Digital Commons Network^™

Developmental Differentiation Of Mouse Inner Ear Neuron Subpopulations Resolved With A Peripherin-Promoter Reporter Within The Grm8 Locus, Lily J Pearson, Jeremy L Pinyon, Jennie M E Cederholm, Georg Von Jonquieres, Florence Bartlett, Xabier Vázquez-Campos, Fabien Delerue, Lars M Ittner, Gary D Housley

Faculty, Staff and Student Publications

Molecular profiling of inner ear neurons has broadened the classification of the primary afferents that support neural coding for hearing and balance. To extend spatiotemporal characterization of auditory and vestibular neuron diversity, we established a transgenic reporter mouse model (Prphp-mCherry), where elements of the peripherin promoter (Prphp) drive expression of the mCherry fluorescent reporter. Type III intermediate filament protein peripherin expression is a marker for type II spiral ganglion neurons (SGN) that innervate the cochlear outer hair cells, and the small diameter 'bouton' vestibular ganglion neurons (VGN) innervating the type II vestibular hair cells. Using Nanopore genome sequencing, the integration …

Rapid Laser Ablation-Based Fabrication Of High-Density Polymer Microwell Arrays For High-Throughput Cellular Studies, Desh Deepak Dixit, Kavya L Singampalli, Amit S Niyogi, Amanda Montoya, Alexandre Reuben, Peter B Lillehoj

Faculty, Staff and Student Publications

Polymer-based microwell platforms have garnered much interest due to their usefulness in culturing and analyzing small quantities of biological cells and spheroids. Existing methods for fabricating polymer microwell arrays involve complex fabrication processes and/or are limited in their ability to create dense arrays of very small (< 50 μm in diameter) microwells. Here, we present a simple and rapid technique for fabricating high-density arrays of microwells ranging from 20 to 160 μm in diameter on a variety of polymer substrates. In this approach, a polymer surface is ablated using a CO2 laser that is rastered over a stainless steel mesh, which serves as a shadow mask. A theoretical laser-polymer interaction model was developed for predicting the microwell volume based on the substrate properties and laser settings. Microwell volumes predicted by the model were within 5.4% of fabricated microwell volumes determined experimentally. Cellulose acetate microwell arrays fabricated using this technique were used to culture Lewis lung carcinoma cells expressing ovalbumin (LLC-OVA), which were maintained for up to 72 h with a negligible (< 5%) loss in viability. As a second proof of principle demonstration, LLC-OVA cells grown in microwell arrays were co-cultured with OT-I T cells and measurements of interferon gamma (IFN-γ), a marker for T cell activation, were performed which revealed a positive correlation between LLC-OVA cell-T cell interaction time and T cell activation. These two in vitro demonstrations showcase the capability of this technique in generating polymer microwell arrays for high-throughput cellular studies, including cell growth dynamics studies and cell interaction studies. Furthermore, we envision that these platforms can be used with different cell types and for other biological applications, such as spheroid formation and single cell analysis, …

Effects Of Intensive Blood Pressure Treatment On Orthostatic Hypertension: Individual Level Meta-Analysis, Stephen P Juraschek, Jiun-Ruey Hu, Jennifer L Cluett, Carol Mita, Lewis A Lipsitz, Lawrence J Appel, Nigel S Beckett, Barry R Davis, Rury R Holman, Edgar R Miller, Kenneth J Mukamal, Ruth Peters, Jan A Staessen, Addison A Taylor, Jackson T Wright, William C Cushman

Faculty, Staff and Students Publications

Objective: To determine the effects of intensive blood pressure treatment on orthostatic hypertension.

Design: Systematic review and individual participant data meta-analysis.

Data sources: MEDLINE, Embase, and Cochrane CENTRAL databases through 13 November 2023.

Inclusion criteria: Population: ≥500 adults, age ≥18 years with hypertension or elevated blood pressure; intervention: randomized trials of more intensive antihypertensive drug treatment (lower blood pressure goal or active agent) with duration ≥6 months; control: less intensive antihypertensive drug treatment (higher blood pressure goal or placebo); outcome: measured standing blood pressure.

