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Reprogramming CD8 T Cell Metabolic Fitness Using MicroRNA-29a to Enhance CAR T Cell Function
No full textCAR T cell immunotherapy has revolutionized cancer treatment, yet low persistence and progressive T cell exhaustion continue to limit durable clinical responses. In a mouse model of chronic LCMV, we recently demonstrated that microRNA-29a overexpression (miR-29aOE) attenuates exhaustion and promotes long-term persistence of antigen-specific CD8 T cells, while retaining their effector functions. Transcriptomic profiling revealed that miR-29aOE T cells are enriched for gene signatures linked to favorable clinical responses to CAR T therapy and enhanced metabolic programs, including fatty-acid oxidation and oxidative phosphorylation. In contrast, miR-29a-deficient T cells displayed diminished spare respiratory capacity and mitochondrial content, underscoring a central role for miR-29a in maintaining metabolic fitness. These findings led us to hypothesize that miR-29aOE could bolster CAR T-cell persistence and amplify anti-tumor potency. To test this hypothesis, we incorporated miR-29a into second-generation CAR T constructs and evaluated their performance in murine lymphoma models. The results revealed that miR-29a-engineered CAR T cells exhibited superior metabolic capacity pre-infusion, and enhanced post-infusion survival, tumor burden and persistence of tumor infiltrating CAR T cells. These findings establish miR-29a as a promising molecular lever for improving the longevity and efficacy of CAR T cell therapies. </p
Core Mechanisms that Contribute to Inhibition of Wound Healing in Diabetic Foot and Venous Leg Ulcers
No full textDiabetic foot ulcers (DFU) and venous leg ulcers (VLU) are prevalent chronic wounds with a debilitating impact on patient morbidity and mortality. Effective treatments for chronic wounds are limited and the absence of valid chronic wound animal models has driven the use of bioinformatics to gain new insights into dysregulated mechanisms shared in chronic wound healing. Because chronic wounds share features such as a hyperproliferative, non-migratory epidermis, fibrosis, decreased angiogenesis, and a de-regulated inflammatory response, it was predicted that a bioinformatic comparison of DFUs and VLUs would identify a core chronic wound transcriptome. Analysis of the newly identified core chronic wound transcriptome highlighted shared mechanisms, including a host response pathway modulated by the microbiome: the aryl hydrocarbon receptor signaling pathway. Aryl hydrocarbon receptor signaling was found to be suppressed in chronic wounds which contributes to wound healing inhibition. Additionally, comparisons of prototypical skin commensal bacteria strains isolated from chronic wounds found that increased antimicrobial resistance was a driver of bacterial fitness, pathogenicity, and wound healing impairment in chronic wounds. Further studies of the chronic wound microbiome identified an intracellular niche of S. aureus present which contributes to inflammatory cell death, pyroptosis. A postbiotic derived from Lactobacillus was found to effectively reduce the intracellular niche of S. aureus in keratinocytes while simultaneously promoting wound healing and strengthening the skin barrier. To validate the core chronic wound transcriptome and impacts of the microbiome, an integrative approach that included patients’ wound samples, primary human cells, and human skin ex vivo infection models were used. The results herein characterize mechanisms important for chronic wound healing and for future development of targeted therapeutics.</p
Navigating Caregiving Challenges: An Intersectional and Mixed-Methods Analysis of Resilience among Family Cancer Caregivers
No full textFramed by the Communication Theory of Resilience (CTR) and intersectionality framework, this explanatory sequential mixed-methods study examined how family cancer caregivers with diverse identities experience and enact communicative resilience. In Phase 1, a U.S.-based online survey (N = 240) assessed caregivers’ resilience and posttraumatic growth (PTG), producing four profiles: Vulnerable Reflectors (high PTG-low resilience), Survival Seekers (low PTG-high resilience), Adaptive Strivers (high PTG-high resilience), and At-Risk Strugglers (low PTG-low resilience). In Phase 2, twenty semi-structured interviews were conducted across these profiles to explore resilience triggers, resilience processes, and coping strategies.Findings revealed five common resilience triggers that intersected across gender, race/ethnicity, and socioeconomic status, often emerging simultaneously rather than sequentially. While some communicative processes stabilized caregivers, others created additional