Higher Engagement Research Articles

Abstract CT117: A phase 1 study of D3S-001, a second-generation GDP-bound KRAS G12C inhibitor, as monotherapy in patients with KRAS G12C-mutated solid tumors

Abstract Background: D3S-001 is a second-generation (2G) GDP-bound KRAS G12C inhibitor (G12Ci). Its high covalent potency and rapid target engagement kinetics correlated with robust anti-tumor activity preclinically and translated into promising clinical activity in a phase 1 first-in-human trial (FIH). Here we report clinical data from D3S-001 FIH trial (NCT05410145). Methods: D3S-001 was administered as monotherapy to patients (pts) with KRAS G12C mutated advanced solid tumors at 6 planned dose levels (50-900mg QD) from 3 countries. The key objectives were safety, PK, antitumor activity, and ctDNA kinetics. Results: As of 6 Feb 2024, a total of 41 pts (25 non-small cell lung cancer [NSCLC], 12 colorectal cancer [CRC] and 4 pancreatic cancer [PDAC]) were dosed. Median follow-up was 5.1 months (m, range 0.2-15.4m) and 28 pts (68.3%) remain on-study treatment. No treatment-related DLT or deaths were observed. Treatment-related AEs (TRAE) of any grade occurred in 30 pts (73.2%). Of which, 6 (14.6%) were Grade 3 (no Grade 4 or higher). D3S-001 dose was modified in 11 pts (26.8%) due to TRAE, and no pts had dose discontinuation due to TRAE. PK analysis indicates dose/exposure linearity and terminal plasma T1/2 of ~11 hours. Of 37 pts with post-baseline tumor assessments, 33 were naïve to G12Ci and 4 were G12Ci pre-treated. In 33 G12Ci naïve pts, PRs were achieved in 25/33 overall population (75.8%, 95% CI 57.7, 88.9%), in 14/20 NSCLC pts (70.0%, 95% CI 45.7, 87.2%), in 7/9 CRC pts (77.8%, 95% CI 40.2, 96.1%), and in 4/4 PDAC pts (100.0%, 95%CI 39.6, 100.0%). CNS efficacy was observed in 2/6 NSCLC pts. Of all G12Ci naive pts (n=36), 6-month PFS rate is 69.1% (95% CI 46.3, 83.7%), but median PFS and DoR are not yet mature. Deeper tumor reductions were observed in 5 out of 9 G12Ci naïve pts after intra-subject dose escalation. All 4 G12Ci pre-treated pts (2 NSCLC, 2 CRC) showed stable disease at the first post-baseline assessment. Serial assessment of ctDNA showed significant declines in G12C VAF as early as on Day 8 of treatment. 600mg QD was selected as RP2D. Conclusions: D3S-001, a 2G G12Ci, is well tolerated and delivers promising anti-tumor activity in pts with NSCLC, CRC, and PDAC carrying KRAS G12C mutation across all dose levels in FIH trial. Citation Format: Byoung Chul Cho, Shun Lu, Myung Ah Lee, Zhengbo Song, John Park, Sun Min Lim, Ziming Li, Jun Zhao, Gary Richardson, Yanqiao Zhang, Jun Zhang, Anwen Liu, Cheng Chen, Jia Wang, Jingtao Lu, Haopeng Rui, Qian Chen, Hui Wang, Jing Zhang, Zhi Jian Chen, Tony Mok. A phase 1 study of D3S-001, a second-generation GDP-bound KRAS G12C inhibitor, as monotherapy in patients with KRAS G12C-mutated solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT117.

Synthesis and Evaluation of [64Cu]Cu-NOTA-HFn for PET Imaging of Transferrin Receptor 1 Expression in Nasopharyngeal Carcinoma.

