Citations

Abstract Patients with cancer and their caregivers face challenges accessing clinical trials because trial information, eligibility criteria, search, and referral pathways are complex and fragmented. These barriers can contribute to unequal access across racial, ethnic, and language groups. ALEX (Agents Leveraging Empathy for eXams) is a web-based portal that uses AI-enabled virtual health educators with synthesized voices and lip-synced facial animation to deliver trial education and a large language model to simplify trial information for search and referral. AI-generated content and virtual humans require human and community evaluation for accuracy, authenticity, and trust. This study examined how community feedback informed the iterative design and refinement of ALEX. The dataset included 34 English- and Spanish-language transcripts (about 44 hours) from focus groups and usability interviews using think-aloud procedures to evaluate the portal. The sessions were conducted from 2023 to 2025 at Mayo Clinic, UF-Gainesville, UF-Jacksonville, and the University of Miami. They examined 136 participants’ responses to the virtual health educators and their use of the portal for trial education, search, and referral. Participants reported their race as White (48.5%), Black or African American (47.1%), Native American or Alaska Native (0.7%), or other (3.7%). Separately, 50.7% identified as Hispanic or Latino, and nearly 25% reported Spanish as their primary language. Throughout data collection, feedback was reviewed and translated into design requirements for successive portal updates. We used deductive and inductive qualitative analysis to identify feedback patterns and user needs and reviewed version history to document portal changes. Three of the six themes derived from 1,653 coded excerpts were Trust Before Trial Search (“Who is Alex?”), Layered and Controllable Education (“If it was more in short bullets, maybe better”), and Motivation, Burden, and Research Trust (“There has to be some trust, some transparency or at least some acknowledgement”). Feedback informed portal refinements, including clearer language and institutional branding and content that was easier to scan. The virtual health educators were evaluated on representation, voice authenticity, lip-sync, warmth, and human likeness. Words like “sponsored study,” “diagnosis,” and “symptoms” guided language refinement. Suggested improvements included sample search terms, easy-to-read study cards, the ability to save results, a question guide, and direct coordinator contact. Research trust, privacy, security, and participation burden remained key priorities. To create an AI-enabled clinical trial portal that meets user needs, we used community feedback to identify modifiable barriers to communication, search, and referral. The goal of this formative process is to transparently incorporate that feedback into trial tools that are more credible, usable, acceptable, and equitable. Future work should evaluate whether these revisions improve referral outcomes. Citation Format: Fan Wang, Rashi Ghosh, Christopher You, Trevor Kauer, Andrew H. Maxim, Courtny Franco, Stephen Anton, Elizabeth Flood-Grady, Trudy Gaillard, Thomas J. George, Benjamin Lok, Carolyn Tucker, Melissa Vilaro, Tuo Lin, Fern Webb, Diana Wilkie, Danyell Wilson-Howard, Olveen Carrasquillo, Janice L. Krieger. Can artificial intelligence amplify community voice? Evidence from a multisite formative evaluation of the AI-Powered ALEX Portal to enhance equity in clinical trial access [abstract]. In: Proceedings of the 19th AACR Conference on the Science of Cancer Health Disparities; 2026 Oct 18-21; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2026;35(10 Suppl):Abstract nr B034.

Background: Monitored anesthesia care (MAC) combined with regional anesthetic techniques is commonly used for open reduction and internal fixation (ORIF) of unstable ankle fractures. When compared to general anesthesia (GA), MAC with regional anesthesia has been associated with reduced systemic adverse effects and shorter recovery times, although regional anesthesia carries additional costs and potential complications of its own. A new technique involving the infiltration of high-volume, low-concentration (VL) local anesthetic was therefore developed. When used in conjunction with MAC, we refer to this technique as MAC-VL. This study evaluates outcomes and recovery metrics following outpatient ankle ORIF performed under GA vs MAC-VL without regional anesthesia. Methods: An IRB-approved retrospective cohort study was conducted including 159 adults who underwent outpatient ankle ORIF between February 1, 2023, and January 31, 2026. Patients were identified using standardized diagnostic and procedural codes and grouped according to anesthesia type. All patients received a standardized injection of local anesthetic around the proposed operative sites before the procedure; anesthesia type was MAC (n = 48) or GA (n = 111). The primary outcome was time to discharge, defined as the interval from incision closed to hospital discharge. Secondary outcomes were considered exploratory and included tourniquet, operative, anesthesia time, time in room, Post Anesthesia Care Unit length of stay, conversion from MAC to GA, reported postoperative nausea and vomiting, admissions, and postoperative emergency department visits. Results: Among 160 procedures for which no significant difference in case mix could be detected with the numbers available, MAC-VL was associated with a significantly shorter time to discharge—reducing discharge time by 55.2 minutes ( P < .001) following adjustment for demographic, clinical, and operative covariates—and shortened total anesthesia and operating room time compared with GA. With the numbers available, no significant difference was detected for the remaining secondary outcomes. Conclusion: The MAC-VL protocol was associated with shorter operating room and recovery times and may improve health care resource use. Level of Evidence: Level III, retrospective cohort study.

