Digital Commons Network^™

Functional Brain Connectivity Of The Salience Network In Alcohol Use And Anxiety Disorders, Dhruv M Patel, Guillermo F Poblete, Alexandra Castellanos, Ramiro Salas

Staff and Researcher Publications

The interplay between alcohol use disorder (AUD) and anxiety disorders (ANX) is well-documented, yet the underlying neurobiological mechanisms remain elusive. This study aims to elucidate these mechanisms by examining the resting-state functional connectivity (RSFC) within the salience network and to the amygdala, both implicated in alcohol and anxiety disorders. We analyzed data from 264 inpatient participants culled from a wider group of 518 inpatients at The Menninger Clinic in Houston, TX, categorized into four groups (n = 66 each) based on DSM-IV diagnoses: AUD without ANX (AUD), ANX without AUD (ANX), concurrent AUD and ANX (BOTH), and neither (NEITHER). Our …

Label-Free Multimodal Optical Biopsy Reveals Biomolecular And Morphological Features Of Diabetic Kidney Tissue In 2d And 3d, Anthony A Fung, Zhi Li, Craig Boote, Petar Markov, Joseph P Gaut, Sanjay Jain, Lingyan Shi

2020-Current year OA Pubs

Kidney disease, the ninth leading cause of death in the United States, suffers from poor diagnostic efficiency (10%). Traditional biopsies use molecular reagents to enhance diagnostic power but are limited by overlapping spatial and chromatic signals, product quality variability, and additional processing. To address these challenges without disrupting routine diagnostics, we implement label-free imaging modalities-stimulated Raman scattering (SRS), second harmonic generation (SHG), and two-photon fluorescence (TPF)-within a single setup. We identify morphological, lipidomic, and metabolic biomarkers in control and diabetic kidney samples at subcellular resolution. Label-free Stimulated Raman Histology (SRH) reveals distinct collagen morphology, mesangial-glomerular volumes, lipid saturation, redox status, …

Meningeal Lymphatics-Microglia Axis Regulates Synaptic Physiology, Kyungdeok Kim, Daviti Abramishvili, Siling Du, Zachary Papadopoulos, Jay Cao, Jasmin Herz, Igor Smirnov, Jean-Leon Thomas, Marco Colonna, Jonathan Kipnis

2020-Current year OA Pubs

Meningeal lymphatics serve as an outlet for cerebrospinal fluid, and their dysfunction is associated with various neurodegenerative conditions. Previous studies have demonstrated that dysfunctional meningeal lymphatics evoke behavioral changes, but the neural mechanisms underlying these changes have remained elusive. Here, we show that prolonged impairment of meningeal lymphatics alters the balance of cortical excitatory and inhibitory synaptic inputs, accompanied by deficits in memory tasks. These synaptic and behavioral alterations induced by lymphatic dysfunction are mediated by microglia, leading to increased expression of the interleukin 6 gene (Il6). IL-6 drives inhibitory synapse phenotypes via a combination of trans- and classical IL-6 …

Network Analysis Of The Cerebrospinal Fluid Proteome Reveals Shared And Unique Differences Between Sporadic And Familial Forms Of Amyotrophic Lateral Sclerosis, Adam N Trautwig, Cindy V Ly, Timothy M Miller, Et Al.

2020-Current year OA Pubs

BACKGROUND: Amyotrophic Lateral Sclerosis (ALS), a neurodegenerative disease involving loss of motor neurons, typically results in death within 3-5 years of disease onset. Although roughly 10% of cases can be linked to a specific inherited mutation (e.g., C9orf72 hexanucleotide repeat expansion or SOD1 mutation), the cause(s) of most cases are unknown. Consequently, there is a critical need for biomarkers that reflect disease onset and progression across ALS subgroups.

