Digital Commons Network^™

Mechanical Regulation Of Macrophage Metabolism By Allograft Inflammatory Factor 1 Leads To Adverse Remodeling After Cardiac Injury, Matthew Deberge, Kristofor Glinton, Connor Lantz, Zhi-Dong Ge, David P Sullivan, Swapna Patil, Bo Ryung Lee, Minori I Thorp, Adam Mullick, Steve Yeh, Shuling Han, Anja M Van Der Laan, Hans W M Niessen, Xunrong Luo, Nicholas E S Sibinga, Edward B Thorp

Faculty, Staff and Student Publications

Myocardial infarction (MI) mobilizes macrophages, the central protagonists of tissue repair in the infarcted heart. Although necessary for repair, macrophages also contribute to adverse remodeling and progression to heart failure. In this context, specific targeting of inflammatory macrophage activation may attenuate maladaptive responses and enhance cardiac repair. Allograft inflammatory factor 1 (AIF1) is a macrophage-specific protein expressed in a variety of inflammatory settings, but its function after MI is unknown. Here we identify a maladaptive role for macrophage AIF1 after MI in mice. Mechanistic studies show that AIF1 increases actin remodeling in macrophages to promote reactive oxygen species-dependent activation of …

Mutation Of Conserved Mhc Class I Cytoplasmic Tyrosine Affects Cd8+ T Cell Priming, Effector Function, And Memory Response, Yimo Sun, Yitao Tang, Priscilla Ortiz, Barbara Nassif Rausseo, Barbara Pazdrak, Lama Elzohary, Arjun Katailiha, Amjad Talukder, Cassian Yee, Richard Eric Davis, Gregory Lizée

Faculty, Staff and Student Publications

The cytoplasmic domain of MHC class I (MHC-I) molecules contains a single, highly conserved tyrosine residue (Y320). In previous work, we found that mice expressing a Y320F-mutated form of H-2Kb had reduced capacity to generate Kb-restricted cytotoxic T lymphocyte (CTL) responses following viral infection, due at least in part to defects in endolysosomal trafficking of H-2Kb and antigen cross-presentation by dendritic cells (DCs). In this study, we investigated whether there are additional, post-presentation dependencies on Y320 for T cell priming. We engineered both human- and mouse-derived antigen-presenting cells (APCs) to express either wild-type MHC-I or variants of MHC-I containing Y320F …

Correction: Bronchoalveolar Lavage Cell Percentages As Diagnostic Markers Of Immune Checkpoint Inhibitor Pneumonitis, Mahnoor Mir, Felipe Soto, Pedro Antonio Amezcua Gomez, Rodrigo Del Rio Arroyo, Adarsh Suresh, Amber Su, Qiong Gan, John Stewart, Roberto Adachi, Diwakar D Balachandran, Lara Bashoura, Roberto F Casal, Burton F Dickey, George A Eapen, Scott E Evans, Horiana Grosu, Carlos A Jimenez, Julie Lin, David E Ost, Bruce F Sabath, Vickie R Shannon, Aung Naing, Jianjun Gao, Jia Wu, Karthik Suresh, Saadia A Faiz, Mehmet Altan, Ajay Sheshadri

Faculty, Staff and Student Publications

[This corrects the article DOI: 10.3389/fmed.2025.1582714.].

Effect Of Digital Health Coaching On Self-Efficacy And Patient-Reported Outcomes In Individuals With Acute Myeloid And Chronic Lymphocytic Leukemia: A Pilot Randomized Controlled Trial, Jennifer Marvin-Peek, Valerie Shelton, Kelly Brassil, Bryan Fellman, Austin Barr, Kelly Sharon Chien, Danielle Hammond, Mahesh Swaminathan, Nitin Jain, William Wierda, Alessandra Ferrajoli, Courtney Dinardo

Faculty, Staff and Student Publications

Introduction: Promotion of self-efficacy can enhance engagement with health care and treatment adherence in patients with cancer. We report the outcomes of a pilot trial of a digital health coach intervention in patients with leukemia with the aim of improving self-efficacy.

Methods: Adult patients with newly diagnosed acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) were randomized 1:1 to a digital health coach intervention or standard of care. The primary outcome of self-efficacy was measured by the Cancer Behavior Inventory (CBI) score.

Results: A total of 147 patients (37 AML, 110 CLL) were enrolled from July 2020 to December …

A Prospective Cohort Study On Stereotactic Radiotherapy In The Management Of Dural Recurrence Of Olfactory Neuroblastoma, Christopher D Goodman, Franco Demonte, Theresa P Nguyen, Adam S Garden, Catherine He Wang, Xin A Wang, Kevin Diao, Anna Lee, Jay Reddy, Amy Moreno, Michael Spiotto, Clifton D Fuller, David Rosenthal, Renata Ferrarotto, Shaan M Raza, Shirley Y Su, Andrew Warner, Ehab Hanna, Jack Phan

Faculty, Staff and Student Publications

Background: Treatment for dural recurrence of olfactory neuroblastoma (ONB) is not standardized. We assess the outcomes of stereotactic body radiotherapy (SBRT) in this population.

