Translational Medical Research Commons^™

Novel Electrophysiological Biomarkers In Pediatric Drug Resistant Epilepsy And Genetic Epilepsy Syndromes, Sakar Rijal

Bioengineering Dissertations - Archive

Pediatric epilepsies, particularly those that are drug-resistant or genetically driven, represent some of the most complex neurological disorders encountered in childhood. Central to their pathophysiology is a disruption in the delicate balance between cortical excitation and inhibition (E/I), often resulting from impaired GABAergic interneuron function. This imbalance manifests as aberrant network dynamics and altered neural oscillations, giving rise to seizures and long-term cognitive impairments. In this thesis, we developed a translational framework to identify electrophysiological biomarkers that (i) assess cortical E/I imbalance and (ii) map epileptogenic zones, with the aim of enhancing diagnosis, guiding surgical planning, and informing therapeutic monitoring …

Optimizing Decision-Making In A Cerebral Palsy Model Using Reinforcement Learning, Richard Ampah

Pitzer Senior Theses

This study presents an original interdisciplinary investigation into how reinforcement learning (RL) can model motor and cognitive defects and potentially improve motor and cognitive functions in individuals with cerebral palsy (CP), a non-progressive neurological disorder that impairs movement and adaptability. Integrating computational neuroscience and machine learning, the research applies policy gradient methods and Markov Decision Processes (MDPs) to simulate adaptive learning in agents with and without CP-related constraints.

The central aim is to compare the cumulative rewards of optimal policies, derived from value iteration, and human-like learning policies using the REINFORCE algorithm, both with and without the Bellman baseline. The …

Summary Of: Ai Diabetic Retinopathy Screening In A Primary Care Setting In Rural Maine, Rachel Heuer Md, Emma Daybranch Mph, Anastasia Tsomides Do, Jessica F. Dibiase Mph, Neil Korsen Md, Brian Nolan Md

Northern New England Clinical & Translational Research

Diabetic retinopathy (DR) is the leading cause of blindness globally. Early diagnosis and treatment reduce the risk of vision loss by 98%.

Study found @ "AI Diabetic Retinopathy Screening in a Primary Care Setting in Rural M" by Rachel Heuer, Emma DayBranch et al.

Environment Scan Of Generative Ai Infrastructure For Clinical And Translational Science, Hua Xu, Jiang Bian, Chunhua Weng, Yifan Peng, Betina Idnay, Zihan Xu, William G. Adams, Mohammad Adibuzzaman, Nicholas R. Anderson, Neil Bahroos, Douglas S. Bell, Cody Bumgardner, Thomas Campion, Mario Castro, James J. Cimino, I. Glenn Cohen, David Dorr, Peter L. Elkin, Jungwei W. Fan, Todd Ferris, David J. Foran, David Hanauer, Mike Hogarth, Kun Huang, Jayashree Kalpathy-Cramer, Manoj Kandpal, Niranjan S. Karnik, Avnish Katoch, Albert M. Lai, Christophe G. Lambert, Lang Li, Christopher Lindsell, Jinze Liu, Zhiyong Lu, Yuan Luo, Peter Mcgarvey, Eneida A. Mendonca, Parsa Mirhaji, Shawn Murphy, John D. Osborne, Ioannis C. Paschalidis, Paul A. Harris, Fred Prior, Nicholas J. Shaheen, Nawar Shara, Ida Sim, Umberto Tachinardi, Lemuel R. Waitman, Rosalind J. Wright, Adrian H. Zai, Kai Zheng, Sandra Soo-Jin Lee, Bradley A. Malin, Karthik Natarajan, Nicholson Price, Rui Zhang, Yiye Zhang

Articles

This study reports a comprehensive environmental scan of the generative AI (GenAI) infrastructure in the national network for clinical and translational science across 36 institutions supported by the CTSA Program led by the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH) at the United States. Key findings indicate a diverse range of institutional strategies, with most organizations in the experimental phase of GenAI deployment. The results underscore the need for a more coordinated approach to GenAI governance, emphasizing collaboration among senior leaders, clinicians, information technology staff, and researchers. Our analysis reveals that 53% of …

Leveraging Clinical Standards To Improve The Translational Relevance Of Therapies For Experimental Spinal Cord Injury, Aaron L. Silverstein

Theses and Dissertations--Neuroscience

Efforts to improve treatment of spinal cord injury (SCI) often use animals to develop effective therapeutics, intending to improve the survival and the quality of life of persons with SCI. Over half of all SCIs in the United States occur at the cervical level and often cause locomotor deficits and life-threatening breathing dysfunction. Thus, my dissertation is focused on this important patient population.

