Medical Specialties Commons^™

Investigating The Neuronal Role Of The Proteasomal Atpase Subunit Gene Psmc5 In Neurodevelopmental Proteasomopathies, Sébastien Küry, Janelle E Stanton, Geeske M Van Woerden, Amélie Bosc-Rosati, Tzung-Chien Hsieh, Lise Bray, Marielle Oloudé, Cory Rosenfelt, Marie Pier Scott-Boyer, Victoria Most, Tianyun Wang, Jonas J Papendorf, Charlotte De Konink, Wallid Deb, Virginie Vignard, Maja Studencka-Turski, Thomas Besnard, Anna M Hajdukowicz, Franziska G Thiel, Sophie Wolfgramm, Laëtitia Florenceau, Silvestre Cuinat, Sylvain Marsac, Yann Verrès, Audrey Dangoumau, Léa Poirier, Ingrid M Wentzensen, Annabelle Tuttle, Cara Forster, Johanna Striesow, Richard Golnik, Damara Ortiz, Laura Jenkins, Jill A Rosenfeld, Alban Ziegler, Clara Houdayer, Dominique Bonneau, Erin Torti, Amber Begtrup, Kristin G Monaghan, Sureni V Mullegama, Catharina M L Nienke Volker-Touw, Koen L I Van Gassen, Renske Oegema, Mirjam S De Pagter, Katharina Steindl, Anita Rauch, Ivan Ivanovski, Kimberly Mcdonald, Emily Boothe, Andrew Dauber, Janice Baker, Noelle Andrea V Fabie, Raphael A Bernier, Tychele N Turner, Siddharth Srivastava, Kira A Dies, Lindsay C Swanson, Carrie Costin, Alali Abdulrazak, Rebekah K Jobling, John Pappas, Rachel Rabin, Dmitriy Niyazov, Anne Chun-Hui Tsai, Karen Kovak, David B Beck, May Christine V Malicdan, David R Adams, Lynne Wolfe, Rebecca D Ganetzky, Colleen C Muraresku, Davit Babikyan, Zdeněk Sedláček, Miroslava Hančárová, Andrew T Timberlake, Hind Al Saif, Berkley Nestler, Kayla King, M J Hajianpour, Gregory Costain, D'Arcy Prendergast, Chumei Li, David Geneviève, Antonio Vitobello, Arthur Sorlin, Christophe Philippe, Tamar Harel, Ori Toker, Ataf Sabir, Derek Lim, Mark J Hamilton, Lisa J Bryson, Elaine Cleary, Sacha Weber, Trevor L Hoffman, Anna M Cueto-González, Eduardo F Tizzano, David Gómez-Andrés, Marta Codina-Solà, Athina Ververi, Efterpi Pavlidou, Alexandros Lambropoulos, Kyriakos Garganis, Marlène Rio, Jonathan Levy, Sarah J Langas, Anne M Mcrae, Mathieu K Lessard, Maria Daniela D'Agostino, Isabelle De Bie, Meret Wegler, Rami Abou Jamra, Susanne B Kamphausen, Viktoria Bothe, Lorraine Potocki, Eric Olinger, Yves Sznajer, Elsa Wiame, Michelle L Thompson, Molly C Schroeder, Catherine Gooch, Raphael A Smith, Arti Pandya, Larissa M Busch, Uwe Völker, Elke Hammer, Kristian Wende, Benjamin Cogné, Bertrand Isidor, Jens Meiler, Clémentine Ripoll, Stéphanie Bigou, Frédéric Laumonnier, Peter W Hildebrand, Evan E Eichler, Kirsty Mcwalter, Peter M Krawitz, Florence Roux-Dalvai, Ype Elgersma, Julien Marcoux, Marie-Pierre Bousquet, Arnaud Droit, Jeremie Poschmann, Andreas M Grabrucker, Francois V Bolduc, Stéphane Bézieau, Frédéric Ebstein, Elke Krüger

Faculty, Staff and Students Publications

Neurodevelopmental proteasomopathies are a group of disorders caused by variants in proteasome subunit genes, that disrupt protein homeostasis and brain development through poorly characterized mechanisms. Here, we report 26 distinct variants in PSMC5, encoding the AAA⁺ ATPase subunit PSMC5/RPT6, in individuals with syndromic neurodevelopmental conditions. Combining genetic, multi-omics and biochemical approaches across cellular models and Drosophila, we unveil the essential role of proteasomes in sustaining key cellular processes. Loss of PSMC5/RPT6 function impairs proteasome activity, leading to protein aggregation, disruption of mitochondrial homeostasis, and dysregulation of lipid metabolism and immune signaling. It also compromises synaptic balance, neuritogenesis, and neural progenitor …