Methods: ONB patients with dural recurrences treated between 2013 and 2022 on a prospective registry were included. Tumor control, survival, and patient-reported quality of life were analyzed.

Results: Fourteen patients with 32 dural lesions were evaluated. Time to dural recurrence was 58.3 months. Thirty lesions (94%) were treated with SBRT to a median dose of 27 Gy in three fractions. Two patients (3 of 32 lesions; 9%) developed in-field radiographic progression, five patients (38%) experienced progression …

Keygan: Synthetic Keystroke Data Generation In The Context Of Digital Phenotyping, Alejandro Acien, Aythami Morales, Luca Giancardo, Ruben Vera-Rodriguez, Ashley A Holmes, Julian Fierrez, Teresa Arroyo-Gallego

Faculty, Staff and Student Publications

Objective: This paper aims to introduce and assess KeyGAN, a generative modeling-based keystroke data synthesizer. The synthesizer is designed to generate realistic synthetic keystroke data capturing the nuances of fine motor control and cognitive processes that govern finger-keyboard kinematics, thereby paving the way to support biomarker development for psychomotor impairment due to neurodegeneration.

Methods: KeyGAN is designed with two primary objectives: (i) to ensure high realism in the synthetic distributions of the keystroke features and (ii) to analyze its ability to replicate the subtleties of natural typing for enhancing biomarker development. The quality of synthetic keystroke data produced by KeyGAN …

Comparison Of Primary Care Experiences And Outpatient Health Service Utilization Among Black And Latino Homeless-Experienced Veterans: An Analysis Of Patient-Centered Medical Homes, Melissa Chinchilla, Audrey L Jones, Aerin Derussy, Michael F Green, Lillian Gelberg, Alexander S Young, Jack Tsai, Sonya E Gabrielian, Stefan G Kertesz

Faculty, Staff and Student Publications

Objectives: To examine whether, among persons with recent homeless experience, minoritized clients rate primary care differently from non-minoritized clients in Veterans Affairs (VA) mainstream and homeless tailored clinics, through the largest survey of homeless-experienced Black, White, and Latino Veterans to date.

Methods: Surveys were collected from HEVs in Homeless-tailored Patient-Aligned Care Teams (HPACTs) and mainstream Patient Aligned Care Teams (PACTs; n = 4894). We tested multivariable associations between race/ethnicity, clinic (HPACT vs mainstream-PACT), and their interaction, on care experience ratings and service utilization.

Results: There were no major differences in care ratings by race/ethnicity; medical and social vulnerability factors were …

Racial And Ethnic Disparities In Longitudinal Trajectories Of Cardiovascular Risk Factors In Us Middle-Aged And Older Adults, Matthew E Dupre, Radha Dhingra, Hanzhang Xu, Scott M Lynch, Qing Yang, Cassie Ford, Michael D Green, Ying Xian, Ann Marie Navar, Eric D Peterson

Faculty, Staff and Student Publications

Background: Racial and ethnic disparities in cardiovascular disease (CVD) risk factors are well-documented. However, racial and ethnic differences in the longitudinal changes among multiple CVD risk factors are unknown.

Methods: We used prospective cohort data of U.S. adults aged ≥50 in the 2006-2016 Health and Retirement Study. Group-based multi-trajectory models characterized age-related trajectories of systolic blood pressure ([BP] mmHg), non-HDL cholesterol (mg/dL), diabetes mellitus (DM), and smoking. Racial and ethnic differences in the multi-trajectory profiles were examined using multinomial logistic regression. Karlson-Holm-Breen methods were used to assess factors contributing to these associations.

