBM (p < 0.05). Moreover, higher villus height (p < 0.05) and villus height to crypt depth ratio (p < 0.05) and lower crypt depth (p < 0.05) in the duodenum of pigs fed FSBM were observed, and pigs fed FSBM had a lower (p < 0.05) TNF-α concentration in jejunum compared with those fed SBM. CONCLUSIONS: In conclusion, dietary FSBM supplementation to replace SBM, SPC and FM could improve piglets' growth performance, intestinal health and immune function.

Carboplatin versus cisplatin in combination with etoposide in the first-line treatment of small cell lung cancer: a pooled analysis.

BACKGROUND: Extensive-stage small cell lung cancer (ES-SCLC) is an aggressive disease with poor survival, and platinum-etoposide chemotherapy is indicated as the mainstay of treatment. In this study, we compared the efficacy and safety between the cisplatin plus etoposide (EP) and carboplatin plus etoposide (EC) regimens. METHODS: A total of 1305 patients with previously untreated ES-SCLC were included in this study. Data from five trials were collected from the public database Project Data Sphere. Survival analysis and adverse events (AEs) analysis were conducted. RESULTS: Of the 1305 patients, 800 received the EC regimen whereas 505 received the EP regimen as their front-line treatment. Overall, the median progression-free survival (PFS) and the median overall survival (OS) were 172 and 289 days, respectively. The EP and EC treatment groups did not have significantly different PFS or OS. After adjusting for age, sex, body mass index (BMI) and Eastern Cooperative Oncology Group (ECOG) performance status (PS), the EP regimen was independently associated with better PFS (hazard ratio [HR] = 0.76, 95% CI = 0.63-0.92, p = 0.0041) and OS (HR = 0.79, 95% CI = 0.64-0.97, p = 0.0220) among patients who were overweight and obese (BMI ≥ 25 kg/m2). In the safety analysis, patients who received the EC treatment experienced significantly more grade ≥ 3 AEs (n = 599, 74.9%) than those who received the EP treatment (n = 337, 66.7%; p = 0.002). Furthermore, the EC regimen was associated with a higher risk of grade 3-4 neutropaenia (p = 0.001), thrombocytopaenia (p < 0.001) and hyponatraemia (p = 0.036), whereas the EP regimen was associated with a higher risk of grade 3-4 vomiting (p = 0.021). CONCLUSIONS: In summary, this study presented the efficacy and safety of the EC and EP regimens in patients with ES-SCLC in the first-line setting. Patients who are overweight and obese benefit more from the EP regimen than EC regimen. Approaches to define the optimal chemotherapy regimen in different BMI subgroups are needed.

Tobacco Industry Marketing Exposure and Commercial Tobacco Product Use Disparities among American Indians and Alaska Natives.

Background: Non-Hispanic American Indians and Alaska Natives (NH AI/AN) have the highest commercial tobacco use (CTU) among U.S. racial/ethnic groups. Tobacco marketing is a risk factor, however few studies examine it among NH AI/AN. Objective: We identified prevalence of tobacco industry marketing exposure and correlates of CTU among NH AI/AN compared to other racial/ethnic groups. Methods: Data were from wave 1 (2013-2014; N = 32,320) of the Population Assessment of Tobacco and Health Study, analyzing self-reported exposure to tobacco ads from stores, tobacco package displays, direct mail and email marketing. Correlates of CTU were identified and interactions between racial/ethnic groups and tobacco marketing were assessed. Results: NH AI/AN (n = 955) had a higher prevalence of exposure to retail tobacco ads (64.5% vs 59.3%; p < 0.05), mail (20.2% vs.14.3%; p < 0.001) and email (17.0% vs.10.6%; p < 0.001) marketing than NH Whites (n = 19,297). Adjusting for tobacco use and related risk factors, exposure to email marketing remained higher among NH AI/AN than NH Whites. Interactions between racial/ethnic groups and marketing exposures on CTU were nonsignificant. CTU was higher among NH AI/AN than NH Whites and among adults who reported exposure to tobacco ads, mail, and email marketing. Conclusions/importance: There is higher tobacco marketing exposure in stores and via mail for NH AI/AN. Email marketing exposure was higher, even after controlling for tobacco-related risk factors. The tobacco industry may be targeting NH AI/AN through emails, which include coupons and other marketing promotions. Culturally relevant strategies that counter-act tobacco industry direct marketing tactics are needed to reduce disparities in this population.

Cigarette Constituent Health Communications for Smokers: Impact of Chemical, Imagery, and Source.