Transcription-Replication Collisions Trigger High-Fidelity Replication Reset, Matthew B Cooke, Kobie T Welch, Laura Deus Ramirez, Katelin M Hagstrom, Alice X Wen, Jennifer A Halliday, Susan M Rosenberg, Christophe Herman

Faculty, Staff and Students Publications

Double-stranded DNA ends arise from external agents or cellular processes like transcription-replication collisions (TRCs), threatening genome stability. Here, we performed genomic CRISPRi screens to uncover DNA end formation factors in Escherichia coli. We discovered that translation-transcription decoupling causes DNA end formation through a TRC-dependent pathway, which is lethal when DNA end processing by RecBCD is disrupted, but not when recombination is disrupted. We find that TRCs cause replisome stalling followed by "rear-ending" from trailing replisomes which generates free DNA ends, rather than strand breaks. Surprisingly, these DNA ends are resolved through a process we call "replication reset", where the stalled …

Loss Of Idh1 And Idh2 Mutations During The Evolution Of Metastatic Chondrosarcoma, William Cross, Iben Lyskjær, Christopher Davies, Abigail Bunkum, Ana Maia Rocha, Tom Lesluyes, Fernanda Amary, Roberto Tirabosco, Cristina Naceur-Lombardelli, Mariam Jamal-Hanjani, Charles Swanton, Nischalan Pillay, Simone Zaccaria, Adrienne M Flanagan, Peter Van Loo

Faculty, Staff and Student Publications

Driver mutations in IDH1 and IDH2 are initiating events in the evolution of chondrosarcoma and several other cancer types. Here, we present evidence that mutant IDH1 is recurrently lost in metastatic central chondrosarcoma. This may reflect either relaxed positive selection for the mutant IDH1 locus, or negative selection for the hypermethylation phenotype later in tumor evolution. This finding highlights the challenge for therapeutic intervention by mutant IDH1 inhibitors in chondrosarcoma.

Interplay Of Menopause, Coronary Artery Calcium Score And Cardiovascular Disease Risk, Tanisha Mishra, Diksha Sanjana Pasnoor, Murtaza Gandhi, Nida Mohamed, Shaylika Chauhan, Kokou Adompreh-Fia, Kesha Mayank Doshi, Prerana Sevella, Rupak Desai

Abington Jefferson Health Papers

BACKGROUND: Postmenopausal women face an increased risk of cardiovascular disease (CVD) due to estrogen withdrawal, which exacerbates traditional cardiovascular risk factors such as dyslipidemia, glucose intolerance, and hypertension. Coronary Artery Calcium Score (CACS), a well-established marker of subclinical atherosclerosis, has emerged as a key predictor of adverse cardiovascular events. Despite the recognized association between menopause and heightened CVD risk, there remains a paucity of literature exploring the specific role of menopause in influencing CACS and its implications for cardiovascular morbidity and mortality.

AIM: To examine the interplay between menopause, CACS, and cardiovascular health by synthesizing existing literature.

METHODS: A comprehensive …

Predicting The Response Of Triple Negative Breast Cancer To Neoadjuvant Systemic Therapy Via Biology-Based Modeling And Habitat Analysis, Casey E Stowers, Chengyue Wu, Clinton Yam, Jingfei Ma, Gaiane M Rauch, Thomas E Yankeelov

Faculty, Staff and Student Publications

Despite being the standard-of-care treatment, neoadjuvant therapy (NAT) attains a complete response only in approximately half of the patients with triple negative breast cancer. Thus, methods to predict and optimize patient response to NAT are needed. Previously, we employed patient-specific MRI data to calibrate a biology-based mathematical model that describes cell movement, proliferation, and death due to drug at the tumor level and cell proliferation at an image voxel level. We now extend our approach by using MRI data to group voxels into "habitats" whereby tumor cells of a habitat share the same proliferation. With this approach, we now calibrate …

Possible Involvement Of Keratinocyte-Derived Microvesicle Particles In Human Photosensitivity Disorders, Risha Annamraju, Madison S. Owens, Anita Thyagarajan, Danielle A. Corbin, Catherine M.T. Sherwin, Jade Bryant, Garrett W. Fisher, Winston R. Owens, Alycia Ketter, Craig A. Rohan, Michael G. Kemp, Robyn K. Crow, Jeffrey B. Travers

Pediatrics Faculty Publications

BACKGROUND: Previous murine studies have implicated acid sphingomyelinase-(aSMase) generated subcellular microvesicle particles (MVP) in photosensitivity. Objective: The current double-blinded placebo-controlled studies examined if a single localized ultraviolet B radiation (UVB) treatment generated more MVP in human subjects with self-identified photosensitivity versus normal controls. A topical 4% formulation of the aSMase inhibitor imipramine applied immediately after UVB blocked the MVP release and erythema responses. Erythema responses at 24 and 72 h in response to multiple UVB fluences and minimal erythema doses (MED) at 24 h and effects of imipramine were also tested.

