Unraveling the Efficacy of AR Antagonists Bearing N-(4-(Benzyloxy)phenyl)piperidine-1-sulfonamide Scaffold in Prostate Cancer Therapy by Targeting LBP Mutations.
Jun 2025· Journal of Medicinal Chemistry· 2 citations· 27 references
Medicine
Abstract
Point mutations in the androgen receptor (AR) are significant drivers of resistance in prostate cancer (PCa), posing a great challenge to the development of effective treatment strategies. Building on our previous discovery of the suboptimal AR antagonist T1-12, we developed LT16, which contains an N-(4-(benzyloxy)phenyl)piperidine-1-sulfonamide scaffold through structural optimization and comprehensive screening against T878A-mutated AR. LT16 outperformed existing antiandrogens by fully antagonizing clinical AR mutations and effectively suppressing castration- and enzalutamide-resistant LNCaP cells proliferation in vitro. Mechanically, LT16 was found to disrupt AR nuclear translocation, hinder AR homodimerization, and suppress transcription of AR-regulated genes by competitive binding to the ligand binding pocket. Further in vivo experiments demonstrated that LT16 significantly reduced both regular- and enzalutamide-resistant LNCaP tumor volume and serum prostate-specific antigen levels in mice. These findings position LT16 as a promising and innovative therapeutic for advanced PCa, particularly in cases where resistance to current therapies is a concern.
In the context of cloud computing, risks associated with underlying technologies, risks involving service models and outsourcing, and enterprise readiness have been recognized as potential barriers for the adoption. To accelerate cloud adoption, the concrete barriers negatively influencing the adoption decision need to be identified. Our study aims at understanding the impact of technical and security-related barriers on the organizational decision to adopt the cloud. We analyzed data collected through a web survey of 352 individuals working for enterprises consisting of decision makers as well as employees from other levels within an organization. The comparison of adopter and non-adopter sample reveals three potential adoption inhibitor, security, data privacy, and portability. The result from our logistic regression analysis confirms the criticality of the security concern, which results in an up to 26-fold increase in the non-adoption likelihood. Our study underlines the importance of the technical and security perspectives for research investigating the adoption of technology.
Nattakarn Phaphoom, Xiaofeng Wang, S. Samuel et al.· Journal of Systems and Softw...· 111 citations· ⚡8
Some claim that especially in the field of agile software development the research lags years behind of the practice. In this paper, we characterize the status and main challenges for research on agile software development, and propose a preliminary roadmap, focusing on providing more empirical research, primarily on experienced agile teams and organizations, connecting better to existing streams of research in more established fields, giving more attention to management-oriented approaches, and finally give more emphasis to the core ideas in agile software development in order to increase our understanding. We hope that this preliminary roadmap serves as a starting point for creating a common research agenda and enables the generation of fruitful discussions and research results from the field.
Torgeir Dingsøyr, T. Dybå, P. Abrahamsson· Agile Conference· 91 citations· ⚡7
The happy-productive worker thesis states that happy workers are more productive. Recent research in software engineering supports the thesis, and the ideal of flourishing happiness among software developers is often expressed among industry practitioners. However, the literature suggests that a cost-effective way to foster happiness and productivity among workers could be to limit unhappiness. Psychological disorders such as job burnout and anxiety could also be reduced by limiting the negative experiences of software developers. Simultaneously, a baseline assessment of (un)happiness and knowledge about how developers experience it are missing. In this paper, we broaden the understanding of unhappiness among software developers in terms of (1) the software developer population distribution of (un)happiness, and (2) the causes of unhappiness while developing software. We conducted a large-scale quantitative and qualitative survey, incorporating a psychometrically validated instrument for measuring (un)happiness, with 2 220 developers, yielding a rich and balanced sample of 1318 complete responses. Our results indicate that software developers are a slightly happy population, but the need for limiting the unhappiness of developers remains. We also identified 219 factors representing causes of unhappiness while developing software. Our results, which are available as open data, can act as guidelines for practitioners in management positions and developers in general for fostering happiness on the job. We suggest considering happiness in future studies of both human and technical aspects in software engineering.