Main outcomes: Orthostatic hypertension, defined as an increase in systolic blood pressure ≥20 mm Hg or …

Haploinsufficiency Of Itsn1 Is Associated With A Substantial Increased Risk Of Parkinson’S Disease, Thomas P Spargo, Chloe F Sands, Isabella R Juan, Jonathan Mitchell, Vida Ravanmehr, Jessica C Butts, Ruth B De-Paula, Youngdoo Kim, Fengyuan Hu, Quanli Wang, Dimitrios Vitsios, Manik Garg, Lawrence Middleton, Michal Tyrlik, Mirko Messa, Guillermo Del Angel, Daniel G Calame, Hiba Saade, Laurie Robak, Ben Hollis, Vishnu A Cuddapah, Huda Y Zoghbi, Joshua M Shulman, Slavé Petrovski, Ismael Al-Ramahi, Ioanna Tachmazidou, Ryan S Dhindsa

Faculty, Staff and Students Publications

Despite its significant heritability, the genetic basis of Parkinson's disease (PD) remains incompletely understood. Here, in analyzing whole-genome sequence data from 3,809 PD cases and 247,101 controls in the UK Biobank, we discover that protein-truncating variants in ITSN1 confer a substantially increased risk of PD (p = 6.1 × 10

Adverse Health Effects Of Waste Anesthetic Gases (Wags): A Scoping Review Of Genetic, Immunotoxic, And Reproductive Impacts, Cozette Wilkins

Student Works

1 Background/Introduction: Occupational exposure to Waste Anesthetic Gases (WAGs) is a well-known concern for healthcare workers, especially those working in high-risk areas like the operating room (OR). Despite the implementation of safety measures such as WAG scavenging systems, there remains ongoing concern about the potential adverse health effects linked to exposure. This scoping review aims to map the existing evidence on the health risks associated with repeated WAG exposure, specifically focusing on genetic, immunotoxic, and reproductive health impacts. By synthesizing available data, this review seeks to better understand the extent of these risks and identify key gaps in the literature …

A Workflow Enabling The Automated Synthesis, Chain-End Degradation, And Rapid Mass Spectrometry Analysis For Molecular Information Storage In Sequence-Defined Oligourethanes, Julia R Shuluk, Christopher D Wight, James R Howard, Mary E King, Sarah R Moor, Rachel J Dehoog, Samuel D Dahlhauser, Livia S Eberlin, Eric V Anslyn

Faculty, Staff and Students Publications

The field of molecular information storage has recently expanded to include abiotic sequence-defined polymers. While robust methods have been developed, there is a current bottleneck in the throughput of this work as information density is increased. Herein, we introduce an automated workflow in which a commercial peptide synthesizer composed of a single XYZ liquid-handling robot was adapted to both synthesize and sequence sequence-defined oligourethanes. Our sequencing method was improved to cut down the number of samples required for each oligomer from 13 to one. Additionally, we introduce the use of desorption electrospray ionization mass spectrometry as our analysis method for …

Sexual Health In The Era Of Artificial Intelligence: A Scoping Review Of The Literature, Elia Abou Chawareb, Brian H. Im, Sherry Lu, Muhammed A.M. Hammad, Tiffany R. Huang, Henry Chen, Faysal A. Yafi

Student Papers, Posters & Projects

INTRODUCTION: Artificial Intelligence (AI) has witnessed significant growth in the field of medicine, leveraging machine learning, artificial neuron networks, and large language models. These technologies are effective in disease diagnosis, education, and prevention, while raising ethical concerns and potential challenges. However, their utility in sexual medicine remains relatively unexplored.

OBJECTIVE: We aim to provide a comprehensive summary of the status of AI in the field of sexual medicine.

METHODS: A comprehensive search was conducted using MeSH keywords, including "artificial intelligence," "sexual medicine," "sexual health," and "machine learning." Two investigators screened articles for eligibility within the PubMed and MEDLINE databases, with …