INTRODUCTION: Communication campaigns are incorporating tobacco constituent messaging to reach smokers, yet there is a dearth of research on how such messages should be constructed or will be received by smokers. METHODS: In a 2 × 2 × 2 experiment, we manipulated three cigarette constituent message components: (1) the toxic constituent of tobacco (arsenic vs. lead) with a corresponding health effect, (2) the presence or absence of an evocative image, and (3) the source of the message (FDA vs. no source). We recruited smokers (N = 1669, 55.4% women) via an online platform and randomized them to one of the eight message conditions. Participants viewed the message and rated its believability and perceived effectiveness, the credibility of the message source, and action expectancies (ie, likelihood of seeking additional information and help with quitting as a result of seeing the message). RESULTS: We found significant main effects of image, constituent, and source on outcomes. The use of arsenic as the constituent, the presence of an evocative image, and the FDA as the source increased the believability, source credibility, and perceived effectiveness of the tobacco constituent health message. CONCLUSIONS: Multiple elements of a constituent message, including type of constituent, imagery, and message source, impact their reception among smokers. Specifically, communication campaigns targeting smokers that utilize arsenic as the tobacco constituent, visual imagery, and the FDA logo may be particularly effective in changing key outcomes that are associated with subsequent attitude and behavioral changes. IMPLICATIONS: This article describes how components of communication campaigns about cigarette constituents are perceived. Multiple elements of a tobacco constituent message, including type of constituent, image, and message source may influence the reception of messages among current smokers. Communication campaigns targeting smokers that utilize arsenic as the tobacco constituent, visual imagery, and the FDA logo may be particularly effective in changing key outcomes among smokers. The effects of such campaigns should be examined, as well as the mechanisms through which such campaigns affect change.

Tobacco Advertisement Liking, Vulnerability Factors, and Tobacco Use Among Young Adults.

INTRODUCTION: Young adulthood (aged 18-24) is a crucial period in the development of long-term tobacco use patterns. Tobacco advertising and promotion lead to the initiation and continuation of smoking among young adults. We examined whether vulnerability factors moderated the association between tobacco advertisement liking and tobacco use in the United States. METHODS: Analyses were conducted among 9109 US young adults in the nationally representative Population Assessment of Tobacco and Health (PATH) Study wave 1 (2013-14). Participants viewed 20 randomly selected sets of tobacco advertisements (five each for cigarettes, e-cigarettes, cigars, and smokeless tobacco) and indicated whether they liked each ad. The outcome variables were past 30-day cigarette, e-cigarette, cigar, and smokeless tobacco use. Covariates included tobacco advertisement liking, age, sex, race or ethnicity, sexual orientation, education, poverty level, military service, and internalizing and externalizing mental health symptoms. RESULTS: Liking tobacco advertisements was associated with tobacco use, and this association was particularly strong among those with lower educational attainment (cigarettes, cigars) and living below the poverty level (e-cigarettes, smokeless tobacco). CONCLUSIONS: The association between tobacco advertisement liking and tobacco use was stronger among young adults with lower educational attainment and those living below the poverty level. Policies that restrict advertising exposure and promote counter-marketing messages in this population could reduce their risk. IMPLICATIONS: This study shows that liking tobacco advertisements is associated with current tobacco use among young adults, with stronger associations for vulnerable young adults (ie, lower education levels and living below the poverty level). Findings suggest a need for counter-marketing messages, policies that restrict advertising exposure, and educational interventions such as health and media literacy interventions to address the negative influences of tobacco advertisements, especially among young adults with a high school education or less and those living below the poverty level.

Believability of Cigarette Warnings About Addiction: National Experiments of Adolescents and Adults.

Introduction: We conducted two experiments to examine the believability of three addiction-focused cigarette warnings and the influence of message source on believability among adolescents and adults in the United States. Methods: Experimental data were collected using national phone surveys of adolescents (age 13-17; n = 1125; response rate, 66%) and adults (age 18+; n = 5014; response rate, 42%). We assessed the believability of three cigarette warnings about addiction attributed to four message sources (Food and Drug Administration [FDA], Surgeon General, Centers for Disease Control and Prevention [CDC], no source). Results: The majority of adolescents and adults reported the three cigarette warnings were very believable (49%-81% for adolescents; 47%-76% for adults). We found four to five times higher odds of adolescents believing a warning that cigarettes are addictive (warning 1) or that nicotine was an addictive chemical (warning 2) compared to a warning that differentiated the addictive risks of menthol versus traditional cigarettes (warning 3), warning 1 adjusted odds ratio (aOR): 4.53, 95% confidence interval (CI): 3.10, 6.63; warning 2 aOR: 3.87, 95% CI: 2.70, 5.50. Similarly, we found three to five times higher odds of adults (including current smokers) believing the same warnings, warning 1 aOR: 3.74, 95% CI: 2.82, 4.95; warning 2 aOR: 3.24, 95% CI: 2.45, 4.28. Message source had no overall impact on the believability of warnings for either population. Conclusions: Our findings support the implementation of FDA's required warnings that cigarettes are addictive and that nicotine is an addictive chemical. These believable warnings may deter adolescents from initiating smoking and encourage adults to quit smoking. Implications: This article describes, for the first time, the believability of different cigarette warnings about addiction. We now know that the majority of adolescents and adults believe cigarette warnings that highlight cigarettes as addictive and that nicotine is an addictive chemical in tobacco. However, a warning that highlighted the relative risk of addiction for menthol cigarettes compared to traditional cigarettes was not as believable among either population. Our findings support the implementation of FDA's required warnings that cigarettes are addictive and that nicotine is an addictive chemical that may deter adolescents from initiating smoking and encourage adults to quit smoking.

