Digital Commons Network^™

Rna Methyltransferase Spout1/Cenp-32 Links Mitotic Spindle Organization With The Neurodevelopmental Disorder Spadmiss, Avinash V Dharmadhikari, Maria Alba Abad, Sheraz Khan, Reza Maroofian, Tristan T Sands, Farid Ullah, Itaru Samejima, Yanwen Shen, Martin A Wear, Kiara E Moore, Elena Kondakova, Natalia Mitina, Theres Schaub, Grace K Lee, Christine H Umandap, Sara M Berger, Alejandro D Iglesias, Bernt Popp, Rami Abou Jamra, Heinz Gabriel, Stefan Rentas, Alyssa L Rippert, Christopher Gray, Kosuke Izumi, Laura K Conlin, Daniel C Koboldt, Theresa Mihalic Mosher, Scott E Hickey, Dara V F Albert, Haley Norwood, Amy Feldman Lewanda, Hongzheng Dai, Pengfei Liu, Tadahiro Mitani, Dana Marafi, Hatice Koçak Eker, Davut Pehlivan, Jennifer E Posey, Natalie C Lippa, Natalie Vena, Erin L Heinzen, David B Goldstein, Cyril Mignot, Jean-Madeleine De Sainte Agathe, Nouriya Abbas Al-Sannaa, Mina Zamani, Saeid Sadeghian, Reza Azizimalamiri, Tahere Seifia, Maha S Zaki, Ghada M H Abdel-Salam, Mohamed S Abdel-Hamid, Lama Alabdi, Fowzan Sami Alkuraya, Heba Dawoud, Aya Lofty, Peter Bauer, Giovanni Zifarelli, Erum Afzal, Faisal Zafar, Stephanie Efthymiou, Daniel Gossett, Meghan C Towne, Raey Yeneabat, Belen Perez-Duenas, Ana Cazurro-Gutierrez, Edgard Verdura, Veronica Cantarin-Extremera, Ana Do Vale Marques, Aleksandra Helwak, David Tollervey, Sandeep N Wontakal, Vimla S Aggarwal, Jill A Rosenfeld, Victor Tarabykin, Shinya Ohta, James R Lupski, Henry Houlden, William C Earnshaw, Erica E Davis, A Arockia Jeyaprakash, Jun Liao

Faculty, Staff and Students Publications

SPOUT1/CENP-32 encodes a putative SPOUT RNA methyltransferase previously identified as a mitotic chromosome associated protein. SPOUT1/CENP-32 depletion leads to centrosome detachment from the spindle poles and chromosome misalignment. Aided by gene matching platforms, here we identify 28 individuals with neurodevelopmental delays from 21 families with bi-allelic variants in SPOUT1/CENP-32 detected by exome/genome sequencing. Zebrafish spout1/cenp-32 mutants show reduction in larval head size with concomitant apoptosis likely associated with altered cell cycle progression. In vivo complementation assays in zebrafish indicate that SPOUT1/CENP-32 missense variants identified in humans are pathogenic. Crystal structure analysis of SPOUT1/CENP-32 reveals that most disease-associated missense variants are …

The Unfolding Story Of Protein Misfolding Causing Alzheimer Disease In Recipients Of Human Pituitary Growth Hormone, Evan G. Graber, Sayed M. Hadi Hosseini, Darrell M. Wilson, Alan D. Rogol

Division of Endocrinology, Diabetes and Metabolic Diseases Faculty Papers

Human growth hormone (hGH) has been in clinical use for children with GH deficiency (GHD) since the late 1950s. The original formulations were considered very safe with few adverse events reported. That changed remarkably in 1985 when the first patients with GHD, who had been treated with cadaveric hGH, were diagnosed with Creutzfeldt-Jakob disease (CJD). Fortunately, that same year a robust supply of recombinant hGH was released to the market whose adverse event profile did not include CJD. Patients who had received National Hormone and Pituitary Program hGH have been continuously followed since 1985. It is clear that prions are …

