Public Health & Health Science Division, ULAB

RNA modifications including adenosine-to-inosine (A-to-I) editing and N6-methyladenosine (m6A) play important roles in post-transcriptional gene regulation and havebeen identified as major factors in the initiation and spread of cancer. The most prevalent internal alteration in eukaryotic mRNA, m6A, is dynamically controlled by "writers"(METTL3/METTL14), "erasers" (FTO/ALKBH5), and "readers" (YTH domain proteins), whichcollectively affect RNA stability, splicing, translation, and destruction. Studies have shown that dysregulation of m6A plays a role in cancers such leukemia, breast cancer, and clear cell renal cell carcinoma through pathways involving METTL3 and SETD2 mutations. This dysregulation has been closely linked to tumor growth, metastasis, and therapeutic resistance. Similar to this,A-to-I RNA editing, which is mostly mediated by ADAR1, modifies RNA transcripts withoutaltering DNA sequences and promotes protein variety and immune control. By modifyingendogenous double-stranded RNA, blocking immune identification by sensors like MDA5 and PKR, and facilitating immune evasion in interferon-rich environments, ADAR1 enhances tumor survival in cancer. Through changed transcripts like AZIN1 and GLI1, overexpression of ADAR1 has also been connected to the development of tumors. These results collectively show that A-to-I RNA editing and m6A alteration are both attractive therapeutic targets for precision cancer therapy approaches in addition to being biomarkers of disease progression.

KRAS mutations are among the most common oncogenic drivers in human cancer,affecting switch control pathways that regulate cell growth, survival, and metabolism. Mutations in KRAS interfere with this regulation by keeping the protein in an active state, which causes constant signaling and is linked to cancers like pancreatic, lung, and colorectal cancer. Although significant progress has been made in developing KRAS-target therapies, many approaches focus on static protein structures and may not fully capture its dynamic behavior within living cells. This paper investigates how KRAS mutations affect signaling pathways, with a particular focuson the MAPK pathway and its role in tumor progression and therapeutic resistance. Aliterature-based methodology was used, focusing on recent peer-reviewed studies with strong mechanistic and experimental evidence, while excluding outdated or non-translational models.The analysis shows that different intervention points in the MAPK signal transduction pathway vary in their ability to shut down oncogenic signaling and prevent pathway reactivation. This question is critical because KRAS mutations drive sustained activation of the MAPK pathway,which is vital for determining whether treatments will fail due to pathway reactivation (e.g., alternative signaling routes or errors in feedback mechanisms). By understanding how targeting different points in the pathways affects both initial suppression and long-term reactivation, this paper allows for innovations and findings of new therapeutic strategies.

Climate change poses growing threats to public health, with mounting evidence linkingenvironmental exposures to various mental health outcomes. While climate change isincreasingly recognized as a threat to mental health with well-established research on acuteclimate disasters, less is understood about the psychological effects of environmental stressors experienced during upbringing. This study examined whether perceived environmental quality during childhood and adolescence, such as air quality, water quality, and access to green space, is associated with mental health outcomes in adulthood. Participants (n = 33) completed ananonymous online survey assessing self-reported environmental exposures alongside a modified Mental Health Inventory (MHI) measuring anxiety, depression, tension, and hopelessness. Statistics utilizing regression analysis revealed that participants reported moderate environmental quality and moderate levels of psychological distress. Results include significant associations between environment and feelings of calm (R2 = 0.16, p = 0.019), water quality and calm (R2 = 0.19, p = 0.012), and green space access and calm (R2 = 0.13, p = 0.042), while no significant associations were found for nervousness, tension, or hopelessness. Overall, environmental quality was not a strong predictor of mental health in this sample, future research should use larger, more diverse samples and objective environmental measures to better clarify theserelationships.

