Shoggoth: A Formal Foundation for Strategic Rewriting

Rewriting is a versatile and powerful technique used in many domains. Strategic rewriting allows programmers to control the application of rewrite rules by composing individual rewrite rules into complex rewrite strategies. These strategies are semantically complex, as they may be nondeterministic, they may raise errors that trigger backtracking, and they may not terminate.Given such semantic complexity, it is necessary to establish a formal understanding of rewrite strategies and to enable reasoning about them in order to answer questions like: How do we know that a rewrite strategy terminates? How do we know that a rewrite strategy does not fail because we compose two incompatible rewrites? How do we know that a desired property holds after applying a rewrite strategy?In this paper, we introduce Shoggoth: a formal foundation for understanding, analysing and reasoning about strategic rewriting that is capable of answering these questions. We provide a denotational semantics of System S, a core language for strategic rewriting, and prove its equivalence to our big-step operational semantics, which extends existing work by explicitly accounting for divergence. We further define a location-based weakest precondition calculus to enable formal reasoning about rewriting strategies, and we prove this calculus sound with respect to the denotational semantics. We show how this calculus can be used in practice to reason about properties of rewriting strategies, including termination, that they are well-composed, and that desired postconditions hold. The semantics and calculus are formalised in Isabelle/HOL and all proofs are mechanised

Mechanisms and applications of radiation-induced oxidative stress in regulating cancer immunotherapy

Radiotherapy (RT) is an effective treatment option for cancer patients, which induces the production of reactive oxygen species (ROS) and causes oxidative stress (OS), leading to the death of tumor cells. OS not only causes apoptosis, autophagy and ferroptosis, but also affects tumor immune response. The combination of RT and immunotherapy has revolutionized the management of various cancers. In this process, OS caused by ROS plays a critical role. Specifically, RT-induced ROS can promote the release of tumor-associated antigens (TAAs), regulate the infiltration and differentiation of immune cells, manipulate the expression of immune checkpoints, and change the tumor immune microenvironment (TME). In this review, we briefly summarize several ways in which IR induces tumor cell death and discuss the interrelationship between RT-induced OS and antitumor immunity, with a focus on the interaction of ferroptosis with immunogenic death. We also summarize the potential mechanisms by which ROS regulates immune checkpoint expression, immune cells activity, and differentiation. In addition, we conclude the therapeutic opportunity improving radiotherapy in combination with immunotherapy by regulating OS, which may be beneficial for clinical treatment

Risk Prediction of Second Primary Malignancies in Primary Early-Stage Ovarian Cancer Survivors: A SEER-Based National Population-Based Cohort Study

Purpose: This study aimed to characterize the clinical features of early-stage ovarian cancer (OC) survivors with second primary malignancies (SPMs) and provided a prediction tool for individualized risk of developing SPMs. Methods: Data were obtained from the Surveillance, Epidemiology and End Results (SEER) database during 1998–2013. Considering non-SPM death as a competing event, the Fine and Gray model and the corresponding nomogram were used to identify the risk factors for SPMs and predict the SPM probabilities after the initial OC diagnosis. The decision curve analysis (DCA) was performed to evaluate the clinical utility of our proposed model. Results: A total of 14,314 qualified patients were enrolled. The diagnosis rate and the cumulative incidence of SPMs were 7.9% and 13.6% [95% confidence interval (CI) = 13.5% to 13.6%], respectively, during the median follow-up of 8.6 years. The multivariable competing risk analysis suggested that older age at initial cancer diagnosis, white race, epithelial histologic subtypes of OC (serous, endometrioid, mucinous, and Brenner tumor), number of lymph nodes examined (<12), and radiotherapy were significantly associated with an elevated SPM risk. The DCA revealed that the net benefit obtained by our proposed model was higher than the all-screening or no-screening scenarios within a wide range of risk thresholds (1% to 23%). Conclusion: The competing risk nomogram can be potentially helpful for assisting physicians in identifying patients with different risks of SPMs and scheduling risk-adapted clinical management. More comprehensive data on treatment regimens and patient characteristics may help improve the predictability of the risk model for SPMs