Digital Commons Network^™

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 …

Letter To The Editor On “Timing Of Puberty Suppression In Transgender Adolescents And Sexual Functioning After Vaginoplasty (Van Der Meulen Et Al., 2024)”, Alison Clayton, Jilles Smids, Kathleen Mcdeavitt

Faculty, Staff and Students Publications

No abstract provided.

New First Trimester Circulating Angiogenic Biomarkers In Predicting Early-Onset And Late-Onset Fetal Growth Restriction: A Case-Control Study, Xiaoyi Bai, Wei Li, Wenjing Ding, Oi Ka Chan, Maran Bo Wah Leung, So Ling Lau, Daljit Singh Sahota, Chi Chiu Wang, Tak Yeung Leung

Faculty, Staff and Students Publications

Background: First trimester prediction of fetal growth restriction (FGR) remain suboptimal. We aimed to search for new circulating angiogenic biomarkers for improvement.

Methods: This case-control study compared 73 singleton pregnancies with early or late-onset FGR based on Delphi consensus and 73 matched normal controls. Their maternal serum samples stored during 11-13 weeks were retrieved for measurement of 36 angiogenic biomarkers by MILLIPLEX® human angiogenesis magnetic bead panels. Those biomarkers that showed significant differences between the study groups were further analysed with receiver operating characteristic (ROC) curve.

Results: In the early-onset FGR group, log10MoM of soluble neuropilin-1 (sNRP-1: 0.08 ± 0.11 …

Characterizing Spatial Epidemiology In A Heterogeneous Transmission Landscape Using The Spatial Transmission Count Statistic, Leke Lyu, Gabriella Veytsel, Guppy Stott, Spencer Fox, Cody Dailey, Lambodhar Damodaran, Kayo Fujimoto, Pamela Brown, Roger Sealy, Armand Brown, Magdy Alabady, Justin Bahl

Faculty, Staff and Student Publications

Background: Viral genomes contain records of geographic movements and cross-scale transmission dynamics. However, the impact of regional heterogeneity, particularly among rural and urban centers, on viral spread and epidemic trajectory has been less explored due to limited data availability. Intensive and widespread efforts to collect and sequence SARS-CoV-2 viral samples have enabled the development of comparative genomic approaches to reconstruct spatial transmission history and understand viral transmission across different scales.

Methods: We proposed the spatial transmission count statistic that efficiently summarizes the geographic transmission patterns imprinted in viral phylogenies. Guided by a time-scaled tree with ancestral trait states, we identified …

Ligand-Activated Egfr/Mapk Signaling But Not Pi3k, Are Key Resistance Mechanisms To Egfr-Therapy In Colorectal Cancer, Xueping Qu, Habib Hamidi, Radia M Johnson, Ethan S Sokol, Eva Lin, Cathy Eng, Tae Won Kim, Johanna Bendell, Smruthy Sivakumar, Benjamin Kaplan, Felipe De Sousa E Melo, Andrew Mancini, Matthew Wongchenko, Yi Shi, David Shames, Yibing Yan, Fortunato Ciardiello, Carlos Bais

Faculty, Staff and Student Publications

Understanding mechanisms of resistance to active therapies is crucial for developing more effective treatments. Here, we investigate resistance to anti-EGFR and anti-VEGF plus chemotherapy treatment in colorectal cancer (CRC) patients from the IMblaze370 trial (NCT02788279). While anti-VEGF does not select for secondary mutations, anti-EGFR leads to simultaneous mutations in EGFR and MAPK, but not PI3K pathway genes. Notably, we observe frequent acquired mutations in the EGFR extracellular but not intracellular domain and that patients with higher baseline expression of EGFR-ligands are prone to acquire resistant mutations. This data reveals a ligand-activated EGFR/MAPK-signaling dependency in CRC. We also observe enrichment for …

Covid-19 Infection History As A Risk Factor For Early Pregnancy Loss: Results From The Electronic Health Record-Based Southeast Texas Covid And Pregnancy Cohort Study, Micaela N Sandoval, Michelle R Klawans, Mackinsey A Bach, Jennifer Mikhail, Edward A Graviss, Tru Cao, Jacqueline G Parchem, Junaid Husain, Eric Boerwinkle

Faculty, Staff and Student Publications

Background: The effects of SARS-CoV-2 infection before or during pregnancy on pregnancy outcomes are still largely unknown. We hypothesized that COVID-19 in early pregnancy is a risk factor for adverse pregnancy outcomes, particularly miscarriage.

