Digital Commons Network^™

Successful Implementation Of Stroke Risk Screening For Sickle Cell Anemia In The Displace Study: Results Of A Cluster Randomized Trial, Alyssa M Schlenz, Monica L Hulbert, Et Al.

2020-Current year OA Pubs

BACKGROUND: Stroke risk screening using transcranial Doppler (TCD) is a critical evidence-based tool for children with sickle cell anemia (SCA) that has been poorly implemented in the United States. The Dissemination and Implementation of Stroke Prevention Looking at the Care Environment (DISPLACE) study was designed to improve rates of stroke risk screening for SCA using interventions informed by an extensive multi-level barriers and facilitators assessment. This report describes the final outcomes of a large, randomized implementation trial comparing two intervention arms: 1) an application designed to track TCD implementation, ProviderMinder™, versus 2) ProviderMinder™ plus a single coordinator intervention. All sites …

Molecular Basis Of Nfib-Mediated Regulation Of Oncogenic Transcription, Ci Zhu, Ding Xiao, Yueyu Wang, Hong Han, Chengxiao Qin, Shuang Liu, Xi Chen, Hejin Xiao, Xin Chen, Junfeng Shi, Juyu Tang, Jie Shen, He Song

2020-Current year OA Pubs

The Nuclear Factor I (NFI) family of transcription factors orchestrates key regulatory programs in development, differentiation, and metabolism, with dysregulation implicated in diverse pathological conditions, including cancer. Among the paralogs, NFIB has emerged as an oncogenic driver in multiple tumor types, yet the mechanisms through which it engages DNA and directs oncogenic transcriptional programs remain undefined. Here, using cancer cells with high NFIB expression, we demonstrate that NFIB promotes malignant phenotypes, as CRISPR-Cas9 knockout impairs proliferation, migration, and invasion. Transcriptomic profiling reveals that NFIB regulates a cancer-enriched gene network that includes FGFR3 and PDGFRB. Biophysical analyses show that NFIB, including …

Implementation Outcomes From The Hypertension Treatment In Nigeria Program: Results From A Type 2 Hybrid Interrupted Time Series Trial, Jiancheng Ye, Erica L Jamro, Guhan Iyer, Mark D Huffman, Et Al.

2020-Current year OA Pubs

BACKGROUND: The Hypertension Treatment in Nigeria Program was implemented across 60 primary healthcare centers (PHCs) in Nigeria to improve hypertension treatment and control using the World Health Organization's HEARTS package. This study reports the program's implementation outcomes.

METHODS: The Hypertension Treatment in Nigeria Program used a type 2 hybrid interrupted time series design, and data were collected from January 2020 to December 2023. The RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework guided the evaluation, focusing on key metrics such as patients' and clinics' characteristics, prescription rate of fixed dose combination (FDC) drugs, medication availability, and retention.

RESULTS: Among 21,922 …

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 …

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 …

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 …

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, …

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 …

Botulinum Toxin Combined With Robot-Assisted Therapy For Post-Stroke Spasticity: A Systematic Review, Salvatore Facciorusso, Stefania Spina, Mirko Filippetti, Rajiv Reebye, Gerard E Francisco, Andrea Santamato

Faculty, Staff and Student Publications

Background: Post-stroke spasticity limits motor recovery and independence. Combining botulinum toxin type-A (BoNT-A) injection with intensive, task-specific robot-assisted therapy (RAT) might enhance neuroplasticity and functional gains, but its additive effect and optimal timing are uncertain. (

Methods: We systematically searched major medical databases and trial registries up to April 2025 for randomized controlled trials in adults with post-stroke spasticity comparing botulinum toxin type-A injection plus RAT with toxin injection plus conventional therapy, or RAT alone with RAT combined with toxin injection. Risk of bias was assessed using the RoB 2 tool, and findings were synthesized narratively.

