Age Appropriate Design: Assessment of TikTok, Twitch, and YouTube Kids

The presence of children in the online world is increasing at a rapid pace. As children interact with services such as video sharing, live streaming, and gaming, a number of concerns arise regarding their security and privacy as well as their safety. To address such concerns, the UK's Information Commissioner's Office (ICO) sets out 15 criteria alongside a risk management process for developers of online services for children. We present an analysis of 15 ICO criteria for age appropriate design. More precisely, we investigate whether those criteria provide actionable requirements for developers and whether video sharing and live streaming platforms that are used by children of different age ranges (i.e., TikTok, Twitch and YouTube Kids) comply with them. Our findings regarding the ICO criteria suggest that some criteria such as age verification and transparency provide adequate guidance for assessment whereas other criteria such as parental controls, reporting of inappropriate content, and handling of sensitive data need further clarification. Our findings regarding the platforms themselves suggest that they choose to implement the simplest form of self-declared age verification with limited parental controls and plenty of opportunities

Use of AD Informer Set compounds to explore validity of novel targets in Alzheimer's disease pathology

Abstract Introduction A chemogenomic set of small molecules with annotated activities and implicated roles in Alzheimer's disease (AD) called the AD Informer Set was recently developed and made available to the AD research community: https://treatad.org/data‐tools/ad‐informer‐set/. Methods Small subsets of AD Informer Set compounds were selected for AD‐relevant profiling. Nine compounds targeting proteins expressed by six AD‐implicated genes prioritized for study by Target Enablement to Accelerate Therapy Development for Alzheimer's Disease (TREAT‐AD) teams were selected for G‐protein coupled receptor (GPCR), amyloid beta (Aβ) and tau, and pharmacokinetic (PK) studies. Four non‐overlapping compounds were analyzed in microglial cytotoxicity and phagocytosis assays. Results The nine compounds targeting CAPN2, EPHX2, MDK, MerTK/FLT3, or SYK proteins were profiled in 46 to 47 primary GPCR binding assays. Human induced pluripotent stem cell (iPSC)‐derived neurons were treated with the same nine compounds and secretion of Aβ peptides (Aβ40 and Aβ42) as well as levels of phosphophorylated tau (p‐tau, Thr231) and total tau (t‐tau) peptides measured at two concentrations and two timepoints. Finally, CD1 mice were dosed intravenously to determine preliminary PK and/or brain‐specific penetrance values for these compounds. As a final cell‐based study, a non‐overlapping subset of four compounds was selected based on single‐concentration screening for analysis of both cytotoxicity and phagocytosis in murine and human microglia cells. Discussion We have demonstrated the utility of the AD Informer Set in the validation of novel AD hypotheses using biochemical, cellular (primary and immortalized), and in vivo studies. The selectivity for their primary targets versus essential GPCRs in the brain was established for our compounds. Statistical changes in tau, p‐tau, Aβ40, and/or Aβ42 and blood–brain barrier penetrance were observed, solidifying the utility of specific compounds for AD. Single‐concentration phagocytosis results were validated as predictive of dose–response findings. These studies established workflows, validated assays, and illuminated next steps for protein targets and compounds

AD Informer Set: Chemical tools to facilitate Alzheimer's disease drug discovery

Abstract Introduction The portfolio of novel targets to treat Alzheimer's disease (AD) has been enriched by the Accelerating Medicines Partnership Program for Alzheimer's Disease (AMP AD) program. Methods Publicly available resources, such as literature and databases, enabled a data‐driven effort to identify existing small molecule modulators for many protein products expressed by the genes nominated by AMP AD and suitable positive control compounds to be included in the set. Compounds contained within the set were manually selected and annotated with associated published, predicted, and/or experimental data. Results We built an annotated set of 171 small molecule modulators targeting 98 unique proteins that have been nominated by AMP AD consortium members as novel targets for the treatment of AD. The majority of compounds included in the set are inhibitors. These small molecules vary in their quality and should be considered chemical tools that can be used in efforts to validate therapeutic hypotheses, but which will require further optimization. A physical copy of the AD Informer Set can be requested on the Target Enablement to Accelerate Therapy Development for Alzheimer's Disease (TREAT‐AD) website. Discussion Small molecules that enable target validation are important tools for the translation of novel hypotheses into viable therapeutic strategies for AD