Favorable Relationship Research Articles

Corporate social responsibility and firm performance in the financial industry in Vietnam: The mediating role of digital transformation

Purpose: This study evaluated the influence of corporate social responsibility (CSR) initiatives undertaken by banks in Vietnam on their overall performance. Additionally, it sought to examine the relationship between corporate social responsibility and digital transformation efforts within the framework of the ongoing Fourth Industrial Revolution. Design/Methodology/Approach: The research uses a survey sample from Southeast Vietnam, specifically Binh Duong Province, Dong Nai Province, Tay Ninh Province, Ba RIA Vung Tau Province and Ho Chi Minh City. A total of 245 valid questionnaires were gathered from mid- and senior-level executives, senior employees and department heads who have implemented digital transformation strategies in banks. Findings: This study explores the relationship between corporate social responsibility and firm performance in Vietnam's financial industry focusing on the banking sector. The study discovered a favourable relationship between corporate social responsibility (CSR) and enterprise digital transformation as well as a good relationship between CSR and digital transformation and Vietnamese banks' business success. Conclusion: The digital economy has increasingly contributed to global economic development. Today’s digital landscape is undergoing a widespread phenomenon known as digital transformation. Hence, it is crucial to examine the impact of digital transformation on business processes. Practical Implications: The data also supports the idea that digital transformation serves as a mediator between corporate CSR and financial performance contributing to filling the gap when there is limited research in Vietnam on this relationship. Contribution to the Literature: This research aims to help banks in Vietnam enhance operational efficiency when banks actively engage in CSR and digital transformation.

The Dynamics of Human Capital Development, Employee Commitment, and Sustainable Competitive Advantage: A Strategic Perspective

The purpose of this study was to see the impact of “strategic human resources management (HRM) practices” on achieving “competitive advantages” that will be long-lasting, as well as the contribution of “human capital development” and “employee commitment” in information technology sector. IT sector works to establish, preserve, and perpetuate their competitive advantages, similar to other corporate organisations. The data were collected using questionnaire method and this study was conducted on 277 randomly selected employees working in different reputed IT companies. To achieve the objective of the study primary and secondary data were used and were analyzed using descriptive statistics, exploratory factor analysis, confirmatory factor analysis, mediation analysis and likewise using AMOS 22.0, SPSS23. The results of the study showed a linear and favourable relationship between strategic HRM practices and sustainable competitive advantage (SCA). Strategic HRM was also found to positively influence human capital development and employee commitment of the IT sector firms. This study further suggests IT sector to prioritise human resources management in their businesses, which will improve human capital development by allowing staff members to acquire implicit expertise that will be challenging and difficult for the rivals to mimic and also add to the literature on sustainable competitive advantages, employment, and human capital development. The finding highlights about IT sector management as well and also the results made an additional argument for employee commitment to achieving a sustained competitive edge. The study further suggested some theoretical and other implications for researchers as well.

Fostering environmental, social and governance-oriented startups: Accessing the moderating effect of universities on entrepreneurial leadership

This study explores the complex factors influencing the achievement of Environmental, Social and Governance (ESG) companies. This study examines the impact of several antecedents such as Entrepreneurial Leadership Programs (ELP), Incubator and Accelerator Support (IAS), Access to Mentorship and Network Opportunities (AMNO) and Availability of Funds and Financial Resources (AFFR) on the development of ESG startups drawing upon the theoretical framework of Resource-Based View (RBV). A cross-sectional survey design was used to collect data from academic institutions in Saudi Arabia including state and private universities. Three public and private universities from various geographic locations were chosen for this study. The results suggest a favorable relationship between ELP and the establishment of ESG startups. This highlights the significance of education and the cultivation of skills in fostering entrepreneurial endeavours. The analysis revealed no statistically significant relationship between IAS and ESG startup performance. However, a positive relationship between AMNO and the establishment of ESG startups underscoring the importance of networking and mentorship was found. The research findings also indicate universities’ substantial influence in shaping these associations highlighting the need for additional exploration of the factors that motivate university participation in ESG entrepreneurship. The findings significantly contribute to the overall comprehension of the elements and interactions that impact the growth of ESG startups. Moreover, they offer vital insights for policymakers and practitioners involved in the realm of socially responsible entrepreneurship.

