Digital Commons Network^™

Genetic Analysis Of Psychosis Biotypes: Shared Ancestry-Adjusted Polygenic Risk And Unique Genomic Associations, Cuihua Xia, Ney Alliey Rodriguez, Carol A. Tamminga, Matcheri S. Keshavan, Godfrey Pearlson

School of Medicine Publications

The Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) created psychosis Biotypes based on neurobiological measurements in a multi-ancestry sample. These Biotypes cut across DSM diagnoses of schizophrenia, schizoaffective disorder, and bipolar disorder with psychosis. Two recently developed post hoc ancestry adjustment methods of Polygenic Risk Scores (PRSs) generate Ancestry-Adjusted PRSs (AAPRSs), which allow for PRS analysis of multi-ancestry samples. Applied to schizophrenia PRS, we found the Khera AAPRS method to show superior portability and comparable prediction accuracy as compared with the Ge method. The three Biotypes of psychosis disorders had similar AAPRSs across ancestries. In genomic analysis of Biotypes, 12 genes, …

Memory Interference In The Lateral Entorhinal Cortex, Omar Ghazy

Dissertations, Theses, and Capstone Projects

Memory interference occurs when previously formed memories disrupt the acquisition or retrieval of new information. A prominent example of proactive interference is latent inhibition (LI), defined as a reduced ability to form or express Pavlovian associations with a stimulus following non-reinforced exposure. The interference-based model suggests that LI arises because the memory that the pre-exposed stimulus is inconsequential interferes with the memory that it predicts a reinforcer.

Because interference increases with age, identifying its neural basis may help prevent or slow cognitive decline. Prior studies using the LI paradigm implicate the entorhinal cortex (EC) in retrieving the memory that a …

Cross-Institutional Dental Electronic Health Record Entity Extraction Via Generative Artificial Intelligence And Synthetic Notes, Xiaoqian Jiang, Muhammad F Walji, Oluwabunmi Tokede

Faculty, Staff and Student Publications

Background: While most health-care providers now use electronic health records (EHRs) to document clinical care, many still treat them as digital versions of paper records. As a result, documentation often remains unstructured, with free-text entries in progress notes. This limits the potential for secondary use and analysis, as machine-learning and data analysis algorithms are more effective with structured data.

Objective: This study aims to use advanced artificial intelligence (AI) and natural language processing (NLP) techniques to improve diagnostic information extraction from clinical notes in a periodontal use case. By automating this process, the study seeks to reduce missing data in …

Baseline Predictors Of Responders To Auricular Point Acupressure In Chronic Low Back Pain, Claudia M Campbell, Johannes Thrul, Xinran Huang, Paul Christo, Constance M Johnson

Faculty, Staff and Student Publications

Background: Chronic low back pain (cLBP) is a major cause of disability, with varied patient responses to treatments. Auricular point acupressure (APA) has shown potential as a non-pharmacological intervention, but individual responses may differ significantly.

Objective: This study aimed to determine the predictability of baseline characteristics, including functional disability, symptom severity, and treatment expectancy, on clinically significant responses to APA in reducing pain and improving function.

Methods: A secondary analysis was performed using data from a randomized controlled trial with 263 cLBP patients. Participants were randomly assigned to targeted APA (T-APA), non-targeted APA (NT-APA), or to a control group. APA …

The Ethnobotany And Pharmacology Of Medicinal Plants For Caribbean Women’S Health, Ella Thomas Vardeman

Dissertations, Theses, and Capstone Projects

Approximately 55% of the world’s population lives in cities, and the United Nations estimates that this number will rise to 68% by 2050. Urban ethnobotany, the study of people’s traditional knowledge and use of plants in cities, is increasingly important as people adapt their cultural traditions to changing environments. In New York City (NYC), there have been several urban ethnobotany investigations in collaboration with Caribbean immigrant groups. However, there has yet to be an ethnobotanical survey that documents and botanically authenticates the medicinal plants used in the Haitian community. Previous collaborative research with women from the Caribbean in NYC has …

Environmental Enrichment Reduces Cue-Induced Reinstatement Of Heroin-Seeking Following Prolonged Use And Reverses Region-Specific Heroin-Induced Neuroadaptations, Apoorva Vashisht