Methods: We examined the relationship between COVID-19 and adverse pregnancy outcomes, including spontaneous abortion, ectopic pregnancy, and preterm delivery in a large, retrospective, electronic health record (EHR)-based cohort, from 2019 to 2023. Generalized estimating equation modeling was performed to identify risk factors for adverse pregnancy outcomes. Study exposures included COVID-19 before pregnancy, COVID-19 during pregnancy, age, race/ethnicity, comorbidity burden, and neighborhood-level social vulnerability.

Results: In the …

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 …

Cognitive Interviews With Emergency Physicians To Understand Disposition Decisions With People With Dementia With Borderline Cases, Anita N Chary, Annika R Bhananker, Rebecca Franks, Adrian Haimovich, Aanand D Naik, Maura Kennedy, Kei Ouchi

Faculty, Staff and Students Publications

People with dementia are often hospitalized from the emergency department (ED) for "borderline cases," where outpatient or inpatient management may be clinically reasonable. We sought to investigate how ED physicians make and communicate about decisions in borderline cases. Through cognitive interviews, we asked attending ED physicians from an academic hospital to share their approach to scenarios representing borderline cases with people with dementia and verbalize communication about ED disposition with patients and care partners. We deductively coded responses related to patient/care partner engagement and key features of communication and then elucidated themes related to content and phrasing of communication. Of …

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. …

Reply To: Is Gauchian Genotyping Of Gba1 Variants Reliable?, Marco Toffoli, Anthony H V Schapira, Fritz J Sedlazeck, Christos Proukakis

Faculty, Staff and Students Publications

No abstract provided.

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. …

Three Cases Of Adolescent Orf Virus Skin And Soft Tissue Infection In Southeast Texas, Margaret Taylor Danner, Caroline A Schrodt, Alexandra Tuttle, Victoria Shelus, Brendan Sullivan, Ankhi Dutta, Claire Bocchini, Denver Niles

Faculty, Staff and Students Publications

We report 3 adolescents who presented to a tertiary care hospital in Houston, Texas, with cutaneous skin lesions after contact with sheep and/or goats. The cases presented a diagnostic challenge initially but were later suspected or confirmed as orf virus infection after consultation with infectious diseases specialists.

50 Years Of Child And Adolescent Suicide Prevention Interventions: A Review Of Randomized Controlled Trials And Their Moderators And Mediators, Pauline Goger, Rachel Nam, Nathan Lowry, Christine B. Cha, Jessica Ribeiro, Xieyining Huang, Kathryn R. Fox

Journal of Applied Research on Children: Informing Policy for Children at Risk

Suicidal thoughts and behaviors (STBs) in youth are prevalent and impairing, but available psychosocial treatments are difficult to access and show limited efficacy. Prevention strategies are interventions intended to be implemented during relative well-periods before impairment or other adverse outcomes set in and therefore help avoid undue distress or psychological sequelae. However, prevention strategies have not always been clearly distinguished from treatment strategies in prior reviews. Additionally, increasing prevention efficacy by identifying what works how and for whom to allow for personalization of interventions could be impactful, but has not been sufficiently probed. To help address these knowledge gaps, a …

Institutional Betrayal And Suicidal Thoughts And Behaviors: A Retrospective Examination Of Lgbtq School Experiences, Mavis L. Gallo, Mark A. Hammond, Stephanie Luther, Geovanna Rodriguez, James Sinclair, Rhonda N.T. Nese, Marielena R. Mcwhirter Boisen, Skylar Steffes, James R. Muruthi, John R. Seeley

