Medical Specialties Commons^™

Biobehavioral Correlates Of Multidimensional Fatigue In Men With Prostate Cancer, Kristin Dickinson

Theses & Dissertations

The purpose of this thesis project was to 1) examine trajectories of multidimensional cancer-related fatigue (CRF) in men with prostate cancer during and after radiation treatment completion, and 2) identify biobehavioral correlates (demographic, clinical, co-occurring symptoms, and biologic [inflammatory cytokines]) for the different CRF dimensions.

Data for this secondary analysis were obtained from a descriptive, longitudinal IRB-approved study investigating men with non-metastatic prostate cancer receiving radiation therapy (RT). Data were obtained from 68 participant medical records, self-report questionnaires, and blood samples. Data were collected at: baseline (T1), completion of RT (T2), 6 months (T3) and 2 years (T4) after completion …

Epidemiology Of Older Patients Presenting To Irish Emergency Departments: A Subgroup Analysis Of The Egers Dataset, Sean Croughan, Arina Kruis Dr, Kelly Ann Catherine Janssens Dr, Pro Mukerjee Dr, Denys Shchetkovskyy Dr, Áine Mitchell Dr, Mehmet Akif Karamercan Dr, Zerrin Defne Dundar Dr, Anna Slagman Dr, Effie Polyzogopoulou Dr, Sandor Somodi Dr, Andrea Fabbri Dr, Lars Peter Bjornsen Dr, Wilma Beetge, Said Laribi, Rebecca Ann Sealy, Visnja Nesek Adam, Comfort Adedokun Dr, Lucy Gibbons, Pamela O’Brien, Jessica Lynch Dr, Laura Kenny, Conor Deasy Dr, John Ryan Dr, David Menzies Dr, John Cronin Dr, Vijay Narayanan Dr, Nurali Noorani Dr, Waslet Bakhshi Dr, Ahmed Al Rasheed Ahmed Dr, Rosa Mcnamara Dr

Journal of Geriatric Emergency Medicine

Introduction

Within Emergency Medicine, older adults represent a distinct population with unique needs and challenges. There is a scarcity of epidemiologic data on the requirements of Ireland’s older population for, and their utilisation of, emergency care networks. We sought to assess this deficit utilising data from the recently published European Geriatric Emergency Departments Registry Study (EGERS) dataset.

Methodology

A prospective, cohort study of older adult patients (≥65) presenting to Irish Emergency Departments over a 7-day period. The dataset was originally collected as part of the EGERS study. The Irish subpopulation was extracted, analysed in further detail, and compared to the …

Pancreaticoduodenectomy In Trauma Patients With Grade Iv-V Duodenal Or Pancreatic Injuries: A Post Hoc Analysis Of An East Multicenter Trial, Rachel Leah Choron, Charoo Piplani, Julia Kuzinar, Amanda L. Teichman, Christopher Bargoud, Jason D. Sciarretta, Randi N. Smith, Dustin Hanos, Iman N. Afif, Jessica H. Beard, Navpreet Kaur Dhillon, Ashling Zhang, Mira Ghneim, Rebekah Devasahayam, Oliver Gunter, Alison A. Smith, Brandi Sun, Chloe S. Cao, Jessica K. Reynolds, Lauren A. Hilt, Daniel N. Holena, Grace Chang, Meghan Jonikas, Karla Echeverria-Rosario, Nathaniel S. Fung, Aaron Anderson, Caitlin A. Fitzgerald, Ryan Peter Dumas, Jeremy H. Levin, Christine T. Trankiem, Jaehee Yoon, Jacqueline Blank, Joshua P. Hazelton, Christopher J. Mclaughlin, Rami Al-Aref, Jordan Michael Kirsch, Daniel S. Howard, Dane R. Scantling, Kate Dellonte, Michael A. Vella, Brent Hopkins, Chloe Shell, Pascal Udekwu, Evan G. Wong, Bellal Joseph, Howard Lieberman, Walter A. Ramsey, Collin H. Stewart, Claudia Alvarez, John D. Berne, Jeffry Nahmias, Ivan Puente, Joe Patton, Ilya Rakitin, Lindsey Perea, Odessa Pulido, Hashim Ahmed, Jane Keating, Lisa M Kodadek, Jason Wade, Henry Reynold, Martin Schreiber, Andrew Benjamin, Abid Khan, Laura K. Mann, Caleb Mentzer, Vasileios Mousafeiris, Francesk Mulita, Shari Reid-Gruner, Erica Sais, Christopher W. Foote, Carlos H. Palacio, Dias Argandykov, Haytham Kaafarani, Michelle T. Bover Manderski, Lilamarie Moko, Mayur Narayan, Mark Seamon

SKMC Student Presentations and Publications

INTRODUCTION: The utility of pancreaticoduodenectomy (PD) for high-grade traumatic injuries remains unclear and data surrounding its use are limited. We hypothesized that PD does not result in improved outcomes when compared with non-PD surgical management of grade IV-V pancreaticoduodenal injuries.