Results: Seven trials ( …

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 …

Deep Learning Reveals How Cells Pull, Buckle, And Navigate Fibrous Environments, Abinash Padhi, Arka Daw, Atharva Agashe, Medha Sawhney, Maahi M Talukder, Mehran M H Pour, Mohammad Jafari, Guy M Genin, Farid Alisafaei, Sohan Kale, Anuj Karpatne, Amrinder S Nain

2020-Current year OA Pubs

Cells in tissues navigate fibrous environments fundamentally differently than they do on flat substrates, but the establishment of cell forces in physiological fibrous settings remains poorly understood. Although factors such as the stiffness of the extracellular matrix (ECM) are known to drive behaviors, including cell motility on flat nonfibrous substrates, the interplay between fiber architecture and stiffness in fibrous ECM is not known. Here, we find that in fibrous environments, the directionality of mechanical forces overrides ECM stiffness as the primary regulator of contractility in migrating cells. Using an approach combining phase microscopy with deep learning to map forces in …

The Global Hypophosphatasia Registry: Lessons Learned From A Decade Of Real-World Data., Priya S. Kishnani, Lothar Seefried, Keiichi Ozono, Gabriel Ángel Martos-Moreno, Cheryl Rockman-Greenberg, Deborah Fowler, Luke K. Burke, William R. Mowrey, Eric T. Rush, Peter R. Ebeling, Wolfgang Högler, Agnès Linglart, Shona Fang, Anna Petryk, Kathryn M. Dahir

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Hypophosphatasia (HPP) is an inherited, metabolic, rare disease characterized by a high level of clinical heterogeneity. In response to this robust heterogeneity, the Global HPP Registry was formed to characterize the types of manifestations that patients may experience, as well as to compile information on genetic underpinnings of the disease, overall impact on patient quality of life, and safety and effectiveness of enzyme replacement therapy. The objective of this review was to synthesize key learnings gained from the Global HPP Registry, which is now in its tenth year of enrolling patients.

METHODS: Registry data were analyzed to provide up-to-date …

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 …

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 …

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 …

Cohort Profile: The Pharmacogenomics And Pharmacokinetics Study In Ghanaian Hiv Patients (Genopharm-Gh), Nicholas Ekow Thomford, Oksana Ryabinina, Joel Adu Twum, John Anyimadu, Samuel Badu Nyarko, Akwasi Anyanful, Martins Ekor, George Boateng Kyei

2020-Current year OA Pubs

BACKGROUND: The GenoPharm-GH project initiated in 2019, as a longitudinal, multi-site observational cohort study aimed at bridging gaps in understanding the influence of host genetics, pharmacokinetics and comorbidities on treatment outcome among persons living with HIV (PLWH) in Ghana.

METHODS: The study is ongoing prospective, longitudinal, multi-site cohort associated with diverse projects being conducted throughout health facilities across Ghana. So far 2044 persons living with HIV (PLWH) aged ≥ 8 years have been registered. These participants are on treatment with antiretroviral therapies (ART). Viral suppression, treatment adherence (self-reported and pill count), clinical data, genetic variations, coinfections, and comorbidities are being …

Traumatic Fracture Of Kager's Fat Pad: A Case Report., Victoria Di Castro Horn, Margaret Hurley, Emily Andrews, Alberto Giardini

PCOM Scholarly Works

BACKGROUND: Kager's fat pad is a metabolically active adipose structure within Kager's triangle anterior to the Achilles tendon, involved in shock absorption, vascular support, and tendon lubrication. Although most research has focused on its role in Achilles tendinopathy and inflammatory conditions, isolated traumatic disruption without concurrent tendon damage has been rarely documented in the literature, to our knowledge. We report a case of an isolated traumatic fracture of the Kager's fat pad in the absence of concomitant Achilles tendon injury.

CASE PRESENTATION: An otherwise healthy 31 year-old female presented to the outpatient musculoskeletal office with reported pain at the distal …

Identifying Compounds To Treat Opiate Use Disorder By Leveraging Multi-Omic Data Integration And Multiple Drug Repurposing Databases, Jeran K Stratford, Megan Ulmer Carnes, Caryn Willis, Melyssa S Minto, Logain Elnimeiry, Ravi Mathur, Matthew Schu, Bryan C Quach, Javan Carter, Tracy Nolen, Nathan Vandergrift, Thomas R Kosten, Eric Otto Johnson, Bradley T Webb

Faculty, Staff and Students Publications

Genes influencing opioid use disorder (OUD) biology have been identified via genome-wide association studies (GWAS), gene expression, and network analyses. These discoveries provide opportunities to identifying existing compounds targeting these genes for drug repurposing studies. However, systematically integrating discovery results and identifying relevant available pharmacotherapies for OUD repurposing studies is challenging. To address this, we've constructed a framework that uses existing results and drug databases to identify candidate pharmacotherapies. For this study, two independent OUD related meta-analyses were used including a GWAS and a differential gene expression (DGE) study of post-mortem human brain. Protein-Protein Interaction (PPI) sub-networks enriched for GWAS …

