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The rearrangement of carbon-carbon (C-C) single bonds in readily available carbocyclic scaffolds can yield uniquely substituted carbocycles that would be challenging to construct otherwise. This is a powerful and often non-intuitive approach for complex molecule synthesis. The transition-metal-mediated cleavage of C-C bonds has the potential to broaden the scope of this type of skeletal remodeling by providing orthogonal selectivities compared to more traditional pericyclic and carbocation-based rearrangements. To highlight this emerging technology, a unified, asymmetric, total synthesis of the phomactin terpenoids was developed, enabled by the selective C-C bond cleavage of hydroxylated pinene derivatives obtained from carvone. In this full account, the challenges, solutions, and intricacies of Rh(I)-catalyzed cyclobutanol C-C cleavage in a complex molecule setting are described. In addition, details of the evolution of strategies that ultimately led to the total synthesis of phomactins A, K, P, R, and T, as well as the synthesis and structural reassignment of Sch 49027, are given.

Introduction: Androgen deprivation therapy has been shown to improve cancer control when combined with radiotherapy. Relugolix is an oral GnRH receptor antagonist that achieves rapid profound testosterone suppression, which may increase the perception and/or impact of fatigue. This study sought to evaluate neoadjuvant relugolix-induced fatigue in prostate cancer patients prior to the start of stereotactic body radiation therapy (SBRT). Methods: Relugolix was initiated at least two months before SBRT. The 13-item Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire was collected at baseline and one hour prior to SBRT initiation. A five-point scale was used to score individual items. Overall scores range from 0- 52 and individual item scores were converted to 0-100, with higher scores reflecting less fatigue. Five "experience" items explored self-perceptions of fatigue, and eight "impact" items sought to evaluate the effect of fatigue on daily activities. Items were evaluated for statistical significance (paired t-test, p < 0.05) and clinical significance (minimally important difference (MID); 0.5 standard deviation from baseline). Results: Between March 2021 to December 2023, 89 men were treated at Georgetown with neoadjuvant relugolix and SBRT. Mean age was 71 years (range: 49-87). Median initiation of relugolix was 4.5 months prior to SBRT (range: 2-14.2 months). 93% patients achieved castration (testosterone levels ≤ 50 ng/dL) and 85% patients achieved profound castration (testosterone levels ≤ 20 ng/dL). 87 patients completed the FACIT-F questionnaire, with an average overall score of 45.6 at baseline and 41.0 at SBRT initiation. This difference was statistically and clinically significant (p < 0.01, MID = 3.55). Patients experienced an increase in fatigue for 12 of 13 items, with statistically significant changes for 11 items. Three of five experience items showed a clinically significant increase in fatigue. Only two of eight impact items were clinically significant. Discussion: Our study shows that relugolix significantly increases fatigue, affecting multiple areas of life. While the fatigue does not appear to generally impact a patient's ability to carry out normal activities, patients demonstrate frustration with being too tired for these activities. It is essential for clinicians to counsel prostate cancer patients on the impact of neoadjuvant relugolix on quality-of-life issues like fatigue. [ABSTRACT FROM AUTHOR]

Chinese cross-border e-commerce has become the largest in the world, overtaking US e-commerce and representing about 40% of total global e-commerce spending in 2018. This market is highly complex, uncertain, and poorly understood. Surveys and statistics have been used to characterise it, but new approaches are required to better understand its complexity. To address this gap, we present an agent-based model of Chinese cross-border e-commerce. For a realistic representation of the buyers' decision-making mechanism and some elements of their communication, including word of mouth (WOM), we use endorsements theory, and a survey is used to specify the model. The aim of the study is twofold: (1) to present an agent-based simulation (ABS) model of the Chinese cross-border e-commerce market; and (2) to illustrate the potential of the model to explore future possible configurations of the market and to guide stakeholders' decision making. [ABSTRACT FROM AUTHOR]

Spain ranks second in the world for the number of international tourists. These tourists have different preferences, which influence their choice of tourist routes depending on the activities offered by provinces. There are currently no routes customised according to the preferences of a travel party, which makes the supply of tourist packages complex. We propose an agent-based model, named ABM RoutePlanner, which simulates the behaviour of travel parties through provinces of Spain. The model is developed as an application of the ODD protocol. This paper makes two contributions. First, we describe a model applicable to the identification of appropriate routes for different combinations of tourists' preferences in some (hypothetical) environments. Second, we present the actual routes that will allow tour operators to define strategic plans that motivate tourists to visit the provinces included in the routes. The simulation model was calibrated with data extracted from TripAdvisor and Spanish tourist surveys. [ABSTRACT FROM AUTHOR]

Many factors influence the problems that currently exist in the learning-teaching process of programming. The use of an Integrated Development Environment (IDE) makes the experience a complicated process because these IDEs focus on professional programmers and not on novice learners. This also affects the classrooms of the university "Pontificia Universidad Católica de Valparaíso (PUCV)" (Chile). The use of professional IDEs negatively affects the learning process of first-year students who face the development of the algorithms for the first time. One of the IDE widely used for teaching programming courses is Code::Blocks, which is a tool for professional developers. Through a heuristic and usability evaluation, we found that Code::Blocks has a complex user interface and a functional overload. Using these two findings, as well as recommendations given during these tests, we highlight the important aspects that an IDE for novice learners should have. Taking into account previous observations and state-of-the-art/practice of IDEs, a functional IDE prototype, named Incre-IDLE, is developed. In addition to Code::Blocks evaluations, this paper reports the results of a heuristic and usability evaluation applied to first-year students at PUCV about functionalities provided by Incre-IDLE. These results suggest that Incre-IDLE has a simple interface, is easy to install and use, and does not have functional overload (i.e., spend a considerable amount of time learning the tool). Concretely, the results show that 66.7% of the students could complete tasks easily and 100% of them found the GUI intuitive. In terms of GUI, 83.3% considered the application interface "very simple"; and the text, concepts, and icons "very understandable" by 66.7%. The students also found the tool "motivating" (66.7%) or "very motivating" (33.3%). These results closely match the findings obtained by the heuristic evaluation of Incre-IDLE from the experts: 83.3% of them rated it as "useful" or "very useful", and only a 16.7% rated it as. [ABSTRACT FROM AUTHOR]