As recurrent and metastatic nasopharyngeal carcinoma (NPC) is the most common cause of death among patients with NPC, there is an urgent clinical need for the development of precision diagnosis to guide personalized treatment. Recent emerging evidence substantiates the increased expression of transferrin receptor 1 (also known as cluster of differentiation 71, CD71) within tumor tissues and the inherent targeting capability of natural heavy-chain ferritin (HFn) toward CD71. This study aimed to synthesize and assess a radiotracer ([64Cu]Cu-NOTA-HFn) designed to target CD71 for positron emission tomography (PET) imaging in an NPC tumor-bearing mouse model. The entire radiolabeling process of [64Cu]Cu-NOTA-HFn was completed within 15 min with high yield (>98.5%) and high molar activity (72.96 ± 21.33 GBq/μmol). The in vitro solubility and stability experiments indicated that [64Cu]Cu-NOTA-HFn had a high water solubility (log P = -2.42 ± 0.52, n = 6) and good stability in phosphate-buffered saline (PBS) for up to 48 h. The cell saturation binding assay indicated that [64Cu]Cu-NOTA-HFn had a nanomolar affinity (Kd = 10.9 ± 6.1 nM) for CD71-overexpressing C666-1 cells. To test the target engagement in vivo, prolonged-time PET imaging was performed at 1, 6, 12, 24, and 36 h postinjection (p.i.) of [64Cu]Cu-NOTA-HFn to C666-1 NPC tumor-bearing mice. The C666-1 tumors could be visualized by [64Cu]Cu-NOTA-HFn and blocked by nonradiolabeled HFn. PET imaging quantitative analysis demonstrated that the uptake of [64Cu]Cu-NOTA-HFn in C666-1 tumors peaked at 6 h p.i. and the best radioactive tumor-to-muscle ratio was 10.53 ± 3.11 (n = 3). Ex vivo biodistribution assay at 6 h p.i. showed that the tumor uptakes were 1.43 ± 0.23%ID/g in the nonblock group and 0.92 ± 0.2%ID/g in the block group (n = 3, p < 0.05). Immunohistochemistry and immunofluorescence staining confirmed positive expression of CD71 and the uptake of HFn in C666-1 tumor tissues. In conclusion, our experiments demonstrated that [64Cu]Cu-NOTA-HFn possesses a very high target engagement for CD71-positive NPC tumors and provided a fundamental basis for further clinical translation.

Behavioral Activation Mobile App to Motivate Smokers to Quit: Feasibility and Pilot Randomized Controlled Trial.

Behavioral activation (BA) is an evidence-based treatment for depression that fosters engagement in values-based activities to increase access to positive reinforcement. Depressed mood has been shown to hinder smoking cessation. This study determined the feasibility and preliminary efficacy of a mobile app to motivate smokers to quit by using BA and integrating motivational messages to quit smoking. Adult smokers (N=56; mean age 34.5, SD 9.52 years) who were not ready to quit smoking within 30 days were recruited from advertisements and randomized to either 8 weeks of the BA app (set 2 values-based activities per week+motivational messages+feedback on changes in smoking, mood, and values-based activities) or the control group (no app; received resources for quitting smoking). All participants completed the baseline and end-of-treatment web-based questionnaires. Controls also completed weekly web-based assessments, and BA app participants completed assessments through the app. There were no dropouts and only 2 participants in each condition did not complete the end-of-treatment questionnaire. The results demonstrated that it is feasible to recruit smokers who are unmotivated to quit into a smoking cessation induction trial: 86% (57/66) of eligible participants were randomized (BA app: n=27; control: n=29). Participants reported high levels of satisfaction: 80% (20/25) of participants said they would recommend the BA app, there were moderate-to-high scores on the Mobile App Rating Scale, and 88% (22/25) of participants rated the app 3 stars or higher (out of 5). There were high levels of BA app engagement: 96% (26/27) of participants planned activities, and 67% (18/27) of participants planned 7 or more activities. High engagement was found even among those who were at the highest risk for continued smoking (low motivation to quit, low confidence to quit, and high negative affect). The results provided support for the hypothesized relationships between BA constructs: greater pleasant activity completion was associated with greater positive affect (b=0.37, SE 0.21; 95% CI -0.05 to 0.79; P=.08), and greater positive affect tended to predict fewer cigarettes smoked the next day (b=-0.19, SE 0.10; 95% CI -0.39 to 0.01; P=.06). Additionally, a greater number of activities planned was associated with lower negative affect (b=-0.26, SE 0.15; 95% CI -0.55 to 0.04; P=.09). Overall, 16% (4/25) of BA app participants set a quit date versus 4% (1/27) among controls, and there were promising (but not significant) trends for motivation and confidence to quit. The findings suggest that a mobile app intervention can be made appealing to smokers who are unmotivated to quit by focusing on aspects most important to them, such as mood management. This theory-based intervention has shown some initial support for the underlying theoretical constructs, and further efficacy testing is warranted in a fully powered trial.