RESULTS: Small cohorts of 10 adult self-identified photosensitive subjects …

Single-Cell Transcriptomic Analysis Of Peripheral Blood Mononuclear Cells Reveals Key Immune Responses In St-Segment Elevation Myocardial Infarction, Zheng Zhang, Shengfang Wang, Yahui Liu, Gaohan Li, Qianqian Cheng, Wei Yang, Gan-Xin Yan, Chuanyu Gao

Department of Medicine Faculty Papers

BACKGROUND: Inflammation plays a crucial role in the pathogenesis of ST-segment elevation myocardial infarction (STEMI). However, the precise immunological mechanisms remain incompletely understood. Single-cell RNA sequencing (scRNA-seq) provides a powerful approach to dissect immune cell heterogeneity and dynamic changes at single-cell resolution.

METHODS: Peripheral blood mononuclear cells (PBMCs) were collected from 7 STEMI patients (within 6h after primary percutaneous coronary intervention) and 3 healthy controls. Single-cell suspensions were prepared and subjected to scRNA-seq using the 10x Genomics Chromium platform and Illumina NovaSeq 6000. Data were processed using Cell Ranger and analyzed with Seurat for quality control, clustering, and annotation. Differentially …

Bilateral Endogenous Fungal Endophthalmitis Following Elective Surgical Abortion: A Single Center Case Series, Viet Q. Chau, Jesse D. Sengillo, Flavius A. Beca, Julia L. Hudson, Thomas A. Albini, Harry W. Flynn

Wills Eye Hospital Papers

BACKGROUND: To describe the clinical features and management of three cases of bilateral endogenous fungal endophthalmitis following elective surgical abortion performed at the same outpatient surgical center.

METHODS: Case series.

OBSERVATIONS: Three immunocompetent women presented with vision loss days to weeks following elective surgical abortions performed at a single outpatient clinic. Initial visual acuities ranged from 20/20 to 20/300. Fundoscopic examination revealed multiple white round chorioretinal lesions with vitreous infiltration bilaterally in all three patients. Vitreous tap samples were obtained for culture and broad-spectrum intravitreal antimicrobials were administered. Despite negative cultures and systemic workup, the clinical presentation was consistent with …

Ash Sickle Cell Disease Cpkd Guidelines Report, Robert I. Liem, Madeleine Verhovsek, Ted Wun, Sophie Lanzkron

Cardeza Foundation for Hematologic Research

No abstract provided.

Hemolysis Detection Using The Gem 7000 At The Point Of Care In A Pediatric Hospital Setting: Does It Affect Outcomes?, Ridwan B Ibrahim, Nazmin Bithi, Charlene Hernandez, Hanna Uhrova, Brandy D Recio, Sridevi Devaraj

Faculty, Staff and Students Publications

No abstract provided.

Hemorrhage-Related Maternal Morbidity Of Secondary Compared To Primary Postpartum Hemorrhage, Matthew R Carroll, Sarah Tounsi, Jessica L Gerard, Susan M Leong-Kee, Laurie S Swaim, Mark A Turrentine

Faculty, Staff and Students Publications

Objectives: To compare a composite hemorrhage-related maternal morbidity in individuals with secondary to primary postpartum hemorrhage and treatment interventions utilized.

Methods: A retrospective case-control study of deliveries complicated by secondary postpartum hemorrhage was performed at a tertiary care center. To estimate a clinically relevant increase of 50 % in the composite maternal hemorrhage-related maternal morbidity (35-53 % absolute increase) in individuals with secondary postpartum hemorrhage, a correlation coefficient of 0.2, at an 80 % power with a p < 0.05 with a two-sided test would require 95 individuals with secondary postpartum hemorrhage be matched to 95 individuals with a primary postpartum hemorrhage. Logistic regression analysis was used to evaluate the outcome of the composite of hemorrhage-related maternal morbidity.