After beginning with a description of translational research and surveying SCI from a clinical standpoint, I turned to describe experimental models of cervical SCI and more detailed neuroimmunological findings relevant to my work. Then, I conducted a …

The Impact Of Maternal Environmental Exposures On The Immune Landscape Of The Maternal-Fetal Interface, Heather E. True

Theses and Dissertations--Pharmacy

Maternal environmental exposures and inflammation are known to impact fetal development in utero as well as increase the risk for chronic diseases later in life. Therefore, it is essential that we understand how the maternal environment alters placental structure and immune function.

Therefore, we isolated fetal (chorionic villous) tissues from the placentas of healthy pregnant participants (control) and those with inflammatory conditions, including SARS-COV-2 infection, pregravid obesity, and opioid use disorder. Isolated placental leukocytes were subjected to a series of assays to uncover the phenotypic, functional, and transcriptional (single-cell RNA-sequencing) landscape of placental immune cells. Additional placental tissues were subjected …

Impact Of Hyperthermia And Mitomycin C On Heat Shock Proteins, Mismatch Repair Proteins, And Cytotoxicity In Colon Cancer, Anna M. Reagan

Theses and Dissertations--Clinical and Translational Science

Cytoreductive surgery and heated intraperitoneal chemotherapy (HIPEC) is a treatment used for primary peritoneal malignancy or metastases, including colon cancer. We aimed to explore the effects of hyperthermia and/or mitomycin C (MMC) on mismatch repair (MMR) proteins and heat shock proteins (hsps) and the potential for post-HIPEC treatment with pembrolizumab treatment. Colon cancer cells were treated with hyperthermia and/or MMC for 90 minutes. Subcellular fractionation and immunofluorescent imaging were performed to identify protein abundance and localization of MSH2, MLH1, hsp70, and hsp27. Proteomics analysis was performed for HT29 cells. HT29 cells and patient-derived organoids (PDOs) underwent simulated HIPEC and treatment …

Enhancing Public Health Surveillance: Development And Validation Of Machine Learning Models For Suspected Opioid Overdose Detection In Emergency Medical Services Data, Peter J. Rock

Theses and Dissertations--Clinical and Translational Science

The ongoing opioid overdose crisis in the United States requires timely and accurate surveillance systems to inform public health responses. Traditional public health surveillance methods rely on hospital discharge data and death certificates, which suffer from significant reporting delays and miss cases where patients refuse hospital transportation. Emergency Medical Services (EMS) data presents a promising alternative with advantages in timeliness and case ascertainment but lacks validated definitions for suspected opioid overdose (SOO).

This dissertation addresses this critical gap through the development, validation, and fairness assessment of machine learning models with natural language processing (ML-NLP) for identifying SOOs in EMS data. …

Fabricating Silver-Ceria Polymer Nanocomposite Scaffolds For Biomedical Therapeutic Applications, Shreya S. Pawar

Honors Undergraduate Theses

Improper healing of bone fractures and limited regeneration of bone following bone tumor resection remain a prevalent complication worldwide. Long-term effects of this include joint instability, limited movement, and arthritis. Bone infections (osteomyelitis), reactive oxygen species (ROS) generation via excessive inflammation, and underlying conditions such as osteoporosis can contribute to suboptimal bone tissue regeneration. ROS accumulation stimulates osteoblast apoptosis, while promoting osteoclast differentiation. These processes inhibit mineralization and osteogenesis. Conventional therapeutics involve the utilization of drugs and bone grafts. However, these approaches pose limitations and can result in subsequent complications. Microbial infections, ROS accumulation, and excessive inflammations are factors that …

Therapy-Induced Senescence In Cancer: Developing Senolytic-Based Combination Strategies To Delay Re-Emergence Of Triple-Negative Breast Cancer, Eesha Chakraborty

Theses and Dissertations

Therapy-induce senescence (TIS) represents a major biological outcome of many anticancer treatments and is increasingly recognized as a strategic vulnerability in triple negative breast cancer, which is a highly aggressive subtype with limited therapeutic options and frequent relapse. Here, we probed TIS as a primary cellular response that may ultimately compromise long-term outcomes using standard chemotherapeutic agents in TNBC as well as the antibody-drug conjugate sacituzumab govitecan (SG). Both chemotherapy and SG reliably induced pronounced senescence across TNBC models, yielding durable growth arrest, however, also generating a persistent reservoir of viable tumor cells capable of eventual proliferative recovery, a hallmark …

Analysis Of Differential Gene Expression In Androgen-Independent Clones Derived From The Mycap Pca Cell Line, Jessie L. Tignor, Melanie Sinanian, Richard Inho Joh, David Gewirtz, Jason Reed

UROP Posters

Androgen deprivation therapy (ADT) is a primary treatment strategy for prostate cancer (PCa), yet many tumors eventually develop androgen independence, leading to treatment resistance. To investigate the molecular changes underlying this transition, we analyzed differential gene expression in four androgen-independent (AI) clones derived from the Myc-CaP prostate cancer cell line using RNA sequencing. Gene expression profiles were compared to the parental Myc-CaP line, and differentially expressed genes (DEGs) were identified using DESeq2 and edgeR. The AI clones exhibited significant downregulation of senescence-associated genes, including Ezh2 and lamin B1, suggesting a loss of senescence-related chromatin repression. Additionally, upregulation of Wnt pathway …