Exploring the Nexus of Organizational Culture, Digital Capabilities, and Organizational Readiness for Change in Primary School in Digital Transformation: A Quantitative Analysis

<p style="text-align:justify">In the context of Vietnam's primary schools undergoing a digital transformation, this research investigates the relationship between organizational culture (OC), digital capabilities (DC), and organizational readiness (OR) for change. This survey, which employs a quantitative methodology, includes 892 teachers and school managers from different elementary schools. Analyses were conducted using SPSS Statistics 26.0. The study shows a favorable relationship between digital skills and organizational readiness, suggesting that more digitally capable institutions are better equipped to handle change. Furthermore, a significant correlation exists between corporate culture, digital skills, and organizational readiness, indicating that schools with a creative and supportive culture are more prone to embrace digital change. These results advance knowledge of the variables affecting organizational change-readiness in Vietnam's primary school digital transformation. These results also have significant implications for educational policymakers, school administrators, and other stakeholders facilitating digital transformation in primary schools. By recognizing the benefits of digital capabilities and organizational culture for organizational change readiness, decision-makers can implement strategies to foster a supportive culture and enhance digital capabilities within educational institutions, ultimately leading to more successful and effective digital transformation initiatives.</p>

Genetic diversity and stability analysis of the improved cultivars of guava and their related species

Guava (Psidium guajava L.) is an important fruit crop in the tropical and sub-tropical world. The morphological, biochemical, and molecular (using 56 microsatellite markers) characterization was carried out on 18 guava genotypes and related species (P. guineense) during 2018–2022. The present study exhibited a wider range of variability: fruit weight (61.5–68.4 g); fruit diameter (4.20–7.91 cm); total soluble solids (8.50–13.40 °Brix); titrable acidity (0.20–0.64%); reducing sugar (2.55–7.00 mg glucose /g); ascorbic acid (76.4–196.3 mg/100 g); total phenol (125.9–305.4 mg GAE/100 g pulp); and total flavonoid content (172.30–948.5 mg QE/100 g pulp). The antioxidant activities (FRAP and DPPH) showed a favorable relationship with ascorbic acid, total phenol, total flavonoid, and total flavonol content. Red-fleshed genotypes were found superior for all the quality parameters over white-fleshed genotypes. The molecular analysis generated 213 alleles from 56 markers, with 2–9 alleles per locus (mean = 3.80). Apart from the genetic diversity, the improved cultivars were also distinguished by a set of markers: RCGH-4 (mPGCIR-184 and mPGCIR-194); RCGH-1 (mPGCIR-108 and mPGCIR-243); RCG-11 (mPGCIR-206 and mPGCIR-325); and RCGH-7 (mPGCIR-16 and mPGCIR-19). The cluster analysis indicated that P. guineense was the most diverse of the cultivated species, and all the red flesh genotypes were close to each other. Furthermore, RCG-11 had a lower seed content (58.89 per 100 g pulp), while RCGH-1 and RCGH-4 were stable for fruit weight and seed number, which can be promoted for commercial production and future crop improvement programs.

From a Penny to Self-Disgust: How Cashback Rewards for Favorable Comments and Relationship Norms Affect Consumers’ Post-Purchase Behavioral Intentions

Sellers of platforms offering cashback rewards for favorable comments (hereinafter CRFC) to generate positive online reviews are ubiquitous. This research examines when and how a CRFC influences consumers’ post-purchase behavioral intentions regarding repurchase and recommendation. Anchoring on the relationship norms theory and casting light on consumers’ self-perceptions, the effect of a CRFC on consumers’ post-purchase behavioral intentions is contingent on the relationship norms. The findings of a pilot study and two experimental studies show that after a CRFC offer, communal consumers experienced lower post-purchase behavioral intentions than exchange consumers, and that consumers’ feeling of self-disgust is the mechanism underlying this interactive effect. Specifically, a CRFC is effective for exchange consumers but not for communal consumers because it triggers self-disgust in communal consumers. This paper thus reveals the mediating role of self-disgust in the interactive effect of CRFC and relationship norms on post-purchase behavioral intentions. The implications for sellers, platforms and consumers are discussed.