Dissertations, Theses, and Capstone Projects

Background: Relapse remains the greatest barrier to long-term recovery and the consequential rising overdose-related mortality in heroin use disorder (HUD). Currently available behavioral and pharmacological interventions fail to extend their benefits beyond the duration of the treatment. Additionally, opioid agonist-based medications accompany harmful neurobiological risks and propensity to promote further drug-seeking post-treatment. We have shown that environmental enrichment (EE), as a therapeutic strategy applied after drug intravenous-self administration (IVSA), can effectively facilitate abstinence and reduce reinstatement of drug-seeking in animal models of drug abuse. Moreover, dopamine receptors like D1 and D3, and mu-opioid (MO) receptors are well known for their …

Disturbance And Diversity: Lichens In Changing Landscapes, Laura Boggess

Dissertations, Theses, and Capstone Projects

Disturbance is a fundamental ecological force that shapes biodiversity, community composition, and ecosystem function. Human-driven disturbances—such as habitat fragmentation, deforestation, and air pollution—are increasing worldwide, altering ecosystems at unprecedented rates. While ecological research has illuminated many effects of disturbance, significant knowledge gaps remain for underappreciated but ecologically vital organisms, such as lichens. Lichens are obligate symbioses between at least one fungus and one alga or cyanobacterium. As such, they are sensitive bioindicators of environmental change, offering unique insights into ecosystem health due to their responses to stressors such as poor air quality, habitat fragmentation, and deforestation. Yet, their responses to …

Understanding How Genetic Mutations Induce Oligodendrocyte Progenitors To Become Cancer Cells, Dennis Huang

Dissertations, Theses, and Capstone Projects

Gliomas are the most devastating adult brain tumors characterized by poor survival rate and limited options for treatment. Previous studies have shown that they are very heterogeneous and can be further sub-classified based on their transcriptional signature and the presence of specific mutations. One such subtype, is the “proneural glioma”, which is characterized by the enrichment in oligodendrocyte progenitor cell (OPC) transcripts and mutations in genes encoding for the tumor suppressor P53 (Trp53) and for Platelet Derived Grow Factor (PDGF) signaling. Since OPCs are the most abundant proliferative population in the adult brain, in this …

Advancing The Development Of Trip13 Inhibitors: A High-Throughput Screening Approach, Rae M Sammons, Soma Ghosh, Lacin Yapindi, Eun Jeong Cho, Faye M Johnson

Faculty, Staff and Student Publications

TRIP13, a promising target for cancer therapy, has been identified as a key regulator of the mitotic checkpoint. Overexpression of TRIP13 is associated with poor clinical outcomes in various cancers. Inhibition of TRIP13 has the potential to address therapeutic challenges in cancer, particularly in therapy-resistant and Rb-deficient cancers. Despite the potential therapeutic benefits of TRIP13 inhibition, the development of TRIP13 inhibitors has been hindered by the lack of a robust high-throughput screening (HTS) assay. We developed a luminescence-based biochemical assay for TRIP13 activity to address this challenge using the ADP-Glo detection system. This assay offers high sensitivity, low background signal, …

Aapm Task Group No 249b-Essentials And Guidelines For Clinical Medical Physics Residency Training Programs, Jonathon A Nye, Joseph P Dugas, William D Erwin, David P Gierga, Darryl G Kaurin, Ho-Ling Anthony Liu, Alphonso W Magri, Lynn N Rill, Leah K Schubert, Beth A Schueler, Irina Vergalasova, John Vetter, Brian D Wichman, Amy Shu-Jung Yu, Dandan Zheng

Faculty, Staff and Student Publications

The establishment of guidelines and curriculum standards for medical physics residency training is a critical component of setting expectations and competencies for the profession. Since the last publication of these standards, residency training has become integrated into the eligibility criteria for most medical physics certification bodies. The rapid growth of medical physics requires periodic review of the curriculum to remove outdated approaches, update established knowledge, and add emerging technologies. The goal of this document is to provide a reference standard for residency training program directors, training mentors, and residents to guide creation and/or optimization of their program's curriculum. The document …

Nlrp3 Inflammasome Activation Expands The Immunosuppressive Myeloid Stroma And Antagonizes The Therapeutic Benefit Of Sting Activation In Glioblastoma, Spencer T Lea, Chao-Hsien Chen, Jun Wei, Ivana William, Inés Lopez Del Castillo