Uv- Altered Macrophages: Impact Of Uv Radiation On Phagocytic Receptor Expression In M2 Macrophages And Implications For Tissue Repair And Immunosuppression, Hala Hafez

Honors Undergraduate Theses

Ultraviolet radiation is an environmental stressor known to suppress immune function in the skin, but its effect on the immunoregulatory M2 phenotype macrophages is poorly studied. This study aims to investigate the impact of UV exposure on key markers of the M2 macrophage, which are critical for tissue repair and immunosuppression. THP-1 monocytes were differentiated and polarized into the M2 phenotype using Phorbol-12 myristate (PMA) and Cytokines IL-4 and IL-10. Once differentiation was confirmed, the macrophages were exposed to varying durations of UV radiation. Real Time Quantitative PCR was used to analyze expression changes in phagocytic receptors (CD206, CD163, Arg-1), …

Effectiveness Of Fu's Subcutaneous Needling In Pain Management And Rehabilitation: A Narrative Review, Po-En Chiu, Chun-Chang Wu, De-Jian Lu, Zhonghua Fu, Li-Wei Chou

Rehabilitation Practice and Science

Fu’s Subcutaneous Needling (FSN) is a modern needling technique distinct from traditional acupuncture, primarily used for musculoskeletal pain, neuropathic conditions, and emerging applications in rehabilitation. FSN is also designated as a kind of dry needling focusing on deactivating myofascial trigger points. This review categorizes FSN-related studies into case reports, clinical trials, and animal studies, evaluating its therapeutic efficacy, safety, and mechanisms. Case reports suggest that FSN provides rapid pain relief and functional improvement, while clinical trials, including randomized controlled trials (RCTs), support its role in reducing pain and enhancing neuromuscular function despite limitations in sample size and protocol consistency. Animal …

Grade Notes 4: How To Use Grade When There Is "No" Evidence? A Case Study Of Using Unpublished Registry Data., Ibrahim K. El Mikati, Brandy Begin, Dagmara Borzych-Duzalka, Alicia M. Neu, Troy Richardson, Rebecca G. Same, Franz Schaefer, Bradley A. Warady, Reem A. Mustafa

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: Trustworthy guidelines rely on systematic reviews of the best available published evidence. The GRADE (Grading of Recommendations Assessment, Development, and Evaluation) Working Group has provided guidance about developing evidence-based recommendations when published direct evidence is lacking. In this article, we provide a case example as an alternate solution to generate primary data using registries prior to collecting expert evidence.

STUDY DESIGN AND SETTING: When direct published literature was absent, a team of clinical and statistical expertise can utilize registries, when available, for primary data generation in a way that allows for answering clinically important questions.

RESULTS: Out of 54 …

Contributions Of Pathobiological And Translational Science To Understanding And Managing Ischemic Heart Disease: Progress, Impediments, And Future Directions, L Maximilian Buja

The Texas Heart Institute Journal

Key pathobiological components of ischemic heart disease have been identified as follows: (1) In 1970 to 1973, myocardial infarct size was found to be the primary determinant of prognosis after acute myocardial infarction (AMI); (2) in 1973 to 1989, vulnerable coronary artery plaques were found to predispose individuals to coronary plaque disruption and thrombosis, causing major AMI; (3) in 1972, timely coronary reperfusion was demonstrated to limit the size of evolving AMI but with risk of reperfusion injury; and (4) in 1986, myocardial conditioning was found to be a clinically significant modulator capable of delaying AMI progression. Promising cardioprotective strategies …

Maternal Lipidomics For The Accurate Prediction Of Fetal Cyanotic Congenital Heart Defects, Onur Turkoglu, Nadia Ashrafi, Ali Yilmaz, Romana Ashrafi Mimi, Abdullah Khan, Perry Friedman, Ciara Talbot, Stewart Graham, Ray Bahado-Singh

Conference Presentation Abstracts

Objective: Late diagnosis of cyanotic congenital heart defects (CCHD) significantly increases newborn morbidity and mortality. However, a significant percentage of CCHD cases remain undetected prenatally. Our objectives were therefore to evaluate the accuracy of maternal serum lipidomic markers for the prenatal detection of CCHD and also to elucidate the pathogenesis of these disorders. Study Design: This prospective case-control study included 40 cases of CHD (22 cyanotic, 18 acyanotic) and 39 unaffected controls. Maternal serum samples were profiled via a combination of Ultra-High-Performance Liquid Chromatography coupled with Mass Spectrometry and Nuclear Magnetic Resonance. The mean of each lipid specie was compared …