Journal of Applied Research on Children: Informing Policy for Children at Risk

Extant literature has established an elevated risk for suicidal thoughts and behaviors (STB) among lesbian, gay, bisexual, transgender, and/or queer (LGBTQ) youth when compared to their non-LGBTQ peers. Not yet studied is the impact of institutional betrayal on STB among LGBTQ youth. Institutional betrayals refers to misconduct carried out by an institution upon individuals reliant on the institution. Using retrospective data from 229 LGBTQ adults, we examined: (a) whether institutional betrayal was associated with STB among LGBTQ individuals in grades 5 through 12, (b) whether the association between institutional betrayal and STB was significant after controlling for the covariates, and …

Policy To Decrease Attrition Rates Amongst Mental Health Nurses, Ashley E. Burnett

Doctor of Nursing Practice Final Project Abstract

The high attrition rate among mental health nurses in the United States presents a critical challenge, leading to increased operational costs, workforce shortages, and compromised patient care. This policy proposal seeks to address the issue of mental health nurse turnover by offering a structured approach to enhancing job contentment and dealing with stress factors within the workplace. In line with the purpose of the study, quantitative and qualitative data from workforce surveys, peer-reviewed literature, and policy evaluations are combined to determine common retention strategies. Findings indicate that mentorship programs, competitive salaries, flexible scheduling, and workplace support systems significantly reduce burnout …

Investigating Social Network Peer Effects On Hiv Care Engagement Using A Fuzzy-Like Matching Approach: Cross-Sectional Secondary Analysis Of The N2 Cohort Study, Cho-Hee Shrader, Dustin T Duncan, Redd Driver, Juan G Arroyo-Flores, Makella S Coudray, Raymond Moody, Yen-Tyng Chen, Britt Skaathun, Lindsay Young, Natascha Del Vecchio, Kayo Fujimoto, Justin R Knox, Mariano Kanamori, John A Schneider

Faculty, Staff and Student Publications

BACKGROUND: Social network data are essential and informative for public health research and implementation as they provide details on individuals and their social context. For example, health information and behaviors, such as HIV-related prevention and care, may disseminate within a network or across society. By harmonizing egocentric and digital networks, researchers may construct a sociocentric-like "fuzzy" network based on a subgroup of the population.

OBJECTIVE: We aimed to generate a more complete sociocentric-like "fuzzy" network by harmonizing alternative sources of egocentric and digital network data to examine relationships between participants in the Neighborhoods and Networks (N2) cohort study. Further, we …

Rationale For A 4-Month, Parallel-Group, Randomized Controlled Trial To Assess The Feasibility And Efficacy Of A Remotely Delivered Exercise Training Intervention For Hispanics/Latinos With Multiple Sclerosis (Ferla Ms), Victoria A Flores, Stephanie L Silveira, David X Marquez, Dominique Kinnett-Hopkins, Augusto Miravalle, Fabian Sierra-Morales, Zulma Hernández-Peraza, Robert W Motl

Faculty, Staff and Student Publications

Background: Hispanic/Latino individuals with multiple sclerosis (MS) face greater disease burden and comorbidity due to limited healthcare access, underrepresentation in research, and social determinants of health (SDOH). Exercise training could manage health outcomes, but existing intervention research lacks Hispanic/Latino representation.

Methods: We propose a feasibility and efficacy study of a theory-based, remotely delivered exercise training intervention for enhancing health outcomes in Hispanics/Latinos with MS. This study involves a randomized controlled trial (RCT) design and compares an MS-specific exercise training program with an active control condition over a 4-month period in a sample of 50 individuals who self-identified as Hispanic/Latino with …

Overconfidence And Financial Risk Tolerance In Older Age, Colleen C Frank, Gary R Mottola, Meiru Chen, Lei Yu, Patricia A Boyle, Gregory R Samanez-Larkin, Kendra L Seaman

Faculty, Staff and Student Publications

Objectives: Excessive financial risk-taking in older age can have harmful consequences as opportunities to recover lost wealth are limited. Understanding financial risk-taking in older age is important for identifying vulnerabilities and developing interventions to empower aging investors to make wise financial choices. In this paper, we explore how overconfidence in financial knowledge affects financial risk-taking among older adults.

Methods: We examine this research question in older adults aged 58-101 (N = 1,242) using data from the Rush Memory and Aging Project (MAP).