Faculty, Staff and Student Publications

Glioblastoma (GBM) is the most common and deadly primary brain malignancy and is clinically refractory to immunotherapy. Active NLRP3 inflammasome signaling and IL-1β secretion have been observed in GBM, and NLRP3-driven myeloid-derived suppressor cell (MDSC) recruitment can mediate cancer immune evasion. Agonists of the cytosolic double-stranded DNA-sensing stimulator of IFN gene (STING) pathway can mediate proinflammatory conversion of cancer MDSCs; however, secretion of the NLRP3 products IL-1β and IL-18 has also been observed in certain myeloid populations following STING activation. In this study, we aimed to determine both the potential mechanistic synergy between STING and NLRP3 agonists, and the effects …

Multicancer Early Detection Tests At A Crossroads: Commercial Availability Ahead Of Definitive Evidence, Carmen E Guerra, Jennifer Keating Litton, Carolina E Viswanath, A Mark Fendrick

Faculty, Staff and Student Publications

Multicancer early detection tests (MCEDs), sometimes referred to as liquid biopsies, are tests that can screen for multiple cancers by analyzing blood, urine, and other bodily fluids for biomarkers released by cancer cells. These tests have the potential to change the cancer screening paradigm if they are shown to reduce cancer mortality. However, it is not yet known whether MCEDs reduce mortality. Randomized controlled trials, the gold standard for evaluating cancer screening programs, are currently evaluating the effectiveness of MCEDs. However, because cancer-specific and all-cause mortality are end points that can take years to reach, trials are being designed with …

An Enzyme-Linked Immunosorbent Assay (Elisa)-Based Activity Assay For Amp-Activated Protein Kinase (Ampk), Trezze P Nguyen, Shangze Lyu, Yang Liu

Faculty, Staff and Student Publications

AMP-activated protein kinase (AMPK) is the master regulator of cellular and organismal energy homeostasis, playing an essential role in modulating metabolism and other cellular processes. Substantial efforts have been made to develop pharmacological modulators of AMPK activity due to their therapeutic potential against various diseases. Measuring AMPK activity in vitro is a fundamental step for testing AMPK activators and inhibitors. Here, we report an enzyme-linked immunosorbent assay (ELISA)-based AMPK activity assay with simple steps and high sensitivity. This assay offers a robust, in-house alternative to the traditional radioactive methods and other approaches that rely on specialized reagents or commercial kits.

Comparing Stroke Risk Factors Among Sexual Minority Groups In Texas, Brittany Krenek, Samuel Tundealao, Jennifer E S Beauchamp, Sean I Savitz, Irene Tamí-Maury

Faculty, Staff and Student Publications

Background: Knowledge gaps remain on stroke risk and disparities between sexual minority (SM) subgroups. In this study, stroke risk between SM subgroups, specifically gay/bisexual men and lesbian/bisexual women (G/BM and L/BW), was assessed.

Method: Data were collected in June 2022 using a bilingual (English and Spanish) cross-sectional paper-and-pen survey distributed among 183 SM individuals attending the 2022 Houston Pride Parade and Festival, as well as across Texas via phone call or online format. Relevant sociodemographic and stroke risk factors were compared between G/BM and L/BW using chi-square (or Fisher's exact, when appropriate) and two-sample t-tests. Sexual orientation was used to …

A Plain Language Summary Of The Molecular Changes In The Tumors Of People With Braf V600e-Mutant Colorectal Cancer In The Beacon Study, Scott Kopetz, Danielle A Murphy, Jie Pu, Fortunato Ciardiello, Jayesh Desai, Harpreet Singh Wasan, Hedieh Saffari, Xiaosong Zhang, Phineas Hamilton, Tao Xie, Rona Yaeger, Josep Tabernero

Faculty, Staff and Student Publications

What is this summary about?This summary discusses the genetic and molecular changes in tumors of participants with BRAF V600E–mutant metastatic colorectal cancer who were treated with encorafenib plus cetuximab, with or without binimetinib, in the BEACON study.

What were the results?Encorafenib plus cetuximab, with or without binimetinib, reduced the risk of participants dying compared with cetuximab plus chemotherapy, regardless of genetic or molecular colorectal cancer subtypes.The study also found genetic and molecular changes in the participants’ tumors during treatment that were associated with how long they lived.

