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Assessing Availability, Accessibility and Integration of Breast and Cervical Cancer Services in Sub-Saharan Africa: A Ghana Case Study
No full textIntroduction: Breast and cervical cancers are leading causes of mortality among women in sub-Saharan Africa (SSA), including Ghana. Despite existing evidence-based interventions (EBIs) for prevention, screening, and treatment, service penetration and integration remain inadequate. This dissertation aimed to (1) assess breast and cervical cancer service integration in SSA through a scoping review, (2) evaluate the penetration and geographic accessibility of cervical cancer EBIs in Ghana, and (3) analyze the implementation and integration potential of these services relative to Ghana’s National Cancer Control Strategy (2012–2016) using the RE-AIM framework.
Methods: A scoping review synthesized evidence on service integration in SSA using the Implementation Research Logic Model (IRLM) and Consolidated Framework for Implementation Research (CFIR). A retrospective cross-sectional analysis of 328 hospitals in Ghana (2020–2021) assessed cervical cancer EBI penetration and geographic accessibility using GIS mapping. Implementation of breast and cervical cancer EBIs was evaluated through the RE-AIM framework, analyzing adoption, implementation, maintenance and opportunities for service integration.
Results: Our scoping review of 739 studies identified 10 that met the inclusion criteria, highlighting service integration strategies and challenges related to sustainability and funding (Chapter Two). For cervical cancer service EBI penetration, only 54.3% of hospitals offered at least one intervention, with screening EBIs available in 50%, while advanced treatment options remained scarce, particularly in rural areas (Chapter Three). Although 93.3% of hospitals provided some breast and cervical cancer services, only 3.7% had dedicated clinics for both. Hospitals offering onsite diagnostic and treatment services maintained high service continuity (>80%), yet most lacked onsite EBI capabilities. Comprehensive treatment was available in just 0.6% of hospitals, and only 15.2% had both screening and diagnostic services, highlighting low integration preparedness. Expanding geographic access could improve integrated screening and diagnosis services for 97% of Ghanaian women (Chapter Four).
Conclusion: Cancer service integration in SSA is promising but hindered by workforce shortages, funding gaps, and weak implementation models. In Ghana, cervical cancer services are highly uneven, with limited access to advanced care. Strengthening policy frameworks, workforce capacity, and geographic service expansion is critical for improving cancer care accessibility and integration. Future research should assess patient outcomes from integrated services and explore scalable implementation models
The role of histone crotonylation in DNA damage response
No full textHistone modifications play an important role in DNA damage response. For example, gamma-H2AX is increased at DSB sites in order to recruit repair enzymes to the damage site and promote DNA repair. After DNA damage, H3K36me2 is increased to suppress transcription and recruit NHEJ factors to DSBs. Lysine crotonylation (Kcr) is a newly identified histone modification which can promote transcription. However, its role in DNA damage response remains elusive. Since gene expression is switched off at DNA damage sites and given the positive role of Kcr in gene transcription, we hypothesized that Kcr may decrease upon DNA damage to silence transcription, thus avoiding transcription-replication conflicts. In our study, we found that H2BK16cr, H3K14cr and H4K8cr decrease upon DNA damage. We also demonstrated that EZHIP positively regulates H4K8cr via blocking the recruitment of CDYL1 to chromatin. Together, these results suggest that histone crotonylation decreases upon DNA damage and EZHIP acts as an important regulator of H4K8 crotonylation
What is going on with student writing? An exploration of teacher factors that impact student writing proficiency
Get PDFThis dissertation explores the teacher factors that impact students’ writing proficiency within Title I elementary schools in a suburban Washington, DC, school district. Using Bronfenbrenner's ecological systems theory as a framework, this study explores how teachers' instructional practices, self-efficacy, feedback methods, and identities as writers impact their ability to align with Common Core State Standards and improve student outcomes. A convergent parallel mixed-methods design was used to collect data through surveys and semi-structured interviews with third- to fifth-grade teachers. The findings suggest that teachers exhibit high self-efficacy in motivating students to write and teaching students how to orient their writing but have moderate self-efficacy in teaching research writing skills, such as teaching students how to structure their writing, and using text elements, such as vocabulary, grammar, and punctuation. Teachers identified challenges to teaching writing as a lack of time for instruction and a lack of resources, as well as students’ current writing ability. This research highlights the significance of understanding teacher factors that contribute to or hinder student writing development by offering insights into the complexities of writing instruction in low-performing schools
Nurses’ Perceived Quality of Care and Its Influencing Factors: An Exploratory Study in Mainland China
No full textBackground: Nurses' perceived quality of care is directly related to actual care outcomes, with the nursing work environment and occupational burnout being significant influencing factors. Although the COVID-19 pandemic heightened concerns about burnout, research findings on its specific impact remain inconsistent.