Voucher incentives to improve viral suppression among HIV-positive people who inject drugs and men who have sex with men in India: a cluster randomised trial

Progress on HIV treatment outcomes for people who inject drugs and men who have sex with men in India has been slow compared with that in other populations. We assessed whether HIV treatment incentives would improve outcomes among these groups. We did a matched-pair, cluster randomised trial in 16 sites (eight for people who inject drugs and eight for men who have sex with men) across 15 cities in India. We recruited cohorts of HIV-positive people who inject drugs or men who have sex with men who were antiretroviral therapy (ART)-naive or had less than 12 months of ART exposure. We randomised sites to provide incentives or usual care. At intervention sites, we provided incentive vouchers, which could be exchanged for food or household goods, for attending motivational interviewing sessions and timely appointments at government ART clinics. An ART-naive participant meeting all targets could earn the equivalent to 14 days' wages over 12 months. The primary outcome was survival with viral suppression at 12 months. We used an intention-to-treat analytic approach appropriate for matched-pair cluster randomised trials, adjusting for baseline viral suppression. This study was registered with ClinicalTrials.gov, NCT02969915, and is complete. Between Oct 30, 2017, and Oct 12, 2018, we recruited 1200 people who inject drugs and 1114 men who have sex with men living with HIV. Among people who inject drugs, 154 (12·8%) identified as female gender and 1046 (87·2%) as male. The site median percentage of participants earning one or more incentives was 96·1% (IQR 93·7-98·1). At 12 months, HIV viral suppression was 31·9% (n=383) among people who inject drugs and 52·1% (n=580) among men who have sex with men. The incentive intervention was not associated with significantly improved survival with viral suppression compared with usual care (adjusted prevalence difference 9·6 percentage points, 95% CI -4·4 to 23·7). Despite high intervention engagement, incentives did not improve survival with viral suppression among people who inject drugs and men who have sex with men living with HIV in India. The poor outcomes overall underscore the need for innovative, multilevel approaches to engage marginalised people living with HIV in low-income and middle-income settings. US National Institutes of Health, Elton John AIDS Foundation.

Bi-directional association between outdoor or social activities and cognitive function: do the PM2.5 exposure catalyze the detrimental inactivity-poor cognition cycle?

BackgroundPrevious research has shown that lack of leisure activities, either outdoor or social activities, impedes cognitive function. However, the interrelationship between poor cognition and deficient activities is understudied. In addition, whether exposure to air pollution, such as PM2.5, can accelerate the detrimental ‘inactivity-poor cognition’ cycle, is worthy of investigation. MethodsWe used data from the 2008, 2011, 2014, and 2018 waves of the Chinese Longitudinal Healthy Longevity Survey (CLHLS). We assessed the frequency of outdoor or social activities at each wave. The cognitive function was examined using a China-Modified Mini-mental State Examination. We estimated the residential exposure to fine particular matter (PM2.5) via a satellite-based model. We applied cross-lagged panel (CLP) model to examine the bi-directional relationship between outdoor or social activities and cognitive function. We then examined the effect of PM2.5 exposure with sequent cognitive function and activities using generalized estimation equation (GEE) model. FindingsOverall, we observed significant bi-directional associations between outdoor or social activities and cognitive function. Participants with better cognitive function in the last wave were more likely to engage in outdoor or social activities in the following wave (outdoor activities: β = 0.37, 95% CI [0.27,0.48], P < 0.01; social activities: β = 0.05, 95% CI [0.02,0.09] P < 0.01). Meanwhile, higher engagement in outdoor or social activities in the last wave was associated with more favorable cognitive function in the following wave (outdoor activities: β = 0.06, 95% CI [0.03,0.09], P < 0.01; social activities: β = 0.10, 95% CI [0.03,0.18], P < 0.01). Notably, an increase in PM2.5 exposure during the preceding year was significantly associated with a declining cognitive function (β = −0.05, 95% CI [−0.08,−0.03], P < 0.01), outdoor activities (β = −0.02, 95% CI [−0.04, −0.01], P < 0.01) and social activities (β = −0.02, 95% CI [−0.02, −0.01], P < 0.01) in the current year; the lagged effects of the PM2.5 exposure in the past year of the last wave on activities and cognitive function of the following wave were also observed. InterpretationOur findings not only indicate the bi-directional links between the frequency of outdoor or social activities and cognitive function, but also report that PM2.5 exposure plays a role in catalyzing the detrimental inactivity-poor cognition cycle. Future research should investigate whether the policy-driven interventions, such as clean air policies, can break the unfavorable activity-cognition cycle, and thereby promoting health from the dual gains in leisure activities and cognition.