METHODS: We employed tandem mass tag mass spectrometry (TMT-MS) based proteomics on cerebrospinal fluid (CSF) to identify and quantify 2105 proteins from sporadic, C9orf72, and SOD1 ALS patients, asymptomatic C9orf72 expansion carriers, …

A Phase I Dose-Escalation Study Of The Hif-2 Alpha Inhibitor Dff332 In Patients With Advanced Clear-Cell Renal Cell Carcinoma, Sumanta K Pal, Joel Picus, Et Al.

2020-Current year OA Pubs

PURPOSE: Mutations or silencing of the von Hippel-Lindau tumor suppressor gene accumulate hypoxia-inducible factors (HIF). HIF-2α is implicated in the oncogenesis of ∼50% of patients with clear-cell renal cell carcinoma (ccRCC) but has been considered "undruggable." DFF332, an orally administered novel allosteric inhibitor of HIF-2α, showed dose-dependent antitumor efficacy in preclinical models of ccRCC.

PATIENTS AND METHODS: This first-in-human study evaluated the safety, tolerability, antitumor activity, pharmacokinetics, and pharmacodynamics of DFF332 in patients with heavily pretreated advanced ccRCC. Preliminary data from the dose escalation of DFF332 monotherapy, administered orally at 50 or 100 mg weekly or 25, 50, 100, or …

Acute Kidney Injury Triggers Hypoxemia By Lung Intravascular Neutrophil Retention That Reduces Capillary Blood Flow, Yohei Komaru, Liang Ning, Carine Lama, Anusha Suresh, Eirini Kefaloyianni, Mark J. Miller, Shinichi Kawana, Hailey M Shepherd, Wenjun Li, Daniel Kreisel, Andreas Herrlich

2020-Current year OA Pubs

Sterile acute kidney injury (AKI) is common in the clinic and frequently associated with unexplained hypoxemia that does not improve with dialysis. AKI induces remote lung inflammation with neutrophil recruitment in mice and humans, but which cellular cues establish neutrophilic inflammation and how it contributes to hypoxemia is not known. Here we report that AKI induced rapid intravascular neutrophil retention in lung alveolar capillaries without extravasation into tissue or alveoli, causing hypoxemia by reducing lung capillary blood flow in the absence of substantial lung interstitial or alveolar edema. In contrast to direct ischemic lung injury, lung neutrophil recruitment during remote …

Modulation Of Her2 Internalization Enhances Single-Dose Antibody-Drug Potency In Her2+ Gastric Cancer, Abbey Zidel, Alex Benton, Emma Brown, Shayla Shmuel, Alex Vanover, Sandeep Surendra Panikar, Ron Bose, Haeseong Park, Andrew A Davis, Patrícia M R Pereira

2020-Current year OA Pubs

HER2 is a membrane receptor tyrosine kinase overexpressed in 18-20% of gastric tumors. Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate (ADC) that targets HER2-positive (HER2

Causes Of Death Among Us Medical Residents, Nicholas A. Yaghmour, William E. Bynum, Frederic W. Hafferty, Karen D. Könings, Thomas Richter, Timothy P. Brigham, Thomas J. Nasca

Division of Nephrology Faculty Papers

IMPORTANCE: From 2000 to 2014, the leading causes of medical resident death in the United States were neoplastic diseases and suicide.

OBJECTIVE: To examine whether US medical resident rates of death have changed since 2014 and whether causes of resident death differ by specialty.

DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, residents and fellows who were enrolled in Accreditation Council for Graduate Medical Education (ACGME)-accredited training programs and who died from January 2015 to December 2021 were submitted to the National Death Index to obtain causes of death. These decedents were compared with residents and fellows who died between …

Molecular Characterization And Predictors Of Relapse In Patients With Ph + All After Frontline Ponatinib And Blinatumomab, Nicholas J Short, Hagop Kantarjian, Ken Furudate, Nitin Jain, Farhad Ravandi, Omer Karrar, Sanam Loghavi, Lewis Nasr, Fadi G Haddad, Jayastu Senapati, Rebecca Garris, Koichi Takahashi, Elias Jabbour

Faculty, Staff and Student Publications

Background: Several studies have suggested that chemotherapy-free regimens consisting of blinatumomab and a BCR::ABL1 tyrosine kinase inhibitor are highly effective in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). However, the clinical and molecular characteristics that predict for relapse with these chemotherapy-free regimens are largely unknown.