Results: From January 2018 through December 2022, 33,026 deliveries occurred, and 94 individuals were identified that were admitted with secondary postpartum hemorrhage, …

Optimizing Lower Intensity Triplet Therapy In Acute Myeloid Leukemia: A Practical Guide, Wei-Ying Jen, Curtis A Lachowiez, Jennifer Marvin-Peek, Jessica K Altman, Musa Yilmaz, Jacqueline S Garcia, Yasmin Abaza, Nicholas J Short, Joshua F Zeidner, Naval G Daver, Andrew H Wei, Ghayas C Issa, Courtney D Dinardo

Faculty, Staff and Student Publications

Venetoclax-based doublets with azacitidine or low dose cytarabine are the standard of care for the treatment of acute myeloid leukemia (AML) in older patients or those unfit for intensive chemotherapy. However, some patients do not attain complete remission, and over time, most patients relapse. Frontline triplet therapy incorporating a targeted therapy (FLT3, IDH or menin inhibitor) is an emerging treatment concept under investigation for this population. Initial triplet regimens have yielded encouraging composite complete remission and measurable residual disease negativity rates, enabling the transition to allogeneic stem cell transplantation for eligible patients. While effective, triplets are associated with myelosuppression and …

Targeting The Hepatic Circadian Clock Concomitant With Tyrosine Kinase Inhibition Reverses Late-Stage Hepatocellular Carcinoma, Baharan Fekry, Savera Aggarwal, Rachel Van Drunen, Rafael Bravo, Andy Escalante, Constance Atkins, Sheng Pan, Zheng Chen, Kai Sun, David R Hall, Mamoun Younes, Kristin Eckel-Mahan

Faculty, Staff and Student Publications

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths. Most patients present at advanced stages, and the effectiveness of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors is constrained by limited patient response. A subset of HCC shows elevated expression of the promoter 2 ("P2")-driven hepatocyte nuclear factor 4 alpha (HNF4α) isoform, which directly transcriptionally represses the circadian brain and muscle ARNT-like protein 1 (BMAL1) transcription factor. This subtype of HCC is robustly inhibited by the plant-based flavonoid nobiletin (NOB), a circadian-fortifying compound. Using patient-matched human HCC and serum, we show that BMAL1-deficient HCC shows exaggerated carnitine palmitoyl transferase …

Patient-Reported Outcomes After Ipsilateral Radiation Therapy For N2b Tonsillar Squamous Cell Carcinoma, Chike O Abana, Adam S Garden, G Brandon Gunn, Gregory M Chronowski, Abdallah S R Mohamed, Andrew J Frankart, Natalie Geier, Houda Bahig, Carly E A Barbon, Kate Hutcheson, Vinita Takiar, Clifton D Fuller, Steven J Frank, David I Rosenthal, Jack Phan

Faculty, Staff and Student Publications

Background: Previous studies have reported excellent disease control and survival in patients with well-lateralized, American Joint Committee on Cancer (AJCC)-7 T1-2N2b tonsillar squamous cell carcinoma (SCC). The reduced treatment volume is associated with lower rates of physician-assessed toxicity. Patient-reported outcomes (PROs) have been proposed as a similarly reliable measure, but the body of literature is limited for unilaterally treated patients. Our goal was to review PROs of such patients who had reduced treatment volumes.

Methods: We reviewed PROs of patients with AJCC-7 T1-2N2b disease treated with ipsilateral radiation therapy (RT), with or without surgery or chemotherapy before RT. PROs were …

Coordinated Transfer Of Dna Between Pol Θ And Pol Δ Resets Microhomology Choice During Double-Strand Break Repair, Yuzhen Li, Mark Returan, Adele T Guerin, April M Averill, Dorcas Oladapo, Sylvie Doublié, Richard D Wood

Faculty, Staff and Student Publications

DNA polymerase theta (Pol θ)-mediated end joining (TMEJ) initiates DNA double-strand break repair by using short homologies (microhomologies) between single-stranded DNA tails. This repair process is particularly important in cancer cells defective in homologous recombination. The exonuclease function of DNA polymerase delta (Pol δ) has been identified as an essential component for TMEJ, functioning to remove unpaired bases flanking a microhomology (MH). It is not known if the exonuclease removes all unpaired bases at once and how this removal might affect subsequent MH selection. Here, we reconstituted a functional TMEJ repair process using purified human Pol θ and Pol δ. …

An Analysis Of Diagnostic Metabolomic Profiles Associated With Hepatotoxicity During Childhood All Induction Therapy, Emily J Mason, Anna M Crain, Michael E Scheurer, Philip J Lupo, Karen R Rabin, Olga A Taylor, Marley Roberts, John P Woodhouse, Ashley Chavana, Kathleen Ludwig, Laura Klesse, Kenneth Heym, Timothy Griffin, Rodrigo Erana, Juan Carlos Bernini, M Monica Gramatges, Joanna S Yi, Sandi L Pruitt, M Brooke Bernhardt, Hong Zhu, Steven D Mittelman, Van Huynh, Etan Orgel, Jeremy M Schraw, Austin L Brown

