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Full-Text Articles in Translational Medical Research

Perinuclear Organelle Trauma At The Nexus Of Cardiomyopathy Pathogenesis Arising From Loss Of Function Lmna Mutation, Jason C. Choi Jan 2025

Perinuclear Organelle Trauma At The Nexus Of Cardiomyopathy Pathogenesis Arising From Loss Of Function Lmna Mutation, Jason C. Choi

Center for Translational Medicine Faculty Papers

Over the past 25 years, nuclear envelope (NE) perturbations have been reported in various experimental models with mutations in the LMNA gene. Although the hypothesis that NE perturbations from LMNA mutations are a fundamental feature of striated muscle damage has garnered wide acceptance, the molecular sequalae provoked by the NE damage and how they underlie disease pathogenesis such as cardiomyopathy (LMNA cardiomyopathy) remain poorly understood. We recently shed light on one such consequence, by employing a cardiomyocyte-specific Lmna deletion in vivo in the adult heart. We observed extensive NE perturbations prior to cardiac function deterioration with collateral damage in the …


Research Annual Report Fy2025, Children's Mercy Kansas City Jan 2025

Research Annual Report Fy2025, Children's Mercy Kansas City

Research Annual Reports

Annual report of the research at Children's Mercy Kansas City in Kansas City MO, a pediatric medical center.


Optimizing Decision-Making In A Cerebral Palsy Model Using Reinforcement Learning, Richard Ampah Jan 2025

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 Jan 2025

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.


Leveraging Clinical Standards To Improve The Translational Relevance Of Therapies For Experimental Spinal Cord Injury, Aaron L. Silverstein Jan 2025

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 …


Fabricating Silver-Ceria Polymer Nanocomposite Scaffolds For Biomedical Therapeutic Applications, Shreya S. Pawar Jan 2025

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 …


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 Jan 2025

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 …


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 Jan 2025

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 …


Contributions Of Pathobiological And Translational Science To Understanding And Managing Ischemic Heart Disease: Progress, Impediments, And Future Directions, L Maximilian Buja Jan 2025

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 Jan 2025

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 …


Sk609, A Novel Dopamine D3 Receptor Agonist And Norepinephrine Transporter Blocker With Putative Pro-Cognitive Actions, Does Not Induce Psychostimulant-Like Increases In Risky Choice During Probabilistic Discounting, Christopher P. Knapp, Brooke Fallon, Sandhya Kortagere, Barry D. Waterhouse, Stan B Floresco, Rachel L Navarra Dec 2024

Sk609, A Novel Dopamine D3 Receptor Agonist And Norepinephrine Transporter Blocker With Putative Pro-Cognitive Actions, Does Not Induce Psychostimulant-Like Increases In Risky Choice During Probabilistic Discounting, Christopher P. Knapp, Brooke Fallon, Sandhya Kortagere, Barry D. Waterhouse, Stan B Floresco, Rachel L Navarra

Rowan-Virtua School of Osteopathic Medicine Departmental Research

RATIONALE: Psychostimulants, such as amphetamine (AMPH) and methylphenidate (MPH), non-selectively elevate extracellular concentrations of the catecholamine neurotransmitters, dopamine (DA) and norepinephrine (NE), and are common pharmacological strategies used to improve prefrontal cortex (PFC)-dependent cognitive dysfunction. However, this approach can be problematic given AMPH has been shown to increase preference for risky choices in a rodent assay of risk/reward decision making. SK609 is a novel NE reuptake blocker that selectively activates DA D3 receptors without affinity for the DA transporter. SK609 has been shown to improve cognitive performance without increasing psychostimulant-like spontaneous locomotor activity, suggesting SK609 may benefit neurocognitive function without …


Exploring Alternative Treatments For Acute Exacerbations Of Cannabis Hyperemesis Syndrome In Patients Who Plan To Continue Using Cannabis, Tabitha E H Moses Nov 2024

Exploring Alternative Treatments For Acute Exacerbations Of Cannabis Hyperemesis Syndrome In Patients Who Plan To Continue Using Cannabis, Tabitha E H Moses

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Dean DJ, Sabagha N, Rose K, et al. A Pilot Trial of Topical Capsaicin Cream for Treatment of Cannabinoid Hyperemesis Syndrome. Acad Emerg Med. 2020;27(11):1166-1172. https://doi.org/10.1111/acem.14062

for a patient with cannabis hyperemesis syndrome.