Prediction Of Persistent Incomplete Occlusion Of Intracranial Aneurysms Treated With Woven Endobridge Device, Muhammed Amir Essibayi, Mohamed Sobhi Jabal, Hasan Jamil, Hamza Adel Salim, Basel Musmar, Nimer Adeeb, Mahmoud Dibas, Nicole M. Cancelliere, Jose Danilo Bengzon, Oktay Algin, Sherief Ghozy, Sovann V. Lay, Adrien Guenego, Leonardo Renieri, Joseph Carnevale, Guillaume Saliou, Panagiotis Mastorakos, Kareem El Naamani, Eimad Shotar, Markus Möhlenbruch, Michael Kral, Charlotte Chung, Mohamed M. Salem, Ivan Lylyk, Paul M. Foreman, Hamza Shaikh, Vedran Župančić, Muhammad U. Hafeez, Joshua Catapano, Muhammad Waqas, Muhammed Said Besler, Yasin Celal Gunes, James D. Rabinov, Julian Maingard, Clemens M. Schirmer, Mariangela Piano, Anna L. Kühn, Caterina Michelozzi, Robert M. Starke, Ameer Hassan, Mark Ogilvie, Anh Nguyen, Jesse Jones, Waleed Brinjikji, Marie T. Nawka, Marios Psychogios, Christian Ulfert, Bryan Pukenas, Jan-Karl Burkhardt, Thien Huynh, Juan Carlos Martinez-Gutierrez, Sunil A. Sheth, Diana Slawski, Rabih Tawk, Benjamin Pulli, Boris Lubicz, Pietro Panni, Ajit S. Puri, Guglielmo Pero, Eytan Raz, Christoph J. Griessenauer, Hamed Asadi, Adnan Siddiqui, Elad I. Levy, Deepak Khatri, Neil Haranhalli, Andrew F. Ducruet, Felipe C. Albuquerque, Robert W. Regenhardt, Christopher J. Stapleton, Peter Kan, Vladimir Kalousek, Pedro Lylyk, Srikanth Boddu, Jared Knopman, Stavropoula I. Tjoumakaris, Hugo H. Cuellar-Saenz, Pascal Jabbour, Frédéric Clarençon, Nicola Limbucci, Vitor Mendes Pereira, Aman B. Patel, David J. Altschul, Adam A. Dmytriw, Worldwideweb Consortium Collaborators

Department of Neurosurgery Faculty Papers

While the Woven EndoBridge (WEB) device has transformed the treatment of wide-neck intracranial aneurysms, incomplete occlusion remains a significant challenge requiring better understanding of contributing factors. A retrospective analysis was conducted on multicenter data from patients who underwent WEB device treatment for intracranial aneurysms between January 2011 and December 2022. Using machine learning models, Cox regression, and time-stratified analyses, we evaluated factors associated with persistent incomplete occlusion, defined as non-improving Raymond-Roy Occlusion Classification grade 2 or 3 at final follow-up. Among 813 patients (607 with < 24 months follow-up, 206 with ≥ 24 months), machine learning analysis identified aneurysm height, Acom location, neck diameter, and pretreatment mRS as predictors of persistent incomplete occlusion. On Cox regression. larger aneurysm neck diameter (HR 1.13, 95% CI 1.01-1.27, p = 0.027) and height (HR 1.14, 95% CI 1.02-1.26, p = 0.017), and radial …

Lower Cytoplasmic Expression Of Ddit4 Is Associated With Poor Prognosis In Gastric Cancer Patients, Masoumeh Dehghan Manshadi, Fatemeh Tajik, Leili Saeednejad Zanjani, Farideh Hashemi, Mandana Rahimi, Fahimeh Fattahi, Sadegh Safaei, Zahra Madjd, Roya Ghods

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

INTRODUCTION: DNA damage-inducible transcript 4 (DDIT4), also known as Redd1, Dig2, and RTP801 was identified to be upregulated in response to a variety of cellular stresses, including DNA damage, endoplasmic reticulum stress, and energy stress. Several studies have discovered that dysregulation of DDIT4 involved in various cancers with paradoxical expression and roles. Hence, this study was designed to investigate the clinical significance and prognostic value of DDIT4 in different subtypes of gastric cancer (GC).

MATERIALS AND METHODS: To evaluate the expression pattern of DDIT4 in GC tissues as well as adjacent normal tissue, we utilized immunohistochemistry on tissue microarray (TMA) …

Evaluation Of The Distress Thermometer In Older Patients With Cancer, Charlotte Zuber, Kristine Swartz, Andrew Chapman, Lora Rhodes, Tingting Zhan, Kuang-Yi Wen

Kimmel Cancer Center Faculty Papers

INTRODUCTION: The Geriatric Depression Scale is a useful tool in screening for depression in older adults, a particularly vulnerable population in oncology. The National Comprehensive Cancer Network (NCCN) Distress Thermometer (DT) has been validated as a fast and effective screening tool for psychological distress in general oncology populations, and it could possibly be used as a surrogate for the longer Geriatric Depression Scale (GDS) test in older adults with cancer.