What do the results of the study mean?The types of …

Cll Cell-Derived Exosomes Alter The Immune And Hematopoietic Systems, Ivo Veletic, David M Harris, Uri Rozovski, Maria Teresa S Bertilaccio, George A Calin, Ping Li, Taghi Manshouri, Rares-Constantin Drula, Ken Furudate, Muharrem Muftuoglu, Anwar Hossain, William G Wierda, Michael J Keating, Zeev Estrov

Faculty, Staff and Student Publications

The origins of immunosuppression, neutropenia, and anemia in patients with chronic lymphocytic leukemia (CLL) are not fully understood. Because in patients with CLL, circulating exosomes, which participate in cell-to-cell interactions, are CLL cell-derived, we examined whether those exosomes contribute to abnormal features of this disease. Our data revealed that CLL cell-derived exosomes engulfed by healthy donors’ monocytes, fibrocytes, and lymphocytes altered target-cell gene and protein expression and suppressed normal hematopoiesis. CLL cell-derived exosomes increased normal monocytes’ CD14 and CD16 expression such that it mimicked the accessory cell profile and upregulated T cells’ checkpoint PD-1 and CD160 protein levels, potentially reducing …

Emerging Technologies Of Single-Cell Multi-Omics, Yi June Kim, Koichi Takahashi

Faculty, Staff and Student Publications

The heterogeneity of the hematopoietic system was largely veiled by traditional bulk sequencing methods, which measure the averaged signals from mixed cellular populations. In contrast, single-cell sequencing has enabled the direct measurement of individual signals from each cell, significantly enhancing our ability to unveil such heterogeneity. Building on these advances, numerous single-cell multi-omics techniques have been developed into high-throughput, routinely accessible platforms, delineating the precise relationships among different layers of the central dogma in molecular biology. These technologies have uncovered the intricate landscape of genetic clonality and transcriptional heterogeneity in both normal and malignant hematopoietic systems, highlighting their roles in …

Externally Validated Digital Decision Support Tool For Time-To-Osteoradionecrosis Risk-Stratification Using Right-Censored Multi-Institutional Observational Cohorts, Laia Humbert-Vidan, Serageldin Kamel, Andrew Wentzel, Zaphanlene Kaffey, Moamen Abdelaal, Natalie A West, Guadalupe Canahuate, Xinhua Zhang, Melissa M Chen, Kareem A Wahid, Jillian Rigert, Seyedmohammadhossein Hosseinian, Andrew J Schaefer, Kristy K Brock, Mark Chambers, Adegbenga O Otun, Ruth Aponte-Wesson, Vinod Patel, Andrew Hope, Jack Phan, Adam S Garden, Steven J Frank, William H Morrison, Michael T Spiotto, David Rosenthal, Anna Lee, Renjie He, Mohamed A Naser, Erin Watson, Katherine A Hutcheson, Abdallah S R Mohamed, Vlad C Sandulache, Lisanne V Van Dijk, Amy C Moreno, Teresa Guerrero Urbano, Clifton D Fuller, Stephen Y Lai

Faculty, Staff and Student Publications

Background: Existing studies on osteoradionecrosis of the jaw (ORNJ) have primarily used cross-sectional data, assessing risk factors at a single time point. Determining the time-to-event profile of ORNJ has important implications to monitor oral health in head and neck cancer (HNC) long-term survivors.

Methods: Data were retrospectively obtained for a clinical observational cohort of 1129 patients (198 ORNJ cases) with HNC treated with radiotherapy (RT) at The University of Texas MD Anderson Cancer Center. A Weibull Accelerated Failure Time model was trained on previously identified dosimetric, clinical and demographic predictors. External validation was performed using an independent cohort of 265 …

Targeted Sting Activation Using Modified Ultrasound-Responsive Microbubbles Enhances Immune Checkpoint Blockade Against Melanoma, Sina Khorsandi, Kristin Huntoon, Yifan Wang, Adam Woodward, Abin Antony, Nazia Hafeez, Nicole Mccuen, Prasanna G Alluri, Betty Y S Kim, Wen Jiang, Jacques Lux