Next-Generation Sequencing-Based Msi Scoring Predicts Benefit In Mismatch Repair-Deficient Tumors Treated With Nivolumab: Follow-Up On Nci-Match Arm Z1d, Jonathan D Schoenfeld, Nilofer S Azad, Jacob Gross, Li Chen, Michael J Overman, Katrina Kao, Latifa Jackson, Donna Brunnquell, Xiangning Bu, Christina Coppola, Ping Guan, Jennifer Lee, David Sims, Rebecca Fuchs, Jason L Weirather, Kathleen L Pfaff, Lauren Gunasti, Srin Ranasinghe, Stanley R Hamilton, Victoria Wang, Peter J O'Dwyer, Catherine J Wu, Scott J Rodig, David R Patton, Lyndsay Harris

Faculty, Staff and Student Publications

Purpose: Mismatch repair-deficient (dMMR) tumors have demonstrated favorable responses to immune checkpoint inhibition targeting PD-1. However, more in-depth identification of predictors of response could further refine patient selection for immunotherapy treatment.

Patients and methods: We undertook integrated evaluation performed on samples collected from 28 of 42 patients enrolled on the NCI-Molecular Analysis for Therapy Choice arm Z1D trial that evaluated PD-1 inhibition treatment with nivolumab in patients with noncolorectal dMMR tumors. Genomic analyses were performed using next-generation sequencing (NGS), whole-exome sequencing, and RNA sequencing and supplemented by multiplex immunofluorescence performed on tissue samples.

Results: In this dMMR population, more extensive …

Markedly Elevated Blood Pressure, Tachycardia, And Altered Consciousness In Patients With Bacteremia During Transurethral Surgeries: Two Case Reports, Arisa Hotta, Momoka Nishimura, Daisuke Nakada, Riko Uchida, Hiroshi Matsuura, Naoko Torii, Naoko Fujita, Taku Hamada, Ai Nakamoto, Noriko Yoshikawa

Faculty, Staff and Students Publications

Background: Transurethral surgery is often accompanied by postoperative urinary tract infection. Although early detection and adequate treatment of bacteremia are required to prevent sepsis, it is usually undetectable during surgery. We report two cases with remarkable hypertension and tachycardia during transurethral surgery in which bacteremia was diagnosed by an intraoperative blood test.

Case presentation: An 80-year-old man (Case 1) underwent transurethral holmium laser prostate enucleation under spinal anesthesia, and an 88-year-old woman (Case 2) underwent transurethral resection of bladder tumor under general anesthesia. Altered consciousness (Case 1) and postoperative delirium (Case 2) were noted, in addition to remarkable intraoperative hypertension …

Self Supervised Artificial Intelligence Predicts Poor Outcome From Primary Cutaneous Squamous Cell Carcinoma At Diagnosis, Nicolas Coudray, Michelle C. Juarez, Maressa C. Criscito, Adalberto Claudio Quiros, Reason Wilken, Stephanie R. Jackson Cullison, Mary L. Stevenson, Nicole A. Doudican, Ke Yuan, Jamie D. Aquino, Daniel M. Klufas, Jeffrey P. North, Siegrid S. Yu, Fadi Murad, Emily Ruiz, Chrysalyne D. Schmults, Cristian D. Cardona Machado, Javier Cañueto, Anirudh Choudhary, Alysia N. Hughes, Alyssa Stockard, Zachary Leibovit-Reiben, Aaron R. Mangold, Aristotelis Tsirigos, John A. Carucci

Department of Dermatology and Cutaneous Biology Faculty Papers

Primary cutaneous squamous cell carcinoma (cSCC) is responsible for ~10,000 deaths annually in the United States. Stratification of risk of poor outcome at initial biopsy would significantly impact clinical decision-making during the initial post operative period where intervention has been shown to be most effective. Using whole-slide images (WSI) from 163 patients from 3 institutions, we developed a self supervised deep-learning model to predict poor outcomes in cSCC patients from histopathological features at initial diagnosis, and validated it using WSI from 563 patients, collected from two other academic institutions. For disease-free survival prediction, the model attained a concordance index of …

Patient Perception Of Delays In The Dermatology Clinic, Emily Hunter, Safiyyah Bhatti, Lauren N. Mcgrath, Stephanie R. Jackson Cullison, Elizabeth Jones