MATERIALS AND METHODS: In this retrospective cross-sectional study in older adults prior to starting cancer treatment, we evaluated the relationship between the DT and GDS by comparing 242 older adults …

Gene Expression Profiling Of Pancreatic Ductal Adenocarcinoma Cells In Hypercapnia Identifies Siah3 As A Novel Prognostic Biomarker, Nitzan Zohar, Ryan Maguire, Saed Khalilieh, Aditi Jain, Dmitriy Bosykh, Wilbur B. Bowne, Harish Lavu, Charles J. Yeo, Avinoam Nevler

Department of Surgery Faculty Papers

Hypercapnia is a key feature of the respiratory microenvironment in many pathologic conditions. It occurs both as a regional and as a systemic process, and it is associated with multiple metabolic changes such as mitochondrial dysfunction, decreased ATP production, and metabolic shift from glycolytic energy production to fatty acid metabolism. In the cancer tumor microenvironment, hypercapnia has been linked at times to enhanced cell migration, invasion, and chemoresistance. Our previous work has shown that hypercapnia-associated gene signatures can be used as prognostic biomarkers. However, unlike the hypoxia-inducible factor pathway, there are no validated targets to quantify hypercapnia. In this study, …

Rare Damaging Ccr2 Variants Are Associated With Lower Lifetime Cardiovascular Risk, Marios K Georgakis, Rainer Malik, Omar El Bounkari, Natalie R Hasbani, Jiang Li, Jennifer E Huffman, Gabrielle Shakt, Reinier W P Tack, Tamara N Kimball, Yaw Asare, Alanna C Morrison, Noah L Tsao, Renae Judy, Braxton D Mitchell, Huichun Xu, May E Montasser, Ron Do, Eimear E Kenny, Ruth J F Loos, James G Terry, John Jeffrey Carr, Joshua C Bis, Bruce M Psaty, W T Longstreth, Kendra A Young, Sharon M Lutz, Michael H Cho, Jai Broome, Alyna T Khan, Fei Fei Wang, Nancy Heard-Costa, Sudha Seshadri, Ramachandran S Vasan, Nicholette D Palmer, Barry I Freedman, Donald W Bowden, Lisa R Yanek, Brian G Kral, Lewis C Becker, Patricia A Peyser, Lawrence F Bielak, Farah Ammous, April P Carson, Michael E Hall, Laura M Raffield, Stephen S Rich, Wendy S Post, Russel P Tracy, Kent D Taylor, Xiuqing Guo, Michael C Mahaney, Joanne E Curran, John Blangero, Shoa L Clarke, Jeffrey W Haessler, Yao Hu, Themistocles L Assimes, Charles Kooperberg, Jürgen Bernhagen, Christopher D Anderson, Scott M Damrauer, Ramin Zand, Jerome I Rotter, Paul S De Vries, Martin Dichgans

Faculty, Staff and Student Publications

BACKGROUND: Previous work has shown a role of CCL2, a key chemokine governing monocyte trafficking, in atherosclerosis. However, it remains unknown whether targeting CCR2, the cognate receptor of CCL2, provides protection against human atherosclerotic cardiovascular disease.

METHODS: Computationally predicted damaging or loss-of-function (REVEL > 0.5) variants within CCR2 were detected in whole-exome-sequencing data from 454,775 UK Biobank participants and tested for association with cardiovascular endpoints in gene-burden tests. Given the key role of CCR2 in monocyte mobilization, variants associated with lower monocyte count were prioritized for experimental validation. The response to CCL2 of human cells transfected with these variants was tested …

Dna-Pk Inhibition Sustains The Antitumor Innate Immune Response In Small Cell Lung Cancer, Caterina De Rosa, Floriana Morgillo, Luisa Amato, Francesca Iommelli, Viviana De Rosa, Virginia Tirino, Federica Papaccio, Concetta Tuccillo, Gaetano Di Guida, Domenico Michele D'Angiolella, Alessandra Di Liello, Silvia Zappavigna, Michele Caraglia, Antonio Gambardella, Valerio Nardone, Kavya Ramkumar, Qi Wang, Jing Wang, Ferdinando De Vita, Davide Ciardiello, Erika Martinelli, Teresa Troiani, Stefania Napolitano, Giulia Martini, Alberto Servetto, Lauren Averett Byers, Fortunato Ciardiello, Carminia Maria Della Corte