Faculty, Staff and Student Publications

Despite the recent successes of immune checkpoint inhibitors (ICIs) in treating advanced melanoma, durable clinical responses still remain limited. To boost immune responses, agents that target immune regulators, such as the Stimulator of Interferon Genes (STING) agonist cyclic GMP-AMP (cGAMP), are being investigated. However, their clinical translation is impeded by poor serum stability, rapid tissue clearance, and T-cell death due to off-target activation. Recently, a novel strategy termed Microbubble-assisted UltraSound-guided Immunotherapy of Cancer (MUSIC) has been reported to selectively deliver cGAMP directly into the cytosol of antigen-presenting cells with spatiotemporal control. The resulting activation of STING and downstream proinflammatory pathways …

International Expert-Based Consensus Definition, Classification Criteria, And Minimum Data Elements For Osteoradionecrosis Of The Jaw: An Interdisciplinary Modified Delphi Study, Amy C Moreno, Erin E Watson, Laia Humbert-Vidan, Douglas E Peterson, Lisanne V Van Dijk, Lisa Van Den Bosch, Matthew S Katz, Frank J P Hoebers, Ruth A Aponte Wesson, James E Bates, Paolo Bossi, Adeyinka F Dayo, Mélanie Doré, Eduardo Rodrigues Fregnani, Thomas J Galloway, Daphna Y Gelblum, Issa A Hanna, Christina E Henson, Sudarat Kiat-Amnuay, Anke Korfage, Nancy Y Lee, Carol M Lewis, Charlotte Duch Lynggaard, Antti A Mäkitie, Marco Magalhaes, Yvonne M Mowery, Carles Muñoz-Montplet, Jeffrey N Myers, Ester Orlandi, Jaymit Patel, Jillian M Rigert, Deborah Saunders, Jonathan D Schoenfeld, Ugur Selek, Efsun Somay, Vinita Takiar, Juliette Thariat, Gerda M Verduijn, Alessandro Villa, Nicholas S West, Max J H Witjes, Alex M Won, Mark E Wong, Christopher M K L Yao, Simon W Young, Kamal Al-Eryani, Carly E A Barbon, Doke J M Buurman, François J Dieleman, Theresa M Hofstede, Abdul Ahad Khan, Adegbenga O Otun, John C Robinson, Lauren Hum, Jorgen Johansen, Rajesh Lalla, Alexander Lin, Vinod Patel, Richard J Shaw, Mark S Chambers, Daniel Ma, Mabi Singh, Noam Yarom, Abdallah Sherif Radwan Mohamed, Katherine A Hutcheson, Stephen Y Lai, Clifton David Fuller

Faculty, Staff and Student Publications

Purpose: Osteoradionecrosis of the jaw (ORNJ) is a severe iatrogenic disease characterized by bone death after radiation therapy to the head and neck. With >9 published definitions and at least 16 classification systems, the true incidence and severity of ORNJ are obscured by lack of a standard for disease definition and severity assessment, leading to inaccurate estimation of incidence, reporting ambiguity, and likely underdiagnosis worldwide. This study aimed to achieve consensus on an explicit definition and phenotype of ORNJ and related precursor states through data standardization to facilitate effective diagnosis, monitoring, and multidisciplinary management of ORNJ.

Methods and materials: The …

Gsk-3484862, A Dnmt1 Degrader, Promotes Dnmt3b Expression In Lung Cancer Cells, Qin Chen, Swanand Hardikar, Kimie Kondo, Nan Dai, Ivan R Corrêa Jr, Marcos R Estecio, Taiping Chen, Xiaodong Cheng

Faculty, Staff and Student Publications

DNA methylation alterations, including hypermethylation and silencing of tumor suppressor genes, contribute to cancer formation and progression. The FDA-approved nucleoside analogs azacytidine and decitabine are effective demethylating agents for hematologic malignancies but their general use has been limited by their toxicity and ineffectiveness against solid tumors. GSK-3484862, a dicyanopyridine-containing, DNMT1-selective inhibitor and degrader, offers a promising lead for developing novel demethylating therapeutics. Here, we demonstrate that GSK-3484862 treatment upregulates DNMT3B expression in lung cancer cell lines (A549 and NCI-H1299). Disrupting DNMT3B in NCI-H1299 sensitizes these cells to GSK-3484862, enhancing its inhibitory effects on cell viability and growth. GSK-3484862 treatment induces …