Understanding how tourists with disabilities’ perceptions of residents’ emotional solidarity influence their behavioural intention: the mediating role of perceived fairness

Tourists with disabilities face several constraints when travelling, including interpersonal issues. The intergroup contact theory suggests that intergroup contact can diminish social prejudice. This study aims to understand how tourists with disabilities’ perceptions of residents’ emotional solidarity influence their attitude and behavioural intention towards a destination and the mediating role of perceived fairness. A systematic sampling survey was conducted among 359 tourists with disabilities in China. The results revealed that emotional closeness and sympathetic understanding had a positive effect on perceived fairness and attitude towards the destination, but a welcoming nature affected attitude alone. Ultimately, perceived fairness and the attitude towards the destination impacted behavioural intention. Additionally, the results confirmed the mediating role of perceived fairness between emotional solidarity and behavioural intention. The contribution of this study to accessible tourism research is to provide a model that helps to explain how tourists with disabilities’ psychological mechanisms and behavioural patterns are affected by favourable interpersonal relationships with destinations. In short, it promotes the concept of perceived fairness. The study also argues that greater social inclusion contributes to the quest for good health and well-being (SDG #3), equality (SDG #10), and inclusive and sustainable cities (SDG #11).

Causes of High Turnover Intention: Due to Work Family Conflict and Work Environment Factors

Purpose: This study aims to empirically test a research model that further investigates the influence of the work environment on turnover, the influence of work-family conflict on turnover, and whether there is a mediating effect of work-family conflict on turnover intention. Theoritical Framework: This research uses the Theory of Planned Behavior. The intention to move comes from individual intentions that cannot be felt and after feeling out of control they will decide to leave their job which is also supported by other factors. This theory can also see that the nurse's work environment and WFC contain three standards (time-based conflict, tension-based conflict, and behavior-based conflict) which function as the main predictors of turnover intention in nurses. Design/methodology/approach: This study uses a quantitative approach. The respondents of this research were employees of private Hospitals in Karasidenan Banyumas, with a population of 285 employees with a sample of 240 people calculated using the Slovin formula with a margin of error of 10%. Respondents in this study were dominated by women. The average age of respondents is 20-25 years. The sampling technique used was quota sampling by setting quotas based on the proportion of each hospital. This research uses a Structured Equation Modeling (SEM) application based on Partial Least Square (PLS). Findings: This finding shows that a favorable relationship between the work environment and work-family conflict both have a significant effect on turnover turnover because the P-value shows <0.05. And the mediation results showed that work-family conflict can mediate the relationship between the work environment and the intention to move with a significance value of 0.040. Research, Pratical & Social Implication: The study is similar to research conducted by Abdou et al., (2022) in the hospitality sector which revealed that the perception of work environment hospitality has a direct impact on employee turnover intentions through WFC which partially mediates the relationship between research components. This study has a limitation, namely concentrating on the variable Work-Family Conflict as a mediator in the relationship between the nurse's work environment and turnover intention. WFC as a mediation hopefully can be a reference for further research. Another limitation is that this research only examines the nursing sector, and in the future it could be carried out in other sectors such as the hotel sector or other service sectors. Originality/value: This study examines the impact of the work environment on turnover turnover, the effect of work-family conflict on turnover turnover, and whether there is a mediating effect of work-family conflict on the intention to move.

The adapted French version of the Academic and Athletic Identity Scale (AAIS-FR): Evidence of validity and reliability and relationships with sport well-being.

Effectively managing their athletic and academic projects is a major challenge for student-athletes. The salience of the identity they develop in each of these contexts can affect their well-being and is therefore an important variable to consider. Examining these mechanisms in countries and student-athlete support systems other than the United States is also important. This study aims to both translate and evaluate the psychometric properties of a French version of the Academic and Athletic Identity Scale, the AAIS-FR, and to examine the additive and interactive relationships of the two identities with sport burnout and engagement. Participants were 359 French student-athletes (50.42% female) who were competing at various levels (ranging from regional to international). Results from analyses using a slightly modified version of the original scale provided evidence of construct (i.e., factor structure) and concurrent (i.e., expected relationships between both identities and several correlates identified in previous work) validity, as well as reliability (i.e., internal consistency) and invariance across gender and sport competition levels of the AAIS-FR. In addition, regression analyses revealed a favourable relationship between athletic identity and sport well-being (i.e., positive with engagement and negative with burnout), no relationship between academic identity and sport well-being, and no interaction between the two identities. While further research is needed to provide additional evidence for the validity of the AAIS-FR, researchers can still use this tool to measure the salience of the two identities of French-speaking student-athletes.

