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Open Access Publications from the University of California

Scholarly Works (10 results)

  • Thesis
  • Peer Reviewed
UC San Diego Electronic Theses and Dissertations (2012)
Mature B lymphocytes are capable of acquiring adaptive immune function based upon several selective and diversification processes, which allow potent antibody responses. It is speculated that E proteins play an important role in such events, as they are a class of basic helix-loop-helix transcription factors involved in a multitude of hematopoetic developmental pathways. While the function of E proteins in early B lymphopoiesis is well characterized, less is known about these DNA binding factors in the later stages of B cell maturation. Here, using a combination of in vivo and in vitro methods, we studied the germinal center reaction, class switch recombination, and plasma cell development in mice lacking the E proteins E2A and HEB in an attempt to better understand the participation of E2A and HEB in antigen- activated B cell formation. In vivo, lethally irradiated mice transplanted with E2A and HEB null bone marrow are deficient in class switch recombination and subsequent plasma cell function. In vitro experiments show that the E proteins E2A and HEB are both required for efficient humoral immunity. Mice lacking one or both of these E proteins demonstrate perturbed isotype switching and plasma cell differentiation in activated B cell cultures. We further identify impaired expression of genes involved in the germinal center reaction and plasma cell development. Taken together, these data suggest that E2A and HEB function in the germinal center by controlling two mutually exclusive transcriptional programs that ultimately drive B cell activation. We additionally examined genome-wide H3K3 monomethylation patterns in naïve and germinal center B cells. This analysis has confirmed the importance of E2A in late and end stage B cell development and ultimately suggests differences in the enhancer repertoire of naïve B lymphocytes in comparison to antigen-dependent B cell lineages
    Cover page: E protein function in activated B cell subsets
    • Thesis
    • Peer Reviewed
    UCLA Electronic Theses and Dissertations (2024)

    Personalized assessment measures focusing on caregiver-reported problems have been found to be psychometrically robust and useful in monitoring the clinical response of typically developing children in psychological interventions due to the high sensitivity to change of such measures (e.g., Weisz et al., 2011). However, until recently, these measures have not addressed autism-related challenges, and there is still a need for a personalized assessment of children and youth with autism that 1) is broadly inclusive of the heterogeneity of autism-related needs, 2) addresses the critical perspective of caregivers, and 3) facilitates intervention monitoring for specific children. This project explores the development and psychometric properties of a newly developed personalized semi-structured interview for caregivers of children with autism drawing from the ratings methodology used in the Top Problems Assessment (TPA) developed by Weisz and colleagues (2011) in two phases. The newly developed semi-structured interview (known namely as the YTP-Interview) protocol addresses multiple autism-related clinical areas and identifies the top problems salient to the caregivers, allowing for rapid repeated administration throughout intervention. Through qualitative exploration, the pilot study (Phase 1) of the project found that extensive clinical information can be obtained from this personalized semi-structured interview. Caregivers reported individualized problems in relation to six clinical domains (e.g., externalizing behavior, peer engagement), demonstrating rich insight into their child’s specific challenges and needs. Phase 2 of the project examined the test-retest reliability, convergent and discriminant validity, sensitivity and specificity, and face validity of the YTP-Interview across six domains: Dysregulated and Disruptive Behavior, Anxiety and Depression, Restricted and Repetitive Behaviors, Peer Engagement in School and Community, Conversation and Friendship, and Self-Care Skills. Data was collected from 31 caregivers of children with autism at three time points: Baseline, Week 1, and Week 2 of intervention. Spearman’s rho correlations indicated strong test-retest reliability for all domains, with particularly high correlations for the Peer Engagement and Conversation and Friendship domains. The ROC curve analysis provided valuable insights into the utility of the YTP-Interview for identifying clinically significant problems in children with autism. The analysis revealed that the optimal cut-scores demonstrated acceptable levels of sensitivity and specificity across five of the six clinical areas. The face validity results demonstrated high accuracy across all domains, with percentages ranging from 98% to 100%. Furthermore, caregiver satisfaction with the YTP-Interview was overwhelmingly positive, with 100% of participants indicating they were very satisfied with the process. Overall, the findings suggest that the YTP-Interview is a reliable and valid tool for identifying and monitoring the top problems in children with autism as reported by their caregivers, demonstrating strong psychometric properties that support its use in clinical practice and research applications. The results from this study are promising, suggesting that this new measure has the potential to align assessment and intervention foci with the needs and aspirations of families.