METHODS: This is a retrospective, multicenter analysis from 35 level 1 trauma centers from January 2010 to December 2020. Included patients were ≥15 years of age with the American Association for the Surgery of Trauma grade IV-V duodenal and/or pancreatic injuries. The study compared operative repair strategy: PD versus non-PD.

RESULTS: The sample (n=95) was young (26 years), male (82%), …

Novel Digital Anomalies, Hippocampal Atrophy, And Mutations Expand The Genotypic And Phenotypic Spectra Of Cnksr2 In The Houge Type Of X-Linked Syndromic Intellectual Development Disorder (Mrxshg), Mohammad Reza Ghasemi, Sahand Tehrani Fateh, Afif Ben-Mahmoud, Vijay Gupta, Lara G. Stühn, Gaetan Lesca, Nicolas Chatron, Konrad Platzer, Patrick Edery, Hossein Sadeghi, Bertrand Isidor, Benjamin Cogné, Heidi L. Schulz, Ilona Krauspe-Stübecke, Radhakrishnan Periyasamy, Sheela Nampoothiri, Reza Mirfakhraie, Sahar Alijanpour, Steffen Syrbe, Ulrich Pfeifer, Stephanie Spranger, Kathrin Grundmann-Hauser, Tobias B. Haack, Maria T. Papadopoulou, Tayrine Da Silva Gonçalves, Eleni Panagiotakaki, Alexis Arzimanoglou, Seyed Hassan Tonekaboni, Yves Lacassie, Et Al

School of Medicine Faculty Publications

The Houge type of X-linked syndromic intellectual developmental disorder (MRXSHG) encompasses a spectrum of neurodevelopmental disorders characterized by intellectual disability (ID), language/speech delay, attention issues, and epilepsy. These conditions arise from hemizygous or heterozygous deletions, along with point mutations, affecting CNKSR2, a gene located at Xp22.12. CNKSR2, also known as CNK2 or MAGUIN, functions as a synaptic scaffolding molecule within the neuronal postsynaptic density (PSD) of the central nervous system. It acts as a link connecting postsynaptic structural proteins, such as PSD95 and S-SCAM, by employing multiple functional domains crucial for synaptic signaling and protein–protein interactions. Predominantly expressed in dendrites, …

Influence Of Antibody–Drug Conjugate Cleavability, Drug-To-Antibody Ratio, And Free Payload Concentration On Systemic Toxicities: A Systematic Review And Meta-Analysis, Shou Ching Tang, Carrie Wynn, Tran Le, Martin Mccandless, Yunxi Zhang, Ritesh Patel, Nita Maihle, William Hillegass

School of Medicine Faculty Publications

While in theory antibody drug conjugates (ADCs) deliver high-dose chemotherapy directly to target cells, numerous side effects are observed in clinical practice. We sought to determine the effect of linker design (cleavable versus non-cleavable), drug-to-antibody ratio (DAR), and free payload concentration on systemic toxicity. Two systematic reviews were performed via PubMed search of clinical trials published between January 1998—July 2022. Eligible studies: (1) clinical trial for cancer therapy in adults, (2) ≥ 1 study arm included a single-agent ADC, (3) ADC used was commercially available/FDA-approved. Data was extracted and pooled using generalized linear mixed effects logistic models. 40 clinical trials …

Statins Decrease The Risk Of Hepatocellular Carcinoma In Metabolic Dysfunction-Associated Steatotic Liver Disease: A Systematic Review And Meta-Analysis, Zahid Ijaz Tarar, Umer Farooq, Faisal Inayat, Sanket D. Basida, Faisal Ibrahim, Mustafa Gandhi, Gul Nawaz, Arslan Afzal, Ammad J. Chaudhary, Faisal Kamal, Ahmad H. Ali, Yezaz A. Ghouri

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease with a significant risk of developing hepatocellular carcinoma (HCC). Recent clinical evidence indicates the potential benefits of statins in cancer chemoprevention and therapeutics. However, it is still unclear if these drugs can lower the specific risk of HCC among patients with MASLD.