Clinical Utility Of Abbreviated Eeg Monitoring In Patients Unable To Tolerate A Long-Term, Ambulatory Eeg, Jack T. Mcconnell Nov 2024

Clinical Utility Of Abbreviated Eeg Monitoring In Patients Unable To Tolerate A Long-Term, Ambulatory Eeg, Jack T. Mcconnell

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Lee C, Lim S-N, Lien F, et al. Duration of electroencephalographic recordings in patients with epilepsy. Seizure. 2013;22(6):438-442. https://10.1016/j.seizure.2013.02.016

for a patient with an inability to tolerate a long-term, ambulatory EEG.


Breast Cancer Screening In Transgender Women With High-Risk Family History, John F. Lloyd Nov 2024

Breast Cancer Screening In Transgender Women With High-Risk Family History, John F. Lloyd

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

de Blok CJM, Wiepjes CM, Nota NM, et al. Breast cancer risk in transgender people receiving hormone treatment: nationwide cohort study in the Netherlands. BMJ. 2019;365:l1652. https://doi.org/10.1136/bmj.l1652

for a transgender woman with family history of breast cancer.


Ansa Cervicalis-To-Phrenic Nerve Transfer: Technical Note With Potential Application For Diaphragmatic Reanimation In Patients With High Cervical Spinal Cord Injury, Jonathan Melnick, Mohammadali M. Shoja, Gary B. Schwartz Nov 2024

Ansa Cervicalis-To-Phrenic Nerve Transfer: Technical Note With Potential Application For Diaphragmatic Reanimation In Patients With High Cervical Spinal Cord Injury, Jonathan Melnick, Mohammadali M. Shoja, Gary B. Schwartz

HCA-NSU MD Research Day

Objective. This study was conducted to determine whether utilization of the superior root of ansa cervicalis (SRAC) as the donor for phrenic nerve (PN) transfer is technically feasible. Background. In patients with high cervical spinal cord injury resulting in diaphragmatic paralysis, another donor, the spinal accessory nerve, has been used successfully to reinnervate the PN and restore diaphragmatic function. Methods. Eight neck sides underwent cadaveric surgery. The sternocleidomastoid muscle was retracted posteriorly, the SRAC and PN were isolated, and the SRAC was cut near its distal end and transposed to the ipsilateral PN as it crossed the anterior scalene muscle. …


Metastatic Recurrence In Women Diagnosed With Non-Metastatic Breast Cancer: A Systematic Review And Meta-Analysis, Eileen Morgan, Colette O’Neill, Richa Shah, Oliver Langselius, Yaqi Su, Clara Frick, Hanna Fink, Aude Bardot, Miriam Mutebi, Paul Walsh Nov 2024

Metastatic Recurrence In Women Diagnosed With Non-Metastatic Breast Cancer: A Systematic Review And Meta-Analysis, Eileen Morgan, Colette O’Neill, Richa Shah, Oliver Langselius, Yaqi Su, Clara Frick, Hanna Fink, Aude Bardot, Miriam Mutebi, Paul Walsh

General Surgery, East Africa

Background: To assess proportions of metastatic recurrence in women initially diagnosed with non-metastatic breast cancer by stage at diagnosis, breast cancer subtype, calendar period and age.