strain when structural resources were lacking. Notably, resilience and PTG followed divergent patterns. High PTG was often rooted in meaning-making through relational talk, whereas high resilience centered on routine-based coping. Based on these findings, we propose the concept of resilience-switching—the fluid movement between anticipatory and reactive caregiving responses—as a micro-temporal mechanism within the resilience construct. This concept refines CTR by emphasizing temporal flexibility and structural constraints in communicative adaptation.Together, the results suggest that resilience is not a uniform process but one shaped by identity, context, and communicative access. The study offers theoretical contributions to CTR and practical guidance for tailoring intervention tools for diverse family cancer caregivers.</p
The Reciprocal Processes between Personal and Professional Development among Psychoanalytically Oriented Psychotherapists
No full textPsychoanalytically oriented psychotherapies (POP) emphasize understanding unconscious thoughts and feelings, their origins, and using relationships as a catalyst for change. While research supports POP’s efficacy and long-term benefits (Abbass et al., 2014; Shedler, 2010), little is known about how practitioners develop expertise through personal and professional experiences beyond a theoretical and anecdotal nature. This study investigates the professional and personal developmental processes of POP practitioners and how these processes reciprocally influence one another. This researcher recruited 13 middle, senior, and late senior career POP practitioners who graduated with their terminal degrees between 1990 and 2014 and are practicing in the U.S. Efforts were made to recruit practitioners across developmental stages. This researcher conducted semi-structured interviews and used interpretive phenomenological analysis (IPA) to analyze interview data, allowing for rich, deep examinations of the meaning that participants created out of their lived experience (Smith & Shinebourne, 2012). Five themes and 22 subthemes depicted practitioners’ change processes emerged from the interviews: (a) Deepening Clinical Presence Through Personal Experience, (b) Developing Awareness and Insight, (c) Transformation Through Relational Encounters, (d) Internalizing Theory Enriches Clinical Practice and Personal Experiences, and (e) Reflecting on Cultural Identity and Social Consciousness Promotes Humility, Empathy, and Responsibility These themes and subthemes were explained in detail with examples to illustrate participants’ developmental processes. Findings of this study may better inform future avenues for research, education and training, the field of psychoanalytic psychology, and policy regarding promoting growth among POP practitioners.</p
A Novel Blockchain Paradigm for Creating, Maintaining, and Sharing Personal Blockchain Ledgers
No full textBlockchain technology was first created to enable a peer-to-peer payment system known as Bitcoin. Since its inception, blockchain technology has evolved to satisfy more diverse use cases, with blockchain development platforms like Ethereum, allowing for complex applications to be built using blockchain. However, despite its utility, blockchain has failed to gain widespread utilization outside of a few niche use cases. In this work, we analyze the most popular blockchain development platforms to identify the limitations of current blockchain technology; finding that the failure to adopt blockchain is due to scalability, data privacy protections, and complexity. To overcome the identified limitations we propose a new blockchain paradigm, Personal Blockchain Ledgers. In our this paradigm, each user stores data on a separate blockchain, in contrast to the traditional blockchain, where all users store data on a single large blockchain. To support our paradigm, we propose the PBL System, which creates and maintains Personal Blockchain Ledgers. We provide a theoretical soundness for our system. We then provide an extension to our system for sharing blockchain data. We show how users can utilize our extension to selectively share data with third parties who may not participate in the PBL System. Finally, we present a prototype implementation of our system. To show the effectiveness of our system, we conduct empirical evaluations to compare it to existing popular blockchain platforms. Likewise, to show the scalability of our system, we simulate high system load using a High Performance Computer. Through this work we have proposed a novel paradigm, a system for utilizing the paradigm, and an empirical implementation of the system.</p
Integration of Holistic Admissions in the University of Miami Doctor of Physical Therapy Program