Methods: We conducted a prospective phase II clinical trial of the combination of blinatumomab and ponatinib in 76 patients with newly diagnosed Ph + ALL. Patients received 12-15 doses of intrathecal chemotherapy as central nervous systemic (CNS) prophylaxis. The patterns of relapse and the clinical and molecular predictors of relapse were analyzed.

Results: With …

Theta Oscillons In Behaving Rats, M S Zobaer, Nastaran Lotfi, Carli M Domenico, Clarissa Hoffman, Luca Perotti, Daoyun Ji, Yuri Dabaghian

Faculty, Staff and Students Publications

Recently discovered constituents of the brain waves—the oscillons—provide a high-resolution representation of the extracellular field dynamics. Here, we study the most robust, highest-amplitude oscillons recorded in actively behaving male rats, which underlie the traditional θ-waves. The resemblances between θ-oscillons and the conventional θ-waves are manifested primarily at the ballpark level—mean frequencies, mean amplitudes, and bandwidths. In addition, both hippocampal and cortical oscillons exhibit a number of intricate, behavior-attuned, transient properties that suggest a new vantage point for understanding the θ-rhythms’ structure, origins and functions. In particular, we demonstrate that oscillons are frequency-modulated waves, with speed-controlled …

Developing The Mycancergene Digital Health Portal To Improve Patients' Understanding Of Germline Cancer Genetic Test Results: Development, User, And Usability Testing Study, Phillip Trieu, Dominique Fetzer, Briana Mcleod, Kathryn Schweickert, Lauren Gutstein, Brian Egleston, Susan Domchek, Linda Fleisher, Lynne Wagner, Kuang-Yi Wen, Cara Cacioppo, Jessica E. Ebrahimzadeh, Dana Falcone, Claire Langer, Elisabeth Wood, Kelsey Karpink, Shelby Posen, Enida Selmani, Angela R. Bradbury

Department of Medical Oncology Faculty Papers

BACKGROUND: The use of multigene panels has significantly increased the likelihood that genetic testing will leave patients with uncertainties regarding test interpretation, implications, and recommendations, which will change over time. Effective longitudinal care models are needed to provide patients with updated information and to obtain patient and family history updates.

OBJECTIVE: To bridge this gap, we aimed to develop a patient- and genetic provider-informed digital genetic health portal (GHP), MyCancerGene, to improve longitudinal patient understanding of and responses to genetic testing.

METHODS: We used a 5-step process to develop MyCancerGene. To better understand their interest in and willingness to use …

A Role For Δ Subunit-Containing Gabaa Receptors On Parvalbumin-Positive Neurons In Maintaining Electrocortical Signatures Of Sleep States, Peter M Lambert, Sofia V Salvatore, Xinguo Lu, Hong-Jin Shu, Ann Benz, Nicholas Rensing, Carla M Yuede, Michael Wong, Charles F Zorumski, Steven Mennerick

2020-Current year OA Pubs

GABA

Genome-Wide Allele-Specific Expression In Multi-Tissue Samples From Healthy Male Baboons Reveals The Transcriptional Complexity Of Mammals, Ramesh Ramasamy, Muthuswamy Raveendran, R Alan Harris, Hiep D Le, Ludovic S Mure, Giorgia Benegiamo, Ouria Dkhissi-Benyahya, Howard Cooper, Jeffrey Rogers, Satchidananda Panda