Egfr Controls Transcriptional And Metabolic Rewiring In Krasg12d Colorectal Cancer, Dana Krauß, Veronica Moreno-Viedma, Emi Adachi-Fernandez, Cristiano De Sá Fernandes, Jakob-Wendelin Genger, Bernadette Blauensteiner, Nikolina Bradaric, Valeriya Gushchina, Georgios Fotakis, Thomas Mohr, Ifat Abramovich, Inbal Mor, Martin Holcmann, Andreas Bergthaler, Arvand Haschemi, Zlatko Trajanoski, Juliane Winkler, Eyal Gottlieb, Maria Sibilia

Faculty, Staff and Student Publications

Inhibition of the epidermal growth factor receptor (EGFR) shows clinical benefit in metastatic colorectal cancer (CRC) patients, but KRAS-mutations are known to confer resistance. However, recent reports highlight EGFR as a crucial target to be co-inhibited with RAS inhibitors for effective treatment of KRAS mutant CRC. Here, we investigated the tumor cell-intrinsic contribution of EGFR in KRASG12D tumors by establishing murine CRC organoids with key CRC mutations (KRAS, APC, TP53) and inducible EGFR deletion. Metabolomic, transcriptomic, and scRNA-analyses revealed that EGFR deletion in KRAS-mutant organoids reduced their phenotypic heterogeneity and activated a distinct cancer-stem-cell/WNT signature associated with reduced cell size …

National Institutes Of Health Funding To Support Radiation Oncology Research: A Comparative Trend Analysis Over A Decade, 2011-2021, Amir Razavi, Michael K Rooney, Clifton D Fuller, James B Yu, Neil T Pfister, John M Buatti, Heather M Mcgee, Debra Nana Yeboa, Ana P Kiess, Andrew M Baschnagel, Randall J Kimple

Faculty, Staff and Student Publications

Purpose: Funding to support radiation oncology discovery and research is essential for advancement in therapeutic strategies to improve outcomes for patients with cancer. We aimed to comprehensively characterize trends in National Institutes of Health (NIH) funding that supports radiation oncology research over time to identify trends, successes, and areas for improvement.

Methods and materials: We queried the NIH Research Portfolio Online Reporting Tools Expenditures and Results database to identify all awarded grants to support radiation oncology research conducted by principal investigators at academic centers, using 3 individual years as representative samples (2011, 2016, and 2021). Abstracts and keywords for resulting …

Novel Treatment-Specific Causal Biomarkers For Colorectal Cancer By Omics Integration, Akram Yazdani, Azam Yazdani, Raul Mendez-Giraldez, Gianluigi Pillonetto, Esmat Samiei, Heinz-Josef Lenz, Ahmad Samiei, Andrew B Nixon, Joseph A Lucci, Scott Kopetz, Monica M Bertagnolli, Federico Innocenti

Faculty, Staff and Student Publications

While monoclonal antibody-based targeted therapies have substantially improved progression-free survival in cancer patients, the variability in individual responses poses a significant challenge in patient care. Therefore, identifying cancer subtypes and their associated biomarkers is required for assigning effective treatment. In this study, we integrated genotype and pre-treatment tissue RNA-seq data and identified biomarkers causally associated with the overall survival (OS) of colorectal cancer (CRC) patients treated with either cetuximab or bevacizumab. We performed enrichment analysis for specific consensus molecular subtypes (CMS) of CRC and evaluated differential expression of identified genes using paired tumor and normal tissue from an external cohort. …

Building Community Through Data: The Value Of A Researcher Driven Open Science Ecosystem, Meredith C B Adams, Carla M Bann, Emine Ozgur Bayman, Maria Chao, Georgene W Hergenroeder, Martin A Lindquist, Rosemarie Martin, Maryann E Martone, John Mccarthy, Micah Mccumber, Sharon B Meropol, Ty A Ridenour, Lissette M Saavedra, Abeed Sarker, Kevin J Anstrom, Wesley K Thompson

Faculty, Staff and Student Publications

No abstract provided.