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

Outcomes Of Arteriovenous Malformation Patients With Multiple Versus Single Feeders: A Multicenter Retrospective Study With Propensity-Score Matching, Basel Musmar, Nimer Adeeb, Hammam Abdalrazeq, Joanna M Roy, Stavropoula I Tjoumakaris, Hamza Adel Salim, Douglas Kondziolka, Jason Sheehan, Christopher S Ogilvy, Howard Riina, Sandeep Kandregula, Adam A Dmytriw, Kareem El Naamani, Ahmed Abdelsalam, Natasha Ironside, Deepak Kumbhare, Cagdas Ataoglu, Muhammed Amir Essibayi, Abdullah Keles, Sandeep Muram, Daniel Sconzo, Arwin Rezai, Omar Alwakaa, Salem M Tos, Ufuk Erginoglu, Johannes Pöppe, Rajeev D Sen, Christoph J Griessenauer, Jan-Karl Burkhardt, Robert M Starke, Mustafa K Baskaya, Laligam N Sekhar, Michael R Levitt, David J Altschul, Malia Mcavoy, Assala Aslan, Abdallah Abushehab, Christian Swaid, Adib A Abla, Saman Sizdahkhani, Sravanthi Koduri, Elias Atallah, Spyridon Karadimas, M Reid Gooch, Robert H Rosenwasser, Christopher Stapleton, Matthew Koch, Visish M Srinivasan, Peng R Chen, Spiros Blackburn, Joseph Cochran, Omar Choudhri, Bryan Pukenas, Darren Orbach, Edward Smith, Pascal J Mosimann, Ali Alaraj, Mohammad A Aziz-Sultan, Aman B Patel, Hugo H Cuellar, Michael Lawton, Bharat Guthikonda, Jacques Morcos, Pascal Jabbour

Faculty, Staff and Student Publications

Introduction: The impact of multiple feeding arteries on clinical outcomes of cerebral arteriovenous malformations (AVMs) is not well understood. This study aims to compare outcomes between AVMs with multiple versus single feeding arteries.

Patients and methods: Data from the Multicenter International Study for Treatment of Brain AVMs (MISTA) consortium were analyzed. Propensity score matching (PSM) was used to balance cohorts. Subgroup analysis was conducted for ruptured and unruptured AVMs and different treatment options, and multivariable logistic regression was applied to assess the impact of feeding artery origin.

Results: Among 953 patients, 661(69.4%) had multiple feeding arteries, and 292 (30.6%) had …

Genetic And Environmental Contribution To Phenotypic Resemblance Between Iranian Couples: Tehran Cardiometabolic And Genetic Study (Tcgs), Parisa Riahi, Amir Hossein Saeidian, Albert Tenesa, Carolyn T Hogan, Michael March, Kamran Guity, Mahmoud Amiri Roudbar, Asieh Zahedi, Maryam Zarkesh, Farideh Neshati, Mehdi Hedayati, Fereidoun Azizi, Hakon Hakonarson, Maryam S Daneshpour, Mahdi Akbarzadeh

Faculty, Staff and Students Publications

Objective: To provide an applied framework for assessing the genetic contribution to assortative mating (AM) using height as a model trait and disclose the trace of certain pieces of evidence of AM in the form of the shared environmental effects from long-term cohabitation on spouses' anthropometric traits and lipid serum levels.

Methods: 2315 genotyped couples were extracted from the Tehran Cardiometabolic Genetic Study (TCGS). Pearson correlation analysis was used to assess the relationship between spouses' height. The GCTA-GREML was used to assess the SNP-based heritability of individual and spousal heights with AM adjustments. We used a recent GWAS meta-analysis of …

Reassessing Estrogen Receptor Expression Thresholds For Breast Cancer Prognosis In Her2-Negative Patients Using Shape Restricted Modeling, Wenli Dong, Takeo Fujii, Jing Ning, Toshiaki Iwase, Jing Qin, Naoto T Ueno, Yu Shen