Synthesis and application of bismuth nanoparticle-loaded longan porous carbon for simultaneous electrochemical determination of Pb(II) and cd(II) in seafoods

The discarded longan shell-derived porous carbon material (LPC) served as a scaffold for synthesizing bismuth nanoparticle-loaded longan porous carbon nanocomposite (BiNPs@LPC) via a hydrothermal method. Then BiNPs@LPC was utilized to modify screen-printed carbon electrodes (SPCE) for simultaneous detection of Pb(II) and Cd(II) by square wave anodic stripping voltammetry (SWASV). The material was thoroughly characterized by scanning electron microscopy, X-ray diffraction, Raman spectra, Brunauer-Emmett-Teller analysis, electrochemical impedance spectroscopy and cyclic voltammetry. BiNPs@LPC exhibited abundant porous structures, high surface area, and numerous active sites, which could improve significantly response sensitivity. Under optimal conditions, the peak currents of Pb(II) and Cd(II) exhibited favorable linear relationships with the concentration within a range of 0.1–150 μg L−1, with detection limits (S/N = 3) of 0.02 μg L−1 and 0.03 μg L−1, respectively. BiNPs@LPC/SPCE demonstrated remarkable selectivity, stability and repeatability. The proposed method was successfully applied for the detection of Pb(II) and Cd(II) in seafoods achieving satisfying recovery of 97.8%–108.3% and 96.7%–106.4%. These excellent test properties were coupled with convenience for batch preparation of the modified electrodes, highlighting its potential for practical applications in heavy metal detection of real samples.

WHEN AND HOW GREEN TRANSFORMATIONAL LEADERSHIP LEADS TO GREEN TECHNOLOGY INNOVATION: THE MEDIATION EFFECT OF GREEN INNOVATION CAPABILITY

Realising the customers’ demands for green products, green technology innovation (GTI) serves as the way for businesses to grow, seek continued profit, and attain a competitive edge. Based on a paper-based survey of 337 respondents from Chinese hi-tech companies, this study utilised PROCESS Macro to analyse the impact of green transformational leadership (GTL) style on GTI through green innovation capability (GIC). Also, the study examined the adjustment effect of green market orientation (GMO). The findings indicated a statistically significant and favorable relationship between GTL and GTI through GIC. It also provided evidence to support the notion that GMO has a constructive role in moderating the association between GIC and GTI. These findings provide valuable insights into sustainable practises within Chinese high-tech enterprises, thereby enhancing our comprehension of this subject. Additionally, the study offers practical implications for leadership tactics that promote green innovation.

In vitro Antibacterial, ADME and Toxicity Screening of Newly Synthesized 4-(Substituted phenyl)-2-(2-chloroquinolin-3-yl)thiazoles

A series of novel thiazole (Va-o) compounds were synthesized following multi-step synthetic process. Using analytical methods like nuclear magnetic resonance, mass spectrometry and FTIR, the elucidation of the structure of the synthesized compounds was performed. All the 15 novel thiazoles were assessed for their antibacterial activity. The synthesized thiazoles were examined for inhibitory antibacterial activity against a panel Gram-positive strain viz. Staphylococcus aureus (NCTC 65710), Streptococcus pyogenes (MTCC-442), Bacillus subtilis (NCIM 2250) and Gram-negative bacteria Pseudomonas aeruginosa (NCTC 10662) and Escherichia coli (NCTC 10418) by agar well diffusion technique. It was observed that some of the compounds, particularly those having substitution groups like chloro, fluoro and bromo in the phenyl ring bonded to thiazole nucleus, had moderate to good antibacterial activity. Quinoline clubbed thiazoles compounds Vk, Vl, Vn and Vo showed significant antibacterial against all bacterial strains having values of minimum inhibitory concentration (MIC) from 12.5 to 25 µg/mL. The results of antimicrobial investigation suggest that 2-chloroquinoline incorporated thiazole scaffold appears to more promising for developing potent antibacterial agents. Genome gyrase docking experiments (PDB ID: 1KZN) revealed a favourable binding relationship similar to that of the pre-occupied ligand clorobiocin. The study also provides in silico ADME and toxicity studies evaluation which revealed that compounds are impartially compatible and were devoid of potential toxicity except the hepatotoxicity.