No full textThe University of Miami Doctor of Physical Therapy (UMDPT) program and DPT programs nationwide are experiencing unprecedented change in their admissions processes as they transition to holistic admissions (HA). The movement to HA stems from elimination of the GRE as a considered metric and the emphasis on promoting diversity in the physical therapy workforce. Due to a lack of evidence on how to implement HA successfully, the purpose of this dissertation was to synthesize current evidence and best practices related to HA from other DPT programs, medical schools, and colleges of health sciences. The goal was to provide data-driven, evidence-based policy and procedure recommendations for the implementation of HA at UMDPT. Based on the literature, guidance should be derived from the mission/vision of each DPT program and two frameworks inherent to physical therapy. Specific recommendations for UMDPT include: 1) continuing applicant interviews with the addition of bias training for interviewers, 2) holding a holistic admissions workshop for faculty, 3) using personal statements and letters of recommendation minimally, 4) providing a better capture of key elements of the department’s vision (leadership and community service), 5) modifying current rubrics, and 6) embarking on retrospective and prospective cohort studies to determine which elements of GPA predict academic outcomes for students. Successful integration may position UMDPT at the forefront of the HA movement nationally.</p
"This printing blood": Reproductive Materialities in Early Modern English Literature
No full textThis dissertation examines the language of reproduction in early modern literary and non-literary texts by centering a shared vocabulary of liquidity and fluidity. This fluid language is found in Classical texts such as Ovid’s Metamorphoses which were formative in the early modern classroom and consistently appears in genres including the sonnet sequence, lyric poetry, medical texts, agricultural manuals, and recipe books. Chapter 2 examines reproductive language in William Shakespeare’s Sonnets and Philip Sidney’s Astrophil and Stella sequence, finding that the fluid vocabulary destabilizes the poetry’s portrayal of literary production. Chapter 3 applies a similar fluid reading to the language of patronage verse letters by John Donne to his female patron, the Countess of Bedford. The chapter argues that the language employed in this genre hinges on the understanding of the female body as fluid. Chapter 4 reads misogynist manuscript lyric together with woman authored receipt books to examine the portrayal of the reproductive female body as both corrupt and erotic. Bodily fluids are central to interpreting the status of the body and exerting control over it. Chapter 5 reads the dairy as a site of reproductive female labor, centered around milk and its physical and interpretive possibilities, rooted in cheesemaking as a common metaphor for pregnancy. Ending with a reading of Hester Pulter’s childbirth poetics, this dissertation centers women’s bodies in creative narratives that often elide their lived experiences in metaphorical representations. </p
Informant Discrepancies in the Treatment of Youth Internalizing Disorders: Implications for Clinical Outcomes and the Effect of Measurement-Based Care
No full text The integration of evidence-based assessment practices in treatment has been shown to enhance clinical outcomes for youth, however discrepancies in the views of youth and parents on the presence, severity, and effects of youth psychopathology often complicate the treatment process. Measurement-based care (MBC), the routine collection, evaluation, and sharing of assessment data to monitor and support treatment progress, may promote the alignment of varied perspectives. This study sought to further understand the link between parent-youth informant discrepancies and youth treatment outcomes and the potential moderating effects of engagement in and dosage of measurement-based care. Participants included 196 parent-youth dyads, with youth ages 12 to 18. Informants completed ratings of anxiety, depression, and overall symptom severity at the outset and throughout treatment, and youth clinical outcomes were assessed at multiple timepoints. Two of the three treatment conditions incorporated MBC and clinicians within these conditions reported on their MBC practices at each session. Hierarchical linear and logistic modeling using polynomial regression was used to examine the proposed models. Exploratory analyses were also conducted to assess descriptive changes in parent-youth discrepancies on symptom measures over the course of treatment. Results showed that youth reported significantly greater anxiety symptoms than parents at baseline and greater depressive symptoms than parents at the 8-week timepoint. Greater pre-treatment parent-youth discrepancies in anxiety ratings were found to predict a lower likelihood of treatment response at the 16-week timepoint. Engagement in and dosage of measurement-based care were not found to moderate associations between pre-treatment discrepancies and youth treatment outcomes. Exploratory analyses revealed descriptive trends of increased concordance in average symptom ratings over the course of treatment for anxiety measures across conditions, for those who received MBC, and for those who were treatment responders.</p