Nirsevimab Effectiveness Against Intensive Care Unit Admission For Respiratory Syncytial Virus In Infants - 24 States, December 2024-April 2025., Laura D. Zambrano, Regina M. Simeone, Margaret M. Newhams, Amanda B. Payne, Natasha B. Halasa, Amber O. Orzel-Lockwood, Jemima M. Calixte, Satoshi Kamidani, Hillary Crandall, Melissa A. Cameron, Jennifer E. Schuster, Aline B. Maddux, Kathleen Chiotos, Katherine Irby, Steven L. Shein, Mary Allen Staat, Lora M. Martin, Samina S. Bhumbra, Ryan A. Nofziger, Jigar C. Chauhan, Danielle M. Zerr, Shira J. Gertz, Judith A. Guzman-Cottrill, Michele Kong, Janet R. Hume, Bria M. Coates, Kelly N. Michelson, Emily R. Levy, Tamara T. Bradford, Stephanie P. Schwartz, Tracie C. Walker, Melissa S. Stockwell, Austin Biggs, Alexander H. Hogan, Katherine Lindsey, Angela P. Campbell, Adrienne G. Randolph, Overcoming Rsv Investigators

Manuscripts, Articles, Book Chapters and Other Papers

Respiratory syncytial virus (RSV) is a leading cause of intensive care unit (ICU) admission and respiratory failure among infants (children aged < 1 year) in the United States. In August 2023, CDC's Advisory Committee on Immunization Practices recommended nirsevimab, a long-acting monoclonal antibody, to protect against RSV-associated lower respiratory tract infection among all infants aged < 8 months born during or entering their first RSV season. Following licensure, nirsevimab effectiveness has been demonstrated against RSV-associated infant hospitalization, but evidence regarding effectiveness against RSV-associated critical illness is limited. In a 27-hospital case-control investigation, nirsevimab effectiveness against both RSV-associated infant ICU admission and acute respiratory failure (illness requiring continuous positive airway pressure, bilevel positive airway pressure, or invasive mechanical ventilation) after hospital admission was evaluated during December 1, 2024-April 15, 2025. Among 457 case-patients who received a positive RSV test result and 302 control patients who received a negative RSV test result admitted to an ICU with respiratory symptoms, 14% and 45%, respectively, had received nirsevimab ≥7 days before symptom onset. Nirsevimab was 80% effective (95% CI = 70%-86%) against RSV-associated ICU admission and 83% effective (95% CI = 74%-90%) against acute respiratory failure when received a median of 52 days (IQR = 32-89 days) and 50 days (IQR = 32-86 days) before onset for each respective endpoint. These estimates support the recommendation for use of nirsevimab as a prevention strategy to protect infants against severe outcomes from RSV infection.

Five-Year Follow-Up Analysis Of Zuma-5: Axicabtagene Ciloleucel In Relapsed/Refractory Indolent Non-Hodgkin Lymphoma, Sattva S Neelapu, Julio C Chavez, Alison R Sehgal, Narendranath Epperla, Matthew L Ulrickson, Emmanuel Bachy, Pashna N Munshi, Carla Casulo, David G Maloney, Sven De Vos, Ran Reshef, Lori A Leslie, Olalekan O Oluwole, Ibrahim Yakoub-Agha, Rashmi Khanal, Joseph D Rosenblatt, Jacob Wulff, Rhine R Shen, Wangshu Zhang, Soumya Poddar, Harry Miao, Olga Nikolajeva, Caron A Jacobson

Faculty, Staff and Student Publications

Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) follicular lymphoma (FL). Here, we report updated clinical outcomes from ZUMA-5 in 159 enrolled patients with R/R indolent non-Hodgkin lymphoma (iNHL; 127 with FL and 31 with marginal zone lymphoma) after a median follow-up of 64.6 months. Patients underwent leukapheresis and received lymphodepleting chemotherapy and axi-cel (2 × 106 CAR T cells/kg). The overall response rate was 90% (75% complete response rate). The median duration of response was 60.4 months, and the median progression-free survival (PFS) was 62.2 months; median time to next …