Faculty, Staff and Students Publications

Hepatotoxicity is a well-documented complication of induction chemotherapy for acute lymphoblastic leukemia (ALL), but our understanding of its biological mechanisms is limited. We identified 314 patients with ALL (aged 1-19 years) treated at Texas Children’s Hospital (2008-2019) with diagnostic bone marrow plasma available for metabolomic profiling: 234 for discovery and 80 for replication. Hepatotoxicity during induction was defined as follows: (1) transaminitis: grade ≥3 aspartate aminotransferase or alanine aminotransferase or (2) conjugated hyperbilirubinemia: conjugated bilirubin (c.bili) >3 mg/dL. Untargeted profiling detected 519 metabolites. Adjusted odds ratios (aORs) for each metabolite were calculated with logistic regression, accounting for sex, age, body …

Nivolumab Plus Ipilimumab Induce Hyper-Progression In Renal Medullary Carcinoma: Results Of A Phase Ii Trial And Preclinical Evidence, Melinda Soeung, Xinmiao Yan, Ciro Zanca, Jing Qian, Menuka Karki, Fei Duan, Hania Khan, Li Zhang, David H Peng, Mariah Williams, Rong He, Ziheng Chen, Luigi Perelli, Jianfeng Chen, Rebecca S Tidwell, Pankaj K Chauhan, Courtney N Le, Truong N A Lam, Nirjar Bhattacharya, Rutvi Shah, I-Lin Ho, Jason P Gay, Caroline C Carrillo, Ningping Feng, Kang Le, Guang Gao, Teresa L Perry, Faika Mseeh, Yongying Jiang, Quanyun A Xu, Niki Marie Zacharias, Rahul A Sheth, Tharakeswara K Bathala, Priya Rao, Najat C Daw, Durga N Tripathi, Cheryl L Walker, Mohammad M Mohammad, Jianhua Zhang, Guangchun Han, Yanshuo Chu, Ruiping Wang, Minghao Dang, Enyu Dai, Fuduan Peng, Yunhe Liu, Akshaya Jadhav, Wenhua Lang, Claudio A Arrechedera, Leticia Campos Clemente, Edwin R Parra, Hsinyi Lu, Cara L Haymaker, Ignacio I Wistuba, Andrew Futreal, Andrea Viale, Michael J Soth, Philip Jones, Joseph R Marszalek, Timothy Heffernan, Giulio F Draetta, Nizar M Tannir, Jianjun Gao, Linghua Wang, Giannicola Genovese, Pavlos Msaouel

Faculty, Staff and Students Publications

Therapeutic options for patients with renal medullary carcinoma (RMC) are limited. Here we report the results of a phase II clinical trial (NCT03274258) of anti-PD1 nivolumab plus anti-CTLA4 ipilimumab in patients with RMC, with objective response rate as primary outcome. Enrollment was halted for futility at a prespecified interim analysis as all 10 treated patients experienced rapid disease progression. 5/10 met radiological criteria for hyperprogression and median progression-free survival (secondary outcome) was 1.38 months (95% confidence interval: 1.28, 1.60). In a post-hoc single-cell RNA sequencing analysis, data from patients with RMC before and after nivolumab plus ipilimumab treatment indicated that …

Leaping Between Branches: Hybridisation And The Tangled Evolutionary History Of True Lemurs, Giacomo Mercuri, Giovanni Merici, Kyle Kai-How Farh, Lukas F K Kuderna, Jeffrey Rogers, Tomàs Marques-Bonet, Giuseppe Donati, Riccardo Percudani, Cristian Capelli

Faculty, Staff and Students Publications

The true lemurs (genus Eulemur) are a genetically diverse and spatially widespread group of species inhabiting most of Madagascar's forests. Including 12 recognized species, the genus can be divided into four major evolutionary groups: E. rubriventer, E. mongoz, the Brown Lemur Species Complex (BLSC), and the coronatus-macaco-flavifrons complex (CMFC), although monophyly for the CMFC is not always supported. Recent genome-based studies highlighted topological and chronological differences between nuclear and mitochondrial phylogenies of true lemurs, which could be explained by events of hybridisation. In order to reconstruct the evolutionary history of the genus, we test for gene-flow between Eulemur clades using …

Turning Patients' Open-Ended Narratives Of Chronic Pain Into Quantitative Measures: Natural Language Processing Study, Raquel Norel, Jennifer Gewandter, Zhengwu Zhang, Anika Tahsin, Chadi G Abdallah, John Markman, Zhiyao Duan, Guillermo Cecchi, Paul Geha

Faculty, Staff and Students Publications

Background: Subjective report of pain remains the gold standard for assessing symptoms in patients with chronic pain and their response to analgesics. This subjectivity underscores the importance of understanding patients' personal narratives, as they offer an accurate representation of the illness experience.