230 Assessing the Role of Youth Sports in Diabetes Prevention and Perceived Discrimination

OBJECTIVES/GOALS: Our study aims to 1) examine the link between engagement in CLR Academy and youth diabetes risk factors—physical activity, nutrition, mental health, and weight status; 2) examine CLR’s role in moderating the relationship between perceived discrimination and these risk factors. Includes a program evaluation of CLR &amp; interviews of members. METHODS/STUDY POPULATION: Youth-onset diabetes is rising in American minority communities. Youth sports programs like the Community Leadership Revolution (CLR) Academy in Washtenaw County, MI are emerging responses to this issue. CLR targets diabetes risk factors through team sports by promoting mindfulness and healthy habits. Employing a mixed-methods, pretest-posttest approach, our study focuses on how the frequency of engagement in CLR impacts CLR’s effect on youth’s diabetes risk factors. Considering the discrimination minority youth experience, we also aim to see if CLR potentially buffers the impact of perceived discrimination on diabetes risk factors. A posttest program evaluation of CLR will also include semi-structured interviews with CLR staff and participants. RESULTS/ANTICIPATED RESULTS: There is potential that youth with high engagement in CLR Academy may see enhanced benefits in managing diabetes risk factors compared to less active participants. This may be particularly true for youth experiencing high perceived discrimination, with potential marked improvements in mental health, like reduced anxiety and depression. Additionally, through a program evaluation and semi-structured interviews, our study aims to uncover the factors contributing to CLR’s success as a community-led intervention while also identifying areas for enhancement. Post-study, CLR will receive financial support to integrate these insights into their program, furthering their effectiveness in youth diabetes prevention and overall well-being. DISCUSSION/SIGNIFICANCE: This study may provide significant insights into the relationship between sports participation, diabetes risk factors, and perceived discrimination. The findings could help CLR improve its program and guide more effective diabetes prevention strategies in minority youth through other youth sports programs.

Heavy Study Investment in Indonesian College Students: Do Studyholism and Study Engagement Predict Academic Resilience?

Studyholism (SH) is a new potential clinical condition introduced in 2017 by Loscalzo and Giannini to refer to problematic overstudying, specifying that it might be associated with either high or low Study Engagement (SE). We aimed to analyze SH and SE’s predictive role on academic resilience. We gathered 609 Indonesian youths, and we performed a path analysis model. Among the main findings, SH predicts a lack of academic resilience, while SE predicts higher academic resilience. However, SH and SE do not predict time spent studying, and GPA is negatively (although weakly) predicted by SH only. Hence, we provided support for the critical role of SH and SE in predicting students’ academic success and for implementing preventive and clinical interventions to reduce SH and foster SE, given their impact on academic resilience, which, in turn, influences students’ well-being and academic success. Finally, we recommend future research on Studyholism in non-Western countries.

Visualizing crisis leadership: Prime ministers on Instagram during the COVID-19 pandemic

This study sheds light on how political leaders engage in visual meaning-making on social media during a major crisis. In addition, it explores which kinds of visual messages by political leaders on social media drive high popular engagement in times of crisis. The study employs content analysis, including automatic facial expression analysis, to investigate visual communication on the Instagram accounts of three Nordic prime ministers (PMs) during the critical initial wave of the COVID-19 pandemic. The analysis covers visual personalization, depicted individuals, national symbols and facial expressions. Furthermore, the study explores the visual elements within the posts that garnered the highest public engagement, as measured by the number of likes and comments. The findings indicate that the PMs primarily projected an image of professional, capable and credible crisis leadership through their visual content. However, the potential for leaders to convey compassion, empathy and authenticity through visual imagery is also evident, particularly exemplified by the Danish PM. The visual content that generated the most significant public engagement predominantly consisted of videos featuring the PMs in formal professional settings, directly addressing the audience about serious matters.

The Role of Peer Support and Patient Navigation for Empowerment in Breast Cancer Survivors: Implications for Community Cancer Control.