Faculty, Staff and Students Publications

Allele-specific expression (ASE) is pivotal in understanding the genetic underpinnings of phenotypic variation within species, differences in disease susceptibility, and responses to environmental factors. We processed 11 different tissue types collected from 12 age-matched healthy olive baboons (Papio anubis) for genome-wide ASE analysis. By sequencing their genomes at a minimum depth of 30×, we identified over 16 million single-nucleotide variants (SNVs). We also generated long-read sequencing data, enabling the phasing of all variants present within the coding regions of 96.5% of assayable protein-coding genes as a single haplotype block. Given the extensive heterozygosity of baboons relative to humans, we could …

Cutaneous Dysbiosis Characterizes The Post-Allogeneic Hematopoietic Stem Cell Transplantation Period., Adela R Cardones, Akintunde Emiola, Russell P Hall, Anthony D Sung, Jennifer Zhang, Amy J Petty, Charles Puza, Lauren M Bohannon, Amy T Bush, Meagan V Lew, Elizabeth Fleming, Yingai J Jin, Krista Rowe Nichols, Vaibhav Jain, Simon G Gregory, Keith M Sullivan, Nelson J Chao, Julia Oh

Faculty Research 2025

Gut dysbiosis is linked to mortality and the development of graft-versus-host disease after hematopoietic stem cell transplantation (HSCT), but the impact of cutaneous dysbiosis remains unexplored. We performed a pilot observational study, obtained retroauricular and forearm skin swabs from 12 adult patients before conditioning chemotherapy/radiation and at 1 week, 1 month, and 3 months after allogeneic HSCT, and performed shotgun metagenomic sequencing. The cutaneous microbiome among HSCT patients was enriched for gram-negative bacteria such as Escherichia coli and Pseudomonas, fungi, and viruses. Enrichment with bacteriophages and Polyomavirus species was observed among patients who died within 1 year. We observed longitudinal …

Multicentre Analysis Of Seizure Outcome Predicted By Removal Of High-Frequency Oscillations, Vasileios Dimakopoulos, Jean Gotman, Petr Klimes, Nicolas Von Ellenrieder, Shi Bei Tan, Garnett Smith, Stephen V. Gliske, Margarita Maltseva, Minette Krisel Manalo, Martin Pail, Milan Brazdil, Dorien Van Blooijs, Maryse A. Van 'T Klooster, Sarah Johnson, Samantha Laboy, Debora Ledergerber, Lukas Imbach, Christos Papadelis, Michael R. Sperling, Maeike Zijlmans, Jan Cimbalnik, Julia Jacobs, William C. Stacey, Birgit Frauscher, Johannes Sarnthein

Department of Neurology Faculty Papers

In drug-resistant focal epilepsy, planning surgical resection can involve presurgical intracranial EEG (iEEG) recordings to detect seizures and other iEEG patterns to improve postsurgical seizure outcome. We hypothesized that resection of tissue generating interictal high-frequency oscillations (HFOs, 80-500 Hz) in the iEEG predicts surgical outcome. In eight international epilepsy centres, iEEG was recorded during the presurgical evaluation of patients. The patients were of all ages, had epilepsy of all types, and underwent surgical resection of a single focus aiming at seizure freedom. In a prospective analysis, we applied a fully automated definition of HFO that was independent of the dataset. …

Soft, Skin-Interfaced Wireless Electrogoniometry Systems For Continuous Monitoring Of Finger And Wrist Joints, Hee-Sup Shin, Jihye Kim, Nicholas Fadell, Logan B Pewitt, Yusuf Shaaban, Claire Liu, Min-Seung Jo, Josif Bozovic, Andreas Tzavelis, Minsu Park, Kelly Koogler, Jin-Tae Kim, Jae-Young Yoo, John A Rogers, Mitchell A Pet

2020-Current year OA Pubs

Continuous kinematic biofeedback during exercise interventions can lead to improved therapeutic outcomes in hand and wrist rehabilitation. Conventional methods for measuring joint kinematics typically allow only static measurements performed by specially trained therapists. This paper introduces skin-conformal, wearable wireless systems designed to continuously and accurately capture the angles of target joints, specifically in hand and wrist. Supported by a computer vision-based calibration protocol run on a smart device, these magnetometer-based standalone systems provide patients and clinicians with continuous, real-time data on joint angles and ranges of motion through an intuitive graphical interface. Human trials in healthy volunteers demonstrate the accuracy …