Objective: In this pilot study involving 20 patients with chronic low back pain (CLBP), we applied emerging tools from natural language processing (NLP) to derive quantitative measures that captured patients' pain narratives.

Methods: Patients' narratives were collected during recorded semistructured interviews in which they spoke about their lives in general and their experiences with CLBP. Given that NLP …

Geographic And Socioeconomic Predictors Of Early Follow-Up Loss In Patients Undergoing Pituitary Neuroendocrine Tumors (Pitnets) Resection: A Retrospective Review Of 1143 Cases, Daniel Quintana, Rithvik Ramesh, Robert C. Osorio, Wesley Shoap, Paul Mcmillan Villalobos, Philip V. Theodosopoulos, Sandeep Kunwar, Jose Gurrola, Ivan H. El Sayed, Manish K. Aghi, Ezequiel Goldschmidt

School of Medicine Faculty Publications

OBJECTIVE: Postoperative follow-up after PitNET resection is essential for monitoring tumor recurrence and endocrinological deficits. Despite advances in telehealth, loss to follow-up remains a persistent challenge across neurosurgical patients. This study aims to identify factors to identify patients are at higher risk of being lost to follow-up after surgery. METHODS: A retrospective analysis was conducted on 1,143 adult patients who underwent PitNET resection between 2012 and 2019 at a single institution. Clinical and radiological data were analyzed to assess loss to follow-up in the cohort. Multivariable logistic and negative binomial regression models were used to identify factors independently associated with …

Neutrophil Lymphocyte Ratio As A Marker Of Skin Disease Activity In Older Children With Juvenile Dermatomyositis, Shreya Swaminathan, Nidhi Naik, Susan Shenoi, Sarah Vandenbergen, Jessica L. Turnier, Zilan Zheng, Jessica Neely, James S. Andrews, Christian Lood

Student Papers, Posters & Projects

BACKGROUND: Neutrophils contribute to the pathogenesis of many autoimmune diseases. While the neutrophil to lymphocyte ratio (NLR) is associated with disease activity in adult dermatomyositis, its clinical utility in juvenile dermatomyositis (JDM) is unknown.

METHODS: Demographic, medication use, autoantibody profile, disease activity markers, and laboratory data from 97 JDM patients was collected using retrospective chart review. Patients were age-stratified (0–9 vs. 9–21 years of age), as white blood cell count stabilizes at 9 years. The relationships between NLR with JDM disease activity measures were analyzed using spearman’s correlation.

RESULTS: Patients were primarily white (56.7%) and female (71.1%). Older children had …

Comparative Analysis Of Robotic-Assisted, Laparoscopic, And Open Radical Nephrectomy: Utilization, Costs, And Clinical Outcomes, Daniel Huang, Costas D. Lallas, Raegan M. Davis, Scott W. Keith, Patrick J. Moeller, Inkyu K. Kim, Anushka Ghosh, Francisco Aguirre, Rasheed A. M. Thompson, Emmanuel F Drabo, Vittorio Maio

College of Population Health Faculty Papers

BACKGROUND: Minimally invasive approaches, including laparoscopic (LARN) and robotic-assisted radical nephrectomy (RARN), have gained adoption over open surgery (ORN) for renal cancer, despite RARN’s higher costs. This contemporary study evaluates trends in RARN, LARN, and ORN use and compares their hospital costs, clinical complications, and mortality rates.

METHODS: Patients undergoing radical nephrectomy (2016–2019) were identified from the National Inpatient Sample (NIS). Procedures were classified as RARN, LARN, or ORN using ICD-10 and Procedure Coding System codes. Patient demographics and comorbidities, hospital characteristics, length of stay (LOS), clinical complications, and hospital costs were analyzed. Trends in utilization were assessed, and regression …

Diurnal Behavioral Outcomes And Bbb Integrity In Adult Male Shr And Wky Rats, Pallavi Shrivastava, Oluchukwu D. Biose, Riya Dahal, Abdallah Jwayyed, Rukayat A. Raji, Huijing Xia, Eric Lazartigues, Ifechukwude J. Biose