Results: After controlling for demographics, overconfidence was associated with self-reported financial risk tolerance such that those who were …

Metabolic Reprogramming Driven By Ant2 Deficiency Augments T Cell Function And Anti-Tumor Immunity In Mice, Omri Yosef, Leonor Cohen-Daniel, Oded Shamriz, Zahala Bar-On, Wajeeh Salaymeh, Amijai Saragovi, Ifat Abramovich, Bella Agranovich, Veronika Lutz, Joseph Tam, Anna Permyakova, Eyal Gottlieb, Magdalena Huber, Michael Berger

Faculty, Staff and Student Publications

T cell activation requires a substantial increase in NAD+ production, often exceeding the capacity of oxidative phosphorylation (OXPHOS). To investigate how T cells adapt to this metabolic challenge, we generate T cell-specific ADP/ATP translocase-2 knockout (Ant2-/-) mice. Loss of Ant2, a crucial protein mediating ADP/ATP exchange between mitochondria and cytoplasm, induces OXPHOS restriction by limiting ATP synthase activity, thereby impeding NAD+ regeneration. Interestingly, Ant2-/- naïve T cells exhibit enhanced activation, proliferation and effector functions compared to wild-type controls. Metabolic profiling reveals that these T cells adopt an activated-like metabolic program with increased mitobiogenesis and anabolism. Lastly, pharmacological inhibition of ANT …

Enhanced Efficacy Of Ipilimumab Plus Nivolumab In Angiogenic Subtypes Of Metastatic Clear-Cell Renal Cell Carcinoma, Xiaofan Lu, Yann-Alexandre Vano, Xiaoping Su, Virginie Verkarre, Cheng-Ming Sun, Wenxuan Cheng, Li Xu, Fangrong Yan, Salma Kotti, Wolf Herman Fridman, Catherine Sautes-Fridman, Stéphane Oudard, Gabriel G Malouf

Faculty, Staff and Student Publications

In metastatic clear-cell renal cell carcinoma (mccRCC), choosing between immuno-oncology (IO) combinations and IO plus anti-VEGF therapies is uncertain. The BIONIKK trial revealed that ipilimumab plus nivolumab (Ipi/Nivo) achieved a 70% objective response rate in angiogenic cluster1/2 versus 41% in cluster4/5, which featured T-effector/cell-cycle signatures (p = 0.048). Complete responses were exclusively observed in cluster1/2 (p = 0.012), with longer progression-free survival (p = 0.014). Ipi/Nivo may particularly benefit angiogenic mccRCC, supporting molecular subtype-based treatment strategies.

Empathy And Psychological Outcomes In Informal Caregivers Of Community-Dwelling Older Adults: A Systematic Review And Meta-Analysis, Meng Huo, Thi Vu, Tomiko Yoneda, Jingkai Wei, Bruce Abbott, Joan K Monin

Faculty, Staff and Student Publications

Objectives: Scholars have increasingly recognized the crucial role that empathy plays as informal caregivers provide unpaid care to their older family and friends (i.e., care recipients). Yet, the existing literature exhibits substantial variability in study approaches and results, which limits the extent to which this literature can inform interventions intended to benefit informal caregivers. We sought to address this critical gap by synthesizing research that examined how caregivers' and care recipients' empathy were associated with caregivers' psychological health.

Methods: We conducted a literature search using PubMed, PsycInfo, CINAHL (Cumulative Index to Nursing and Allied Health Literature), EMBASE, and Scopus databases …

Brain And Cerebrospinal Fluid 3d Center Of Mass Shift After Spaceflight, Katherine G Warthen, Stuart H Sater, Larry A Kramer, Khader M Hasan, Michael A Williams, Millennia Young, Brandon R Macias, Steven S Laurie, Bryn A Martin

Faculty, Staff and Student Publications

A subset of long-duration spaceflight astronauts at the International Space Station has been documented to develop spaceflight associated neuro-ocular syndrome (SANS). Researchers have sought to understand SANS by quantification of ocular and brain structural changes thought to be associated with weightlessness induced headward fluid shift. Brain tissue shift and cerebrospinal fluid (CSF) redistribution has been observed as measured by MRI on return to Earth, and not fully quantified. To improve the understanding of this phenomenon, we developed and applied automated methods to quantify 3D center of mass shift within the skull of the extra-axial cerebrospinal fluid (eaCSF) and brain after …