Alzheimer’s disease (AD) is an irreversible, progressive neurodegenerative disorder andthe leading cause of dementia worldwide, affecting nearly 55 million individuals. Hallmarkpathological features include extracellular amyloid-β plaques and intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein. Despite decades of research, conventional therapeutic approaches targeting tau pathology, including kinase inhibitors, phosphatase activators, and tau aggregation modulators, have demonstrated limited clinical success and primarily address symptoms rather than underlying disease mechanisms. Recent advances in programmable nucleotide editing technologies, including CRISPR-Cas9, base editing, and prime editing, offer promising strategies for both investigating and therapeutically targeting tau-related pathology at the genomic level. This literature review examines the application of CRISPR-based technologies in neuronal cell models, animal models, and induced pluripotent stem cell-derived neurons to evaluate their potential in understanding and treating tau-mediated neurodegeneration. Studies have shown that CRISPR-mediated correction of disease-associated variants, including APOE4 and MAPT-P301S, reduces tau phosphorylation, decreases insoluble tau accumulation, improves neuronal resilience, and restores cognitive function in preclinical models. Genome-wide CRISPR screens have further identified pathways involved in kinase signaling, autophagy, mitochondrial function, mTOR signaling, and vesicular trafficking as important regulators of tau aggregation and propagation. These findings demonstrate how genetic manipulation can directly influence tau pathology through both direct and indirect mechanisms. Although advances in delivery systems and next-generation editing platforms have improved the feasibility of brain-targeted genome editing, significant challenges remain, including delivery efficiency, off-target effects, limited in vivo editing rates, and the lack of studies targeting sporadic AD-associated tau phosphorylation sites. Nevertheless, programmable nucleotide editing represents a promising avenue for addressing the genetic contributors of tau pathology and may provide a foundation for future disease-modifying therapies for Alzheimer’s disease.

Childhood obesity and metabolic disorders have risen sharply as the consumption ofhigh-fat diets (HFDs) increases, yet the neurocognitive consequences - specifically during the juvenile development window - remain under-researched. This paper synthesizes current literature to examine how HFD-induced metabolic shifts suppress brain-derived neurotrophic factor (BDNF) in the hippocampus, leading to impaired learning and memory independent of body weight. Our analysis identifies dual-pathway mechanism of suppression: first, HFD-driven gut dysbiosis reduces the production of microbial short-chain fatty acids (SCFAs), particularly butyrate, hence limiting the histone deacetylase (HDAC) inhibition required for BDNF gene expression. Second, HFD consumption chronically elevates corticosterone levels, which directly downregulates BDNF mRNA and increases neuroinflammation. Synthesis of rodent modelsreveals that these molecular changes manifest as structural hippocampal shrinkage andbehavioral deficits in juvenile populations. While limitations exist regarding animal-to-human translation, these findings underscore a “metabo-psychiatric” crisis where early dietarycomposition impacts long-term cognitive health. We conclude that interventions targeting the gut-brain axis, such as precision prebiotic nutrition, may be essential to mitigate the neurodevelopmental risks of HFD.

Alzheimer’s Disease (AD) pathology has been shown to begin decades before theappearance of cognitive symptoms. This is backed by imaging and biomarker studies showing amyloid and tau abnormalities followed by neurodegeneration (Ottoy et al., 2025). Hence, current research being done to understand the cause of Alzheimer’s focuses on the “plaques and tangles” theory, in which amyloid beta (Aβ) deposits build up, blocking cell communication and tau proteins tangle inside neurons, disrupting nutrient transport (P, Vellapandian, 2024). After surveying existing literature, we seek to better understand the risk factors that influence these biomarkers and the mechanistic pathways that drive AD progression. With age serving as theprimary risk factor, with those over 65 most affected, looking at earlier adulthood allows us to assess the potential role that chronic stress plays in AD pathology throughhypothalamic-pituitary-adrenal (HPA) axis dysregulation and neuroinflammation.

Estrogen receptors drive cancer cell proliferation in hormone receptor-positive cancer, which constitutes 70% of breast cancers. These require long-term endocrine therapy to suppress estrogen signaling and prevent recurrence. While these treatments significantly prolong progression-free and overall survival, the systemic depletion of estrogen and dysregulation of the HPA axis leads to severe, frequently underreported psychiatric toxicities, primarily depression and anxiety. This review evaluates the currentstandard of care and developing therapies, specifically Selective Estrogen Receptor Modulators (SERMs), Aromatase Inhibitors (AIs), Ovarian Function Suppression (OFS), and Selective Estrogen Receptor Degraders (SERDs), and how they balance clinical efficacy against their respective neurobiological andpsychological costs. A comprehensive synthesis of primary literature, clinical trials, and case evaluations was conducted to analyze survival endpoints alongside neuropsychiatric biomarkers, neuroinflammation,and neurotransmitter pathways. It was found that SERMs like Tamoxifen and AIs (Anastrozole, Letrozole) successfully reducerecurrence risks but trigger profound mood disturbances by disrupting serotonergic pathways and neuroprotective mechanisms in the brain. Ovarian suppression significantly boosts disease-free survival inpremenopausal cohorts but incurs high psychosocial distress and premature menopausal symptoms. Emerging targeted therapies, like the oral SERD elacestrant, provide superior progression-free survival fortherapy-resistant ESR1-mutated cancers, though their long-term neuropsychiatric profiles remain a critical gap in current oncology trials. However, the field currently relies heavily on subjective, self-reportedpatient metrics that are difficult to compare across studies, highlighting an urgent need for future clinical trials to incorporate objective neuropsychiatric assessments and inflammatory biomarkers like IL-6.Ultimately, this review establishes a crucial framework and future direction for the field in order to equip oncologists to balance maximum clinical survival with preserved patient quality of life.