Using a Chatbot to Combat Misinformation: Exploring Gratifications, Chatbot Satisfaction and Engagement, and Relationship Quality

Grounded in the framework of uses and gratifications theory, this study investigates the impact of gratifications derived from utilizing Florence, a multilingual chatbot service developed by the World Health Organization (WHO) to disseminate COVID-19-related information. Utilizing data from a national survey comprising 591 participants in the United States, our findings reveal the significant influence of sought-after gratifications, including modality (coolness), agency (enhancement), interaction (activity), and navigability (browsing), on users’ satisfaction with the chatbot. Additionally, our research highlights the inhibiting effect of privacy risks on user satisfaction. Furthermore, we uncover a consequential relationship between chatbot satisfaction, user engagement, and the perceived relationship with the WHO, underscoring the importance of chatbot interaction in fostering favorable organization-public relationships. Empirical and practical implications of these findings are thoroughly discussed, offering valuable insights for scholars and practitioners alike.

Understanding purchase behaviour towards green housing among millennials: the mediating role of purchase intention

Purpose The purpose of this paper is to investigate millennials’ purchase behaviours towards green housing in India. This paper also examines the mediating effect of purchase intention between determinants of buying green housing and purchase behaviour in the real estate industry. Design/methodology/approach A cross-sectional research design was applied to collect data from 393 rural and 388 urban millennials. This study used “partial least squares structural equation modelling” to verify the framed hypotheses. Findings The outcomes indicate that attitude, environmental concern and green trust substantially influence the purchase intention and purchase behaviour towards green housing in rural and urban studies. However, perceived risk has an insignificant effect on purchase intention and purchase behaviour towards green housing in both studies. Likewise, innovativeness insignificantly impacts the purchase intention in study rural while substantially impacting the purchase behaviour in both studies. Additionally, a favourable relationship between purchase intention and purchase behaviour towards green housing in both rural and urban contexts. Practical implications This study provides fruitful evidence for practitioners, marketers and academicians about the drivers of purchase behaviour toward green housing. The results of this study also enable regulatory bodies to design appropriate strategies and tactics to foster the sustainable growth of nations. Originality/value This paper is a preliminary attempt to explore the decision to buy green housing in India. Furthermore, the authors targeted a specific age group, especially millennials, to gain a valuable understanding of how different factors affect green housing decisions in different areas, that is, rural and urban areas.

Human Resource Development and Employee Commitment in Nepalese Commercial Banks

The level of employee commitment is a significant issue for many firms throughout the world. As a result, many firms are using a variety of human resource development techniques to increase employee commitment. Employee dissatisfaction has been voiced in the field of compensation, which is characterized by unequal rewards, inadequate compensation and lack of job security. The purpose of this research is to focus on analyzing the relationship between HRD dimensions and employees' commitment working across various commercial banks in Nepal. The study's independent variables were Training, Compensation, Job Security, and Reward. The dependent variable was employee commitment. The descriptive research design was used. The population of the study was 46408 employees and a simple random sample technique was used to choose 396 employees from 11 commercial banks under probability sampling method. Data were collected using a standardized questionnaire on Likert Scale with 1 specifying a strongly disagreement and 5 a strongly agreement. Descriptive statistics, correlation, and regression analysis were used to analyze the data. Cronbach's Alpha had been used to test for reliability. Reliability is acceptable with a Chronbach's Alpha rating of 0.76 on an average. IBM, SPSS version 26 was used to analyze the data. The study concluded that employees' Training, Compensation and Job Security had a favorable and significant relationship with employee commitment, Reward had a negative but significant impact on Employee Commitment. The study recommended that the policy makers and BOD of Nepalese Commercial banks should design an effective welfare policy to enhance commitment of employees.