Discovery Of Novel, Potent, And Orally Bioavailable Smarca2 Proteolysis-Targeting Chimeras With Synergistic Antitumor Activity In Combination With Kirsten Rat Sarcoma Viral Oncogene Homologue G12c Inhibitors, Sasikumar Kotagiri, Yawen Wang, Yanyan Han, Xiaobing Liang, Nicholas Blazanin, Hira Mazhar, Manu Sebastian, Phuong Kieu Nguyen, Yongying Jiang, Yonathan Lissanu

Faculty, Staff and Student Publications

Cancer genomic studies have identified frequent mutations in subunits of the SWI/SNF chromatin remodeling complex, including SMARCA4 in nonsmall cell lung cancer with a frequency of up to 33% in advanced-stage disease, making it the most frequently mutated complex. We and others have identified SMARCA2 to be synthetic lethal to SMARCA4, indicating that SMARCA2 is a high-value therapeutic target. Here, we disclose the discovery and characterization of potent, selective, and orally bioavailable cereblon-based SMARCA2 PROTACs. Biochemically, we showed that YDR1 and YD54 are potent SMARCA2 degraders. Further, we showed the antitumor growth inhibitory activity of YDR1 and YD54 in SMARCA4 …

Zanidatamab Monotherapy Or Combined With Chemotherapy In Her2-Expressing Gastroesophageal Adenocarcinoma: A Phase 1 Trial, Funda Meric-Bernstam, Sun Young Rha, Erika Hamilton, Yoon-Koo Kang, Diana L Hanna, Syma Iqbal, Keun-Wook Lee, Jeeyun Lee, Muralidhar Beeram, Do-Youn Oh, Jorge Chaves, Rachel A Goodwin, Jaffer A Ajani, Lin Yang, Rajen Oza, Elena Elimova

Faculty, Staff and Student Publications

There is a need for novel therapies for patients with previously treated HER2-positive gastroesophageal adenocarcinoma (GEA). This phase 1 (NCT02892123) dose-escalation and expansion trial evaluated zanidatamab (a dual HER2-targeted bispecific antibody) ± chemotherapy in previously treated patients with HER2-expressing, locally advanced/metastatic cancers. Here, we report the outcomes for GEA cohorts receiving zanidatamab monotherapy or with chemotherapy (paclitaxel or capecitabine). The primary endpoint was safety and tolerability. Secondary endpoints were objective response rate (ORR), disease control rate, progression-free survival, pharmacokinetics, and immunogenicity. Seventy patients were enrolled (n = 29 monotherapy; n = 41 combination therapy); most received prior HER2-targeted agents (monotherapy, …

Human Genetic Variation Determines 24-Hour Rhythmic Gene Expression And Disease Risk, Ying Chen, Panpan Liu, Aniko Sabo, Dongyin Guan

Faculty, Staff and Students Publications

24-hour biological rhythms are essential to maintain physiological homeostasis. Disruption of these rhythms increases the risks of multiple diseases. Biological rhythms are known to have a genetic basis formed by core clock genes, but how individual genetic variation shapes the oscillating transcriptome and contributes to human chronophysiology and disease risk is largely unknown. Here, we mapped interactions between temporal gene expression and genotype to identify quantitative trait loci (QTLs) contributing to rhythmic gene expression. These newly identified QTLs were termed as rhythmic QTLs (rhyQTLs), which determine previously unappreciated rhythmic genes in human subpopulations with specific genotypes. Functionally, rhyQTLs and their …

Improved Outcomes Of Acute Lymphoblastic Leukemia After Allogeneic Blood Or Marrow Transplantation With High-Dose Post-Transplantation Cyclophosphamide In The Era Of More Effective Pre-Transplant Therapy, Jonathan A Webster, Madison Reed, Hua-Ling Tsai, Philip H Imus, Douglas B Smith, Alexander J Ambinder, Mark J Levis, Amy E Dezern, Gabrielle T Prince, Tania Jain, Javier Bolaños-Meade, Lukasz P Gondek, Gabriel Ghiaur, William Brian Dalton, Theodoros Karantanos, Suman Paul, Ephraim J Fuchs, Cole Sterling, Lode J Swinnen, Nina Wagner-Johnston, Richard F Ambinder, Christian B Gocke, Syed Abbas Ali, Carol Ann Huff, Leo Luznik, Ravi Varadhan, Richard J Jones, Ivana Gojo