      Cover page: Personalized Assessment for Youth with Autism: Evaluating the Psychometric Properties of a Semi-Structured Interview
      • Thesis
      • Peer Reviewed
      UC Davis Electronic Theses and Dissertations (2021)

      Tarsila do Amaral (Brazil) and Amrita Sher-Gil (India) both actively participated in their respective country’s struggles to develop an anti-colonial national aesthetic in a global modern context. Both used their paintings as tools to challenge Euro-U.S.-centric and patriarchal hegemonies, and for nearly ninety years, both have been criticized, marginalized, and silenced by the Euro-U.S. art world. Since the 1990s, scholars have made conscious efforts to produce a critical art history that disavows Western artistic supremacy and integrates Amaral and Sher-Gil into the Euro-U.S. art historical canonical discourse. But only in the last few years have major museums, auction houses, and social media accounts in Europe and the United States deemed them worthy of inclusion in the canon. Hitherto unexplored, this integration suggests an ostensible institutional volte-face; however, an examination of the conditions that launched Amaral and Sher-Gil into Euro-U.S. consciousness suggests otherwise. My research explores how shifts in the art market and museum culture have shaped Tarsila do Amaral’s and Amrita Sher-Gil’s relationships to the canon, and how those relationships have changed over time. By examining and questioning the shifts in institutional trends, my analysis exposes the enduring legacy of colonial ideology that pervades the Euro-U.S. art world and holds a mirror to the intrinsic hypocrisy of the canon, even an expanded one.

        Cover page: Why Now?: The Euro-U.S. Canon Adopts Tarsila do Amaral and Amrita Sher-Gil Almost 90 Years Later
        • Article
        • Peer Reviewed
        UC Davis Previously Published Works (2023)
        OBJECTIVES: Vocal fold medialization is commonly performed for glottic insufficiency and vocal fold immobility. Currently available materials are temporary injectables or synthetic implants. Acellular scaffolds may allow vocal fold augmentation with autologous tissue via host cell migration. The purpose of this investigation was to evaluate the use of a novel carbohydrate scaffold as a medialization implant. STUDY DESIGN: Animal model. SETTING: Academic medical center. METHODS: Unilateral type I medialization thyroplasty was performed in 3 Dorper cross ewes using a hypercrosslinked carbohydrate polymer (HCCP) scaffold. Animals were monitored for 4 weeks for general well-being, dyspnea, and weight loss. The animals were euthanized at 4 weeks and the larynges harvested. Histologic evaluation was performed to assess for adverse tissue reaction, migration, degradation, and biocompatibility. RESULTS: No adverse events were reported. No animals lost weight or displayed evidence of dyspnea. Histology demonstrated ingrowth of host cells and neovascularization with minimal peri-implant inflammatory reaction. Cellular ingrowth into the scaffold was predominately made up of fibroblasts and early inflammatory cells. Scaffold shape was grossly maintained as it underwent degradation and replacement with host tissue. Migration of the implant material was not observed. CONCLUSION: Vocal fold medialization in an ovine model with an HCCP scaffold resulted in the ingrowth of host cells with minimal peri-implant inflammation. Scaffold shape was maintained without evidence of migration as it underwent replacement with host tissue. Further research is required to assess long-term efficacy in comparison to currently available implants.
          Cover page: Use of a Novel Hypercrosslinked Carbohydrate Scaffold for Vocal Fold Medialization in an Ovine Model.
          • Article
          • Peer Reviewed
          UC Davis Previously Published Works (2019)
          This report describes an unusual presentation of multicentric B-cell lymphoma with central and peripheral nerve involvement in a horse that was presented with acute onset, severe, multiple limb lameness, and muscle atrophy. This case highlights the importance of including neoplasia in the differential list in horses presenting for severe limb lameness associated with muscle atrophy, muscle fasciculations, and weakness.
            Cover page: An atypical presentation of multi-systemic B-cell lymphoma in a horse.
            • Article
            • Peer Reviewed
            UC San Francisco Previously Published Works (2018)

