Cancer-on-a-Chip: Models for Studying Metastasis.

The microfluidic-based cancer-on-a-chip models work as a powerful tool to study the tumor microenvironment and its role in metastasis. The models recapitulate and systematically simplify the in vitro tumor microenvironment. This enables the study of a metastatic process in unprecedented detail. This review examines the development of cancer-on-a-chip microfluidic platforms at the invasion/intravasation, extravasation, and angiogenesis steps over the last three years. The on-chip modeling of mechanical cues involved in the metastasis cascade are also discussed. Finally, the popular design of microfluidic chip models for each step are discussed along with the challenges and perspectives of cancer-on-a-chip models.

Targeting angiogenic growth factors using therapeutic glycosaminoglycans on doppel-expressing endothelial cells for blocking angiogenic signaling in cancer.

Growth factors (GF) regulate normal development to cancer progression. GFs interact with extracellular matrix (ECM) biomolecules, such as heparin sulfate (HS) glycosaminoglycan (GAG), to enhance their stability and angiogenic signaling. Biomaterials that modulate GF activity by mimicking interactions observed in the native ECM could be designed as an effective treatment strategy. However, these materials failed to attenuate angiogenic signaling site-specifically without sparing normal tissues. In this work, we investigated the effect of a GAG-based biomaterial, which binds to the tumor endothelial cells (TEC), on the interaction among vascular endothelial growth factor (VEGF), its receptors-VEGFR2 and HS-and angiogenesis. Heparin-bile acid based conjugates, as ECM-mimicking component, were synthesized to selectively target the TEC marker doppel and doppel/VEGFR2 axis. The most effective compound LHbisD4 (low molecular weight heparin conjugated with 4 molecules of dimeric dexocholic acid) reduced tumor volume concentrated over doppel-expressing EC, and decreased tumor-interstitial VEGF without affecting its plasma concentration. Doppel-destined LHbisD4 captured VEGF, formed an intermediate complex with doppel, VEGFR2, and VEGF but did not induce active VEGFR2 dimerization, and competitively inhibited HS for VEGF binding. We thus show that GAG-based materials can be designed to imitate and leverage to control tumor microenvironment via bio-inspired interactions.

Bidirectional communication between mast cells and the gut-brain axis in neurodegenerative diseases: Avenues for therapeutic intervention.

Although the global incidence of neurodegenerative diseases has been steadily increasing, especially in adults, there are no effective therapeutic interventions. Neurodegeneration is a heterogeneous group of disorders that is characterized by the activation of immune cells in the central nervous system (CNS) (e.g., mast cells and microglia) and subsequent neuroinflammation. Mast cells are found in the brain and the gastrointestinal tract and play a role in "tuning" neuroimmune responses. The complex bidirectional communication between mast cells and gut microbiota coordinates various dynamic neuro-cellular responses, which propagates neuronal impulses from the gastrointestinal tract into the CNS. Numerous inflammatory mediators from degranulated mast cells alter intestinal gut permeability and disrupt blood-brain barrier, which results in the promotion of neuroinflammatory processes leading to neurological disorders, thereby offsetting the balance in immune-surveillance. Emerging evidence supports the hypothesis that gut-microbiota exert a pivotal role in inflammatory signaling through the activation of immune and inflammatory cells. Communication between inflammatory cytokines and neurocircuits via the gut-brain axis (GBA) affects behavioral responses, activates mast cells and microglia that causes neuroinflammation, which is associated with neurological diseases. In this comprehensive review, we focus on what is currently known about mast cells and the gut-brain axis relationship, and how this relationship is connected to neurodegenerative diseases. We hope that further elucidating the bidirectional communication between mast cells and the GBA will not only stimulate future research on neurodegenerative diseases but will also identify new opportunities for therapeutic interventions.

Artificial Intelligence-Powered Smartphone App to Facilitate Medication Adherence: Protocol for a Human Factors Design Study.