Physiologically Based And Population Pharmacokinetic Modeling Of Midazolam In Children With Obesity Using Real-World Data, Sean Mccann, Victória E. Helfer, Stephen J. Balevic, William J. Muller, John N. Van Den Anker, Amira Al-Uzri, Marisa L. Meyer, Sarah G. Anderson, Sitora Turdalieva, Andrea N. Edginton, Daniel Gonzalez, Best Pharmaceuticals For Children Act Pediatric Trials Network Steering Committee

Department of Pediatrics Faculty Papers

Children represent a highly complex and variable population for treatment, including interindividual differences in drug dose-exposure. Midazolam has been used as a sedative for hospitalized children on- and off-label; however, factors affecting interindividual variability (IIV) in observed clearance for this population are not fully understood and can result in extreme under- or overexposure. Obesity has been described as a significant influence on midazolam in adolescents, which could potentially alter drug exposure. The goal of this study was to use two modeling strategies to evaluate dose-exposure of midazolam in children with and without obesity. Population pharmacokinetic modeling assessed whether measures of …

Smooth Muscle Cells And Fibroblasts In The Ascending Aorta Exhibit Minor Differences Between Embryonic Origins In Angiotensin Ii-Driven Transcriptional Alterations, Sohei Ito, David B Graf, Yuriko Katsumata, Jessica J Moorleghen, Chen Zhang, Yanming Li, Scott A Lemaire, Ying H Shen, Hong S Lu, Alan Daugherty, Hisashi Sawada

Faculty, Staff and Students Publications

Thoracic aortopathy is influenced by angiotensin II (AngII) and exhibits regional heterogeneity with the ascending aorta being particularly susceptible. In this region, smooth muscle cells (SMCs) and selected fibroblasts originate from the second heart field (SHF) and cardiac neural crest (CNC). While our previous study revealed a critical role of SHF-derived cells in AngII-mediated aortopathy, the contribution of CNC-derived cells remains unclear. To investigate lineage-specific responses to AngII, Mef2c-Cre R26RmT/mG mice were infused with AngII. Ascending aortas were harvested at baseline or after 3 days of infusion, representing the prepathological phase. Cells were sorted based on their embryonic origins and …

A Pharmacokinetic And Safety Study Of Oral Arsenic Trioxide In Patients With Acute Promyelocytic Leukemia, Farhad Ravandi, Sravanti Rangaraju, Hagop Kantarjian, Guillermo Garcia-Manero, Musa Yilmaz, Kristen Baker, Terence Hall, Joy Grabenstein, Pourab Roy, Beth A Zamboni, William C Zamboni, Erica Warlick, Michael Kelly, David A Roth, Gabriel Ghiaur

Faculty, Staff and Student Publications

SY-2101 is a novel oral formulation of arsenic trioxide (ATO). Although IV ATO in combination with all trans retinoic acid is highly efficacious in treating acute promyelocytic leukemia (APL), there remains a significant unmet need due to the treatment burden associated with receiving daily ATO infusions for nearly a year and the risk of complications associated with indwelling central catheters. The pharmacokinetics (PK), safety, and tolerability of SY-2101 and ATO IV after single- and multiple-dose administration and the impact of food on PK for SY-2101 were evaluated in this phase 1 study in 15 participants with APL. SY-2101 in the …

White Matter Connections Within The Central Sulcus Subserving The Somato-Cognitive Action Network, Georgios P Skandalakis, Evan M Gordon, Nico U F Dosenbach, Et Al.