Faculty, Staff and Student Publications

We used a novel shape-restricted Cox model to determine the desirable ER expression cutoff to predict breast cancer prognoses. Our model treats ER as a continuous variable using a flexible monotone-shaped Cox regression to assess its association with survival outcomes holistically. The study included 3055 patients with stage II/III HER2-negative breast cancer. The primary outcomes were time to recurrence or death (TTR) and overall survival (OS). The shape-restricted Cox model identified 10% ER as the preferred cutoff to predict TTR. The finding was confirmed by the log-rank test and standard Cox model that patients with ER ≥ 10% had TTR …

Single-Cell Rna Sequencing Identifies Molecular Biomarkers Predicting Late Progression To Cdk4/6 Inhibition In Patients With Hr+/Her2- Metastatic Breast Cancer, Linjie Luo, Peng Yang, Sofia Mastoraki, Xiayu Rao, Yan Wang, Nicole M Kettner, Akshara Singareeka Raghavendra, Debasish Tripathy, Senthil Damodaran, Kelly K Hunt, Jing Wang, Ziyi Li, Khandan Keyomarsi

Faculty, Staff and Student Publications

Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) in combination with endocrine therapy are the standard treatment for patients with hormone receptor-positive, HER2-negative metastatic breast cancer (mBC). Despite the efficacy of CDK4/6is, intrinsic resistance occurs in approximately one-third of patients, highlighting the need for reliable predictive biomarkers.

Methods: Single-cell RNA sequencing analyzed metastatic tumors from HR+/HER2- mBC patients pre-CDK4/6i treatment at baseline (BL) and/or at disease progression. BL samples were from CDK4/6i responders (median progression-free survival [mPFS] = 25.5 months), while progressors were categorized as early-progressors (EP, mPFS = 3 months) and late-progressors (LP, mPFS = 11 months). Metastatic sites included liver, …

Perceived Hbv-Related Stigma Is Associated With Lower Antiviral Medication Adherence In Patients With Chronic Hepatitis B, Hee-Soon Juon, Daniel Yang, Cindy Xin Fang, Hie-Won Hann, Ho Bae, Mimi Chang, Ann C. Klassen

Department of Medical Oncology Faculty Papers

Medication nonadherence among patients with chronic hepatitis B (CHB) can lead to severe liver disease progression, including liver cirrhosis and hepatocellular carcinoma (HCC). Yet the factors that influence adherence in high-risk groups, like Korean Americans, remain unclear. Thus, this study explored the psychosocial and clinical factors affecting medication adherence in CHB patients. A cohort of 365 Korean American patients with CHB from two clinics in Philadelphia and Los Angeles was studied. The 8-item Morisky Medication Adherence Scale (MMAS-8) gauged their adherence to antiviral medication. Using descriptive and multivariable logistic regression analyses, we identified factors associated with MMAS-8 scores. Of the …

Inadequate Intensification Of Ldl-Cholesterol Lowering Therapy After Coronary Revascularization: Insights From The Gould Registry, Benjamin E Peterson, Deepak L Bhatt, Christie M Ballantyne, James A De Lemos, Robert S Rosenson, Mikhail N Kosiborod, Christopher P Cannon

Faculty, Staff and Students Publications

Background: Patients with a history of coronary revascularization are at a higher risk for subsequent cardiovascular events and all-cause mortality. Lowering LDL-cholesterol (LDL-C) levels post-revascularization significantly reduces these risks.

Methods: This analysis compared LDL-C-lowering therapies at baseline and over time among patients with and without prior coronary revascularization in the GOULD registry (a prospective multicenter cohort study). Baseline- and 24-month follow-up characteristics-including LDL-C levels and strategies for lipid-lowering therapy (LLT)-were evaluated.

Results: Out of 5006 patients, 2195 (43.8%) had prior coronary revascularization. At baseline, these patients had lower LDL-C (99.2 mg/dL vs. 102.5 mg/dL; p < 0.001) and were more likely to be on intensive LLT (52.8% vs. 42.7%; p < 0.001). At 24 months, they had small reductions in LDL-C (-15.6% vs. -13.7%; p = 0.145) and were more likely to be on intensive LLT (61.9% vs. 51.5%; p < 0.001). Similar LDL-C reductions were observed in the PCSK9i group regardless of revascularization status.