BACKGROUND: Medication Guides consisting of crucial interactions and side effects are extensive and complex. Due to the exhaustive information, patients do not retain the necessary medication information, which can result in hospitalizations and medication nonadherence. A gap exists in understanding patients' cognition of managing complex medication information. However, advancements in technology and artificial intelligence (AI) allow us to understand patient cognitive processes to design an app to better provide important medication information to patients. OBJECTIVE: Our objective is to improve the design of an innovative AI- and human factor-based interface that supports patients' medication information comprehension that could potentially improve medication adherence. METHODS: This study has three aims. Aim 1 has three phases: (1) an observational study to understand patient perception of fear and biases regarding medication information, (2) an eye-tracking study to understand the attention locus for medication information, and (3) a psychological refractory period (PRP) paradigm study to understand functionalities. Observational data will be collected, such as audio and video recordings, gaze mapping, and time from PRP. A total of 50 patients, aged 18-65 years, who started at least one new medication, for which we developed visualization information, and who have a cognitive status of 34 during cognitive screening using the TICS-M test and health literacy level will be included in this aim of the study. In Aim 2, we will iteratively design and evaluate an AI-powered medication information visualization interface as a smartphone app with the knowledge gained from each component of Aim 1. The interface will be assessed through two usability surveys. A total of 300 patients, aged 18-65 years, with diabetes, cardiovascular diseases, or mental health disorders, will be recruited for the surveys. Data from the surveys will be analyzed through exploratory factor analysis. In Aim 3, in order to test the prototype, there will be a two-arm study design. This aim will include 900 patients, aged 18-65 years, with internet access, without any cognitive impairment, and with at least two medications. Patients will be sequentially randomized. Three surveys will be used to assess the primary outcome of medication information comprehension and the secondary outcome of medication adherence at 12 weeks. RESULTS: Preliminary data collection will be conducted in 2021, and results are expected to be published in 2022. CONCLUSIONS: This study will lead the future of AI-based, innovative, digital interface design and aid in improving medication comprehension, which may improve medication adherence. The results from this study will also open up future research opportunities in understanding how patients manage complex medication information and will inform the format and design for innovative, AI-powered digital interfaces for Medication Guides. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/21659.

Improving Team-Based Decision Making Using Data Analytics and Informatics: Protocol for a Collaborative Decision Support Design.

BACKGROUND: According to the September 2015 Institute of Medicine report, Improving Diagnosis in Health Care, each of us is likely to experience one diagnostic error in our lifetime, often with devastating consequences. Traditionally, diagnostic decision making has been the sole responsibility of an individual clinician. However, diagnosis involves an interaction among interprofessional team members with different training, skills, cultures, knowledge, and backgrounds. Moreover, diagnostic error is prevalent in the interruption-prone environment, such as the emergency department, where the loss of information may hinder a correct diagnosis. OBJECTIVE: The overall purpose of this protocol is to improve team-based diagnostic decision making by focusing on data analytics and informatics tools that improve collective information management. METHODS: To achieve this goal, we will identify the factors contributing to failures in team-based diagnostic decision making (aim 1), understand the barriers of using current health information technology tools for team collaboration (aim 2), and develop and evaluate a collaborative decision-making prototype that can improve team-based diagnostic decision making (aim 3). RESULTS: Between 2019 to 2020, we are collecting data for this study. The results are anticipated to be published between 2020 and 2021. CONCLUSIONS: The results from this study can shed light on improving diagnostic decision making by incorporating diagnostics rationale from team members. We believe a positive direction to move forward in solving diagnostic errors is by incorporating all team members, and using informatics. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/16047.

Improving Medication Information Presentation Through Interactive Visualization in Mobile Apps: Human Factors Design.

BACKGROUND: Despite the detailed patient package inserts (PPIs) with prescription drugs that communicate crucial information about safety, there is a critical gap between patient understanding and the knowledge presented. As a result, patients may suffer from adverse events. We propose using human factors design methodologies such as hierarchical task analysis (HTA) and interactive visualization to bridge this gap. We hypothesize that an innovative mobile app employing human factors design with an interactive visualization can deliver PPI information aligned with patients' information processing heuristics. Such an app may help patients gain an improved overall knowledge of medications. OBJECTIVE: The objective of this study was to explore the feasibility of designing an interactive visualization-based mobile app using an HTA approach through a mobile prototype. METHODS: Two pharmacists constructed the HTA for the drug risperidone. Later, the specific requirements of the design were translated using infographics. We transferred the wireframes of the prototype into an interactive user interface. Finally, a usability evaluation of the mobile health app was conducted. RESULTS: A mobile app prototype using HTA and infographics was successfully created. We reiterated the design based on the specific recommendations from the usability evaluations. CONCLUSIONS: Using HTA methodology, we successfully created a mobile prototype for delivering PPI on the drug risperidone to patients. The hierarchical goals and subgoals were translated into a mobile prototype.