Adolescent tobacco coupon receipt, vulnerability characteristics and subsequent tobacco use: analysis of PATH Study, Waves 1 and 2.

OBJECTIVES: We examine adolescent receipt of tobacco coupons and subsequent tobacco use. METHODS: Data were from the Population Assessment of Tobacco and Health (PATH) Study (2013-2015). We identified correlates of coupon receipt at Wave 1 (youth sample age 12-17 ; n = 13 651) including demographics, additional vulnerability factors that may place youth at risk of tobacco use and correlates of coupon receipt by channel. We examined associations of Wave 1 coupon receipt with Wave 2 tobacco use using weighted multivariable models. RESULTS: Overall, 7.6% of US youth received tobacco coupons in the 6 months before Wave 1. Coupon recipients were more likely to be women, living outside urban areas, living with a tobacco user, current and former (vs never) tobacco users, having high internalising mental health symptoms and having a favourite tobacco advertisement. Coupons were received primarily through direct mail (56%), product packs (28%) and online (25%). Never tobacco users at Wave 1 who received coupons were more likely to be ever users at Wave 2 (adjusted OR (aOR)=1.42; 95% CI 1.06 to 1.91). Coupon recipients were more likely to use a new tobacco product between waves (aOR=1.67; 95% CI 1.18 to 2.36) and report past 30-day tobacco use at Wave 2 (aOR=1.81; 95% CI 1.31 to 2.49). CONCLUSIONS: One in 13 US youth (7.6%) received coupons. Vulnerable youth had the greatest odds of coupon receipt. Coupon recipients had greater odds of tobacco use among never users, trying a new tobacco product and current use. Coupon bans, limits on youth coupon exposure, stronger age verification, pack inserts or restricting coupon redemption may help reduce tobacco use among adolescents, particularly for those at greatest risk.

Which types of anti-smoking television advertisements work better in Taiwan?

Research in high income countries suggests that anti-smoking television advertisements with emotionally evocative graphic messages or personal testimonials that depict serious consequences from smoking are the most effective. Research to determine the most effective smoking cessation messages for low- and middle-income countries is needed to inform campaign development in these countries. Fifty-four male Taiwanese smokers, aged 18-34, rated advertisements and participated in a focus group to evaluate eight antismoking television advertisements with contrasting messaging strategies. Participants individually evaluated advertisements, after which they participated in a semi-structured focus group discussion (10 groups, 2-9 smokers per group). One week after this session, participants were called to assess advertisement recall. Both quantitative and qualitative data indicated that highly emotional testimonial ads that featured a graphic portrayal of personal suffering from the consequences of smoking and visceral graphic ads were more effective. The ad on tobacco industry denormalization that focuses on the responsibility of the industry for smoking-related harms was considered ineffective because smokers perceived it as having little personal relevance. Humorous advertisements were evaluated as the least effective because they lacked strong emotional content linked to smoking consequences. Qualitative results suggest that advertisement characteristics are more important than the demographic characteristics of people featured in advertisements. Study findings provide preliminary evidence that testimonial ads that involve graphic and emotionally evocative portrayals of smoking-attributed diseases and visceral graphic ads may have the greater potential to motivate Taiwanese smokers to quit smoking.

The Dendritic Cell Major Histocompatibility Complex II (MHC II) Peptidome Derives from a Variety of Processing Pathways and Includes Peptides with a Broad Spectrum of HLA-DM Sensitivity.