School of Graduate Studies Faculty Publications

Day and night neurobehavioral tests were performed for Spontaneously Hypertensive rats (SHR) and Wistar Kyoto rats (WKY) to establish an optimal testing window. Also, blood–brain barrier (BBB) integrity in brain areas related to cognition was measured to determine strain-specific differences. Six months old male SHR and WKY were randomly divided into day (i.e., 9–11 a.m.) and nighttime (i.e., 7–9 p.m.) testing regimen. Neurobehavioral tests included: Y-maze spontaneous alternation, open field, novel object recognition (NOR), and tail suspension test (TST). BBB integrity was measured in the cortex, hippocampus and striatum. WKY showed higher recognition memory at night compared to SHR and …

Barriers And Facilitators To Lifestyle Behavior Change And Goal Setting In Adolescents With Polycystic Ovary Syndrome., Manasa Gadiraju, Joy Y. Kim, Erin M. Green, Alexandra Macmillan Uribe, Honghui Chang, Tania S. Burgert, Melissa D. Olfert, Heidi Vanden Brink

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: To identify barriers and facilitators to lifestyle modifications and goal setting and characterize goal setting for adolescents with polycystic ovary syndrome (PCOS).

METHODS: Retrospective chart review of registered dietitian nutritionist (RDN) nutrition notes from 118 adolescents with PCOS 11-21 years evaluated at a multi-specialty PCOS clinic. Goals, barriers, and facilitators were coded using open coding and a priori objectives and characterized for emerging themes using qualitative content analysis.

RESULTS: Five major themes of barriers and facilitators to behavior change emerged: interest and motivation, family involvement, resources and food environment, taste preferences, and self-efficacy. RDNs set ≥3 goals with 52%, …

Design And Refinement Of Cybercelltm, A Virtual Reality Health Education Program For Adolescents And Young Adults With Sickle Cell Disease, Aimee Hildenbrand, Melanie Pitone, Benjamin Bear, Corinna L. Schultz, Sherman Finch, Danielle Morley, Stephanie Hubbard, Alyssa Decino, Melissa A. Alderfer, Lori E. Crosby, Fredric Freeman

Department of Pediatrics Faculty Papers

For people living with sickle cell disease (SCD), the risk for disease complications and premature death rises sharply in adolescence and young adulthood, when chronic organ damage is compounded by reduced preventive care. To make informed health care decisions, adolescents and young adults (AYAs) require effective education about their health condition and treatment options. We aimed to systematically design and develop a user-centered, evidence-based virtual reality (VR) health education program to optimize the use of SCD therapies among AYAs with SCD. We engaged a diverse team including AYAs with SCD and their caregivers, multidisciplinary SCD clinicians and researchers, patient education …

Bladder Prolapse (Cystocele) Among African, Asian, And Middle Eastern Women: A Clinical And Socio-Cultural Perspective, Gayathri Delanerolle, Vindya Pathiraja, Tharanga Mudalige, Nirmala Rathnayake, Abirame Sivakumar, Wijamunige Nimesha Prashadini, Nihal Mohamed Al Riyami, Lamiya Al-Kharusi, Mohammad Haddadi, Fred Tweneboah-Koduah, Om Kurmi, George Uchenna Eleje, Peter Phiri, Lauri Romanzi, Sohier Elneil

Department of Obstetrics and Gynecology Faculty Papers

Bladder prolapse, also known as cystocoele, is the most common form of pelvic organ prolapse (POP), significantly affecting women's physical, sexual, and psychosocial health, particularly in low- and middle-income countries (LMICs). Despite its widespread prevalence and disabling consequences, bladder prolapse remains under-recognised and inadequately addressed in global health strategies. Prevalence estimates vary widely across regions, from 3%-64.6%, influenced by diagnostic methods and cultural reporting biases. Common risk factors include high parity, early childbirth, prolonged labour, poor postpartum care, malnutrition, obesity, and ageing. Clinical diagnosis often relies on simplified grading systems in resource-limited settings. Conservative treatments like pelvic floor muscle training …

Naphthalimide-Based Type-I Nano-Photosensitizers For Enhanced Antitumor Photodynamic Therapy: H2s Synergistically Regulates Pet And Self-Assembly, Huiyu Niu, Songnan Wang, Yang Liu, Nana Ma, Shuaiwei Cheng, Beidou Feng, Hyunsun Jeong, Yonggang Yang, Ge Wang, Tony D James, Juyoung Yoon, Jonathan L Sessler, Hua Zhang

