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Background: Immune checkpoint inhibitors (ICIs) enhance the immune system's ability to target and destroy cancer cells by blocking inhibitory pathways. Despite their efficacy, these treatments can trigger immune-related adverse events (irAEs), such as acute kidney injury (ICI-AKI), complicating patient management. The genetic predispositions to ICI-AKI are not well understood, necessitating comprehensive genomic studies to identify risk factors and improve therapeutic strategies. Objective: To identify genetic predispositions for ICI-AKI using large-scale real-world data. Methods: A systematic literature search led to 14 candidate variants related to irAEs. We performed a candidate variant association study with these 14 variants using the All of Us cohort (AoU, v7, cutoff date: 7/1/2022). A cohort for cancer patients receiving ICI and a general cohort were established to evaluate ICI-AKI risk. Logistic regression, adjusted for sex, was used to evaluate the impact of each candidate genotype, separately for self-reported and ancestry-estimated race. Kaplan-Meier survival analysis assessed the genetic effects on AKI-free survival. Results: The ICI cohort (n=414) showed a one-year AKI incidence rate of 23.2%, significantly higher than the general cohort (6.5%, n=213,282). The rs16957301 variant (chr13:100324308, T>C) in the PCCA gene was a significant risk genotype for ICI-AKI among self-reported Caucasians (Beta=0.93, Bonferroni-corrected P-value=0.047) and ancestry estimated Caucasians (Beta = 0.94, Bonferroni-corrected P-value=0.044). Self-reported Caucasians with the rs16957301 risk genotypes (TC/CC) developed AKI significantly earlier (3.6 months) compared to the reference genotype (TT, 7.0 months, log-rank P=0.04). Consistent results were found in ancestry-estimated Caucasians. This variant did not present significant AKI risks in the general cohort (Beta: -0.008-0.035, FDR: 0.75-0.99). Conclusion: Real-world evidence from the All of Us cohort suggests that, in Caucasians, PCCA variant rs16957301 is a novel AKI risk genotype specific to ICI treatment. Additional studies are warranted to validate rs16957301 as risk marker for AKI in Caucasian patients treated with ICIs and to assess its risk in other ancestral populations.

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Early detection of metallic corrosion is one considerable method to reduce imperceptible disasters nowadays. Fluorescent coatings with high sensitivity and long lifetimes for use in the early detection of metallic corrosion are in high demand, but they are presently difficult to prepare. Inspired by the chameleon's skin, which is capable of switching its color in different atmospheres sensitively and reversibly, we proposed herein a facile and universal all-in-one strategy of combining the fluorescent sensitivity and dynamic hydrogen bonds in a hydrogel to develop a reusable corrosion detection tape to cover metal surfaces. The fluorescent hydrogel tape was constructed using free radical copolymerization of monomers [hydroxyethyl methylacrylate (HEMA) and tetraphenylethene derivatives (TPEPy)]. Due to the aggregation-induced emission (AIE) behavior of TPEPy, the poly(HEMA-co-TPEPy) hydrogel is capable of monitoring the traces of corrosion via the release of ferric ions with a concentration as low as 10-5 M. Moreover, due to the dynamic hydrogen bonds of hydroxyethyl groups in hydrogel networks, the fluorescent hydrogel tape exhibited good adhesion and well reusability for over 10 applications to effectively warn against early corrosion of stainless steel. This non-destructive and reversible method of early corrosion detection can provide valuable signals when maintenance is needed before the metal suffers serious damage.

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Block copolymers with different topologies (linear, loop, 3-armed and 4-armed polymers) containing poly(N-vinylpyrrrolidone) (PVP) antifouling blocks and terminal poly(dopamine-acrylamide) (PDAA) anchoring blocks were synthesized. These polymers can form a robust antifouling nanolayer on various surfaces. The morphologies of the polymer-modified surfaces are strongly dependent on the topologies of the polymers: with the increase of arm numbers, the morphology evolves from the smooth surface to the nanoscale coarse surface. As a result, the hydrophilicity of the coatings increases with the increase of degree of nanoscale roughness, and the 4-armed block copolymer forms a superhydrophilic surface with a water contact angle (WCA) as low as 8.7°. Accordingly, the linear diblock copolymer exhibits the worst antifouling efficiency, while the 4-armed polymer exhibits the best antifouling efficiency. This is the first example systematically showing that the antifouling efficacy could be adjusted simply by the topology of the coatings. Cell viability studies revealed that all of the copolymers exhibit excellent cytocompatibility. These biocompatible polymers with narrowly distributed molecular weight might find niches for antifouling applications in various areas such as anti-protein absorption, anti-bacterial and anti-marine fouling.

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Each year theme parks can see up to 20 million patrons, but often little effort is put into planning for an emergency evacuation. In this study, we built a multiagent simulation model using AnyLogic® 8.5.1. The model was based on a preliminary design of a theme park provided by AOA Builds, Orlando. This research had two goals: the first was to compare evacuation time when the park is full (1) using only the main guest gate and (2) using all seven available exits. The second goal was to model first responder response time between various start and end locations within the park. Using only the main gate, evacuation took an average of 14 minutes and 51 seconds. Using all seven gates results in an average evacuation time of 11 minutes and 58 seconds. This was due to a gate being overwhelmed causing a delay in overall evacuation time. If that gate is not included in the calculation, the average evacuation time drops to 6 minutes and 44 seconds. For the purpose of measuring response times, four starting locations were chosen with the guidance of a subject matter expert. These locations included response teams positioned at the front gate, at a police station, at the service area behind a main attraction, and mobile patrol walking around the park. Based on our testing, walking around the park was the best option in terms of response time, using the main gate was 53.7 percent faster than other options and, using all seven gates, was 60.7 percent faster during an evacuation using all seven exits.

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