Bispecific Antibodies In Hematologic And Solid Tumors: Current Landscape And Therapeutic Advances, Lorenzo Guidi, Julian Etessami, Carmine Valenza, Augusto Valdivia, Funda Meric-Bernstam, Giuseppe Curigliano

Faculty, Staff and Student Publications

Bispecific antibodies (bsAbs) have emerged as a novel class of therapeutics, offering a dual-targeting strategy to enhance the therapeutic efficacy of monoclonal antibodies, which is often limited by tumor heterogeneity and the occurrence of resistance mechanisms. By simultaneously engaging two distinct antigens or pathways, bsAbs disrupt multiple signaling cascades simultaneously, preventing escape mechanisms and offering a more durable response. Furthermore, they can optimize immune activation, improving immune cell recruitment strategies. In particular, T-cell engager bsAbs facilitate immune cell-mediated tumor destruction by linking T cells to tumor antigens. Instead, dual immune checkpoint inhibitors (CPIs) enhance immune activation by blocking inhibitory signals. …

Neighborhood Socioeconomic Disadvantage Is Not Associated With Adverse Outcomes Following Elective Spine Surgery In Older Veterans, Andrea L Strayer, Yubo Gao, Michael A Jacobs, Heather Davila, Carly A Jacobs, Leslie R M Hausmann, George Wehby, Daniel E Hall, Mary Vaughan Sarrazin, Katherine E Hadlandsmyth

Faculty, Staff and Student Publications

Background: In the US, over half of all cervical and lumbar arthrodesis spine surgeries are for people ≥60 years of age. The extent to which adverse outcomes vary by social (eg, disadvantaged neighborhoods) and demographic factors have been scarcely investigated in spine surgery. We investigated the association of social, demographic, and clinical factors with complications, 30-day readmission, and 30-day mortality in older Veterans undergoing elective spine surgery.

Methods: Veterans (N=5,277) aged ≥65 years who underwent inpatient elective spine surgery for degenerative disease in the Veterans Affairs Surgical Quality Improvement Program (VASQIP) comprised our retrospective cohort. VASQIP (2013-2019) data were merged …

Fibroblast Dynamics During Mammary Oncogenesis: Senescence, Wnt9a And Beyond, Viktoria Boeker, Raghu Kalluri

Faculty, Staff and Student Publications

Mammary gland fibroblasts are highly plastic and transition through distinct states during development and disease. A new study by Pascual et al (2025) provides a comprehensive single-cell atlas of murine mammary stromal cell hierarchies, revealing dysregulation of progenitor-driven fibroblast lineages in breast cancer and a senescence role of Wnt9a in cancer-associated myofibroblasts.

Outcomes After Palliative Radiation Therapy In Patients With Symptomatic Locoregionally Advanced Breast Cancer, Luisa E Jacomina, David M Swanson, Melissa P Mitchell, Wendy A Woodward, Benjamin D Smith, Chelain R Goodman, Susie X Sun, Timothy A Yap, Funda Meric-Bernstam, Isidora Y Arzu, Elizabeth S Bloom, Pamela J Schlembach, Eric A Strom, Michael C Stauder, Simona F Shaitelman

Faculty, Staff and Student Publications

Purpose: Symptomatic locoregionally advanced breast cancer (SLABC) can cause troublesome pain or wound complications that negatively impact quality of life. Although palliative radiation therapy (RT) can minimize tumor-related symptoms, how best to tailor RT to achieve the most meaningful and durable response is not well defined.

Methods and materials: This is a single institution, multi-site retrospective review of patients with SLABC treated between 2016 and 2023 with palliative RT to symptomatic disease in the breast, chest wall, and/or regional lymph node basins. Overall survival (OS), locoregional control (LC), clinical and radiographic treatment response, overall pain scores, and treatment-related toxicities were …

Gut Microbiota In Immuno-Oncology: A Practical Guide For Medical Oncologists With A Focus On Antibiotics Stewardship, Arielle Elkrief, Bertrand Routy, Lisa Derosa, Laura Bolte, Jennifer A Wargo, Laurence Zitvogel

Faculty, Staff and Student Publications

The gut microbiota has emerged as a critical determinant of immune checkpoint inhibitor (ICI) efficacy, resistance, and toxicity. Retrospective and prospective studies profiling the taxonomic composition of intestinal microbes of patients treated with ICI have revealed specific gut microbial signatures associated with response. By contrast, dysbiosis, which can be caused by chronic inflammatory processes (such as cancer) or comedications, is a risk factor of resistance to ICI. Recent large-scale meta-analyses have confirmed that antibiotic (ATB) use before or during ICI therapy alters the microbiota repertoire and significantly shortens overall survival, even after adjusting for prognostic factors. These results underscore the …