            Patients and caregivers play a central role in health care safety in the hospital, ambulatory care setting, and community. Despite this, interventions to promote patient engagement in safety are still underexplored. We conducted an overview of review articles on patient engagement interventions in safety to examine the current state of the evidence. Of the 2,795 references we evaluated, 52 articles met our full-text inclusion criteria for synthesis in 2018. We identified robust evidence supporting patients' self-management of anticoagulation medications and mixed-quality evidence supporting patient engagement in medication and chronic disease self-management, adverse event reporting, and medical record accuracy. Promising modes of patient engagement in safety, such as anticoagulation management and patient portal access, are not widely implemented. We discuss major implementation priorities and propose directions for future research and policy to enhance patient partnership within safety efforts.

              Cover page: Patient Engagement In Health Care Safety: An Overview Of Mixed-Quality Evidence.
              • Article
              • Peer Reviewed
              UC San Francisco Previously Published Works (2010)
              Peroxisome proliferator-activated receptors (PPARs; PPAR-alpha, PPAR-delta, and PPAR-gamma) comprise a family of nuclear receptors that sense fatty acid levels and translate this information into altered gene transcription. Previously, it was reported that treatment of mice with a synthetic ligand activator of PPAR-delta, GW0742, ameliorates experimental autoimmune encephalomyelitis (EAE), indicating a possible role for this nuclear receptor in the control of central nervous system (CNS) autoimmune inflammation. We show that mice deficient in PPAR-delta (PPAR-delta(-/-)) develop a severe inflammatory response during EAE characterized by a striking accumulation of IFN-gamma(+)IL-17A(-) and IFN-gamma(+)IL-17A(+) CD4(+) cells in the spinal cord. The preferential expansion of these T helper subsets in the CNS of PPAR-delta(-/-) mice occurred as a result of a constellation of immune system aberrations that included higher CD4(+) cell proliferation, cytokine production, and T-bet expression and enhanced expression of IL-12 family cytokines by myeloid cells. We also show that the effect of PPAR-delta in inhibiting the production of IFN-gamma and IL-12 family cytokines is ligand dependent and is observed in both mouse and human immune cells. Collectively, these findings suggest that PPAR-delta serves as an important molecular brake for the control of autoimmune inflammation.
                Cover page: Peroxisome proliferator–activated receptor δ limits the expansion of pathogenic Th cells during central nervous system autoimmunity
                • Article
                • Peer Reviewed
                UC San Francisco Previously Published Works (2023)
                22q11.2 deletion syndrome, associated with congenital and neuropsychiatric anomalies, is the most common copy number variant (CNV)-associated syndrome. Patient-derived, induced pluripotent stem cell (iPS) models have provided insight into this condition. However, patient-derived iPS cells may harbor underlying genetic heterogeneity that can confound analysis. Furthermore, almost all available models reflect the commonly-found ~ 3 Mb "A-D" deletion at this locus. The ~ 1.5 Mb "A-B" deletion, a variant of the 22q11.2 deletion which may lead to different syndromic features, and is much more frequently inherited than the A-D deletion, remains under-studied due to lack of relevant models. Here we leveraged a CRISPR-based strategy to engineer isogenic iPS models of the 22q11.2 "A-B" deletion. Differentiation to excitatory neurons with subsequent characterization by transcriptomics and cell surface proteomics identified deletion-associated alterations in proliferation and adhesion. To illustrate in vivo applications of this model, we further implanted neuronal progenitor cells into the cortex of neonatal mice and found potential alterations in neuronal maturation. The isogenic models generated here will provide a unique resource to study this less-common variant of the 22q11.2 microdeletion syndrome.
                  Cover page: A CRISPR-engineered isogenic model of the 22q11.2 A-B syndromic deletion
                  • Article
                  • Peer Reviewed
                  UC San Francisco Previously Published Works (2020)

                  Objectives

                  Obese women are at increased risk of cervical cancer, partly due to missed detection of cervical precancers during routine cervical cancer screening. We administered a clinician survey to better understand specific challenges and identify potential solutions to performing cervical cancer screening and management in obese women.