Correlation Between the Type of Psoriasis and the Pattern of Arthritis Among Patients with Psoriatic Arthritis: A Single-center Cross-sectional Study

Background: Psoriatic arthritis (PsA) is an inflammatory condition linked to psoriasis. According to studies, there is little correlation between arthritic patterns and PsA. Objective: To find relationships between psoriasis symptoms and PsA arthritis patterns. Methods: 100 PsA patients were enrolled in a cross-sectional study at Baghdad Teaching Hospital from December 2021 to June 2022, using CASPAR criteria. We gathered thorough demographic and clinical information, examined arthritis patterns, classified them into five kinds, and evaluated eight types and sites of psoriasis. Disease activity was measured using clinical and psoriasis indicators. Results: a weak negative connection among 100 individuals with psoriatic arthritis, plaque psoriasis, and distal interphalangeal (DIP) arthropathy. Erythrodermic psoriasis and spondylitis (with or without sacroiliitis) showed a slight positive connection. There was also a slight positive association between scalp psoriasis and DIP arthropathy. A comparable positive and weak relationship was found between polyarthritis and age, as well as polyarthritis and psoriatic arthritis disease activity. In contrast, asymmetrical oligoarthritis and PsA disease activity had a modest negative connection. Furthermore, enthesitis and DIP arthritis showed a weak negative connection. Body mass index and spondylitis (with or without sacroiliitis) showed a positive and weak correlation. The most significant finding was a modestly favorable relationship between skin psoriasis and psoriatic arthritis disease activity. Conclusions: There are weak but significant associations between particular psoriasis types and locales and arthritis patterns in PsA patients. These findings point to the possibility of developing individualized therapeutic regimens for PsA that take into account both dermatological and rheumatological signs.

The positive side of stress: Investigating the impact of challenge stressors on innovative behavior in higher education

Stress can be a double-edged sword. Given the intricacy of the innovation process, the link between job stress and individual innovation behavior remains uncertain. To clarify the relationship between challenge stressors and the innovative behavior of higher education teachers, this study was based on the conservation of resources (COR) theory and adopted the structural equation modeling method to explore the impact of challenge stressors on the innovative behavior of higher education teachers and reveal its influencing mechanism and boundary conditions. By analyzing the data from 208 questionnaires of higher education teachers, the findings reveal that challenge stressors positively influence innovative behavior, with task crafting serving as a critical bridge. Additionally, a favorable employment relationship climate enhances the positive impact of challenge stressors. Gender dynamics are also explored, adding nuance to the understanding of this relationship. These results shed light on the inherent mechanisms governing the relationship between challenge stressors and innovative behavior among higher education teachers, and underscore the significance of task crafting. In addition, the discoveries provided fresh insights and ideas for investigating how organizational climate affects individual innovative behavior.

Gender Equality in E-commerce Business

In the ever-evolving landscape of e-business, gender equality stands as a pivotal determinant of sustainable economic growth and social progress. This study delves into the multifaceted realm of gender equality within the sphere of electronic business, exploring its significance, challenges, and potential solutions. As women constitute a significant portion of the global workforce, their equitable participation in e-business not only fosters diversity but also harnesses untapped talent and creativity. The study also covers best practises and ideas that companies and legislators may implement to advance gender equality in e-business. The efficacy of programmes including skill development efforts, mentorship programmes, and encouraging work conditions in empowering women in the digital economy is investigated. Furthermore, policy interventions concerning education, financing accessibility, and legislative changes are examined as crucial elements of an all-encompassing strategy for achieving gender equality in e-business. The paper draws attention to the ongoing obstacles that women in e-business confront, which range from severely embedded cultural prejudices to restricted access to opportunities and resources. The paper illuminates the obstacles impeding women's active participation in e-commerce, entrepreneurship, and leadership positions through a review of relevant research and case studies. It also highlights the financial benefits of promoting gender equality in e-business by examining the favourable relationships between gender diversity and improved organisational performance, creativity, and decision-making processes. The paper concludes by arguing for a paradigm change in the e-business sector, where gender equality is now seen as an economic need rather than just a social objective. In the digital age, organisations may drive innovation, economic success, and social change by using the full potential of their workforce via the demolition of barriers, acceptance of diversity, and cultivation of inclusive cultures.