AIM: To investigate the impact of statin use on the risk of HCC development in patients with MASLD.

METHODS: A systematic review and meta-analysis of all the studies was performed that measured the effect of statin use on HCC occurrence in patients with …

Womb, Gravity, And Space: Shifting Towards The Cerebellum-Basal Ganglia Paradigm In Dystonia, Diego Iacono

Department of Neurology Faculty Papers

No abstract provided.

Prospective, Crossover, Comparative Study Of Two Methods Of Chlorhexidine Bathing, Richard J. Hankins

Theses & Dissertations

Bathing intensive care unit (ICU) patients with chlorhexidine gluconate (CHG) decreases hospital acquired infections (HAIs). The optimal method of CHG bathing remains undefined. Prospective cluster crossover study comparing CHG daily bathing with 2% CHG impregnated cloths versus 4% CHG solution. In phase 1, from January 2020 through March 2020, one ICU utilized 2% cloths, while the other ICU utilized 4% solution. After an interruption caused by the COVID-19 pandemic, in phase 2, from July 2020 through September 2020, the unit CHG bathing assignments were reversed. Swabs were performed three times per week from patients’ arms and legs to measure skin …

Mathematical Multi-Compartment Modeling Of Chronic Lymphocytic Leukemia Cell Kinetics Under Ibrutinib, Melanie Schulz, Sanne Bleser, Manouk Groels, Dragan Bošnački, Jan A Burger, Nicholas Chiorazzi, Carsten Marr

Faculty, Staff and Student Publications

The Bruton tyrosine kinase inhibitor ibrutinib is an effective treatment for patients with chronic lymphocytic leukemia (CLL). While it rapidly reduces lymph node and spleen size, it initially increases the number of lymphocytes in the blood due to cell redistribution. A previously published mathematical model described and quantified those cell kinetics. Here, we propose an alternative mechanistic model that outperforms the previous model in 26 of 29 patients. Our model introduces constant subcompartments for healthy lymphocytes and benign tissue and treats spleen and lymph nodes as separate compartments. This three-compartment model (comprising blood, spleen, and lymph nodes) performed significantly better …

Results Of The Simultaneous Combination Of Ponatinib And Blinatumomab In Philadelphia Chromosome-Positive All, Hagop Kantarjian, Nicholas J Short, Fadi G Haddad, Nitin Jain, Xuelin Huang, Guillermo Montalban-Bravo, Rashmi Kanagal-Shamanna, Tapan M Kadia, Naval Daver, Kelly Chien, Yesid Alvarado, Guillermo Garcia-Manero, Ghayas C Issa, Rebecca Garris, Cedric Nasnas, Lewis Nasr, Farhad Ravandi, Elias Jabbour

Faculty, Staff and Student Publications

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.In this analysis, we update our experience with the chemotherapy-free regimen of blinatumomab and ponatinib in 60 patients with newly diagnosed Philadelphia chromosome (Ph)-positive ALL. At a median follow-up of 24 months, the complete molecular response rate …

Protocol For Monitoring Clonal Hematopoiesis In Transgenic Mouse Models Using Multispectral Imaging, Priyanka Khanna, Lauren B Ostermann, Shayaun Khazaei, Ran Zhao, Michael Andreeff, Rasoul Pourebrahim

Faculty, Staff and Student Publications

Clonal hematopoiesis involves the clonal expansion of hematopoietic cells, potentially progressing into hematological malignancies. Here, we present a protocol for the development and characterization of two mouse models designed to simulate clonal hematopoiesis and acute myeloid leukemia. We describe steps for model generation, monitoring clonal expansion, harvesting, fixation, and staining of bone marrow and spleen tissues. We specifically focus on the visualization and analysis of p53 mutant clonal expansions, providing a comprehensive protocol for studying these phenomena in mouse models. For complete details on the use and execution of this protocol, please refer to Pourebrahim et al.