Methods: A systematic search of MEDLINE and Web of Science databases (January 2010–12 May 2022) was conducted. Studies reporting the proportion of distant metastatic recurrence in women with non-metastatic breast cancer were identified and outcomes and characteristics were extracted. Risk of bias was assessed independently by two reviewers. Random-effects meta-analyses of proportions were used to calculate pooled estimates and 95% confidence intervals (CIs).

Results: 193 studies covering over 280,000 patients were included in the …


Recovery After Human Bone Marrow Mesenchymal Stem Cells (Hbm-Mcs)-Derived Extracellular Vesicles (Evs) Treatment In Post-Mcao Rats Requires Repeated Handling, Yolanda Gomez-Galvez, Malvika Gupta, Mandeep Kaur, Salvatore Fusco, Maria Vittoria Podda, Claudio Grassi, Amit K. Srivastava, Lorraine Iacovitti, Elena Blanco-Suarez Oct 2024

Recovery After Human Bone Marrow Mesenchymal Stem Cells (Hbm-Mcs)-Derived Extracellular Vesicles (Evs) Treatment In Post-Mcao Rats Requires Repeated Handling, Yolanda Gomez-Galvez, Malvika Gupta, Mandeep Kaur, Salvatore Fusco, Maria Vittoria Podda, Claudio Grassi, Amit K. Srivastava, Lorraine Iacovitti, Elena Blanco-Suarez

Farber Institute for Neuroscience Faculty Papers

Rehabilitation is the only current intervention that improves sensorimotor function in ischemic stroke patients, similar to task-specific intensive training in animal models of stroke. Bone marrow mesenchymal stem cells (BM-MSCs)-derived extracellular vesicles (EVs) are promising in restoring brain damage and function in stroke models. Additionally, the non-invasive intranasal route allows EVs to reach the brain and target specific ischemic regions. Yet unclear is how handling might enhance recovery or influence other therapies such as EVs after stroke. We used the transient middle cerebral artery occlusion (MCAO) model of stroke in rats to assess how intensive handling alone, in the form …


Evaluating The Impact Of Spot Position Errors On Dose Distribution: A Comparison Between Spot-Scanning Arc Therapy (Sparc) And Intensity-Modulated Proton Therapy (Impt), Peilin Liu, Lewei Zhao, Gang Liu, Xiaoda Cong, Xiaoqiang Li, Xuanfeng Ding Oct 2024

Evaluating The Impact Of Spot Position Errors On Dose Distribution: A Comparison Between Spot-Scanning Arc Therapy (Sparc) And Intensity-Modulated Proton Therapy (Impt), Peilin Liu, Lewei Zhao, Gang Liu, Xiaoda Cong, Xiaoqiang Li, Xuanfeng Ding

Conference Presentation Abstracts

Purpose: To quantitatively investigate the impact of spot position error (PE) on the dose distribution in (Spot-scanning arc therapy) SPArc plans versus Intensity-Modulated Proton Therapy (IMPT).

Methods:

Four representative disease sites, including brain, lung, liver, and prostate cancers, were retrospectively selected. Spot position errors were simulated during dynamic SPArc treatment delivery. Two types of errors were generated, including randomized error and systematic error. For each random error scenario, they were further examined across four sub-scenarios (25%, 50%, 75%, and 100% of spots affected) at 1 mm and 2 mm deviations.The randomized errors used two categories with and without Gaussian distribution …


Downregulation Of Piezo2 In The Detrusor Of Men With Bladder Outlet Obstruction And Its Association With Urinary Retention And Decreased Bladder Compliance, Carlos Henrique Suzuki Bellucci, Thiago Souto Hemerly, Luisa Resende Tenório De Albuquerque, Ruan Pimenta, Vanessa Guimaraes Schreiter, Sabrina Thalita Dos Reis, Jose De Bessa Jr, Katia Ramos Moreira Leite, Alberto Antunes, Boopathi Ettickan, William C. Nahas, Cristiano Mendes Gomes Sep 2024