Community-based organizations (CBO) offer support, including patient navigation (PN), to women at-risk for (e.g., those with BRCA pathogenic variants) and surviving with breast cancer. However, the impacts of CBO efforts on survivors' empowerment (e.g., control, self-confidence, knowledge/skills, coping) are largely unknown. As part of a quality improvement initiative (N=2,247) focused on PN, care satisfaction, peer support, and quality of life (QoL), we conducted a secondary analysis of a CBO care delivery model on women's empowerment. Under CBO-led cancer control, empowerment was high: most survivors felt confident in (71.2%) and knowledgeable about (66.4%) managing their care. Perceived care quality was also high (91%): it was recommendable to others (93.9%), helpful (92.7%), informative (92.6%), timely (92.2%), reliable (91.5%), supportive (91.3%), and effective (88.7%). Regarding CBO care satisfaction, survivors felt supported by abundant resources (92.8%) and programs (91.2%), understood (92.0%), and helped (91.6%). Peer support (offered to >25%) demonstrated high engagement (>85%). Regarding QoL, 25.3% were in fair/poor health and 25.6% endorsed frequent mental distress (M=7.2 physically unhealthy days, M=7.8 mentally unhealthy days, and M=6.4 activity-limited days within the past month). Disparities in empowerment were observed as a function of survivors' QoL: lowest among those with more frequent mental distress (t=-2.13, p<.05), mentally unhealthy days (r=-.083, p<.05), and activity-limited days (r=-.058, p<.05)). These burdens may have influenced survivors' feelings of empowerment, especially among those without peer support (t=3.77, p<.001), who downgraded the quality of PN (t=.60, p<.01), and were least satisfied with CBO cancer control (t=.57, p<.01). In a multivariable model adjusting for mental distress, both perceived PN quality (B=.16, SE=.01, p<.001) and peer support (B=.24, SE=.13, p=.05) were positively associated with empowerment: survivors who rated their PN higher, and offered peer support, felt more empowered. CBO cancer control can uplift most survivors: addressing socially determined disparities, through programs such as peer support, may enhance their effectiveness and particularly among those with poor mental health.

تعليم اللغة العربية بإستخدام طريقة لعبة البطاقة فى المدرسة الإبتدائية نور الجديد كروجيل مدينة بروبولنجو

This research explores the implementation of the Matching Card card game method in teaching Arabic at Madrasah Ibtidaiyah Nurul Jadid, Krucil, Probolinggo Regency, with the aim of improving students' Arabic language skills through an interactive and fun approach. This research method uses a descriptive qualitative approach with data collection in the form of observations and interviews regarding the Arabic language learning process in class 3. Researchers use Matching Cards containing pictures of vocabulary, phrases or sentences in Arabic, and their translations in Indonesian, in class. The results of the research show that the Matching Card card game method is effective in increasing students' understanding of Arabic vocabulary and structure. Students demonstrated high engagement and significant improvement in the ability to use Arabic in communicative situations. This method also increases students' learning motivation, creates a fun learning environment, and strengthens social interaction between students in the classroom.

Impact of Online Learning Platforms on Student Engagement in India

Purpose: The aim of the study was to investigate the impact of online learning platforms on student engagement in India.&#x0D; Methodology: This study adopted a desk methodology. A desk study research design is commonly known as secondary data collection. This is basically collecting data from existing resources preferably because of its low cost advantage as compared to a field research. Our current study looked into already published studies and reports as the data was easily accessed through online journals and libraries.&#x0D; Findings: Research on online learning platforms in India highlights increased access to education, particularly in remote areas. Students show high engagement due to platform convenience and interactive features. Challenges like the digital divide impact equitable access and engagement. Despite these challenges, online platforms have the potential to revolutionize education in India. Addressing accessibility barriers is crucial for maximizing engagement and ensuring inclusive learning.&#x0D; Unique Contribution to Theory, Practice and Policy: Social presence theory, cognitive load theory &amp; technology acceptance model (TAM) effect may be used to anchor future studies on the impact of online learning platforms on student engagement in India. Pedagogical Innovation and Teacher Training - Educational institutions in India should prioritize pedagogical innovation and invest in teacher training programs focused on effective online instruction. Digital Infrastructure and Accessibility - Policymakers must address infrastructural challenges and promote equitable access to digital resources and connectivity across all regions of India.

Differences in the Role of Psychological Well-Being and Subjective Well-Being in Predicting Work Engagement

Employees with high Work Engagement (WE) are believed to be more reliable in achieving organizational goals. This research aims to determine the differences in the role of well-being with the concepts of hedonic and eudemonic in predicting WE. The subjects of this research consisted of 327 people, who were analyzed in 3 stages, namely 110 people who were analyzed in stage-1, 217 people who were analyzed in stage-2, and all research subjects were analyzed in stage-3. All data for this research were collected using the WE scale, PWB scale, SWFL scale, and PANAS, which have a Chronbach alpha reliability coefficient of .773 respectively; .831; .627; 747; 744. In stage-1 research analysis, SWB and PWB show more of just one component, whereas in stage-2 and stage-3 research analysis, they are more likely to be seen as two different factors in predicting WE. The results of the stepwise model multiple regression statistical technique analysis concluded that the regression coefficient on the influence of SWB and PWB on WE from the three analyses stated that PWB was stronger than SWB in predicting WE. Thus, it can be interpreted that to predict WE the Well-Being concept with the eudemonic concept is greater than using well-being with the hedonic concept.