Conclusions: Despite slightly better baseline …

Acute Care For Elders Unit Implementation At Banner Health: A Quality Improvement Analysis, Jacob Lahti, Tony Gaidici, Shreya Bharath, Esha Saraswat, Nimit Agarwal

Annual Research Symposium

There is an increasing need to optimize hospital care for older adults as Age Friendly Health Systems (AFHS) become increasingly popular. Geriatric patients may often be subject to extended hospital stays, which can result in functional decline, increases in hospital-acquired injury, infections, and neurocognitive deterioration. Early acute inpatient rehabilitation (IRF) is known to improve functional optimization of older adults as compared to therapy in a skilled nursing facility (SNF). In this study we demonstrate the effect of a structured program based on the 4Ms of AFHS in our newly established Acute Care for Elders (ACE) unit, a first in Arizona. …

High-Output Cardiac Failure Caused By Large Coronary Artery Fistulas Treated With Coil Embolization, Nawal Mustafa, Blain Tafaesse, Hajra Nadeem, Muhammad Mustafa

The VAD Journal

There are many causes of high-output cardiac failure. We present a unique case of high-output cardiac failure caused by multiple coronary-to-pulmonary artery (PA) fistulas, which, to our knowledge, is a rare finding that has not been previously researched. The purpose of our case report is to highlight the importance of considering coronary-to-PA fistulas in the differential diagnosis of patients presenting with high-output cardiac failure. Our patient presented to the emergency department with shortness of breath and underwent nuclear stress testing, which, through cardiac catheterization, revealed coronary-to-PA fistulas as the cause of the high-output cardiac failure. These fistulas were successfully treated …

Long-Acting Injectables: A Strategy To Mitigate Nonadherence In Bipolar Disorder, Justin Faden, Elina Maymind

Rowan-Virtua School of Osteopathic Medicine Departmental Research

No abstract provided.

Glycemic Variability And Migraine: New Insights From Glucose Monitoring, Christina A. Nelson, Kyle Reavely, Matthew Jennings, Brandon Burger, Jackson Nielsen, Amanda Page, Alexander Kim, David Sant, Kyle Bills

Annual Research Symposium

No abstract provided.

Rideshare Services For Transportation Assistance In Gynecologic Oncology: A Quality Improvement Study, Anna Jo Smith, Sam Pancoe, Mary Pat Lynch, Megan Wachlin, Kristina Powell, Stefanie N. Hinkle, Nathanael C. Koelper, Meredith Doherty, Justin E. Bekelman, Fiona Simpkins, Emily M. Ko

SKMC Student Presentations and Publications

OBJECTIVE: Transportation barriers can lead to delays in care and suboptimal treatment. Our objective was to assess the utilization of a novel transportation pilot intervention in gynecologic oncology.

METHODS: Since May 2022, we have provided donor-funded transportation to patients receiving gynecologic cancer treatment at 5 University of Pennsylvania practices. Patients are screened for transportation barriers at first visit and re-screened during care. Patients who screen positive are referred to the intervention, a HIPAA-compliant ride-sharing service. There are no income or insurance restrictions; distance was limited to 25 miles. We report descriptive statistics on ride completion, distance traveled, and cost.

RESULTS: …

Divergence In Cellular Markers Observed In Single-Cell Transcriptomics Datasets Between Cultured Primary Trabecular Meshwork Cells And Tissues, Alice Tian, Sangbae Kim, Hasna Baidouri, Jin Li, Xuesen Cheng, Janice Vranka, Yumei Li, Rui Chen, Vijaykrishna Raghunathan

Faculty, Staff and Students Publications

The trabecular meshwork within the outflow apparatus is critical in maintaining intraocular pressure homeostasis. In vitro studies employing primary cell cultures of the human trabecular meshwork (hTM) have conventionally served as surrogates for investigating the pathobiology of TM dysfunction. Despite its abundant use, translation of outcomes from in vitro studies to ex vivo and/or in vivo studies remains a challenge. Given the cell heterogeneity, performing single-cell RNA sequencing comparing primary hTM cell cultures to hTM tissue may provide important insights on cellular identity and translatability, as such an approach has not been reported before. In this study, we assembled a …