Abstract T-cell immune tolerance is established in part through the activity of the autoimmune regulator (AIRE) transcription factor in medullary thymic epithelial cells (mTEC) of the thymus. AIRE induces expression of peripheral tissue–specific self-antigens for presentation to naïve T cells to promote activation/deletion of autoreactive T cells. This traditional role of AIRE in mTECs is to prevent autoimmunity. Herein, we demonstrate that tumors mimic the role of AIRE in mTECs to evade immune rejection. We found that AIRE induced a profile of “selfness” at the RNA and protein levels which, when presented on major histocompatibility complexes (MHC), shielded the tumor from inherently self-tolerized T cells. Moreover, we describe an in vivo immunotherapy in which engineered changes in AIRE expression in tumor cells altered their profile of selfness, exposing both AIRE-modified and parental unmodified tumor cells to T-cell attack. Therefore, by resetting the immunologic selfness of cancer cells, this AIRE-mediated immunotherapy (i) converted a highly tolerized T-cell compartment into a tumor-reactive T-cell population; (ii) conferred upon nonimmunogenic tumors de novo sensitivity to immune checkpoint blockade; (iii) removed the need to identify potentially immunogenic tumor-associated antigens as targets for generation of T-cell responses; and (iv) lead to potent T cell–mediated rejection of aggressive, immunologically cold, nonimmunogenic tumors. Patient RNA sequencing data showed that the expression of AIRE predicted response to immune therapies with a strong correlation between AIRE expression and markers of T-cell receptor signaling, suggesting that our studies have therapeutic translational value.

Adult optic nerve axon regeneration has traditionally been framed as a problem of limited intrinsic growth capacity in central nervous system neurons. However, growing evidence suggests that intrinsic factors alone cannot account for regenerative failure: restrictive extrinsic environmental factors largely govern optic nerve regeneration, dictating the intrinsic capacity axons can express. In this review, we frame the extrinsic optic nerve environment as a dynamic regenerative niche, in which vascular, immune, glial, matrix, and metabolic compartments are spatially co-localized and temporally coordinated rather than acting as independent barriers. These compartments follow a shared trajectory, broadly protective in the acute phase, then inhibitory once the underlying response fails to resolve, while also actively driving one another, such as reactive astrocytes promoting the matrix remodeling that subsequently restricts axon regrowth. Consequently, the niche’s overall permissiveness for regeneration reflects the aggregate and interdependent state of these compartments rather than the action of any single barrier. This review integrates current evidence on extrinsic barriers, intervention opportunities, and disease-specific variability relevant to RGC axon regeneration after injury. These interventions must incorporate the spatial, temporal, and metabolic factors that shape the goal of functional recovery and vision restoration.

The kinesin-5 motor protein KIF11 is crucial for mitotic spindle assembly, driving the separation of spindle poles through microtubule sliding. Src-family kinases phosphorylate KIF11 at multiple tyrosine residues within its motor domain, but the mechanistic consequences of these modifications remain unclear. Here, we dissect the role of phosphorylation at Y211 using phospho-mimetic (Y211E) and nonphosphorylatable mutants (Y211F) in biochemical, biophysical, and cellular assays. Optical trapping and Förster resonance energy transfer analyses reveal that Y211 phosphorylation slows neck-linker docking, reducing motor velocity and force generation under load. In human cells, Y211E expression impairs bipolar spindle formation and decreases spindle pole separation velocity, while Y211F shortens steady-state spindle length. Fluorescence recovery after photobleaching analyses show that Y211E accelerates motor turnover on spindle microtubules, consistent with the mutant motor’s heightened load sensitivity. Together, these findings support a model in which Src-mediated phosphorylation at Y211 acts as a rheostat to tune KIF11 mechanochemistry and spindle assembly dynamics, linking cancer-relevant kinase signaling to mitotic force generation.