2020-Current year OA Pubs

The somato-cognitive action network (SCAN) consists of three nodes interspersed within Penfield's motor effector regions. The configuration of the somato-cognitive action network nodes resembles the one of the 'plis de passage' of the central sulcus: small gyri bridging the precentral and postcentral gyri. Thus, we hypothesize that these may provide a structural substrate of the somato-cognitive action network. Using microdissections of 16 human hemispheres, we consistently identified a chain of three distinct plis de passage with increased underlying white matter in locations analogous to the somato-cognitive action network nodes. We mapped localizations of plis de passage into standard stereotactic space …

Temporal Regulation Of Early-Stage Cytokine Expression In Diabetic Wound Healing Under Negative Pressure Wound Therapy, Hua-Sheng Chiu, Ting-Shuo Huang, Chien-Tzung Chen, Xin-Yu Lin, Po-Cheng Liao, Cai-Cin Liou, Chih-Chin Hsu, Sonal Somvanshi, Pavel Sumazin, Pang-Hung Hsu, Chi-Chin Sun, Yu-Chiau Shyu

Faculty, Staff and Students Publications

Negative pressure wound therapy (NPWT) is widely recognized for its efficacy in treating diabetic wounds, but the mechanisms involved in the wound healing process remain unclear. By examining changes in blood cytokine levels as molecular signaling precursors, we aim to provide a comprehensive cytokine profile to support adjunctive therapy research and clinical applications. A diabetic mouse wound model was established to compare cytokine profiles between NPWT-treated and standard dressing groups, identifying key signaling candidates that may facilitate wound healing. By integrating normal mouse data with large-scale cytokine analysis, we developed a time-stratified NPWT approach to track acute-phase cytokine fluctuations in …

Risk Of Coronary Obstruction In Redo-Transcatheter Aortic Valve Replacement Between Bicuspid And Tricuspid Aortic Valves, Atsushi Okada, Syed Zaid, Miho Fukui, Evan Walser-Kuntz, Larissa I Stanberry, Marcus R Burns, John R Lesser, João L Cavalcante, Paul Sorajja, Vinayak N Bapat

Faculty, Staff and Students Publications

Background: Transcatheter aortic valve replacement (TAVR) is approved across all risk profiles, including patients with bicuspid aortic valves. These patients are generally younger, with a higher chance of reintervention.

Objectives: The aim of this study was to compare the feasibility of redo transcatheter aortic valve (TAV) between bicuspid and tricuspid aortic valves.

Methods: A computed tomographic (CT) simulation of redo-TAV was conducted using 913 post-TAVR CT studies from patients who underwent TAVR with SAPIEN 3 or SAPIEN 3 Ultra (S3; n = 623) or Evolut R, Evolut PRO, or Evolut PRO+ (Evolut; n = 290) valves. Fifty-nine cases were for …

Narratives Or Not? Examining The Roles Of Message Format And Individuals' Stages Of Change In The Context Of Hpv Vaccination Promotion, Mengfei Guan, Shawn C. Chiang, Regan M. Murray, Wen-Juo Lo, Larry T. Hill, Ann C. Klassen, Jennifer A. Manganello, Amy E. Leader, Philip M. Massey

Department of Medical Oncology Faculty Papers

Narrative persuasion has been widely used in health communication campaigns and persuasive message design. However, several meta-analyses showed that the relative effectiveness of narratives in promoting behavior change was not consistently observed in the existing literature. With the goal of exploring boundary conditions of narrative effects, this study investigates the interaction effects of narrative persuasion and stages of change on promoting behavior change in the context of encouraging parents to vaccinate their children against human papillomavirus (HPV). Findings from an online experiment (N = 593) showed that non-narrative messages were more effective in bolstering behavioral intention than narrative messages among …

Phase Ii Study Of Venetoclax Added To Bendamustine And Obinutuzumab In Patients With High-Risk Follicular Lymphoma As Front-Line Therapy: Pre0403, Craig A Portell, Opeyemi A Jegede, Nina Wagner-Johnston, Grzegorz S Nowakowski, Christopher Fletcher, Jonathon B Cohen, Andrew M Evens, Lori J Rosenstein, Jeffrey W Craig, Nishitha Reddy, Brad S Kahl