Multimodal Objective Assessment Of Impulsivity In Healthy And Mood Disorder Participants, Bishal Lamichhane, Nidal Moukaddam, Ramiro Salas, Wayne Goodman, Ashutosh Sabharwal

Faculty, Staff and Students Publications

Impulsivity represents an individual's tendency to act on urges without sufficient forethought. Heightened impulsivity is a hallmark of many mental health disorders. Objective impulsivity assessments could improve risk evaluation, diagnosis, and behavioral outcome monitoring in impulsivity-related health disorders. Towards objective impulsivity assessment, in this work, we identify impulsivity correlates in objective measurements, investigate their complementarity, and contrast impulsivity mechanisms across health conditions. We analyzed behavioral tests, heart rate variability (HRV), and fMRI-based brain connectivity in 227 healthy participants and 34 participants with mood disorders. Impulsivity dimensions had complementary correlates in objective measurements, with fMRI providing the strongest correlates. Multimodal assessment …

Mage-A4 Induces Non-Small Cell Lung Cancer And Tumor-Promoting Plasma Cell Accumulation, Dominique Armstrong, Cheng-Yen Chang, Monica J Hong, Linda Green, Yichao Shen, William Hudson, Kelsey E Mauk, Li-Zhen Song, Sheetal Jammi, Benjamin Casal, Brianna Burns, Chad J Creighton, Alexandre Carisey, Xiang H-F Zhang, Neil J Mckenna, Sung Wook Kang, Hyun-Sung Lee, William Decker, David B Corry, Farrah Kheradmand

Faculty, Staff and Students Publications

Adaptive immunity is critical in eliminating tumors, but cancer-intrinsic factors can subvert this function. Melanoma antigen-A4 (MAGE-A4), a cancer-testis antigen, is expressed in solid tumors and correlates with poor survival, but its role in tumorigenesis and antitumor immunity remains unclear. We found that expression of MAGE-A4 was highly associated with the loss of PTEN, a tumor suppressor, in human non–small cell lung cancers (NSCLC). Here, we show that constitutive expression of human MAGE-A4 with Pten loss in mouse airway epithelia results in metastatic adenocarcinoma. Tumors showed distinct enrichment in IgA+ CD138+ CXCR4+ plasma cells (PCs) and increased expression of …

Single-Cell Analysis Identifies Ifi27l2a As A Gene Regulator Of Microglial Inflammation In The Context Of Aging And Stroke In Mice, Gab Seok Kim, Elisabeth Harmon, Manuel C Gutierrez, Sodam Kim, Lauren Vance, Haven Burrous, Jessica M Stephenson, Anjali Chauhan, Anik Banerjee, Zachary Wise, Andrea Doan, John Ahn, Ting Wu, Jesus Bautista-Garrido, Juneyoung Lee, Chunfeng Tan, Joo Eun Jung, Louise D Mccullough, Joshua D Wythe, Sean P Marrelli

Faculty, Staff and Student Publications

Inflammation is a significant driver of ischemic stroke pathology in the brain. To identify potential regulators of inflammation, we performed single-cell RNA sequencing (scRNA-seq) of young and aged mouse brains following stroke and found that interferon alpha-inducible protein 27 like 2 A (Ifi27l2a) was significantly up-regulated, particularly in microglia of aged brain. Ifi27l2a is induced by interferons for viral host defense and has been linked with pro-inflammatory cellular mechanisms. However, its potential role in neurodegeneration is unknown. Using a combination of cell culture, experimental stroke models in mice, and human autopsy brain samples, we demonstrated that induction of Ifi27l2a occurs …

Identification Of Distinct Stool Metabolites In Women With Endometriosis For Non-Invasive Diagnosis And Potential For Microbiota-Based Therapies, Chandni Talwar, Goutham Venkata Naga Davuluri, Abu Hena Mostafa Kamal, Cristian Coarfa, Sang Jun Han, Surabi Veeraragavan, Krishna Parsawar, Nagireddy Putluri, Kristi Hoffman, Patricia Jimenez, Scott Biest, Ramakrishna Kommagani

Faculty, Staff and Students Publications

Background: Endometriosis, a poorly studied gynecological condition, is characterized by the presence of ectopic endometrial lesions resulting in pelvic pain, inflammation, and infertility. These associated symptoms contribute to a significant burden, often exacerbated by delayed diagnosis. Current diagnostic methods involve invasive procedures, and existing treatments provide no cure.

