Studies on the discovery and function of antioxidants are consistently being performed because oxidative stress can cause various diseases. Many compounds and natural products have antioxidant activity in vitro; however, it is often difficult to reproduce their effects in vivo. Additionally, methods to measure antioxidant activities in cells are also scarce. Here, we investigated the antioxidant activity of milk proteins by observing the formation of arsenite‐induced stress granules as a tool to evaluate antioxidant activity in cells. Milk proteins not only decreased the formation of stress granules in several cell types but also scavenged 2,2'‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS) radical cations in vitro. In addition, milk proteins inhibited cellular senescence based on an SA‐β‐galactosidase assay, and increased differentiation to myotubes from myoblasts isolated from the skeletal muscles of mouse pups. Taken together, our results demonstrate that milk proteins have an antiaging effect, especially prevention of skeletal muscle loss, through their antioxidant activities. Practical Application Our results provide that antioxidant effects of milk proteins containing α‐caseins, β‐caseins, and β‐lactoglobulin can mitigate aging‐related damage induced by oxidative stress through showing inhibition of cellular senescence and increase of differentiation and maturation of myoblast. Therefore, we suggest that milk proteins could be potent health supplements to prevent aging‐associated diseases, especially sarcopenia.

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Standardized tests and spontaneous speech sample analysis have been used to measure children's language abilities. However, standardized tests alone cannot provide complete information on each child's interaction skills. To obtain specific performance on interaction skills, spontaneous speech sample analysis is essential in clinical situations. Nevertheless, there is no standardized norm in spontaneous speech sample analysis. Thus, this study is designed to investigate performance in typically developing children (TD) in different age groups by analyzing spontaneous speech samples of four subtypes (the number of utterances, initiations, responses, and turn-takings), compared to those of children with language delay (LD). Methods: A total of 131 children ages 2-5 participated in this study. Spontaneous speech samples were collected during three different structured play settings of 25 minutes each and analyzed for interaction skills. Results: The results are as follows. In the TD group, the number of utterances, responses, and turn-takings increased with age, but there was no significant difference in the number of conversation initiations. There was a significant difference in the number of utterances, conversation initiations, responses, and turn-takings between TD and LD. Conclusion: Results suggest that children's spontaneous speech is representative of their language development and can be an effective measure in screening for children at risk of language delay.

e14552 Background: YBL-006 is an anti-programmed death-1 (PD-1) antibody with a higher affinity compared to that of other PD-1 antibodies, which showed a favorable safety profile in animal models. We designed the first-in-human phase I trial of YBL-006 to assess its safety and efficacy with exploratory biomarker analysis in patients with advanced solid tumors refractory to standard of treatment. Methods: A modified “3+3” design, with the first patient dosed at 0.5 mpk, was followed by conventional dose escalation of 2, 5, and 10 mpk IV. Pharmacokinetics (PK) and pharmacodynamics, including PD-1 receptor occupancy (RO) and serum levels of interferon-gamma (IFN-γ), were assessed. Adverse events (AEs) were graded using the CTCAE v4.03. Tumor response was assessed using the RECIST v1.1 every 8 weeks. For exploratory analysis, tumor mutational burden (TMB) and AI-powered spatial analysis of tumor-infiltrating lymphocyte (TIL) of tumor tissues collected before YBL-006 treatment were performed. The cut-off date for analysis was February 12, 2021. Results: A total of 8 patients enrolled in the 0.5, 2, and 5 mpk cohorts received at least one dose of YBL-006 and median exposure was 15 weeks (ranged 4-26). No dose limiting toxicity occurred and the maximum tolerated dose was not reached until progressing to the 5 mpk. The common treatment-related AEs were G1 fatigue (25%), and G1 hypothyroidism (12.5%). We also observed 1 case of G2 cytokine release syndrome during cycle 1 in 2 mpk which was managed with supportive care alone. No treatment-related deaths have occurred to date. YBL-006 showed a linear PK prolife and both PD-1 RO and serum IFN-γ increased by > 2 times 8 h after the first dose. Tumor evaluation data were available for 7 patients, which showed 1 confirmed complete response (CR, penile squamous cell carcinoma, 2 mpk) and 1 confirmed partial response (PR, anal squamous cell carcinoma, 2 mpk) with durable responses lasting more than 19+ and 10+ weeks respectively, 2 stable disease (SD) and 3 progressive disease (PD). Four tumor samples were available for biomarker analysis. TMBs of patients with CR (8.3/Mb) or PR (9.3/Mb) were higher than those in 2 patients with PD (5.5 and 1.7/Mb). AI-powered spatial analysis of TIL showed that intratumoral TIL density was increased in patients who achieved CR and PR (66.1% and 95.8%, respectively) compared to those in patients who exhibited PD (25.1% and 16.5%, respectively). Conclusions: Interim analysis of phase I study showed that YBL-006 is well tolerated and preliminary biomarker analysis showed that the TMB, and intratumoral TIL infiltration are potentially related to the response to YBL-006. Clinical trial information: NCT04450901.