Shared Spaces, Shared Voices: Predicting Social Vocalizations among Preschoolers With and Without Autism Spectrum Disorder
No full textChildren with autism spectrum disorder (ASD) commonly exhibit differences in social communication behaviors that form the foundation for peer engagement. While prior research has indicated that autistic children vocalize at a reduced rate during classroom social contact with their peers, it is unknown whether these difficulties are influenced by limited social contact with peers, a reduced vocalization rate overall, or both. This study investigated predictors of preschoolers’ rate of vocalizations during peer social contact (i.e., social vocalizations) from their proportion of classroom time in peer social contact and overall classroom vocalization rate (i.e., talkativeness) in children with ASD (n = 51), developmental disabilities (DD; n = 36), and typical development (TD; n = 44) across 14 inclusive classrooms. Automated, child-worn sensors dynamically tracked children’s location, orientation, and vocalizations throughout the school day. Multi-level modeling indicated that, compared to their typically developing peers, autistic preschoolers spent a lower proportion of their classroom time in social contact with peers, did not differ in their overall vocalization rate in the classroom, and vocalized at lower rates while in social contact with peers. While both time in peer social contact and talkativeness positively predicted social vocalization rates for all children, autistic preschoolers showed smaller increases in their social vocalization rate with more social contact time compared to their TD peers. No significant differences emerged between the ASD and DD group on any measure. Overall, these findings highlight the importance of increasing opportunities for social contact while leveraging autistic preschoolers’ existing talkativeness to enhance their social communication with peers.</p
Stuck Between an Inflexible Heart and Mind: Examining Heart Rate Variability, Cognitive and Emotion Flexibility in Relation to Internalizing Symptoms
No full textIndividuals with internalizing disorders (e.g., anxiety, depression) often exhibit difficulties with cognitive and emotion flexibility. Cognitive flexibility is an important control mechanism for adapting human thought and action, while emotion flexibility enables regulation of emotional perception and reactions. Laboratory-based tasks involving cued flexible thinking do not adequately capture an individual’s ability to adapt to environmental changes without guidance or represent the extent to which individuals must exert flexibility in daily life. Thus, researchers need to examine more ecologically valid measures of flexibility in relation to symptoms of internalizing disorders. We developed a novel item-generation task to assess how individuals flexibly generated thoughts within and across cognitive and emotional domains. While flexibility with cognitions and emotions is important for effective adaptation to environmental changes, heart rate variability (HRV), the fluctuations in the time between heart beats, provides a non-invasive measure of autonomic nervous system functioning in response to stressors, both in the laboratory as well as with wearable devices. Using an unselected sample of undergraduate students (n=110, 18-22 years old, 58 % female), we characterized how cognitive and emotion flexibility uniquely relate to clinical symptoms of anxiety. In addition, we characterized both lab-based and ambulatory measures of vagally-mediated HRV in relation to cognitive and emotion flexibility using the novel item-generation. Overall, results indicate that performance on the item-generation task was related to standardized measures of cognitive flexibility. While HRV during the task was not related to performance, higher HRV during a control task prior to item-generation predicted better performance across most trial types. Finally, performance was also related to self-report symptoms of anxiety, although this relationship was more robust in dual category conditions. Limitations and clinical implications of the findings are discussed.</p