2020-Current year OA Pubs

Over-expression of BCL-2 defines follicular lymphoma (FL). Venetoclax (VEN), a selective BCL-2 inhibitor, has previously been evaluated with bendamustine-based chemoimmunotherapy. VEN was given continuously, resulting in promising efficacy but unacceptable toxicity. The Phase II PrE0403 study was designed to evaluate intermittent dosing of VEN (10 days per cycle) combined with obinutuzumab and bendamustine (VEN-OB) in untreated FL subjects with high-risk features defined as a FLIPI-1 score of ≥3 and/or high tumor burden by GELF criteria. A total of 56 subjects were planned to be accrued with a goal of having 51 subjects eligible to improve the historical 50% CR rate …

Allogeneic Chimeric Antigen Receptor T-Cell Products Cemacabtagene Ansegedleucel/Allo-501 In Relapsed/Refractory Large B-Cell Lymphoma: Phase I Experience From The Alpha2/Alpha Clinical Studies, Frederick L Locke, Javier L Munoz, Michael T Tees, Lazaros J Lekakis, Sven De Vos, Rajneesh Nath, Don A Stevens, Shahbaz A Malik, Geoffrey P Shouse, Mehdi Hamadani, Olalekan O Oluwole, Miguel-Angel Perales, David B Miklos, Paul W Fisher, Amy Feng, Lynn Navale, John B Le Gall, Sattva S Neelapu

Faculty, Staff and Student Publications

Purpose: Off-the-shelf, allogeneic CD19 chimeric antigen receptor (CAR) T-cell products may improve access to treatment versus autologous ones. We report the phase I experience of the allogeneic CD19 CAR T-cell product cemacabtagene ansegedleucel (cema-cel) and its predecessor, ALLO-501, in CD19 CAR T-naïve patients with relapsed/refractory large B-cell lymphoma (R/R LBCL).

Methods: In the ALPHA2/ALPHA studies, the safety and efficacy of allogeneic CD19 CAR T cells were evaluated in CD19 CAR T treatment-naïve patients with R/R LBCL. Patients received healthy donor-derived, human leukocyte antigen-unmatched cema-cel/ALLO-501 following a 3-day lymphodepletion regimen of fludarabine (30 mg/m2 once daily), cyclophosphamide (300 or 500 mg/m2 …

Let-7 Restrains An Epigenetic Circuit In At2 Cells To Prevent Fibrogenic Intermediates In Pulmonary Fibrosis, Matthew J Seasock, Md Shafiquzzaman, Maria E Ruiz-Echartea, Rupa S Kanchi, Brandon T Tran, Lukas M Simon, Matthew D Meyer, Phillip A Erice, Shivani L Lotlikar, Stephanie C Wenlock, Scott A Ochsner, Anton Enright, Alex F Carisey, Freddy Romero, Ivan O Rosas, Katherine Y King, Neil J Mckenna, Cristian Coarfa, Antony Rodriguez

Faculty, Staff and Students Publications

MicroRNA-mediated post-transcriptional regulation of lung alveolar type 2 (AT2) and AT1 cell differentiation remains understudied. Here, we demonstrate that the let-7 miRNA family plays a homeostatic role in AT2 quiescence by preventing the uncontrolled accumulation of AT2 transitional cells and promoting AT1 differentiation. Using mouse and organoid models, we show that genetic ablation of let-7a1/let-7f1/let-7d cluster (let-7afd) in AT2 cells prevents AT1 differentiation and leads to KRT8 transitional cell accumulation in progressive pulmonary fibrosis. Integration of AGO2-eCLIP with RNA-sequencing identified direct let-7 targets within an oncogene feed-forward regulatory network, including BACH1/EZH2/MYC, which drives an aberrant fibrotic cascade. Additional CUT&RUN-sequencing analyses …

Outcomes Of 1,021 Consecutive Cases Utilizing A Triple Tapered Collared Stem And Automated Broaching System, Ravi R Agrawal, Maria T Schwabe, Helena F Barber, Ethan Blum, Joseph T Gibian, Ryan M Nunley, Ilya Bendich

2020-Current year OA Pubs

No abstract provided.