Specifically Targeting Muc16 For Fluorescence-Guided Surgery Of Pancreatic Ductal Adenocarcinoma, Kathryn M. Muilenburg

Theses & Dissertations

Pancreatic cancer is a lethal disease with a low 5-year survival rate and a high rate of resection recurrence. However, surgery remains the only treatment with curative potential for pancreatic cancer. Many factors such as high desmoplasia, a lack of intraoperative imaging, and micrometastatic disease contribute to the high rate of incomplete resections in pancreatic cancer. Fluorescence-guided surgery (FGS) is a potential intraoperative tool for application in surgical resection. FGS works through passive or active targeting of a free dye or dye-containing moiety (e.g. antibody, peptide, and nanoparticles) to specifically fluoresce the tumor compared to the surrounding normal, fibrotic, and …

Protocol For Culturing Patient-Derived Organoids Of Cervical Cancer, Rui Wang, Timothy Harris, Dalissa Negrón-Figueroa, David Lo, Allison Judge, D'Shaunique Walters, Bo Jiang, Lauren E Colbert

Faculty, Staff and Student Publications

Herein, we present a protocol for culturing patient-derived organoids (PDOs) of cervical cancer that includes workflows for tumor biopsy/resection tissue and cytobrush-sampled cells. We describe steps for PDO culture initiation, including rinsing, gentle dissociation, Lymphoprep separation, and cell assessment, as well as seeding cells from surgical and cytobrush tissue digestion. We then provide guidance on PDO maintenance and passage and techniques for producing conditioned medium. Overall, this protocol serves as a valuable guide for establishing and maintaining cervical cancer PDOs. For complete details on the use and execution of this protocol, please refer to Colbert et al.

Irregular Assessment Times In Pragmatic Randomized Clinical Trials, Andrea Apter, Frances K Barg, Sanjib Basu, Alex Federman, Winifred J Hamilton, Jerry A Krishnan, Tianjing Li, Russell Localio, Christine Pindle, Daniel O Scharfstein, Justin D Smith, Kaharu Sumino

Faculty, Staff and Students Publications

Deviation from protocolized assessment times is commonplace in pragmatic randomized clinical trials. Working with a stakeholder advisory board for a Patient-Centered Outcomes Research Institute®-funded project on statistical methods for handling potential biases introduced by irregular assessment times, we identified reasons for off-schedule or missed assessments. We used the Consolidated Framework for Implementation Research 2.0 to organize our findings. We conjectured that timely completion of outcome assessments is a function of multiple determinants, only some related to participants' health status. We identified potential determinants that can be modified during the protocol design stage and can be reassessed and mitigated during trial …

Rna-Dependent Rna Polymerase Of Predominant Human Norovirus Forms Liquid-Liquid Phase Condensates As Viral Replication Factories, Soni Kaundal, Ramakrishnan Anish, B Vijayalakshmi Ayyar, Sreejesh Shanker, Gundeep Kaur, Sue E Crawford, Jeroen Pollet, Fabio Stossi, Mary K Estes, B V Venkataram Prasad

Faculty, Staff and Students Publications

Many viral proteins form biomolecular condensates via liquid-liquid phase separation (LLPS) to support viral replication and evade host antiviral responses, and thus, they are potential targets for designing antivirals. In the case of nonenveloped positive-sense RNA viruses, forming such condensates for viral replication is unclear and less understood. Human noroviruses (HuNoVs) are positive-sense RNA viruses that cause epidemic and sporadic gastroenteritis worldwide. Here, we show that the RNA-dependent RNA polymerase (RdRp) of pandemic GII.4 HuNoV forms distinct condensates that exhibit all the signature properties of LLPS with sustained polymerase activity and the capability of recruiting components essential for viral replication. …

Ifrd1 Is Required For Maintenance Of Bladder Epithelial Homeostasis, Bisiayo E Fashemi, Amala K Rougeau, Arnold M Salazar, Steven J Bark, Rayvanth Chappidi, Jeffrey W Brown, Charles J Cho, Jason C Mills, Indira U Mysorekar

Faculty, Staff and Students Publications

The maintenance of homeostasis and rapid regeneration of the urothelium following stress are critical for bladder function. Here, we identify a key role for IFRD1 in maintaining urothelial homeostasis in a mouse model. We demonstrate that the murine bladder expresses IFRD1 at homeostasis, particularly in the urothelium, and its loss alters the global transcriptome with significant accumulation of endolysosomes and dysregulated uroplakin expression pattern. We show that IFRD1 interacts with mRNA-translation-regulating factors in human urothelial cells. Loss of Ifrd1 leads to disrupted proteostasis, enhanced endoplasmic reticulum (ER stress) with activation of the PERK arm of the unfolded protein response pathway, …