                  Materials and methods

                  We administered a web-based survey to 2,319 members of the American Society of Colposcopy and Cervical Pathology including questions related to challenges associated with cervical sampling and visualization in obese compared with normal weight women and potential strategies for improvement. We summarized providers' responses using descriptive statistics and used Fisher exact tests to evaluate associations between provider characteristics and challenges with cervical sampling, visualization, and biopsy.

                  Results

                  Of the 240 providers that completed the survey, 89% and 93% reported that cervical sampling and visualization are more challenging in obese women, respectively, whereas 80% reported that taking a biopsy was more challenging. Commonly reported barriers included vaginal prolapse, difficulty visualizing and accessing the cervix, and lack of long enough sampling devices and large enough speculums. Frequently used techniques to improve sampling and visualization included use of a condom or examination glove finger to sheath a speculum and using a tenaculum. Most providers identified training for cervical sampling and colposcopy in obese women as a learning gap, and only 8% reported receiving such training.

                  Conclusions

                  Cervical cancer screening and management are more challenging in obese compared with normal weight women. Major barriers to cervical sampling and visualization included lack of adequately sized equipment and lack of education and training.
                    Cover page: Challenges Associated With Cervical Cancer Screening and Management in Obese Women: A Provider Perspective.
                    • Article
                    • Peer Reviewed
                    UC San Diego Previously Published Works (2021)

                    Introduction

                    This study examined in youth (12-17 years), young adults (18-24 years), and adults (25+ years): (1) the prevalence of the first menthol cigarette and menthol/mint cigar use among new tobacco users; (2) association between the first menthol/mint use, subsequent tobacco use, and nicotine dependence ~1 year later compared with the first non-menthol/mint use.

                    Aims and methods

                    Longitudinal analysis of data from Waves 1 to 4 of the Population Assessment of Tobacco and Health (PATH) Study (2013-2017; 10 086 youth and 21 281 adults). Main outcome measures were past 12-month and past 30-day cigarette and cigar use, and nicotine dependence.

                    Results

                    Youth and young adult new cigarette users are more likely to smoke a menthol cigarette or indicate that they do not know the flavor compared with adults aged 25+. A greater proportion of adults aged 25+ first used menthol/mint-flavored cigars (13.4%) compared with youth (8.5%) and young adults (7.4%). Among young adults, first use of a menthol cigarette is associated with past 12-month use of cigarettes at the subsequent wave and first use of any menthol/mint-flavored cigars is associated with past 30-day use of these products at the subsequent wave in both youth and young adults. In youth and adults, there were no significant relationships between first use of a menthol/mint cigarette or cigar and nicotine dependence scores at a subsequent wave in multivariable analyses.

                    Conclusions

                    The first use of menthol/mint cigarettes and cigars is associated with subsequent cigarette and cigar use in young people aged 12-24.

                    Implications

                    This study examined the relationship between initiation with menthol cigarettes and menthol/mint cigars, subsequent tobacco use, and nicotine dependence in US youth, young adults, and adults who participated in Waves 1-4 of the Population Assessment of Tobacco and Health study. New use of menthol cigarettes was associated with greater past 12-month cigarette use in young adults and new use of menthol/mint-flavored cigars was associated with greater past 30-day cigar use in youth and young adults compared with non-menthol use. Initiation with menthol/mint cigarette and cigar products may lead to subsequent use of those products.
                      Cover page: Menthol and Mint Cigarettes and Cigars: Initiation and Progression in Youth, Young Adults and Adults in Waves 1-4 of the PATH Study, 2013-2017.
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