D. Graziotin, Fabian Fagerholm, Xiaofeng Wang et al.· International Conference on...· 84 citations· ⚡6
To compete in this age of disruption, large companies cannot rely on cost efficiency, lead time reduction and quality improvement. They are now looking for ways to innovate like startups. Meanwhile, the awareness and use of the Lean startup approach have grown rapidly amongst the software startup community in recent years. This study investigates how Lean internal startup facilitates software product innovation in large companies and identifies its enablers and inhibitors. A multiple case study approach is followed in the investigation. Two software product innovation projects from two large companies are examined, using a conceptual framework that is based on the method-in-action framework and extended with the previously developed Lean-Internal Corporate Venture model. Seven face-to-face in-depth interviews of the employees with different roles are conducted. Within-case analysis and cross-case comparison are applied to draw the findings from the cases. A generic process flow summarises the common key processes of Lean internal startups. The findings suggest that an internal startup that is initiated management or employees faces different challenges. A list of enablers of applying Lean startup in large companies are identified, including top management support and cross-functional team. Both cases face different inhibitors due to the different process of inception, objective of the team and type of the product. Our contributions are threefold. First, this study is one of the first attempt to investigate the use of Lean startup approach in large companies empirically. Second, the study shows the potential of the method-in-action framework to investigate the Lean startup approach in non-startup context. The third is a general process of Lean internal startup and the evidence of the enablers and inhibitors of implementing it, which are both theory-informed and empirically grounded.
Henry Edison, Nina M. Smørsgård, Xiaofeng Wang et al.· Journal of Systems and Softw...· 78 citations· ⚡6
In this paper, we present a novel approach to improving software quality and efficiency through a Large Language Model (LLM)-based model designed to review code and identify potential issues. Our proposed LLM-based AI agent model is trained on large code repositories. This training includes code reviews, bug reports, and documentation of best practices. It aims to detect code smells, identify potential bugs, provide suggestions for improvement, and optimize the code. Unlike traditional static code analysis tools, our LLM-based AI agent has the ability to predict future potential risks in the code. This supports a dual goal of improving code quality and enhancing developer education by encouraging a deeper understanding of best practices and efficient coding techniques. Furthermore, we explore the model's effectiveness in suggesting improvements that significantly reduce post-release bugs and enhance code review processes, as evidenced by an analysis of developer sentiment toward LLM feedback. For future work, we aim to assess the accuracy and efficiency of LLM-generated documentation updates in comparison to manual methods. This will involve an empirical study focusing on manually conducted code reviews to identify code smells and bugs, alongside an evaluation of best practice documentation, augmented by insights from developer discussions and code reviews. Our goal is to not only refine the accuracy of our LLM-based tool but also to underscore its potential in streamlining the software development lifecycle through proactive code improvement and education.
Z. Rasheed, Malik Abdul Sami, Muhammad Waseem et al.· arXiv.org· 62 citations· ⚡3
Agile methods continue to gain popularity. In particular, the Scrum method appears to be on the verge of becoming a de-facto standard in the industry, leading the so called Agile movement. While there are success stories and recommendations, there is little scientifically valid evidence of the challenges in the adoption of Agile methods in general, and Scrum in particular. Little, if anything, is empirically known about the application and adoption of Scrum in a multi-team and multi-project situation. The authors carried out an ethnographically informed longitudinal case study in industrial settings and closely followed how the Scrum method was adopted in a 20-person department, working in a simultaneous multi-project R&D environment. Altogether 10 challenges pertinent to the case of multi-team multi-project Scrum adoption were identified in the study. The authors contend that these results carry great relevance for other industrial teams. Future research avenues arising from the study are indicated.
A. Marchenko, P. Abrahamsson· Agile Conference· 59 citations· ⚡11
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