High-Throughput Echocardiography-Guided Induction Of Myocardial Ischemia/Reperfusion In Mice., Florian Sicklinger, Niklas Hartmann, Attila Kovacs, Carla Weinheimer, Jess Nigro, Tobias Thiemann, Junedh M Amrute, David Schumacher, Moritz P Kornadt, Laura M Wienecke, Lennart Rompel, Johannes Fischer, John F Bachman, Olivia Bedard, Shibali Das, Tim C Kuhn, Mirko Völkers, Ralf P Brandes, Rafael Kramann, Nadia Rosenthal, Norbert Frey, Kory J Lavine, Florian Leuschner

Faculty Research 2025

BACKGROUND: Mouse models of myocardial ischemia with subsequent heart failure are common approaches to examine heart failure pathology and possible treatment strategies. We sought to establish a high-throughput approach for echocardiography-guided induction of myocardial ischemia/reperfusion (IR) in mice.

METHODS: After visualization of the left coronary artery with high-resolution ultrasound imaging and echocardiographic definition of the level of coronary occlusion, the left anterior descending artery was temporarily occluded with 2 micromanipulator-controlled needles. Functional and molecular changes were assessed and compared with commonly performed surgical techniques.

RESULTS: Echocardiography-guided induction of myocardial IR enabled standardized induction of myocardial IR injury with subsequent left …

Sustained Growth-Promoting Effects Of Vosoritide In Children With Achondroplasia From An Ongoing Phase 3 Extension Study, Ravi Savarirayan, Melita Irving, William R Wilcox, Carlos A Bacino, Julie E Hoover-Fong, Paul Harmatz, Lynda E Polgreen, Katja Palm, Carlos E Prada, Takuo Kubota, Paul Arundel, Yumiko Kotani, Antonio Leiva-Gea, Michael B Bober, Jacqueline T Hecht, Janet M Legare, Sue Lawrinson, Andrea Low, Ian Sabir, Alice Huntsman-Labed, Jonathan R S Day

Faculty, Staff and Students Publications

Background: Vosoritide is a C-type natriuretic peptide analog that addresses an underlying pathway causing reduced bone growth in achondroplasia. Understanding the vosoritide treatment effect requires evaluation over an extended duration and comparison with outcomes in untreated children.

Methods: After completing ≥6 months of a baseline observational growth study and 52 weeks in a double-blind, placebo-controlled study (ClinicalTrials.gov: NCT03197766), participants were eligible to continue treatment in an open-label extension (ClinicalTrials.gov: NCT03424018) wherein all received 15 μg/kg vosoritide daily. Data from the CLARITY achondroplasia study provided an external untreated control population and reference data.

Findings: The population comprised 119 participants. …

Intracellular Inclusions Induced By Patient-Derived And Amplified Α-Synuclein Aggregates Are Morphologically Indistinguishable, Rabab Al-Lahham, Mark E Corkins, Mohd Ishtikhar, Prakruti Rabadia, Santiago Ramirez, Victor Banerjee, Mohammad Shahnawaz

Faculty, Staff and Student Publications

Lewy Body Disease (LBD) and Multiple System Atrophy (MSA) are synucleinopathies with distinct prognoses and neuropathologies, however, with overlapping clinical symptoms. Different disease characteristics are proposed to be determined by distinct conformations of alpha-synuclein (α-Syn) aggregates, which can self-propagate and spread between cells via a prion-like mechanism. The goal of this study is to investigate whether α-syn aggregates amplified from brain and CSF samples of LBD and MSA patients using the Seed Amplification Assay (SAA) maintain α-Syn seeding properties similar to those of α-syn aggregates derived from patients' brains. To address this, SAA-amplified and un-amplified α-Syn aggregates from LBD and …