Objective: This study aims to describe the current state of perceived quality of care among frontline nurses in China, analyze the impact of the nursing work environment on perceived care quality while considering gender differences, explore the moderating role of burnout profiles in the relationship between the work environment and perceived quality of care, and evaluate the effect of the COVID-19 pandemic on occupational burnout.
Methods: The study combined cross-sectional data and literature review. Data were drawn from the Chinese Nurses’ Environment of the Work Status (C-NEWS) project. Study variables included perceived quality of care, nursing work environment characteristics, burnout, and demographic characteristics. Logistic regression, network analysis, and latent profile analysis were used to investigate key influencing factors and the moderating role of burnout. Systematic review and Bayesian factor analysis were conducted to evaluate the effect of the COVID-19 pandemic on occupational burnout.
Results: More than half of nurses rated care quality as "good/excellent." Gender, education level, workload, cumulative scores of work environment dimensions, and burnout levels demonstrated both shared patterns and differences in influencing perceived care quality at the hospital and unit levels. Gender analysis revealed that professional development was most strongly associated with care quality among female nurses, while value recognition had a more direct impact on male nurses. Latent profile analysis identified four burnout profiles—self-fulfillment, emotional exhaustion, lack of accomplishment, and self-isolation—that moderated the relationship between the nursing work environment and perceived care quality. Notably, the COVID-19 pandemic did not significantly impact burnout levels among Chinese nurses, with occupational burnout primarily rooted in the accumulation of long-term work stress.
Conclusion: Optimizing the nursing work environment can enhance perceived quality of care and alleviate occupational burnout. Systematic interventions targeting different burnout profiles and gender differences can contribute to the sustainable development of healthcare systems
LIGHT MODULATES GLUCOSE AND LIPID HOMEOSTASIS VIA THE SYMPATHETIC NERVOUS SYSTEM
No full textLight is an important environmental factor for vision and diverse psychological and physiological functions. I studied how light modulates glucose and lipid homeostasis and the underlying neural pathways. I found that in mice, light is critical for glucose and lipid homeostasis by regulating the sympathetic nervous system, independent of circadian disruption. Light deprivation from birth elicits insulin hypersecretion, glucagon hyposecretion, lower gluconeogenesis, and reduced lipolysis by 6-8 weeks in male, but not female mice. These metabolic defects are consistent with blunted sympathetic activity, and indeed, sympathetic responses to a cold stimulus are significantly attenuated in dark-reared mice. Further, long-term dark rearing leads to body weight gain, insulin resistance, and glucose intolerance. Notably, 5 weeks of exposure to a regular light-dark cycle can partially alleviate metabolic dysfunction.
The neural pathway by which light exerts effects on the sympathetic nervous system remains unclear. I found that acute light exposure during the daytime, a time when light has no effects on circadian phase, activates the celiac ganglion-superior mesenteric ganglion (CG-SMG) complex and enhances glucose levels after glucose administration in mice. M4 to M6, but not M1, subtypes of intrinsically photosensitive retinal ganglion cells (ipRGCs) are responsible for transmitting light signals to activate the CG-SMG complex and that the locus coeruleus (LC) is a nodal point of this atypical neural pathway.
My research provided insight into circadian-independent mechanisms by which light directly influences whole-body physiology and a better understanding of metabolic disorders linked to aberrant environmental light conditions
Developing Statistical Models for Cardiovascular Disease Real-Time Dynamic Prediction
No full textCardiovascular disease(CVD) is the leading cause of death worldwide and poses heavy burden to health systems and society. CVD risk prediction is one of the most effective methods for CVD preventions and controls. In this study, we aim to develop and evaluate a dynamic competing-risks prediction model for CVD event and non-CVD death using data from approximately 5000 type-2 diabetes participants in the Look Ahead trial. We applied discrete-time cause-specific hazards regression to model the 5-year competing risks of CVD event versus non-CVD death. Predictors included baseline socio-demographic variables, lifestyle factors, medication history, time-varying biomarker trajectories, and the trial's intervention group assignment. Model discrimination was evaluated using the Area Under the Receiver Operating Characteristic Curve (AUC) with 10-fold cross-validation. Since intervention group assignment is specific to the trial context and unavailable externally, potentially limiting broader applicability, we conducted a sensitivity analysis assessing model performance after excluding this predictor. The primary model including intervention group demonstrated acceptable discrimination with AUCs of 0.7213 for CVD events and 0.7126 for non-CVD death. Performance remained consistent in the sensitivity analysis excluding the intervention group (AUCs: 0.7221 for CVD, 0.7171 for non-CVD death). In conclusion, we developed a dynamic competing risks model in type-2 diabetes patients with acceptable discrimination. The model explicitly accounts for non-CVD death, offering a potentially more realistic risk assessment than single-outcome models, and shows consistence supporting wider applicability
MOLECULAR DETERMINANTS OF PLASMODIUM INFECTION: INDEPENDENT STUDIES ON THE ROLE OF MOSQUITO ENOLASE AND P. BERGHEI SERA5 IN PARASITE TRANSMISSION AND DEVELOPMENT
No full textMalaria, caused by the Plasmodium parasite, is a major parasitic disease that keeps devastating public health, with a significant impact on the sub-Saharan African region. The Plasmodium parasite relies on both vector-derived and parasite-derived factors to initiate and maintain the transmission of malaria. Here, we investigate two molecular determinants, a parasite-derived cysteine protease (SERA5) and mosquito-derived enzyme (enolase), necessary for malaria transmission.