TransfOrming Transnational intErcultural sensitivity for Midwifery students through an inclusive mobility model: A mixed-method evaluation of the TOTEMM project

BackgroundContemporary midwifery curricula require that student midwives have insight and understanding of global health practice and intercultural sensitivity. The current mobility model excludes large numbers of students from engaging in transnational learning. Objectives1) to evaluate midwifery students' experiences of blended mobility; 2) to investigate if the combination of virtual and physical mobility activities supported development of intercultural sensitivity and soft skills. DesignMulti-centre mixed-methods study. SettingsFour European Higher Education Institutions located in England, Italy, Estonia and The Netherlands. ParticipantsSixty-four midwifery students studying in one of the four partner institutions selected as study sites and who participated in the TOTEMM blended mobility scheme took part in the evaluation. MethodsData were collected through two online surveys, face-to-face focus groups and learning analytics. Descriptive summary statistical analysis of survey data was undertaken. Focus group discussions were subjected to thematic analysis. Findings from the quantitative survey and qualitative focus groups were merged using a convergent mixed methods approach. Learning Analytics were interpreted as complementary to the above components, to further triangulate the findings. ResultsBoth virtual and physical components were evaluated positively by students, with high engagement confirmed by learning analytics. A statistically significant increase in the mean of the Total Intercultural Sensitivity Scale score was seen between the pre- and post-mobility surveys, indicating participation in the TOTEMM mobility model was associated with enhanced intercultural sensitivity. Positive effects on confidence, open-mindedness, empathy, interaction and non-judgment were shared by participants. ConclusionsTOTEMM is an innovative inclusive approach to enable a diverse student group to benefit from transnational learning, including the development of intercultural sensitivity. The TOTEMM blended mobility model has potential for integration into future midwifery curricula and programmes in the four partner settings involved in TOTEMM and utility for the wider European context.

The Efficacy of the SinHumo App Combined With a Psychological Treatment to Quit Smoking: A Randomized Clinical Trial.

This study assessed the efficacy of the SinHumo App combined with a cognitive-behavioral smoking cessation treatment on 12-month follow-up abstinence, compared with the same smoking cessation treatment and a control App. A sample of 288 treatment-seeking people who smoke were randomized: SinHumo App plus smoking cessation treatment (n = 140) and control App plus smoking cessation treatment (n = 148). The primary outcome was 7-day point prevalence abstinence (PPA) at the 12-month follow-up. Secondary outcomes were abstinence rates at the end of the intervention and 3- and 6-month follow-ups, cigarette per day (CPD) reduction over the 12-month follow-up, intervention engagement, and satisfaction. Intention-to-treat analyses showed nonsignificant differences in self-reported 7-day PPA at the 12-month follow-up (37.1 and 42.6%, respectively; OR = 0.80). No significant differences were found in abstinence at the end of the treatment (68.6 vs. 62.8%) nor on 7-day PPA at 3- (35.7 vs. 45.9%) and 6-month (35.0 vs. 41.2%) follow-up. Complete case and multiple imputation analyses yielded similar results for abstinence outcomes. A significant reduction in CPD across the 12-month follow-up in the subsample of participants who smoked was observed, but nonsignificant differences between conditions were found. Higher engagement with the SinHumo App was a significant predictor of 12-month abstinence. Satisfaction with the intervention was high and similar in both groups. High abstinence rates over the 12-month follow-up and satisfaction were found in both conditions. The inclusion of the SinHumo App did not improve abstinence rates in the intervention. Scarce research has examined the long-term efficacy of smoking cessation treatments, including Apps, to support the quitting process. The present randomized controlled trial contributes to the existing literature about including information and communication technologies in behavior change interventions. The development of effective smoking cessation apps and information and communication technologies-based interventions is crucial for reducing the prevalence of smoking, as these interventions have the potential to reach a large number of people who smoke and reduce access-related barriers to treatment.

Does Employees’ Trust in the Management Predict Employees’ Work Engagement?