Abstract LB173: Discovery of ALTA-2618, the first allosteric, mutant-selective targeted therapy for AKT1 E17K driven cancers

Abstract BACKGROUND: AKT1 E17K is a clinically validated oncogenic driver mutated in ~1-2% of all cancers and is enriched in several solid tumors including breast (~5%), endometrial (~3%) and prostate (~1.5%) cancer. Over half of AKT1 E17K mutant breast and gynecologic cancers are homozygous for the mutant oncogene with loss of the wildtype (WT) AKT1 allele via copy-neutral loss-of-heterozygosity (CN-LOH), suggesting uniquely potent oncogene addiction in these tumor types. While inhibitors of WT PI3K or AKT have demonstrated clinical efficacy in HR+/HER2- metastatic breast cancers with PI3K/AKT pathway mutations, on-target adverse events - most commonly hyperglycemia, diarrhea, and rash - have hindered the tolerability and durability of these agents. We aimed to exploit the mutant lysine of the E17K variant to develop a covalent, highly mutant-selective inhibitor that would avoid the toxicities associated with WT AKT inhibition. METHODS: Structure-based design was guided by proprietary co-crystal structures, enabling a refined pharmacophore consensus model, which fueled novel small molecule covalent design iterations using an in-house computational chemistry cluster. Lead molecules were identified from cellular signaling assays assessing pAKT S473 suppression and selectivity over WT AKT1 and AKT2. Rapid PK assessments were performed in mice, rats, dogs, and cynomolgus monkeys. Molecules with low clearance and high oral bioavailability were advanced directly to breast and endometrial PDX models driven by AKT1 E17K mutations. RESULTS: We identified ALTA-2618, a potent (7nM EC50) inhibitor of AKT1 E17K with 22x selectivity over WT AKT1 and 140x selectivity over WT AKT2. ALTA-2618 and related analogues demonstrated covalent attachment to the AKT1 E17K protein via intact mass spectrometry, and electron density analysis of co-crystal structures of highly similar family members of ALTA-2618 reveals unambiguous covalent attachment to the K17 side chain. Based on favorable exposure-response relationships and ideal cross-species PK, ALTA-2618 was tested in once daily oral dosing and induced tumor regressions in AKT1 E17K mutant HR+/HER2low breast cancer, TNBC, and endometrial cancer PDXs at doses as low as 10 mg/kg/d. Complete responses were observed with 30 mg/kg/d in the HR+/HER2low breast PDX model that were sustained for 60 days of dosing without significant body weight loss or hyperglycemia. CONCLUSIONS: ALTA-2618 is a potent, highly mutant-selective AKT1 E17K inhibitor that demonstrates favorable PK and tolerability with oral once-daily dosing that enables prolonged tumor regressions in multiple AKT1 E17K-mutant PDX models. These data support a mid-2024 IND submission to investigate ALTA-2618 in patients with AKT1 E17K mutant cancers. Citation Format: Eric A. Murphy, Michael D. Bartberger, Maureen Ibanez, Troy T. Smith, Nicole Alvarez, Noel Timple, Xuefeng Zhu, Kevin Fan, Kevin Yu. Discovery of ALTA-2618, the first allosteric, mutant-selective targeted therapy for AKT1 E17K driven cancers [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 LB173.

Mechanical Characteristics of Tailings in Different Depositional Zones: A Case Study of Caijiagou Tailings Pond in Shaanxi, China

This study examines the widespread practice of upstream tailings dam construction in metallurgical mines in China, conducting comprehensive testing and research on tailings from various depositional zones of the Caijiagou tailings pond. Analysis of the test results from three types of tailings reveals a systematic relationship between the mechanical characteristics of tailings and their depositional zones: the farther from the dam, the finer the tailings particles, categorized as silty clay tailing, silt tailing, and sandy silt tailing. Consistent patterns were observed in the consolidated-drained shear strength and consolidated-undrained effective shear strength of these tailings. Among these, sandy silt tailing exhibited the highest strength, whereas silty clay tailing displayed the lowest. The dynamic stress–strain relationships of all three tailings types are described using the Hardin equivalent viscous-elastic model, where the initial dynamic shear modulus and the maximum dynamic shear stress in the model increased with effective confining pressure. The damping ratios exhibited a three-stage trend with increasing dynamic strain: gradual increase, rapid growth, and then gradual stabilization. Under various consolidated stress conditions, the ratio of the damping ratio to the maximum damping ratio versus the reduction in dynamic shear modulus showed a favorable linear relationship. Under vibration conditions, the dynamic shear stress corresponding to tailings failure increased with higher effective confining pressure and consolidated stress ratio. Finally, this study summarizes the parameters and indicators related to the saturated tailings of iron mines used in the research. Our work provides a foundation and reference for the design of tailings dams and the development and utilization of abandoned tailings ponds.