Faculty, Staff and Student Publications

Small cell lung cancer (SCLC) is a highly aggressive form of lung cancer with limited treatment options. Patients often respond well to initial chemo-immunotherapy but relapse quickly, necessitating new strategies to enhance immune responsiveness. Recent research explores combining DNA-damaging therapies with immunotherapy to activate the STING pathway and improve the antitumor immune response. The addition of DNA Damage Repair (DDR) inhibitors, such as DNA-PKcs inhibitors, after chemotherapy has shown promise in activating innate immune sensors and enhancing CD8

Dependence Of Mitochondrial Calcium Signalling And Dynamics On The Disaggregase, Clpb, Donato D'Angelo, Víctor H. Sánchez-Vázquez, Benjamín Cartes-Saavedra, Denis Vecellio Reane, Ryan R. Cupo, Hilda Delgado De La Herran, Giorgia Ghirardo, James Shorter, Ron A. Wevers, Saskia B. Wortmann, Fabiana Perocchi, Rosario Rizzuto, Anna Raffaello, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Cells utilize protein disaggregases to avoid abnormal protein aggregation that causes many diseases. Among these, caseinolytic peptidase B protein homolog (CLPB) is localized in the mitochondrial intermembrane space and linked to human disease. Upon CLPB loss, MICU1 and MICU2, regulators of the mitochondrial calcium uniporter complex (mtCU), and OPA1, a main mediator of mitochondrial fusion, become insoluble but the functional outcome remains unclear. In this work we demonstrate that CLPB is required to maintain mitochondrial calcium signalling and fusion dynamics. CLPB loss results in altered mtCU composition, interfering with mitochondrial calcium uptake independently of cytosolic calcium and mitochondrial membrane potential. …

Islet Single-Cell Transcriptomic Profiling During Obesity-Induced Beta Cell Expansion In Female Mice, Peter M Masschelin, Scott A Ochsner, Sean M Hartig, Neil J Mckenna, Aaron R Cox

Faculty, Staff and Student Publications

Targeting beta cell proliferation is an appealing approach to restore glucose control in type 1 diabetes. However, the underlying mechanisms of beta cell proliferation remain incompletely understood, limiting identification of new therapeutic targets. Obesity is a naturally occurring process that potently induces human and rodent beta cell replication, representing an ideal model to study mechanisms of beta cell proliferation. We showed previously acute whole-body

Protocol For Unlocking Alternative Polyadenylation Insights From Bulk Rna-Seq Data With Polyaminer-Bulk, Venkata Jonnakuti, Sriya Jonnakuti, Hari Krishna Yalamanchili

Duncan NRI Faculty and Staff Publications

PolyAMiner-Bulk, a deep-learning-based algorithm to decode alternative polyadenylation (APA) dynamics from bulk RNA sequencing (RNA-seq) data, enables scientists to identify and quantify APA events from processed bulk RNA-seq data. The protocol allows researchers to explore differential APA usage between two conditions and gain a better understanding of post-transcriptional regulatory mechanisms. The major steps involve input data preparation, executing PolyAMiner-Bulk, and interpreting the results. A basic familiarity with pre-processing bulk RNA-seq data and command-line tools is suggested.

For complete details on the use and execution of this protocol, please refer to Jonnakuti et al.¹

Antimicrobial Performance Of A Novel Drug-Eluting Bioenvelope, Zerelda Esquer Garrigos, Sunil Kapur, Michelle Leroux Williams, M Rizwan Sohail

Faculty, Staff and Students Publications

No abstract provided.