Postoperative Conundrum: Horner Syndrome Secondary To Anterior Cervical Discectomy And Fusion Procedure, Nicholas Mynarski, Sabrina M. Johnson, Aanchal Sawhney, Christine Giesa Do, Rachel Odeyemi Do

Transformative Medicine

IntroductionHorner syndrome is a rare complication following anterior cervical discectomy and fusion (ACDF) surgeries, with an incidence rate of

Case DescriptionWe report a case of a 45-year-old female with a history of non-Hodgkin's lymphoma and chronic obstructive pulmonary disease who developed Horner syndrome post-ACDF. Initially admitted for suspected cholecystitis found on imaging following a fall, the patient's clinical course was complicated by worsening cervical and lumbar pain. This prompted MRI evaluation revealing cervical stenosis at C5-C6 and ACDF was performed without intraoperative complications. However, on postoperative day three, the patient developed left eye ptosis and miosis, consistent with …

The Camden Study - A Pregnancy Cohort Study Of Pregnancy Complications And Birth Outcomes In Camden, New Jersey, Usa., Stephanie Shiau, Xinhua Chen, Ayana April-Sanders, Ellen C Francis, Shristi Rawal, Megan Hansel, Kehinde Adeyemi, Zorimar Rivera-Núñez, Emily S Barrett

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Pregnancy is a unique stage of the life course characterized by trade-offs between the nutritional, immune, and metabolic needs of the mother and fetus. The Camden Study was originally initiated to examine nutritional status, growth, and birth outcomes in adolescent pregnancies and expanded to study dietary and molecular predictors of pregnancy complications and birth outcomes in young women.

METHODS: From 1985-2006, 4765 pregnant participants aged 12 years and older were recruited from Camden, NJ, one of the poorest cities in the US. The cohort reflects a population under-represented in perinatal cohort studies (45% Hispanic, 38% non-Hispanic Black, 17% White …

Assessing Tolerability With The Functional Assessment Of Cancer Therapy Item Gp5: Psychometric Evidence From Libretto-531, A Phase 3 Trial Of Selpercatinib In Medullary Thyroid Cancer, Antoine Regnault, Laurine Bunod, Angely Loubert, Marcia S. Brose, Lisa M. Hess, Patricia Maeda, Yan Lin, Rebecca M. Speck, Adrienne M. Gilligan, Nalin Payakachat

Department of Medical Oncology Faculty Papers

BACKGROUND: This psychometric analysis generated evidence to support the use of the Functional Assessment of Cancer Therapy item GP5 (GP5) as a measure of tolerability and confirms the appropriateness of categorizing "high side-effect burden" using a rating of 3 or 4 (score ranges 0-4) in patients with advanced/metastatic RET-mutant medullary thyroid cancer (MTC).

METHODOLOGY: Blinded, pooled interim data from the safety population (n=290) enrolled in the phase 3 LIBRETTO-531 trial (NCT04211337) were used. Intraclass correlation coefficients (ICC) were calculated for test-retest reliability using data from cycles 1-2 post-baseline. Construct validity was evaluated by examining the correlations of GP5 ratings with …

Author Correction: Single-Cell And Spatial Proteo-Transcriptomic Profiling Reveals Immune Infiltration Heterogeneity Associated With Neuroendocrine Features In Small Cell Lung Cancer, Ying Jin, Yuefeng Wu, Alexandre Reuben, Liang Zhu, Carl M Gay, Qingzhe Wu, Xintong Zhou, Haomin Mo, Qi Zheng, Junyu Ren, Zhaoyuan Fang, Teng Peng, Nan Wang, Liang Ma, Lungevity Panshi Initiative Consortium, Yun Fan, Hai Song, Jianjun Zhang, Ming Chen

Faculty, Staff and Student Publications

No abstract provided.