Faculty, Staff and Student Publications

Photodynamic therapy (PDT) relies on a combination of light and photosensitizers (PSs) to achieve local control over cancerous lesions. However, it is subject to limitations, including tumor hypoxia, low tumor targeting, off‐target phototoxicity, and always‐on fluorescence. Here, we propose a design strategy for activated nano‐PSs (N‐PSs) to simultaneously overcome the limitations of PDT, wherein photoinduced electron transfer (PeT) is coupled with an endogenous H2S‐regulated self‐association process to promote Type‐I photochemical reactions. Using theoretical calculations, spectral analysis, and microscopic imaging, we verified the generation of self‐assembly and occurrence of PeT. And it was also shown that H2S could synergistically inhibit the …

Analysis Of A Deeply-Phenotyped Familial Hypercholesterolemia Cohort From Mexico Shows A Role For Both Rare And Common Alleles Across Known Dyslipidemia Genes And Reveals Structural Variation In A Novel Locus, Nicholas Katsanis, Niki Mourtzi, Consuelo D Quinto-Cortés, Alexandro J Martagon, Alexander G Ioannidis, Francisco M De La Vega, Jeff Gulcher, Ming Ta Michael Lee, Mohammad A Faghihi, Arturo Lopez-Pineda, Sonia Moreno-Grau, Daniel Mas Montserrat, Míriam Barrabés, David Bonet, Pavel Salazar Fernandez, Jeff Wall, Babak Moatamed, Roopa Mehta, Gabriela A Galan-Ramirez, Rafael Zubirán, Daniel Elias-Lopez, Teresa Tusié-Luna, Carlos A Aguilar-Salinas, Carlos D Bustamante

Faculty, Staff and Student Publications

Familial hypercholesterolemia (FH) is a genetic disorder driven in part by mutations in three genes that encode components of the cholesterol pathway: LDLR, APOB, and PCSK9. However, the majority of FH genetics has been performed in individuals of European descent. Here, we leveraged a cohort of 300 patients from the Mexican FH registry to understand how rare, high liability alleles and common variants might contribute to shaping individual risk. Using a combination of whole exome and of short- and long-read whole genome sequencing, we report three key findings. First, we observed that rare pathogenic point mutations and structural variants in …

Live-Cell Quantitative Monitoring Reveals Distinct, High-Affinity Gβγ Regulations Of Girk2 And Girk1/2 Channels, Reem Handklo-Jamal, Tal Keren Raifman, Boris Shalomov, Patrick Hofer, Uri Kahanovitch, Theres Friesacher, Galit Tabak, Vladimir Tsemakhovich, Haritha P Reddy, Orna Chomsky-Hecht, Debi Ranjan Tripathy, Kerstin Zuhlke, Carmen W Dessauer, Enno Klussmann, Yoni Haitin, Joel A Hirsch, Anna Stary-Weinzinger, Daniel Yakubovich, Nathan Dascal

Faculty, Staff and Student Publications

Gi/o protein-coupled receptors (GPCRs) inhibit cardiac and neuronal excitability via G protein-activated K+ channels (GIRK), assembled by combinations of GIRK1 - GIRK4 subunits. GIRKs are activated by direct binding of the Gβγ dimer of inhibitory Gi/o proteins. However, key aspects of this textbook signaling pathway remain debated. Recent studies suggested no Gi/o-GIRK pre-coupling and low (>250 µM) Gβγ-GIRK interaction affinity, contradicting earlier sub-µM estimates and implying low signaling efficiency. We show that Gγ prenylation, which mediates Gβγ membrane attachment required for GIRK activation, also contributes to the Gβγ-GIRK interaction, explaining the poor affinity obtained with non-prenylated Gβγ. Using quantitative …

Stiefel Md Anderson Oropharynx Cancer (Mda-Opc) Cohort: A Single-Institution, Prospective Longitudinal Outcomes Study, Amy Moreno, Ariana J Sahli, Faye Johnson, Xiaowen Sun, Carly Barbon, Waree Rinsurongkawong, Wenye Song, Flavie M Luciani, Han Liang, Jun Li, Wei Liu, J Jack Lee, S J Frank, Stephen Lai, Clifton Fuller, Katherine Hutcheson

Faculty, Staff and Student Publications

Purpose: The MD Anderson Oropharynx Cancer (MDA-OPC) cohort is a unique single-institution, prospective longitudinal cancer cohort. The cohort aims to enhance the therapeutic index of OPC management by supporting data needs for independent investigators to conduct rigorous observational studies examining exposures and factors associated with acute and late toxicities, cancer progression, recurrence, new malignancies and quality of life in OPC survivors.

Participants: A total of 1811 patients with OPC with a minimum follow-up of 6 months have been consented to our prospective registry between 18 March 2015 and 29 December 2023. Clinical and treatment (Tx) data are available on all …