Longitudinal Changes In Aerodigestive Responses To Varying Nipple Properties In Infant Pigs, François D H Gould, Christopher Mayerl, Khaled Adjerid, Jessica Reibel, Nichole Charles, Chloe Edmonds, Rebecca Z German

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Coordination of respiration and swallowing is critical for survival in infant mammals and changes throughout infant maturation. Infants show sensorimotor feeding responses to changes in physical properties of nipples. Commercial nipples are promoted as improving aerodigestive coordination. However, it is unknown how nipple properties influence coordination of respiration and swallowing. Furthermore, how infant-nipple interactions change throughout maturation is not well understood. We designed and manufactured four silicone nipples of the same shape that varied in two parameters: nipple opening diameter and nipple stiffness. We used our validated infant pig model to test the impact of nipple parameters on aerodigestive coordination …

Using The 5ms Framework To Advance Aging-Responsive Care For Heart Failure With Reduced Ejection Fraction, Abigail Latimer, Debra K. Moser, Jia-Rong Wu, Kim K. Birtcher, Malachy J. Clancy, Jennifer D. Portz, Joanna Paladino, Daniel D. Matlock, Christopher E. Knoepke

Department of Occupational Therapy Faculty Papers

Complexity of care is the inevitable consequence of an aging population and is particularly true in instances where patients are managing chronic conditions such as heart failure with reduced ejection fraction (HFrEF). HFrEF itself is complex, with an undulating course of illness, increased risk of sudden cardiac death, and myriad accompanying treatment considerations. Generalist management of HFrEF among older patients is further complicated by competing comorbidities, potential for financial toxicity, potential for mental health symptoms, and risk of care with does not align with goals and preferences. The 5Ms (multicomplexity, mind, mobility, medications, and matters most) is a holistic conceptualization …

Adipose Progenitor Cell-Derived Extracellular Vesicles Suppress Macrophage M1 Program To Alleviate Midlife Obesity, Qing Zhou, Jia Gao, Guorao Wu, Chenwei Wang, Yan Yang, Teng Huang, Yi Wang, Tiantian Yue, Zhichao Gao, Hao Xie, Fei Xiong, Ke Xiang, Tuying Yong, Wanguang Zhang, Tongtong Zhang, Wen Kong, Cai Chen, Shu Zhang, Qilin Yu, Xuemei Fan, Shiwei Liu, Yanjun Liu, Cong-Yi Wang

Children’s Nutrition Research Center Staff Publications

Among different age groups, middle-aged individuals are particularly susceptible to obesity, with a 22% higher risk of all-cause mortality. However, the underlying mechanisms remain unclear. In this study, we identify adipose progenitor cells (APCs) in the white adipose tissue (WAT) of middle-aged subjects as potential causes of midlife obesity. Specifically, the extracellular vesicles (EVs) derived from APCs display an impaired ability to mitigate the inflammaging of adipose tissue macrophages (ATMs) in middle-aged individuals. Mechanistically, these EVs, lacking miR-145-5p, fail to suppress the expression of L-selectin in ATMs, thereby facilitating their M1 program via the NF-κB signaling pathway. In contrast, EVs …

Do We Need To Add The Type Of Treatment Planning System, Dose Calculation Grid Size, And Ct Density Curve To Predictive Models?, Reza Reiazi, Surendra Prajapati, Leonardo Che Fru, Dongyeon Lee, Mohammad Salehpour

Faculty, Staff and Student Publications

Background: Generalizability and domain dependency are critical challenges in developing predictive models for healthcare, particularly in medical diagnostics and radiation oncology. Predictive models designed to assess tumor recurrence rely on comprehensive and high-quality datasets, encompassing treatment planning parameters, imaging protocols, and patient-specific data. However, domain dependency, arising from variations in dose calculation algorithms, computed tomography (CT) density conversion curves, imaging modalities, and institutional protocols, can significantly undermine model reliability and clinical utility.

Methods: This study evaluated dose calculation differences in the head and neck cancer treatment plans of 19 patients using two treatment planning systems, Pinnacle 9.10 and RayStation 11, …

Evaluation And Surgical Management Of Pediatric Cutaneous Melanoma And Atypical Spitz And Non-Spitz Melanocytic Tumors (Melanocytomas): A Report From Children's Oncology Group, Michael R Sargen, Raymond L Barnhill, David E Elder, Susan M Swetter, Victor G Prieto, Jennifer S Ko, Armita Bahrami, Pedram Gerami, Arivarasan Karunamurthy, Alberto S Pappo, Lynn M Schuchter, Philip E Leboit, Iwei Yeh, John M Kirkwood, Melinda Jen, Ira J Dunkel, Megan M Durham, Emily R Christison-Lagay, Mary T Austin, Jennifer H Aldrink, Casey Mehrhoff, Elena B Hawryluk, Emily Y Chu, Klaus J Busam, Vernon Sondak, Jane Messina, Susana Puig, Andrew J Colebatch, Carrie C Coughlin, Kristen G Berrebi, Theodore W Laetsch, Sarah G Mitchell, Brittani Seynnaeve