The study aimed to measure the effect of employees' trust in management on the work engagement of employees. Deepening the concepts of the study, the literature was reviewed and appropriate research methodology was applied. The study used assessment and correlational research design. The population of the study was employees of the institution (DWCL) and the data was gathered through research questionnaires. The finding of the study demonstrates that employees have a high trust in management competency, integrity and the working relationship and employees also have a high work engagement. However, the result of the ANOVA indicates that employees' trust in management is not associated with the work engagement of the employees. Thus, the hypothesis of the study is rejected. The high work engagement of employees can be influenced by other factors not considered in the study.

Low-carbon behavior between urban and rural residents in China: An online survey study

This study examines the variances in low-carbon behaviors between urban and rural residents in China, highlighting the importance of tailoring strategies to foster sustainable lifestyle shifts. A notable innovation of our research is the detailed assessment of 24 low-carbon behaviors across five categories: clothing, eating, housing, transportation, and using, where the highest engagement was found in eating-related behaviors and the lowest in using. Remarkably, rural residents typically exhibit more favorable low-carbon behaviors than their urban counterparts, except in transportation. Another innovation of our research is the integration of the theory of planned behavior with external factors, we uncover how both internal and external influences shape low-carbon behaviors across demographics. We demonstrate that external factors, such as infrastructure, publicity and education, and economic factors, can both directly and indirectly encourage low-carbon behaviors. Infrastructure, particularly green transportation, emerges as vital for enhancing low-carbon behaviors in rural areas. These insights suggest policymakers can enhance low-carbon behavior promotion through modifications to external factors. Additionally, we advocate for demographic-specific policies to ensure interventions are precisely targeted and more efficacious, underscoring our contribution to the nuanced understanding of low-carbon behavior promotion strategies.

Abstract 4083: Pre-clinical development of IAMA-005, a long-acting cytokine fusion of modified IL-2 and IFN-α

Abstract In 1990s, both IL-2 and IFN-α were approved as the first two immunotherapies for metastatic melanoma and renal cell carcinoma; IFN-α was also approved for hairy cell leukemia. Although the response rates are relatively low, along ~25%, those who responded have long term survival benefits. However, the severe toxicity especially in high dose prohibited their broad use in oncology. Recently, there have been tremendous interests in modifying these two cytokines in the efforts to reduce the toxicity and enhance the activity. One such effort is to enhance the binding of IL-2 to the intermediate affinity β/γ receptors, which are expressed and function on CD8 T cells and NK cells. Another effort is to reduce the binding of IL-2 to high affinity α/β/γ receptors which mostly expressed on Treg and stimulate the growth of Treg cells, which suppress immune responses. Recently, whether it’s better to target intermediate affinity or high affinity for cancer therapy has become controversial with some studies showing that high affinity receptor engagements are required for robust anti-tumor activity while others favoring intermediate affinity receptor engagement for better efficacy; However, the clinical comparison is still lacking to be sure which approach is better. Here we have developed a long-acting novel IL-2-Fc-IFN-α fusion molecule termed IAMA-005 that has mutations to reduce the toxicity effects of IL-2 and IFN-α. We have characterized this molecule preclinically both in vitro and in vivo. IAMA-005 has demonstrated a potent tumor cell killing activities in numerous cancer cell lines including BT-474, SK-OV-3, NCI-N87, OE19, HCC-1954, MDA-MB-231, MDA-MB-468. When combined with IAMA-004 (a Her2-CD47-CD16 tri-specific antibody) in vitro, the tumor cell killing activities were dramatically increased. In addition, IAMA-005 was also tested in patient-derived Ex-Vivo fluids (one malignant pleural effusion and one malignant asities) and demonstrated excellent tumor cell killing efficacies. In addition, the killing activities of IAMA-005 could be attributed to the specific part of the fusion molecule because of the TME immune cell compositions. The in vivo assays to demonstrate efficacy and safety are ongoing and will be presented in the poster. These results suggest that this fusion cytokine molecule may be used in monotherapy in certain indications and an excellent complementary therapeutic to antibody targeted therapies or immunotherapies when used in combination. Citation Format: Liming Liu, Zhen Han, Yang Fan, Qi Pan. Pre-clinical development of IAMA-005, a long-acting cytokine fusion of modified IL-2 and IFN-α [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4083.

