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IntroductionField cancerization is suggested to arise from imbalanced differentiation in individual basal progenitor cells leading to clonal expansion of mutant cells that eventually replace the epithelium, although without evidence.MethodsWe performed deep sequencing analyses to characterize the genomic and transcriptomic landscapes of field change in two patients with synchronous aerodigestive tract tumors.ResultsOur data support the emergence of numerous genetic alterations in cancer-associated genes but refutes the hypothesis that founder mutation(s) underpin this phenomenon. Mutational signature analysis identified defective homologous recombination as a common underlying mutational process unique to synchronous tumors.DiscussionOur analyses suggest a common etiologic factor defined by mutational signatures and/or transcriptomic convergence, which could provide a therapeutic opportunity.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has recently emerged as a palliative alternative for patients with unresectable peritoneal metastasis (PM). Quality of life (QoL) has increasingly been used as an endpoint to evaluate treatment outcomes. This review aims to identify evidence on how PIPAC would impact the QoL of PM patients.

In the humanoid robots, waist mechanism is an important structure to realize the whole body coordinated movement. This paper proposes a series–parallel mechanism of waist structure, and its kinematics and dynamics characteristics are studied. Based on the dynamic model, a backstepping sliding mode controller is designed to simulate control performance. Under the continuous disturbance force, the stability and accuracy of the mechanism are verified. Compared with the experiment, the results prove that the waist mechanism has the biomimetic spine movements and desired control performance, which can be applied to life support robots in the future. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of TRPC5 on intermittent hypoxia-induced myocardial pyroptosis. Methods TRPC5 knock out (TRPC5-/-) and SD rats were each randomly divided into chronic intermittent hypoxia group (CIH group) and normoxia group (Control group) (n = 6 for each group). The myocardial fibrosis in rats was visualized by Masson staining, the levels of serum inflammatory factors were measured by ELISA and the relative expression levels of TRPC 5 and pyroptosis-related proteins were determined by Western blotting. Results Masson staining showed that the collagen volume fraction in the TRPC5-/--CIH group was higher than that in the TRPC5-/--Control group and lower than that in the WT-CIH group. The ELISA results showed that the serum levels of IL-1, IL-6, and TGF- β in the TRPC5-/--CIH group were higher than those in the TRPC5-/--Control group and lower in the WT-CIH group. Western blotting results showed that the relative expression levels of pyroptosis related proteins caspase-1, NLRP3, GSDMD, and GSDMD-N in the TRPC5-/--CIH group were higher than those in the TRPC5-/--Control group and lower than those in the WT-CIH group. Conclusion TRPC5 deficiency alleviates myocardial pyroptosis and myocardial fibrosis induced by hypoxia. [ABSTRACT FROM AUTHOR]

Herein, a digital–analog hybrid resistive random‐access memory (RRAM) is prepared by integrating the structurally similar SiNx‐based digital‐type RRAM with analog‐type RRAM by heterogeneous integration method. The Pt/SiNx/Ta/Ru is a digital RRAM due to the formation and breakage of the internal silicon dangling bonds conductive filaments, and the TiN/SiNx/Ta/Ru structure is an analog RRAM due to the traps‐filled limit region of the space‐charge limited current. The heterogeneously integrated digital RRAM has good cycling stability and endurance characteristics, and the heterogeneously integrated analog RRAM has high linearity and multistate counting characteristics. This heterogeneous integration approach is useful for the implementation of hybrid digital–analog RRAM. [ABSTRACT FROM AUTHOR]

Abstract Ovarian cancer is associated with poor prognosis. Platinum resistance contributes significantly to the high rate of tumour recurrence. We aimed to identify a set of molecular markers for predicting platinum sensitivity. A signature predicting cisplatin sensitivity was generated using the Genomics of Drug Sensitivity in Cancer and The Cancer Genome Atlas databases. Four potential biomarkers (CYTH3, GALNT3, S100A14, and ERI1) were identified and optimized for immunohistochemistry (IHC). Validation was performed on a cohort of patients (n = 50) treated with surgical resection followed by adjuvant carboplatin. Predictive models were established to predict chemosensitivity. The four biomarkers were also assessed for their ability to prognosticate overall survival in three ovarian cancer microarray expression datasets from The Gene Expression Omnibus. The extreme gradient boosting (XGBoost) algorithm was selected for the final model to validate the accuracy in an independent validation dataset (n = 10). CYTH3 and S100A14, followed by nodal stage, were the features with the greatest importance. The four gene signature had comparable prognostication as clinical information for two-year survival. Assessment of tumour biology by means of gene expression can serve as an adjunct for prediction of chemosensitivity and prognostication. Potentially, the assessment of molecular markers alongside clinical information offers a chance to further optimise therapeutic decision making.

Summary: Clinically relevant animal models are crucial for effective development of therapeutics for peritoneal carcinomatosis (PC). This protocol describes the generation of patient-derived ascites-dependent xenograft (PDADX) models from the cellular component of ascites. The use of routine intraperitoneal injection of the fluid component of ascites is analogous to the biological events occurring intra-abdominally in patients with PC. By serving as a proxy, PDADX models represent a valuable tool for preclinical testing of new therapeutics for PC.For complete details on the use and execution of this protocol, please refer to Hendrikson et al. (2022). : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.