Notes From The Field: School-Based Surveillance Of Mycoplasma Pneumoniae Trends And Impact On School Attendance By Students And Staff Members - Missouri, Fall 2024., Olivia M. Almendares, Brittney Fritschmann, Rangaraj Selvarangan, Brian R. Lee, Chris Edens, Maureen Diaz, Brett Whitaker, Shannon Tilsworth, Janelle Porter, Nibha Sagar, Jennifer E. Schuster, Jennifer Goldman, Hannah L. Kirking

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Age-Related Tfeb Downregulation In Proximal Tubules Causes Systemic Metabolic Disorders And Occasional Apolipoprotein A4-Related Amyloidosis, Jun Nakamura, Takeshi Yamamoto, Yoshitsugu Takabatake, Tomoko Namba-Hamano, Atsushi Takahashi, Jun Matsuda, Satoshi Minami, Shinsuke Sakai, Hiroaki Yonishi, Shihomi Maeda, Sho Matsui, Hideaki Kawai, Isao Matsui, Tadashi Yamamuro, Ryuya Edahiro, Seiji Takashima, Akira Takasawa, Yukinori Okada, Tamotsu Yoshimori, Andrea Ballabio, Yoshitaka Isaka

Duncan NRI Faculty and Staff Publications

With the aging of society, the incidence of chronic kidney disease (CKD), a common cause of death, has been increasing. Transcription factor EB (TFEB), the master transcriptional regulator of the autophagy/lysosomal pathway, is regarded as a promising candidate for preventing various age-related diseases. However, whether TFEB in the proximal tubules plays a significant role in elderly patients with CKD remains unknown. First, we found that nuclear TFEB localization in proximal tubular epithelial cells (PTECs) declined with age in both mice and humans. Next, we generated PTEC-specific Tfeb-deficient mice and bred them for up to 24 months. We found that TFEB …

Deuterated Water Labeling In Ibrutinib-Treated Patients With Cll: Leukemia Cell Kinetics Correlate With Ighv, Zap-70, And Mrd, Ekaterina Kim, Shih-Shih Chen, Mariela Sivina, Hyunsoo Hwang, Xuelin Huang, Alessandra Ferrajoli, Nitin Jain, William G Wierda, Dominik Wodarz, Nicholas Chiorazzi, Jan A Burger

Faculty, Staff and Student Publications

Deuterated (“heavy”) water labeling in patients with chronic lymphocytic leukemia (CLL) demonstrates that IGHV unmutated and ZAP-70+ patients have higher blood and tissue CLL death rates on ibrutinib therapy, resulting in lower measurable residual disease levels with long-term ibrutinib treatment. This trial was registered at www.clinicaltrials.gov as #NCT01752426.

The Proteomics Of T-Cell And Early T-Cell Precursor (Etp) Acute Lymphocytic Leukemia: Prognostic Patterns In Adult And Pediatric-Etp All, Fieke W Hoff, Lourdes Sriraja, Yihua Qiu, Gaye N Jenkins, David T Teachey, Brent Wood, Meenakshi Devidas, Shaina Shockley, Mignon L Loh, Evangelia Petsalaki, Steven M Kornblau, Terzah M Horton

Faculty, Staff and Student Publications

Background: The 5-year overall survival (OS) rates of T-cell lymphocytic leukemia (T-ALL) are better for children (>90%) compared to adults (~57%). The early T-cell precursor (ETP) T-ALL subtype is prognostically unfavorable in adults, but less significant in pediatric T-ALL, and the diagnosis and prognosis of "near"-ETP is controversial. We compared protein and RNA expression patterns in pediatric and adult T-ALL to identify prognostic subgroups, and to further characterize ETP and near-ETP T-ALL in both age groups.

Methods: Protein expression was assessed using RPPA methodology for 321 target proteins in 361 T-ALL patient samples from 292 pediatrics and 69 adults, …

Enhancer Reprogramming Underlies Therapeutic Utility Of A Smarca2 Degrader In Smarca4 Mutant Cancer, Sasikumar Kotagiri, Nicholas Blazanin, Yuanxin Xi, Yanyan Han, Md Qudratullah, Xiaobing Liang, Yawen Wang, Poonam Pandey, Hira Mazhar, Truong Nguyen Lam, Anand Kamal Singh, Jing Wang, Yonathan Lissanu

Faculty, Staff and Student Publications

Genomic studies have identified frequent mutations in subunits of the SWI/SNF (switch/sucrose non-fermenting) chromatin remodeling complex including SMARCA4 and ARID1A in non-small cell lung cancer (NSCLC). Genetic evidence indicates that the paralog SMARCA2 is synthetic lethal to SMARCA4 suggesting SMARCA2 is a valuable therapeutic target. However, the discovery of selective inhibitors of SMARCA2 has been challenging. Here, we utilized structure-activity relationship (SAR) studies to develop YD23, a potent and selective proteolysis targeting chimera (PROTAC) targeting SMARCA2. Mechanistically, we show that SMARCA2 degradation induces reprogramming of the enhancer landscape in SMARCA4-mutant cells with loss of chromatin accessibility at enhancers of genes …