RNAi-mediated gene knockdown was employed to silence the mosquito enolase gene and investigate its role as a mosquito host factor aiding the Plasmodium parasite invasion after infecting the enolase-deficient mosquitoes with the standard membrane feeding approach. Gene silencing efficiency was determined by qPCR, and the role of the microbiota in modulating immune response in the leaky gut environment was determined by using the septic and aseptic mosquito treatment. Across all biological replicates, the silencing efficiency was determined, ranging from 90.8% to 98.3%. The results demonstrated a reduction in oocyst burden in enolase-deficient mosquitoes, as well as validated the role of microbiota in immune activation against the Plasmodium parasite, resulting in the upregulation of immune genes such as Tep1, LRIM1, FBN9, and LRRD7 under septic conditions only. This suggests that enolase is essential in maintaining the midgut integrity of the mosquito, and in turn shields the Plasmodium parasite from immune invasion. The disruption of enolase led to a leaky gut syndrome in the mosquito, which influenced microbial-mediated immune response against the parasite.
PbSERA5’s role after sporozoite exit from oocysts was examined by performing a genetic cross between an mCherry-wildtype and a GFP-PbSERA5 KO parasites. The results from the fluorescence assays and qPCR-based quantification demonstrated a ratio of 2:1 wildtype and mutant in salivary glands, supporting Mendelian segregation. The downstream infection assay showed a reduced blood-stage infection level of the PbSERA5-KO mutant compared to the wildtype parasite in a ratio of 1:2. The outcome of this study suggests that PbSERA5 may play a role in facilitating mouse host hepatocyte invasion by sporozoites, hence providing insight into the cascade of molecular events needed for liver-stage infection.
The findings of these studies provide an understanding of the transmission biology of the malaria parasite and suggest potential malaria intervention strategies for global malaria control
Decoding SENP Enzymes: Pivotal Regulators in SUMOylation Dynamics
Get PDFSmall ubiquitin-related modifiers (SUMOs) are small proteins that function as post-translational protein modifications affecting a wide range of cellular functions, including protein stability, chromatin organization, transcription, DNA repair, and signal transduction (Flotho & Melchior, 2013). Humans express four SUMO paralogs (SUMO1-4), which are initially synthesized as precursors that require cleavage at their C-terminal diglycine motifs by Sentrin proteases (SENPs) for maturation and their ability to be conjugated to other proteins (Kunz et al., 2018). SENPs are a family of six individual proteases (SENP1-3 and SENP5-7) with unique specificities and functions. While in vitro studies suggest SENP1 preferentially processes SUMO1 precursors, whereas SENP2, SENP3, and SENP5 exhibit a stronger preference for SUMO2 and SUMO3 precursors (Shen et al., 2006; Xu & Au, 2005), the specific SENPs responsible for individual paralog maturation in vivo remain unidentified.
This thesis explores the roles of different SENP members in SUMO precursor processing in U2OS osteosarcoma cells by investigating whether depletion of different SENPs affects SUMO precursor processing and mature protein levels. Our results show SENP1 depletion led to SUMO1 precursor accumulation and simultaneous reduction of mature SUMO1 levels, highlighting its crucial role in SUMO1 precursor processing. In contrast, SENP2 depletion did not significantly affect SUMO precursor levels, suggesting its primary function is possibly in SUMO deconjugation. SENP3 knockdown substantially increased precursor and mature SUMO1 and SUMO2 protein levels, possibly due to stress-induced compensatory up-regulation of SUMO expression. This suggests SENP3 may play a broader regulatory role in SUMO homeostasis beyond precursor processing. SENP5 knockdown significantly decreased precursor and mature SUMO1 and SUMO2 protein levels, suggesting that SENP3 and SENP5 play unique regulatory roles. Additionally, transcriptional compensation among SENPs was observed, as the depletion of one SENP led to upregulation of other SENPs at the mRNA and protein levels. Such findings suggest feedback mechanisms linking SENP protein expression with gene expression.