Faculty, Staff and Students Publications

The therapeutic landscape in ALL has changed dramatically over the last decade. Allogeneic blood or marrow transplantation (AlloBMT) has also evolved and remains an important option for consolidation. We assessed the interplay between these factors by analyzing the outcomes of 251 adult ALL (214 B and 37 T ALL) patients undergoing alloBMT with post-transplantation cyclophosphamide (PTCy) across two eras: 2008-2014 (ERA1) and 2015-2022 (ERA2). ERA1 patients were younger (median age 45.5 vs. 50, p=0.03), less likely to have an HCT-CI ≥4 (9% vs. 21%, p=0.01), more likely to have MRD by flow cytometry (20% vs. 9%, p=0.01) and receive myeloablative …

Increased Fatty Acid Delivery By Tumor Endothelium Promotes Metastatic Outgrowth, Deanna N Edwards, Shan Wang, Kelby Kane, Wenqiang Song, Laura C Kim, Verra M Ngwa, Yoonha Hwang, Kevin Ess, Mark R Boothby, Jin Chen

Faculty, Staff and Students Publications

Metastatic outgrowth in distant microscopic niches requires sufficient nutrients, including fatty acids (FAs), to support tumor growth and to generate an immunosuppressive tumor microenvironment (TME). However, despite the important role of FAs in metastasis, the regulation of FA supply in metastatic niches has not been defined. In this report, we show that tumor endothelium actively promotes outgrowth and restricts antitumor cytolysis by transferring FAs into developing metastatic tumors. We describe a process of transendothelial FA delivery via endosomes that requires mTORC1 activity. Thus, endothelial cell-specific targeted deletion of Raptor (RptorECKO), a unique component of the mTORC1 complex, significantly reduced metastatic …

Development Of A Risk Score To Aid With The Diagnosis Of Infections After Spinal Cord Injury: Protocol For A Retrospective Cohort Study, Felicia Skelton, Larissa Grigoryan, Joann Pan, Ashley Collazo, Barbara Trautner

Faculty, Staff and Students Publications

Background: Patients with spinal cord injury (SCI) who develop urinary tract infection (UTI) present differently than the non-SCI population. UTIs can cause loss of quality of life and even lead to life-threatening complications including urosepsis. Challenges in SCI management include distinguishing symptomatic UTI from asymptomatic bacteriuria (ASB), which occurs often in patients with SCI, and the lack of standardization in UTI diagnosis in SCI.

Objective: This study aims to set the foundation for the development of a risk score to improve diagnostic accuracy of UTI after SCI.

Methods: This study will use data from the Veterans Health Administration Corporate Data …

The Association Of Resistin With Metabolic Health And Obesity In A Mexican-American Population, Reem Al-Dallal, Keziah Thomas, Minjae Lee, Aysha Chaudhri, Eleanor Davis, Priyanka Vaidya, Miryoung Lee, Joseph B Mccormick, Susan P Fisher-Hoch, Absalon D Gutierrez

Faculty, Staff and Student Publications

Research on the relationship between resistin levels, metabolic health, and obesity has produced inconsistent findings across different ethnic groups, making it unclear whether lower resistin levels are associated with these conditions in Mexican-Americans. This cross-sectional study investigated the relationship between resistin, metabolic health, and obesity in an adult Mexican-American cohort (n = 1511) using multivariable linear regression analysis. Related adipokines (leptin and adiponectin) were measured simultaneously. Participants were categorized into four groups by metabolic health (healthy/unhealthy) and obesity (obese/non-obese) status. “Metabolically unhealthy” was defined as ≥2 cardiometabolic abnormalities. Obesity was defined as a BMI ≥ 30 kg/m2. We also …