Downregulation Of Piezo2 In The Detrusor Of Men With Bladder Outlet Obstruction And Its Association With Urinary Retention And Decreased Bladder Compliance, Carlos Henrique Suzuki Bellucci, Thiago Souto Hemerly, Luisa Resende Tenório De Albuquerque, Ruan Pimenta, Vanessa Guimaraes Schreiter, Sabrina Thalita Dos Reis, Jose De Bessa Jr, Katia Ramos Moreira Leite, Alberto Antunes, Boopathi Ettickan, William C. Nahas, Cristiano Mendes Gomes

Center for Translational Medicine Faculty Papers

PURPOSE: Recent research has highlighted the mechanotransducer PIEZO2 as a crucial factor in lower urinary tract function, demonstrating associations with bladder compliance (BC), bladder wall thickening, and elevated bladder pressure. We explored the hypothesis that PIEZO2 expression may be associated with lower urinary tract dysfunction in men with bladder outlet obstruction (BOO) due to benign prostatic hyperplasia (BPH).

METHODS: The study included a consecutive series of patients undergoing open prostatectomy for BPH at our hospital between September 2014 and January 2016. All participants underwent comprehensive preoperative evaluations, including urodynamic assessments. During prostatectomy, a full-thickness fragment of the bladder wall was …


Utilizing Thalamic Deep Brain Stimulation For An Electronic Seizure Diary In A Definite Sudden Unexpected Death In Epilepsy Case, Surya Suresh, Yash Vakilna, Vladimir Vashin, Samden Lhatoo, Sandipan Pati Sep 2024

Utilizing Thalamic Deep Brain Stimulation For An Electronic Seizure Diary In A Definite Sudden Unexpected Death In Epilepsy Case, Surya Suresh, Yash Vakilna, Vladimir Vashin, Samden Lhatoo, Sandipan Pati

Faculty, Staff and Student Publications

Objective: Sudden unexpected death in epilepsy (SUDEP) is a serious threat to individuals with intractable epilepsies, contributing to premature mortality. Understanding the elusive pathophysiological mechanisms of SUDEP, especially in cases without observable terminal events, remains a crucial area for investigation. This study aimed to shed light on the burden of epileptiform activity preceding SUDEP by utilizing an automated electronic seizure diary derived from a sensing-enabled thalamic deep brain stimulator (DBS).

Methods: Herein, we present the case of a 57-year-old man afflicted with intractable multifocal epilepsy secondary to cortical dysplasia and encephalomalacia resulting from severe traumatic brain injury. Despite an initial …


Quantitative Evaluation Of Gantry Rotation Perturbation Effects On Spot-Scanning Arc Therapy (Sparc), Peilin Liu, Lewei Zhao, Gang Liu, Xiaoda Cong, Xiaoqiang Li, Xuanfeng Ding Sep 2024

Quantitative Evaluation Of Gantry Rotation Perturbation Effects On Spot-Scanning Arc Therapy (Sparc), Peilin Liu, Lewei Zhao, Gang Liu, Xiaoda Cong, Xiaoqiang Li, Xuanfeng Ding

Conference Presentation Abstracts

Purpose: To quantitatively assess the impact of random gantry rotation perturbations on spot-scanning arc (SPArc) therapy.

Methods:

To simulate random gantry rotation perturbations, the initial gantry angle of SPArc treatment plans was modified using an in-house script. Four cases from different disease sites include brain, lung, liver and prostate were selected to evaluate. Original SPArc plans (SPArcorg) were developed through iterative processes, including control point re-sampling, redistribution of control points & energy layers, energy layer filtration, and re-sampling. Considering potential limitations, rotation perturbations of 1mm and 2mm were applied to al SPArcorg plans to generate perturbed SPArc …


Exploit The Potential Clinical Benefit Of Using Proton Arc Therapy For Esophageal Cancer, Peilin Liu, Xiaoda Cong, Raymond Dalfsen, Martin Soukup, James E. Dolan, Shupeng Chen, Craig Stevens, Rohan Deroniyagala, Xiaoqiang Li, Xuanfeng Ding Sep 2024

Exploit The Potential Clinical Benefit Of Using Proton Arc Therapy For Esophageal Cancer, Peilin Liu, Xiaoda Cong, Raymond Dalfsen, Martin Soukup, James E. Dolan, Shupeng Chen, Craig Stevens, Rohan Deroniyagala, Xiaoqiang Li, Xuanfeng Ding

Conference Presentation Abstracts

No abstract provided.