Dysregulation of SENPs can disrupt the homeostasis of SUMOylation and has been linked to the development of various diseases, including cancer and neurodegenerative disorders (Bailey & O’Hare, 2004; Cubeñas-Potts et al., 2013). This thesis presents new insights into the distinct functions and regulation of different SENPs in the maturation of SUMO precursors. The findings will aid in developing SENPs as novel therapeutic targets for diseases linked to SUMO dysregulation
RETROSPECTIVE JOINT MODELS FOR BIOMARKERS AND EVENTS IN PRECISION MEDICINE
Get PDFPrecision medicine seeks to tailor medical decisions to individual patients based on their clinical and biomarker profiles. It is important to accurately model disease states and trajectories, which are often informed by both longitudinal biomarkers and time-to-event outcomes. This dissertation developed and evaluated statistical methods for retrospective longitudinal models across three distinct clinical applications: prostate cancer, COVID-19, and scleroderma.
We first developed a concordance-modulating regression framework within a latent variable modeling structure to quantify the modulation effect of supplementary diagnostic procedures on the accuracy of ordinal diagnostic surrogates with application in prostate cancer.
Second, we analyzed longitudinal biomarker trajectories stratified by clinical outcomes in hospitalized COVID-19 patients. Using retrospective modeling
approaches, we described patterns in eight vital signs and laboratory measures leading up to three competing clinical events: discharge, mechanical ventilation or death.
Third, we introduced a Monte Carlo Expectation-Maximization algorithm for retrospective models under censored survival data, addressing challenges in scleroderma where many patients remain event-free during follow-up.
These contributions illustrated retrospective modeling approaches to analyze
longitudinal biomarkers and clinical outcomes. The proposed methods were implemented in real-world datasets, demonstrating their utility for personalized monitoring and decision support in modern healthcare
ADVANCING CELLULAR IMAGING AND ANALYSIS: UNVEILING ADIPOCYTE AND ASTROCYTE DYNAMICS WITH OPTICAL DIFFRACTION TOMOGRAPHY
No full textCells are highly dynamic, constantly reshaping their morphology and function in response to intrinsic signals and external stimuli. Capturing these transformations in a quantitative, label-free manner is essential to advancing our understanding of cellular processes. Traditional imaging techniques, such as fluorescence microscopy, require labels that can alter cellular function and limit long-term studies. Optical Diffraction Tomography (ODT) addresses these challenges by providing a label-free, three-dimensional imaging approach capable of quantitatively analyzing cellular morphology and biophysical properties. ODT reconstructs the refractive index (RI) distribution of a sample by capturing multiple holographic images at varying illumination angles. This enables the retrieval of key cellular parameters, including volume, dry mass, and RI variations, which reflect intracellular composition and density. Since phase shifts in light correspond to differences in optical path length, ODT allows for the measurement of subtle structural and compositional changes without the need for exogenous labels. Beyond morphological characterization, ODT quantifies biophysical properties that are critical for understanding cellular function. The RI of a cell is directly linked to its macromolecular content, including proteins, lipids, and nucleic acids. By analyzing RI variations, ODT provides insights into intracellular heterogeneity. Its high-resolution, quantitative nature makes it particularly useful for studying dynamic processes such as differentiation and cellular adaptation to microenvironmental cues.
This dissertation utilizes ODT to investigate the morphological and biophysical dynamics of human adipocytes and rat cortical astrocytes. First, ODT was used to study human white and brown preadipocyte differentiation, revealing distinct lipid accumulation patterns and fluctuations in cell dry mass during early adipogenesis. Next, the impact of metabolic microenvironments was examined by exposing brown preadipocytes to glucose and fructose, showing that fructose impairs lipid accumulation and morphology. Expanding beyond adipocytes, ODT was applied to study astrocyte morphology, uncovering distinct structural adaptations and demonstrating that nanostructured glass substrates induce in vivo-like astrocyte morphology with enhanced process branching. By integrating ODT across these diverse cellular systems, this dissertation highlights the influence of microenvironmental factors on cellular morphology and function. These findings underscore the potential of ODT as a transformative tool for studying cellular dynamics in metabolic and neurobiological research