Il-12 Encoding Ondv Synergizes With Car-T Cells In Orthotopic Models Of Non-Small Cell Lung Cancer, Amanda Rosewell Shaw, Daisuke Morita, Caroline E Porter, Eric Tu, Greyson W Biegert, Sonia Agrawal, Nicholas Durham, Malcolm K Brenner, Masataka Suzuki

Faculty, Staff and Students Publications

Systemic administration of oncolytic viruses (OVs) is a promising approach for targeting metastatic solid tumors, but their anti-tumor activity is limited by pre-existing neutralizing antibodies against common human viruses. Therefore, investigators have developed OVs derived from non-human host viruses. Successful implementation of this strategy requires that the viral vector selectively infects and replicates within human cancer cells. Newcastle disease virus (NDV) is an avian paramyxovirus that, as NDV-based OVs (oNDVs), has demonstrated safety and activity against multiple human tumors in clinical trials. Their use as a single agent, however, is insufficient to cure tumors. Similarly, chimeric antigen receptor-modified T cells …

Epilepsy Therapies Symposium | Do We Really "Outgrow" Seizures?, Adam Ostendorf, Genna J Waldman, Lara Jehi, Mohammed Ilyas, Dean Naritoku, Alica M Goldman

Faculty, Staff and Students Publications

Initiation and maintenance of antiseizure therapy can be relatively straightforward in most patients. Depending on epilepsy type, patients may be more or less likely to enter remission or a resolution of their epilepsy and the International League Against Epilepsy developed clinically guiding definitions in this regard. The mechanisms by which resolution or remission are achieved are poorly understood which complicates clinical decision making and risk estimate for future seizure relapse. The impetus for the maintenance of medical therapy in a seizure-free patient is also age-dependent. In children, one ought to consider the unknown effects of antiseizure medications on the developing …

Quinoline-Based Compounds Can Inhibit Diverse Enzymes That Act On Dna, Jujun Zhou, Qin Chen, Ren Ren, Jie Yang, Bigang Liu, John R Horton, Caleb Chang, Chuxuan Li, Leora Maksoud, Yifei Yang, Dante Rotili, Abhinav K Jain, Xing Zhang, Robert M Blumenthal, Taiping Chen, Yang Gao, Sergio Valente, Antonello Mai, Xiaodong Cheng

Faculty, Staff and Students Publications

DNA methylation, as exemplified by cytosine-C5 methylation in mammals and adenine-N6 methylation in bacteria, is a key epigenetic process. Developing non-nucleoside inhibitors to cause DNA hypomethylation is crucial for treating various conditions without the toxicities associated with existing cytidine-based hypomethylating agents. This study characterized fifteen quinoline-based analogs, particularly compounds with additions like a methylamine (9) or methylpiperazine (11), which demonstrate similar low micromolar inhibitory potency against human DNMT1 and Clostridioides difficile CamA. These compounds (9 and 11) intercalate into CamA-bound DNA via the minor groove, causing a conformational shift that moves the catalytic domain away from the DNA. This study …

A Case Of Isolated Sma Dissection With Failed Initial Conservative Management, Salma Emara, Madison Kropp, Masoud Akbari, Kristin Cook

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Isolated superior mesenteric dissection (ISMAD) is an uncommon condition, often diagnosed incidentally for presentations of acute abdominal pain. Early identification and treatment are crucial as complications such as bowel ischemia or vessel rupture can occur. There remain no established treatment guidelines, making surgical and endovascular indications controversial. A 60-year-old male presented with acute abdominal pain, and was diagnosed with ISMAD via computed tomography imaging. He was initially managed conservatively which progressed to worsening abdominal pain, hypertensive crisis, and hemoperitoneum on follow-up computed tomography angiography (CTA). A mesenteric angiogram revealed a pseudoaneurysm in the superior mesenteric artery (SMA) which was subsequently …

Return To Driving For Clients With Tbi: A Guide For Caregivers To Navigate Emotional Barriers Experienced By Clients, Brianna Dorsey, Mary Greer

Fall 2024 OTD Capstone Symposium

The project describes the building of an online resource for caregivers to have easily accessible resources regarding information about brain injuries, emotional barriers, and return to driving programs. Each section provides further resources for caregivers and is intended to help improve their care and medical literacy.