Insights From Targeted Fecal Metabolomic Analysis Reveal Altered Metabolic Pathways In Treatment-Naive Pediatric Subjects With Crohn's Disease, Nadia Ashrafi, Ali Yilmaz, Nicolette Monacelli, Rose E. Callahan, Ilyas Ustun, Nathan M. Novotny, J W. Rattray, Kypros Nicolaides, Stewart Graham Jun 2024

Insights From Targeted Fecal Metabolomic Analysis Reveal Altered Metabolic Pathways In Treatment-Naive Pediatric Subjects With Crohn's Disease, Nadia Ashrafi, Ali Yilmaz, Nicolette Monacelli, Rose E. Callahan, Ilyas Ustun, Nathan M. Novotny, J W. Rattray, Kypros Nicolaides, Stewart Graham

Conference Presentation Abstracts

Crohn’s disease (CD) is a heterogeneous and multifactorial inflammatory bowel disease with a significant global health impact. Genetic and lifestyle factors contribute to its etiology, emphasizing dysregulation of intestinal and dietary habits. Our study aimed to identify fecal metabolites from treatment-naïve, pediatric sufferers of CD, which allowed us to investigate the underlying biochemical perturbations associated with the disease, highlighting potential, translational targets. Using a Waters Acquity UPLC coupled with a Xevo-TQ-S mass spectrometer, we quantified >500 metabolites in fecal samples (n=72) of pediatric CD sufferers. We developed diagnostic tests capable of accurately discriminating between children with CD and healthy individuals …


Small-Molecule Disruptors Of The Interaction Between Calcium- And Integrin-Binding Protein 1 And Integrin Α, Kalyan Golla, Adam Yasgar, Manjuprasanna Voddarahally Nagaraju, Meghna U. Naik, Bolormaa Baljinnyam, Alexey V. Zakharov, Sankalp Jain, Ganesha Rai, Ajit Jadhav, Anton Simeonov, Ulhas P. Naik May 2024

Small-Molecule Disruptors Of The Interaction Between Calcium- And Integrin-Binding Protein 1 And Integrin Α, Kalyan Golla, Adam Yasgar, Manjuprasanna Voddarahally Nagaraju, Meghna U. Naik, Bolormaa Baljinnyam, Alexey V. Zakharov, Sankalp Jain, Ganesha Rai, Ajit Jadhav, Anton Simeonov, Ulhas P. Naik

Cardeza Foundation for Hematologic Research

Thrombosis, a key factor in most cardiovascular diseases, is a major contributor to human mortality. Existing antithrombotic agents carry a risk of bleeding. Consequently, there is a keen interest in discovering innovative antithrombotic agents that can prevent thrombosis without negatively impacting hemostasis. Platelets play crucial roles in both hemostasis and thrombosis. We have previously characterized calcium- and integrin-binding protein 1 (CIB1) as a key regulatory molecule that regulates platelet function. CIB1 interacts with several platelet proteins including integrin αIIbβ3, the major glycoprotein receptor for fibrinogen on platelets. Given that CIB1 regulates platelet function through its interaction with αIIbβ3, we developed …


Honoring Veterans’ Wishes: Efficacy Of An Evidence-Based Shared Decision-Making Tool In Va Icu Goals-Of-Care Discussions, Stephanie Alexander, Anna Astashchanka Md, Venktesh Ramnath Md May 2024

Honoring Veterans’ Wishes: Efficacy Of An Evidence-Based Shared Decision-Making Tool In Va Icu Goals-Of-Care Discussions, Stephanie Alexander, Anna Astashchanka Md, Venktesh Ramnath Md

Doctor of Nursing Practice Final Manuscripts

Abstract

Introduction: This Doctor of Nursing Practice project aimed to enhance the knowledge and confidence of the San Diego Veterans Health Administration’s (VASD) Intensive Care Unit (ICU) medical providers in goals-of-care discussions (GOCD). Additionally, this project aimed to improve the documentation of these discussions.