Tca Cycle Mode Switch Determines The Fate Of Pirtobrutinib-Tolerant Persister Cells In Mantle Cell Lymphoma, Wei Wang, Qingsong Cai, Yang Liu, Lei Nie, Heng-Huan Lee, Fangfang Yan, Yue Fei, Yixin Yao, Yijing Li, Lin Tan, Philip L Lorenzi, Ying-Nai Wang, Jun Yao, Zhihong Chen, Joseph Mitchell Mcintosh, Cheng-Tai Yu, Preetesh Jain, Vivian C Jiang, Jovanny Vargas, Xiaolin Li, Tianci Zhang, Shaoying Li, David Santos, Selvi Thirumurthi, Erin Heather Seeley, Lukas Mikolaj Simon, Christopher Flowers, Chi Young Ok, Michael Wang

Faculty, Staff and Student Publications

Bruton tyrosine kinase inhibitors (BTKis) and cell therapy have successfully been used to treat mantle cell lymphoma (MCL). However, therapy resistance inevitably emerges. Cancer cells can progressively develop stable resistance by traversing through a transient drug-tolerant persister (DTP) state. The mechanisms enabling DTP cells to reversibly adapt to therapies and evolve to acquire heterogeneity remain poorly understood, and characterizing DTP cells in MCL continues to pose a challenge for clinic translation. Here, using pirtobrutinib, a recently US Food and Drug Administration-approved noncovalent BTKi, we identified pirtobrutinib-tolerant persister cells exhibiting morphological variability by presenting a unique population of enlarged cells (giant …

Mu-Glioma Post: A Comprehensive Dataset Of Automated Mr Multi-Sequence Segmentation And Clinical Features, Esmat Mahmoud, Jaime Gass, Yaseen Dhemesh, Josh Greaser, Karolina Pogorzelski, Edvin Isufi, Filip Garrett, Jonathan Thacker, Nourel Hoda Tahon, Jason Sinclair, Lester Layfield, Talissa Altes, Ayman Nada

2020-Current year OA Pubs

Gliomas represent a heterogenous group of primary brain tumors with overlapping imaging phenotypes. Treatment typically includes surgery and/or chemoradiation, however this varies based on the overall lesion and clinical presentation. This heterogeneity in both lesion characteristics and management strategies contributes to a lack of reliable findings when evaluating treatment outcomes with conventional MRI. The overlapping imaging features of radiation necrosis and tumor progression post-treatment can be particularly challenging for radiologists. We present a dataset of 203 glioma patients with 594 post-treatment timepoints of relevant clinical history and routine T1, T1 postcontrast, T2, and FLAIR weighted MR sequences. Preprocessing of the …

Assessing The Usability Of A Novel Toolkit For Creating Visual Key Information Pages For Informed Consent For Research: Mixed Methods Usability Study, Eliana Charlotte Goldstein, Zoe Troubh, Krista E Cooksey, Molly Volkmar, Victor Catalan Gallegos, Kimberly A Kaphingst, Clara N Lee, Ashley J Housten, Jessica Mozersky, Mary C Politi

2020-Current year OA Pubs

BACKGROUND: Key information pages for informed consent require a concise summary of information to improve participant understanding but have not widely incorporated health literacy best practices.

OBJECTIVE: We previously developed a visual key information template to improve informed consent. In this study, we conducted usability testing of this customizable one-page key information template.

METHODS: We used the Designing for Accelerated Translation framework to plan for actionable, efficient usability testing. Participants (N=15) were asked to spend about 20 minutes using the visual key information template and engaging in a think-aloud protocol. They then responded to qualitative debrief questions about the template …

Single Cell Long Read Whole Genome Sequencing Reveals Somatic Transposon Activity In Human Brain, Michal B Izydorczyk, Ester Kalef-Ezra, Dominic W Horner, Xinchang Zheng, Nadine Holmes, Marco Toffoli, Zeliha Sahin, Yi Han, Heer H Mehta, Sonja W Scholz, Clifton L Dalgard, Donna M Muzny, Adam Ameur, Fritz J Sedlazeck, Christos Proukakis

Faculty, Staff and Students Publications

The advent of single cell DNA sequencing revealed astonishing dynamics of genomic variability, but failed at characterizing smaller to mid size variants that on the germline level have a profound impact. In this work we discover previously uncharacterized genomic dynamics in 18 cells from three human brains utilizing single cell long-read whole genome sequencing. This provides key insights into the dynamic of the genomes of individual cells and further highlights brain specific activity of transposable elements, but requires validation in larger studies.