In this paper, we will focus on the demographic and clinical factors that cause open-angleglaucoma. Open-angle glaucoma is a progressive eye disease that increases intraocular pressure (IOP), eventually leading to optic nerve damage and vision loss. Currently, researchers have focused on IOP,depression, sleep apnea, and decreased outer nasal macular perfusion density as strong clinical indicators of glaucoma. Conditions like depression can lead to chronic stress physiology changes, leading to IOP. Sleep apnea is associated with intermittent hypoxia and vascular dysregulation, and decreased nasal macular perfusion density is associated with reduced retinal microvascular circulation, leading to degeneration of the optic nerve. Demographic factors like age and access to medical education also play a significant role, especially since glaucoma remains underdiagnosed in underdeveloped regions due to limited ophthalmologic resources and medical education. Aging is also associated with increased IOP due to a less efficient eye drainage system. While many of these predictors are linked to elevated IOP, IOPalone is not a sufficient predictor of glaucoma risk; it must be interpreted within the broader clinical and demographic context.

Parkinson's disease (PD) is commonly treated with dopaminergic therapies that effectivelyaddress motor symptoms; however, their effects on the non-motor aspects of one’s life remain underexplored. By systematically synthesizing data across mood, sleep, and cognition, this study intends to evaluate how levodopa, dopamine agonists, and monoamine oxidase B (MAO-B) inhibitors influence non-motor symptoms and overall quality of life in patients with PD. Data were collected from nine studies published between 1999 and 2025, spanning longitudinal observational, cross-sectional, within-subject ON/OFF, randomized crossover, systematic review, and case series designs to ensure that both the breadth and depth of current research are considered. Dopamine agonists are associated with reduced motivational and apathy symptoms, while MAO-B inhibitors are associated with reduced depressive symptoms; anxiety scores were higher in the ON medication state. Moreover, higher dopaminergic exposure was associated with impulse control behaviors. Each type of therapy was associated with variable cognitive effects. Ultimately, Levodopa was associated with benefits in attention, processing speed, working memory, executive function, and episodic memory but with worsened cognitive inhibition. At the same time, rasagiline showed benefits in working memory and verbal fluency, and pramipexole and selegiline were linked to worse episodic memory, impulse control, globalcognition, and concept formation. Treatment universally worsened sleep outcomes; totaldopaminergic dose was a stronger predictor of excessive daytime sleepiness than agonists.Although these findings are substantiated, there remains a lack of comparative evidence in current PD literature, so we have a limited understanding of the long-term trade-offs between therapy type and quality of life. This study therefore calls for more patient-centered treatment strategies in the future to address both the motor and non-motor manifestations of PD.

California’s agriculture sector relies heavily on pesticides, with an estimated use of 176million pounds per year. While these pesticides do increase crop yield, long-term exposure toboth organophosphate and organochlorine pesticides has been found to result in variousneurological effects, such as epilepsy. We seek to explore the relationship between exposure to pesticides in agricultural areas of California and epilepsy, and to evaluate the role of structural determinants such as insurance coverage, lack of transportation, unstable housing, and distance from epilepsy specialists in terms of health care utilization. We seek to demonstrate the link between chronic pesticide exposure and increased susceptibility to epilepsy by analyzing studiesand public health surveillance data and by conducting a systematic review and meta-analysis of 14 studies. We found that uninsured patients have 86% lower access to specialty care, transportation barriers reduce access by 58%, and housing instability can increase acute readmission by 87%. We also found that pesticide residues are in nearly 80% of state air samples, despite the fact that access to neurological medical services is extremely limited for uninsured and rural populations. There is additionally no public transportation access within most agricultural communities, and yet, individuals with epilepsy often cannot drive due to restrictions placed on them because of seizures. Thus, the impacts of epilepsy rely largely on the intersection of environment and healthcare inequality. We therefore seek to examine the roles ofpublic health research and epidemiology to understand the factors that may be contributing to the development and treatment structure of epilepsy in agricultural communities in California.