Continuous Saliva Packing Resulting in Feeding Tube Dependence: In-Home Behaviour-Analytic Treatment

Saliva packing can be one of the most severe life-threatening and challenging behaviours to treat. A 9-year-old male with autism spectrum disorder and intellectual disability had 100% nasogastric (NG) feeding tube dependence and significant adaptive behaviour regression (in speaking, using the toilet and his hands, school attendance, sleep). He participated in an intensive behaviour-analytic paediatric feeding treatment programme. Saliva packing, as an automatically-maintained undifferentiated behaviour that persisted in all waking contexts despite high engagement in activities, warranted an additional outside of meal approach. He began swallowing, met 100% of his 21 goals, gained weight, and eliminated tube dependence. He reached a variety of 94 across all food groups, drinks, and supplements. Caregivers were trained and reported high social validity, and gains generalised and maintained in 1-month follow-up. This is the first case to our awareness in Australia of an in-home solely behaviour-analytic intervention to eliminate tube dependence, and it was conducted without hunger provocation, weight loss, or limited nutritional variety.

Parent-adolescent discrepancies in educational expectations, relationship quality, and study engagement: a multi-informant study using response surface analysis.

Whether parental educational expectations for adolescents serve as a source of motivation or stress depends on the extent to which adolescents hold expectations for themselves. Previous research on the discrepancies between parental and adolescent educational expectations and their impact on learning engagement has been limited by traditional statistical tests, and lacking an examination of the internal mediating mechanism of parent-child relational quality from both parental and adolescent perspectives. This cross-sectional study, utilizing a multi-informant design, examined the association between discrepancies in parents' and adolescents' reports of expectations, and adolescents' study engagement, as well as the mediating role of parent-child relational qualities perceived by both parties. The sample for this study consisted of 455 adolescents and their parents from 10 classes in a junior high school in Wuhan, Hubei Province, China. The adolescents had an average age of 12.8 years, and 51.6% of them were boys. Both parents and adolescents reported on their expectations and perceived relational quality, while adolescents also filled out questionnaires assessing their learning engagement. Data were analyzed using polynomial regressions with response surface analysis. The results revealed that when adolescents reported high expectations, regardless of whether their parents reported high or low expectations, adolescents reported satisfied relationships and high learning engagement. In contrast, parents reported satisfied relationships when both parties reported high expectations, or when parents reported higher expectations than adolescents. Lastly, the association between discrepancies in expectations and learning engagement was significantly mediated by adolescent-reported relationships but not parent-reported ones. These findings highlight the importance of considering multiple perspectives when studying the association between expectations and adolescent study engagement. This research advances our comprehension of the dynamics between parent-adolescent educational expectation discrepancies and adolescent learning engagement, offering insights for more nuanced and effective parenting strategies tailored to foster optimal educational outcomes.

Abstract P467: Patterns of Home Blood Pressure Monitoring Among Older Adults With Ischemic Heart Disease: Preliminary Analysis of the RESILIENT Trial

Background: Hypertension (HTN) is highly prevalent among older adults. Despite evidence that home blood pressure monitoring (HBPM) improves HTN awareness, treatment, and control, engagement with HBPM remains understudied in older adults with ischemic heart disease. This study sought to explain trends associated with HBPM engagement. Methods: We performed an interim analysis of the ongoing RESILIENT randomized mobile health cardiac rehabilitation (mHealth-CR) trial of patients age ≥65 years with ischemic heart disease. Participants in the RESILIENT mHealth-CR group were instructed to perform at least weekly home BP measurements over 12 weeks as part of the study intervention. Three engagement groups (high engagement, gradual decline, baseline engagement) were determined by latent class analysis. ANOVA or Chi-Squared tests were used to determine trends in HBPM engagement and changes in blood pressure (BP) overall and between engagement groups over the 12-week study. Results: Of the 111 participants, the mean (SD) HBPM engagement was 2.3 (2.3) days of HBPM/week and 31.6 (33.1) measures over 12 weeks ( Table ). Weekly HBPM declined from 74.8% to 50.5% from week 1 to week 12. Frequency of HBPM declined over time in both the gradual decline and baseline engagement groups, though remained consistent in the high engagement group. There were no significant differences in mean BP levels at week 1 and week 12 overall or between groups. However, there was a non-significant trend toward a lower systolic BP in the gradual decline group (106 (SD 20.5) mmHg) compared to the high engagement and baseline engagement groups (130 (SD 11.5) and 126 (SD 15.5) mmHg, respectively, p = 0.14). Conclusion: The majority of RESILIENT trial participants measured BP weekly as instructed. There was an overall downward trend in HBPM engagement over time. Once enrollment of the full RESILIENT sample is complete (target N=300 intervention participants), our next steps will be to investigate patient-level factors associated with differential HBPM engagement.