Background: Delays in GOCD can lead to futile medical and surgical interventions, inappropriate antibiotic use, and higher rates of mental health conditions in patients and their loved ones. Earlier GOCD are associated with lower ventilation and resuscitation rates, earlier hospice enrollment, reduced ICU admissions, lower financial costs, and better patient and caregiver quality of life. However, …


Keratin 17 Modulates The Immune Topography Of Pancreatic Cancer, Lyanne Delgado-Coka, Michael Horowitz, Mariana Torrente-Goncalves, Lucia Roa-Peña, Cindy Leiton, Mahmudul Hasan, Sruthi Babu, Danielle Fassler, Jaymie Oentoro, Ji-Dong Bai, Emanuel Petricoin, Lynn Matrisian, Edik Matthew Blais, Natalia Marchenko, Felicia Allard, Wei Jiang, Brent Larson, Andrew Hendifar, Chao Chen, Shahira Abousamra, Dimitris Samaras, Tahsin Kurc, Joel Saltz, Luisa Escobar-Hoyos, Kenneth Shroyer May 2024

Keratin 17 Modulates The Immune Topography Of Pancreatic Cancer, Lyanne Delgado-Coka, Michael Horowitz, Mariana Torrente-Goncalves, Lucia Roa-Peña, Cindy Leiton, Mahmudul Hasan, Sruthi Babu, Danielle Fassler, Jaymie Oentoro, Ji-Dong Bai, Emanuel Petricoin, Lynn Matrisian, Edik Matthew Blais, Natalia Marchenko, Felicia Allard, Wei Jiang, Brent Larson, Andrew Hendifar, Chao Chen, Shahira Abousamra, Dimitris Samaras, Tahsin Kurc, Joel Saltz, Luisa Escobar-Hoyos, Kenneth Shroyer

Kimmel Cancer Center Faculty Papers

BACKGROUND: The immune microenvironment impacts tumor growth, invasion, metastasis, and patient survival and may provide opportunities for therapeutic intervention in pancreatic ductal adenocarcinoma (PDAC). Although never studied as a potential modulator of the immune response in most cancers, Keratin 17 (K17), a biomarker of the most aggressive (basal) molecular subtype of PDAC, is intimately involved in the histogenesis of the immune response in psoriasis, basal cell carcinoma, and cervical squamous cell carcinoma. Thus, we hypothesized that K17 expression could also impact the immune cell response in PDAC, and that uncovering this relationship could provide insight to guide the development of …


Perinuclear Damage From Nuclear Envelope Deterioration Elicits Stress Responses That Contribute To Lmna Cardiomyopathy, Kunal Sikder, Elizabeth Phillips, Zhijiu Zhong, Nadan Wang, Jasmine Saunders, David Mothy, Andrew Kossenkov, Timothy Schneider, Zuzana Nichtova, György Csordás, Kenneth B. Margulies, Jason C. Choi May 2024

Perinuclear Damage From Nuclear Envelope Deterioration Elicits Stress Responses That Contribute To Lmna Cardiomyopathy, Kunal Sikder, Elizabeth Phillips, Zhijiu Zhong, Nadan Wang, Jasmine Saunders, David Mothy, Andrew Kossenkov, Timothy Schneider, Zuzana Nichtova, György Csordás, Kenneth B. Margulies, Jason C. Choi