Methods: Microbiome-metabolome signatures in stool samples from individuals with and without endometriosis were determined using unbiased metabolomics and 16S bacteria sequencing. Functional studies for selected microbiota-derived metabolites were conducted in vitro using patient-derived cells and in vivo by employing murine and human xenograft pre-clinical disease models.

Findings: We discovered a unique bacteria-derived …

Role Of Dexmedetomidine In Psychiatry - A Literature Review, Mehar Durah, Dayana Balsalobre Do, Sahar Nadeem Do, Megan De Armond Mslis, Mfa, Sherli Koshy-Chenthittayi Ph.D

Annual Research Symposium

Purpose This literature review aims to evaluate the clinical use of dexmedetomidine in psychiatry, specifically in the management of neurobehavioral manifestations associated with psychiatric diagnoses defined by the DSM-5 or ICD-10. Dexmedetomidine, an alpha-2 receptor agonist, effectively reduces a heightened sympathetic response and provides sedative, analgesic, and anti-inflammatory effects. The neurobehavioral manifestations include psychomotor agitation, delirium, catatonia, impaired focus, hyperactivity, mania, and hallucinations as seen in psychiatric conditions such as bipolar disorder, schizophrenia, alcohol withdrawal syndrome, ADHD, and autism. The purpose of this review is to identify use of dexmedetomidine in clinical psychiatry in controlling neurobehavioral manifestations and identifying its …

Role Of Psychiatric Factors Hindering Physical Rehabilitation After Acl Reconstructive Surgery, Malak Rafik, Davian Caraballo, James Fini Jr., Nathan Barnhurst

Annual Research Symposium

No abstract provided.

Periodontitis Linked With Urinary Tract Infections- Coincidence Or Causality?, Ali Shariff, Shankargouda Patil, Shilpa Bhandi, Frank Licari

Annual Research Symposium

Urinary tract infection is a cumulative term used to describe an infection of any part of the urinary system. Periodontitis is a chronic inflammatory condition of the tooth-supporting structures. The literature points towards an inter-relationship between periodontitis and other systemic diseases such as metabolic syndrome, diabetes mellitus, coronary heart diseases, etc. Several studies indicate a pathophysiologic inter-relationship between periodontitis and urinary tract infections. Considering the inflammatory nature of periodontitis and urinary tract infections, a common link of causality may be present between the two diseases. P. gingivalis, a key periodontal pathogen, is a significant agent in disseminating infection …

How To Avoid Arterial Access During Transcatheter Closure Of Patent Ductus Arteriosus Using Anatomo-Haemodynamic Landmark, Mohit Sachan, Kumar Himanshu, Mukesh Jitendra Jha, Santhosh Kumar Sinha, Mahmodullah Razi, Awadhesh Kumar Sharma, Puneet Aggarwal, Praveen Shukla, Rakesh Verma

Journal of the Saudi Heart Association

Objective- To evaluate the feasibility, safety, and efficacy of transcatheter closure (TCC) of patent ductus arteriosus (PDA) using anatomical-physiological landmark without any arteriography.Method- In this prospective, non-randomized study, all consecutive patients with PDA undergoing transcatheter closure at LPS Institute of Cardiology, Kanpur, India between January 2019 and June 2024 were evaluated. TCC was performed using anatomical and physiological landmark without aortogram, and device was deployed through antegrade route only. Transthoracic echocardiography with colour-Doppler imaging was used to confirm position of the device before final deployment. Primary outcome was procedural and fluoroscopy time, and major complications (access site …

Plasma Micrornas To Select Optimal Patients For Antibody Production From Anti-Addiction Vaccines, Thomas R Kosten, Amrit Koirala, David A Nielsen, Coreen B Domingo, Ynhi T Thomas, Preethi H Gunaratne, Cristian Coarfa