Perioperative Nutrition In Pediatric Patients With Congenital Heart Disease And Heart Failure., Jaime Silva-Gburek, Kelsey May, Bailey Walvoord, Catalina Lozano, Jorge A. Coss-Bu

Manuscripts, Articles, Book Chapters and Other Papers

Optimal nutritional therapy is important for infants and children with perioperative congenital heart disease and heart failure. Medical providers face physiological and metabolic challenges when administering enteral and parenteral nutrition to these patients. Complications related to enteral nutrition can increase morbidity and mortality, although outcomes are improved in those cases in which caloric and nutrient administration can be achieved. Consensus regarding feeding strategies and timing of nutritive care is lacking. This narrative review aims to summarize, analyze and discuss the most recent literature on nutritional therapy in perioperative congenital heart disease, heart failure and pediatric patients requiring mechanical circulatory support …

Infection And Nonunion Rates In Open Fractures: Description Of 6,042 Fractures From The Flow And Prep-It Trials, Roman M Natoli, Lucas S Marchand, Sofia Bzovsky, Jennifer E Hagen, Mark J Gage, Christina A Stennett, Nathan N O'Hara, Kyle J Jeray, Brad Petrisor, Sheila Sprague, Gerard P Slobogean

Faculty, Staff and Student Publications

Background: Infection and nonunion are common sequelae of open fractures. Studies have shown infection and nonunion rates ranging from 2% to 52% and 12% to 17%, respectively. The present article describes the rates of surgical site infection (SSI) and delayed union/nonunion following open fractures in a large contemporary series of patients from prospective clinical trials with adjudicated outcomes.

Methods: A descriptive analysis was performed with use of patient data from the FLOW, Aqueous-PREP, and PREPARE-Open studies. These studies, published within the past 10 years, included multiple international trauma centers and shared definitions for SSI and delayed union/nonunion. SSI and delayed …

14,441 Genomics-Based Validated Automated Comprehensive Clinicopathologic Correlations For Myeloid Neoplasms., Ahmed Elsafty, Yomna Ahmed, Taher F Halawa, Shaoguang Li, Dongguang Li, Elena Agranovsky, Ahmed Soliman, Howida Talaat, Mohamed Montaser, Omar Elnady, Deyaa Elnady, Mohamed Mahmoud Moustafa, Nourhan Ibrahim, Maryana Gumenyak, Yasmin Soliman, Samah Ali, Elshaimaa Abdelrahman, Hatem M S Alahwal, Ahmed S Barefah, Ashraf Abdelghany, Sherif Ammar, Nermeen Abdel-Haleem, Osama Abdel-Kareem, Samir N Shamma, Naglaa Husein, Maha M Sakr, Heba-Allah E Abdelrhman, Menatalla Nadim, Hany Girguis, Manal Othman, Ola Soliman, Walaa H Behery, Lamis Eltoukhy, Heldez A Mohamed, Aya M Hassan, Fatma-Elzahraa A Bebers, Marwa Abdel-Zaher, Sara A Abbas, Shady Attia, Mohamed A Saada, Amira S Eid, Soha E Khorshed, Khaled Talaat, Mohamed Saad Hamed Mahmoud, Mahmoud M S Mahmoud, Ola M S Mahmoud, Abdel-Rahman O Abdel-Kareem, Ahmed K Talaat, Haitham Heneish, Ibrahim I Samaha, Mones Safwat, Mohamed K Talaat, Alaa O Abdel-Kareem, Hadeel Abdel-Monem, Ramy Abaza, Hazem Abaza, Nora Ahmad, May A Maarouf, Iman A Shaheen, Ahmed S Abdelhafiz, Amera Rabee, Yara M Montaser

Faculty, Staff and Student Publications

The dataset (Elsafty_Reports_of_Myeloid_Neoplasms_2024) consists of 14,441 comprehensive clinicopathologic correlations (CPCs) for myeloid neoplasms (MN) with corresponding laboratory results. Specialized online platform utilizing these laboratory results automatically generated the diagnostic and prognostic CPCs. These results include complete blood counts (CBC), peripheral blood smear (PBS) findings, blast/promyelocyte count with dysplasia screening by flow cytometry, and molecular results by NGS/PCR. Two Hematopathologists, who performed the CBC and PBS review, collected their 10,794 real-world reports of cases served in Egypt with molecular studies performed in the USA and Europe. These newly-diagnosed cases included 243 chronic myeloid leukemia (CML) cases with 257 mutations/aberrations; 4,567 non-CML …