Center for Translational Medicine Faculty Papers

Mutations in the LMNA gene encoding lamins A/C cause an array of tissue-selective diseases, with the heart being the most commonly affected organ. Despite progress in understanding the perturbations emanating from LMNA mutations, an integrative understanding of the pathogenesis underlying cardiac dysfunction remains elusive. Using a novel conditional deletion model capable of translatome profiling, we observed that cardiomyocyte-specific Lmna deletion in adult mice led to rapid cardiomyopathy with pathological remodeling. Before cardiac dysfunction, Lmna-deleted cardiomyocytes displayed nuclear abnormalities, Golgi dilation/fragmentation, and CREB3-mediated stress activation. Translatome profiling identified MED25 activation, a transcriptional cofactor that regulates Golgi stress. Autophagy is disrupted …


Assessment Of In-Vitro And In-Vivo Pre-Clinical Pharmacokinetics Of Epz015666; A Novel Small Molecule For Medulloblastoma Treatment, Pratiksha U. Kshirsagar May 2024

Assessment Of In-Vitro And In-Vivo Pre-Clinical Pharmacokinetics Of Epz015666; A Novel Small Molecule For Medulloblastoma Treatment, Pratiksha U. Kshirsagar

Theses & Dissertations

Group 3 medulloblastoma (MB) has the worst prognosis of the MB subgroups associated with elevated MYC expression and a 5-year survival rate of

Quantitation of EPZ was performed on a Shimadzu LC-MS/MS system utilizing electrospray ionization operated in positive mode. The validated assay was linear from 0.2 to 500 ng/mL. Metabolic stability studies demonstrated slow intrinsic clearance of EPZ in mouse and human liver microsomes, suggesting no CYP-mediated metabolism. Additionally, EPZ exhibited low binding affinity to plasma and brain proteins and high apparent permeability across artificial membranes, indicating efficient membrane penetration. Drug transporter studies identified EPZ as a substrate of …


Moonlighting: A Pilot Project To Assess Impact Of Extracurricular Activities On Career Satisfaction And Quality-Of-Life In Graduate Medical Education, Charlotte O'Sullivan, David Lee, Karen Childers, Justine Nasr May 2024

Moonlighting: A Pilot Project To Assess Impact Of Extracurricular Activities On Career Satisfaction And Quality-Of-Life In Graduate Medical Education, Charlotte O'Sullivan, David Lee, Karen Childers, Justine Nasr

Conference Presentation Abstracts

Background: Moonlighting is the delivery of healthcare outside of training programs in exchange for compensation. The Accreditation Council on Graduate Medical Education allows individual training programs to permit or restrict moonlighting, which leads to variation in prevalence and practice. Guidelines and regulations for moonlighting vary greatly across graduate medical education programs. Yet, limited research has been done to determine resident and fellow physician attitudes towards moonlighting and its impact on quality-of-life. Objective: This pilot study investigates how participating in moonlighting and extracurricular activities may impact resident and fellow physicians’ self-perceptions of quality-of-life and career satisfaction. Methods: 442 residents and fellow …


Applications Of Deep Learning With Detecting Intracranial Aneurysms On Ct Angiograms: A Literature Review, Christian Fang, Emily Wang May 2024

Applications Of Deep Learning With Detecting Intracranial Aneurysms On Ct Angiograms: A Literature Review, Christian Fang, Emily Wang

Rowan-Virtua Research Day

INTRODUCTION

Deep learning is a method of artificial intelligence involving progressively layered neural networks to extrapolate patterns from data to provide predictions. Moreover, given the arduous nature required for examining CT scans for intracranial aneurysms, discovering ways to expedite this process is beneficial. The use of deep learning to evaluate CT angiograms for intracranial aneurysms has been sparsely studied. This literature review aims to determine the accuracy and reliability of deep learning to analyze CT angiograms in patients suspected to have intracranial aneurysms.

METHODS

A qualitative review of literature using PubMed, SCOPUS, and EMBASE was conducted. Inclusion criteria comprised articles …