Faculty, Staff and Student Publications

Purpose: The purpose of this study was to develop recommendations for the diagnostic evaluation and surgical management of cutaneous melanoma (CM) and atypical Spitz tumors (AST) and non-Spitz melanocytic tumors (melanocytomas) in pediatric (age 0-10 years) and adolescent (age 11-18 years) patients.

Methods: A Children's Oncology Group-led panel with external, multidisciplinary CM specialists convened to develop recommendations on the basis of available data and expertise.

Results: Thirty-three experts from multiple specialties (cutaneous/medical/surgical oncology, dermatology, and dermatopathology) established recommendations with supporting data from 87 peer-reviewed publications.

Recommendations: (1) Excisional biopsies with 1-3 mm margins should be performed when feasible for clinically …

Sap30, A Novel Autophagy Regulatory Gene In Neuroblastoma, Anup S Pathania, Anjana Murugan, Areem Zahid, Haritha Chava, Don W Coulter, George A Calin, Kishore B Challagundla

Faculty, Staff and Student Publications

Neuroblastoma (NB), a devastating pediatric cancer originating from neural crest cells crucial for nervous system development, poses a significant therapeutic challenge. Despite chemotherapy being the primary treatment, approximately 70% of high-risk NB cases develop resistance. Autophagy is vital for neuronal development, balance, and differentiation of neural stem cells into mature neurons. However, the intricate mechanisms governing autophagy and the pivotal genes orchestrating its regulation in NB remain largely elusive. In this study, we first identified Sin3A Associated Protein 30 (SAP30) as a novel regulator of autophagy in NB. Silencing SAP30 inhibits autophagy and disrupts starvation-induced physiological autophagy in NB cells. …

Do We Need To Add The Type Of Treatment Planning System, Dose Calculation Grid Size, And Ct Density Curve To Predictive Models?, Reza Reiazi, Surendra Prajapati, Leonardo Che Fru, Dongyeon Lee, Mohammad Salehpour

Faculty, Staff and Student Publications

Background: Generalizability and domain dependency are critical challenges in developing predictive models for healthcare, particularly in medical diagnostics and radiation oncology. Predictive models designed to assess tumor recurrence rely on comprehensive and high-quality datasets, encompassing treatment planning parameters, imaging protocols, and patient-specific data. However, domain dependency, arising from variations in dose calculation algorithms, computed tomography (CT) density conversion curves, imaging modalities, and institutional protocols, can significantly undermine model reliability and clinical utility.

Methods: This study evaluated dose calculation differences in the head and neck cancer treatment plans of 19 patients using two treatment planning systems, Pinnacle 9.10 and RayStation 11, …

Dna Damage Response Signatures Are Associated With Frontline Chemotherapy Response And Routes Of Tumor Evolution In Extensive Stage Small Cell Lung Cancer, Benjamin B Morris, Simon Heeke, Yuanxin Xi, Lixia Diao, Qi Wang, Pedro Rocha, Edurne Arriola, Myung Chang Lee, Darren R Tyson, Kyle Concannon, Kavya Ramkumar, C Allison Stewart, Robert J Cardnell, Runsheng Wang, Vito Quaranta, Jing Wang, John V Heymach, Barzin Y Nabet, David S Shames, Carl M Gay, Lauren A Byers

Faculty, Staff and Student Publications

Introduction: A hallmark of small cell lung cancer (SCLC) is its recalcitrance to therapy. While most SCLCs respond to frontline therapy, resistance inevitably develops. Identifying phenotypes potentiating chemoresistance and immune evasion is a crucial unmet need. Previous reports have linked upregulation of the DNA damage response (DDR) machinery to chemoresistance and immune evasion across cancers. However, it is unknown if SCLCs exhibit distinct DDR phenotypes.