Faculty, Staff and Students Publications

Background: Cocaine and illicit amphetamines (disguised as “Adderall”) are being laced with fentanyl and producing accidental and intentional fatal overdoses. Vaccines can prevent these overdoses, but 33% of humans generate insufficient anti-drug antibody (AB) levels. Plasma microRNAs (miRs) can be used to predict non-responders. We have plasma stored from 152 cocaine vaccine trial participants following three vaccinations over 9 weeks and examined miRs as potential response biomarkers. Methods: We compared 2517 miRs before anti-cocaine vaccination in participants with the highest (n = 25) to the lowest (n = 23) antibody levels. False Discovery Rates (FDRs) were applied to identify differentially …

Navigating Epstein-Barr Virus (Ebv) And Post-Transplant Lymphoproliferative Disorder (Ptld) In Pediatric Liver Transplantation: Current Knowledge And Strategies For Treatment And Surveillance, Erin Y Chen, Natasha Dilwali, Krupa R Mysore, Sara Hassan, Sara Kathryn Smith, Wikrom Karnsakul

Faculty, Staff and Students Publications

Epstein-Barr virus (EBV) is strongly associated with the development of post-transplant lymphoproliferative disorder (PTLD) in pediatric liver transplant recipients. PTLD is one of the most common malignancies following liver transplantation and is associated with significant morbidity and mortality. Factors such as EBV-serostatus mismatch and prolonged or high levels of immunosuppression impact a patient's risk of developing PTLD. While pre-transplant EBV serological screening and post-transplant monitoring of EBV-DNA levels are strongly recommended, universal guidelines for its prevention and management are lacking. Due to a lack of robust prospective studies, current clinical practices vary widely. The treatment of PTLD typically involves reducing …

Prediction Of Cognitive Conversion Within The Alzheimer’S Disease Continuum Using Deep Learning, Siyu Yang, Xintong Zhang, Xinyu Du, Peng Yan, Jing Zhang, Wei Wang, Jing Wang, Lei Zhang, Huaiqing Sun, Yin Liu, Xinran Xu, Yaxuan Di, Jin Zhong, Caiyun Wu, Jan D Reinhardt, Yu Zheng, Ting Wu

Faculty, Staff and Students Publications

Background: Early diagnosis and accurate prognosis of cognitive decline in Alzheimer's disease (AD) is important to timely assignment to optimal treatment modes. We aimed to develop a deep learning model to predict cognitive conversion to guide re-assignment decisions to more intensive therapies where needed.

Methods: Longitudinal data including five variable sets, i.e. demographics, medical history, neuropsychological outcomes, laboratory and neuroimaging results, from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort were analyzed. We first developed a deep learning model to predicted cognitive conversion using all five variable sets. We then gradually removed variable sets to obtained parsimonious models for four different …

Inhibition Of Histone Methyltransferase Ezh2 For Immune Interception Of Colorectal Cancer In Lynch Syndrome, Charles M Bowen, Fahriye Duzagac, Abel Martel-Martel, Laura Reyes-Uribe, Mahira Zaheer, Jacklyn Thompson, Nan Deng, Ria Sinha, Soham Mazumdar, Melissa W Taggart, Abhinav K Jain, Elena Tosti, Winfried Edelmann, Krishna M Sinha, Eduardo Vilar

Faculty, Staff and Student Publications

Colorectal precancers in Lynch syndrome (LS) exhibit a distinct immune profile, presenting unique opportunities for developing immune-interception strategies to prevent carcinogenesis. Epigenetic modulation by EZH2 of immune-related genes is implicated in the carcinogenesis of different cancer types, including colorectal cancer. This study utilizes a mouse model of LS and ex vivo colonic organoids to assess the effects of the EZH2 inhibitor GSK503 on immune regulatory pathways, tumorigenesis, and epigenetic reprogramming. Our findings revealed that GSK503 significantly increased CD4+ and CD8+ T cells in both splenocytes and colonic mucosa of treated mice compared with controls. Additionally, a preventive dose of GSK503 …