The repertoire of peptides displayed in vivo by MHC II molecules derives from a wide spectrum of proteins produced by different cell types. Although intracellular endosomal processing in dendritic cells and B cells has been characterized for a few antigens, the overall range of processing pathways responsible for generating the MHC II peptidome are currently unclear. To determine the contribution of non-endosomal processing pathways, we eluted and sequenced over 3000 HLA-DR1-bound peptides presented in vivo by dendritic cells. The processing enzymes were identified by reference to a database of experimentally determined cleavage sites and experimentally validated for four epitopes derived from complement 3, collagen II, thymosin ß4, and gelsolin. We determined that self-antigens processed by tissue-specific proteases, including complement, matrix metalloproteases, caspases, and granzymes, and carried by lymph, contribute significantly to the MHC II self-peptidome presented by conventional dendritic cells in vivo. Additionally, the presented peptides exhibited a wide spectrum of binding affinity and HLA-DM susceptibility. The results indicate that the HLA-DR1-restricted self-peptidome presented under physiological conditions derives from a variety of processing pathways. Non-endosomal processing enzymes add to the number of epitopes cleaved by cathepsins, altogether generating a wider peptide repertoire. Taken together with HLA-DM-dependent and-independent loading pathways, this ensures that a broad self-peptidome is presented by dendritic cells. This work brings attention to the role of "self-recognition" as a dynamic interaction between dendritic cells and the metabolic/catabolic activities ongoing in every parenchymal organ as part of tissue growth, remodeling, and physiological apoptosis.

Can brain impermeable BACE1 inhibitors serve as anti-CAA medicine?

BACKGROUND: Cerebral amyloid angiopathy (CAA) is characterized by the deposition of ß-amyloid peptides (Aß) in and surrounding the wall of microvasculature in the central nervous system, together with parenchymal amyloid plaques collectively referred to as cerebral amyloidosis, which occurs in the brain commonly among the elderly and more frequently in patients with Alzheimer's disease (AD). CAA is associated with vascular injury and may cause devastating neurological outcomes. No therapeutic approach is available for this lesion to date. MAIN BODY: ß-Secretase 1 (BACE1) is the enzyme initiating Aß production. Brain permeable BACE1 inhibitors targeting primarily at the parenchymal plaque pathology are currently evaluated in clinical trials. This article presents findings in support of a role of BACE1 elevation in the development of CAA, in addition to plaque pathogenesis. The rationale, feasibility, benefit and strategic issues for developing BACE1 inhibitors against CAA are discussed. Brain impermeable compounds are considered preferable as they might exhibit sufficient anti-CAA efficacy without causing significant neuronal/synaptic side effects. CONCLUSION: Early pharmacological intervention to the pathogenesis of CAA is expected to provide significant protection for cerebral vascular health and hence brain health. Brain impermeable BACE1 inhibitors should be optimized and tested as potential anti-CAA therapeutics.

Effects of Framing Proximal Benefits of Quitting and Motivation to Quit as a Query on Communications About Tobacco Constituents.

INTRODUCTION: Little is known on how to communicate messages on tobacco constituents to tobacco users. This study manipulated three elements of a message in the context of a theory-based communication campaign about tobacco constituents: (1) latency of response efficacy (how soon expected health benefits would accrue), (2) self-efficacy (confidence about quitting), and (3) interrogative cue ("Ready to be tobacco-free?"). METHODS: Smokers (N = 1669, 55.4% women) were recruited via an online platform, and were randomized to a 3 (Latency of response efficacy) × 2 (Self-efficacy) × 2 (Interrogative cue) factorial design. The dependent variables were believability, credibility, perceived effectiveness of the communication message, and action expectancies (likelihood of seeking additional information and help with quitting). RESULTS: Latency of response efficacy influenced believability, perceived effectiveness, credibility, and action expectancies. In each case, scores were higher when specific health benefits were said to accrue within 1 month, as compared to general health benefits occurring in a few hours. The interrogative cue had a marginal positive effect on perceived effectiveness. The self-efficacy manipulation had no reliable effects, and there were no significant interactions among conditions. CONCLUSIONS: Smokers appear less persuaded by a communication message on constituents where general health benefits accrue immediately (within a few hours) than specific benefits over a longer timeframe (1 month). Additionally, smokers appeared to be more persuaded by messages with an interrogative cue. Such findings may help design more effective communication campaigns on tobacco constituents to smokers. IMPLICATIONS: This paper describes, for the first time, how components of tobacco constituent messages are perceived. We now know that smokers appear to be less persuaded by communication messages where general health benefits accrue immediately (within a few hours) than specific benefits over a longer timeframe (1 month). Additionally, including an interrogative cue ("Ready to be tobacco free?") may make messages more effective, whereas the self-efficacy manipulation designed to increase confidence about quitting had no effect. While messages were universally impactful across smoker subpopulations, everyday smokers and smokers with less trust in the government may be less receptive to communication campaigns.