Methods: To study SCLC DDR phenotypes, we developed a new DDR gene analysis method and applied it to SCLC clinical samples, in vitro, and in vivo model systems. We then investigated how DDR regulation is …

Nutritional Status, Social Determinants Of Health And Clinical Outcomes In Critically Ill Children, Yash Desai, Andrea Marroquín, Paola Hong-Zhu, Nicole Knebusch, Stephanie Vazquez, Marwa Mansour, Thomas P Fogarty, M Hossein Tcharmtchi, Fernando Stein, Jorge A Coss-Bu

Faculty, Staff and Students Publications

Introduction: Childhood malnutrition remains a risk factor for morbidity and mortality. Children admitted to the Pediatric Intensive Care Unit (PICU) are at a higher risk of worsening nutritional status with adverse clinical outcomes. The burden of malnutrition is strongly linked to various well-defined social determinants of health, including race, socioeconomic status, and geography, as these factors influence household food insecurity. This study aimed to analyze the interrelationships of nutritional status, social determinants of health, and health outcomes in critically ill children.

Methods: Retrospective cohort study of 6418 critically ill children admitted to PICU from January 2014 to December 2017. Demographic …

Deciphering The Dark Cancer Phosphoproteome Using Machine-Learned Co-Regulation Of Phosphosites, Wen Jiang, Eric J Jaehnig, Yuxing Liao, Zhiao Shi, Tomer M Yaron-Barir, Jared L Johnson, Lewis C Cantley, Bing Zhang

Faculty, Staff and Students Publications

Mass spectrometry-based phosphoproteomics offers a comprehensive view of protein phosphorylation, yet our limited knowledge about the regulation and function of most phosphosites hampers the extraction of meaningful biological insights. To address this challenge, we integrate machine learning with phosphoproteomic data from 1195 tumor specimens spanning 11 cancer types to construct CoPheeMap, a network that maps the co-regulation of 26,280 phosphosites. By incorporating network features from CoPheeMap into a second machine learning model, namely CoPheeKSA, we achieve superior performance in predicting kinase-substrate associations. CoPheeKSA uncovers 24,015 associations between 9399 phosphosites and 104 serine/threonine kinases, shedding light on many unannotated phosphosites and …

Editorial: Old Drugs: Confronting Recent Advancements And Challenges, Anna Wiktorowska-Owczarek, Diego Iacono, Magdalena Jasińska-Stroschein

Department of Neurology Faculty Papers

No abstract provided.

Utility Of 3-Dimensional Echocardiography In Patients With Complex Intracardiac Connections And Ventricular Septal Defects, Aura Andrea Sanchez Mejia, Tam T Doan, Christian Lilje, Minh B Nguyen, Ricardo H Pignatelli, Shagun Sachdeva, Anitha Parthiban

Faculty, Staff and Students Publications

The surgical management of patients with complex intracardiac connections, ventricular septal defect (VSD), and 2 adequately sized ventricles is challenging. Understanding the VSD anatomy and its spatial relationships with the outflow tracts is critical to determining the suitability for biventricular repair. Transthoracic 2-dimensional echocardiography (2D-echo) is the primary cardiac imaging tool in congenital heart disease. Transthoracic 3-dimensional echocardiography (3D-echo) has an additive role over 2D-echo in the definition of the potential baffle pathway from the VSD to the semilunar valves, the anatomical characteristics of the VSD, and any substrate for systemic outflow tract obstruction postrepair. In this paper, we describe …

Eco-Microbiology: Discovering Biochemical Enhancers Of Pet Biodegradation By Piscinibacter Sakaiensis, Felipe-Andrés Piedra, Miguel A Salazar, Sara Abouelniaj, Raayed Rahman, Justin C Clark, Yimo Han, Zhao Wang, Anthony Maresso

Faculty, Staff and Students Publications

The scale of plastic pollution boggles the mind. Nearly 400 megatons of virgin plastics are produced annually, with an environmental release rate of 80%, and plastic waste, including microplastics and nanoplastics, is associated with a plethora of problems. The naturally evolved abilities of plastic-degrading microbes offer a starting point for generating sustainable and eco-centric solutions to plastic pollution-a field of endeavor we term eco-microbiology. Here, we developed an iterative discovery procedure coupling faster polyethylene terephthalate (PET)-dependent bioactivity screens with longer-term PET biodegradation assays to find biochemical boosters of PET consumption by the bacterium Piscinibacter sakaiensis. We discovered multiple hits …