Results: Among 10,292 participants (median age: 61), approximately …

Refining Breast Cancer Genetic Risk And Biology Through Multi-Ancestry Fine-Mapping Analyses Of 192 Risk Regions, Guochong Jia, Zhishan Chen, Jie Ping, Qiuyin Cai, Ran Tao, Chao Li, Joshua A Bauer, Yuhan Xie, Stefan Ambs, Mollie E Barnard, Yu Chen, Ji-Yeob Choi, Yu-Tang Gao, Montserrat Garcia-Closas, Jian Gu, Jennifer J Hu, Motoki Iwasaki, Esther M John, Sun-Seog Kweon, Christopher I Li, Koichi Matsuda, Keitaro Matsuo, Katherine L Nathanson, Barbara Nemesure, Olufunmilayo I Olopade, Tuya Pal, Sue K Park, Boyoung Park, Michael F Press, Maureen Sanderson, Dale P Sandler, Chen-Yang Shen, Melissa A Troester, Song Yao, Ying Zheng, Thomas Ahearn, Abenaa M Brewster, Adeyinka Falusi, Anselm J M Hennis, Hidemi Ito, Michiaki Kubo, Eun-Sook Lee, Timothy Makumbi, Paul Ndom, Dong-Young Noh, Katie M O'Brien, Oladosu Ojengbede, Andrew F Olshan, Min-Ho Park, Sonya Reid, Taiki Yamaji, Gary Zirpoli, Ebonee N Butler, Maosheng Huang, Siew-Kee Low, John Obafunwa, Clarice R Weinberg, Haoyu Zhang, Hongyu Zhao, Michelle L Cote, Christine B Ambrosone, Dezheng Huo, Bingshan Li, Daehee Kang, Julie R Palmer, Xiao-Ou Shu, Christopher A Haiman, Xingyi Guo, Jirong Long, Wei Zheng

Faculty, Staff and Student Publications

Genome-wide association studies have identified approximately 200 genetic risk loci for breast cancer, but the causal variants and target genes are mostly unknown. We sought to fine-map all known breast cancer risk loci using genome-wide association study data from 172,737 female breast cancer cases and 242,009 controls of African, Asian and European ancestry. We identified 332 independent association signals for breast cancer risk, including 131 signals not reported previously, and for 50 of them, we narrowed the credible causal variants down to a single variant. Analyses integrating functional genomics data identified 195 putative susceptibility genes, enriched in PI3K/AKT, TNF/NF-κB, p53 …

Empathy Unmasked: Patient Perception Of Physician Empathy In An Oncologic Emergency Setting A Randomized Controlled Trial Comparing Personal Protective Equipment Wear Versus Unmasked Video Communication, Kathryn J Burk, John J Stroh, Kelly Larkin, Patrick Chaftari, Denise M Langabeer, Jazmin R Menendez, Jeanie F Woodruff, Jan Hargrave, Hongxu Zhu, James P Long, Sai-Ching J Yeung, Kumar Alagappan, Aiham Qdaisat

Faculty, Staff and Student Publications

Background: Amidst the COVID-19 pandemic, telemedicine emerged as an important option that supports and facilitates clinical practice, however, its usefulness in emergency settings that treat patients with cancer is unclear.

Objective: To evaluate patient perception of physician empathy in an emergency oncology setting, comparing video interaction to an in-person with personal protective equipment (PPE) approach.

Methods: In this single-center, prospective, cross-sectional, survey-based randomized controlled trial, patients were randomized 1:1 for the concluding conversation done in-person which included either interacting with physicians wearing PPE or video interaction with physicians without PPE (virtual). Patients' perceptions of the physicians' relational empathy were assessed …

Plain Language Summary: An Analysis Of The Safety Of Futibatinib Treatment In People With Different Types Of Cancer, Funda Meric-Bernstam, Antoine Hollebecque, Junji Furuse, Do-Youn Oh, John A Bridgewater, Bailey Anderson, Nanae Hangai, Volker Wacheck, Lipika Goyal

Faculty, Staff and Student Publications

What is this summary about?: Researchers combined information from three separate phase 1 and 2 clinical trials, including over 400 people who had one of 33 different cancer types and who all received futibatinib in their clinical trial. This type of study is called a pooled analysis. Futibatinib is taken orally (by mouth) as a tablet and works by reducing the activity of a group of proteins called fibroblast growth factor receptors (FGFRs). FGFRs drive the growth of some cancers, especially cancer cells with changes in FGFR genes that make the proteins more active. Researchers wanted to look at how …

Dose Planning And Radiation Optimization For Thoracic Conventional, Twice Daily, And Stereotactic Radiation Therapy: A Delphi Consensus From A National Survey Of Practitioners, Julius Weng, Jeff Ryckman, Matthew S Katz, Hina Saeed, Christopher Estes, Issam El Naqa, Amy Moreno, Sue S Yom

Faculty, Staff and Student Publications

Purpose: We sent surveys to a large number of radiation oncologists with active thoracic cancer practices and applied the Delphi method over 3 rounds to generate consensus dose-volume histogram metrics. We used these results to create consensus-based organs-at-risk dose constraints and target goal templates for practical implementation.

Methods and materials: In this institutional review board-approved study, data were collected using REDCap electronic data capture on a secure server. Radiation oncologists identified from the Accreditation Council for Graduate Medical Education-accredited departments' websites were asked to confirm their self-identification as thoracic radiation oncologists and nominate other respondents. All invitees were asked to …

Isatuximab For The Treatment Of Multiple Myeloma: Current Clinical Advances And Future Directions, Paul G Richardson, Elisabeth K O'Donnell, Peter O'Gorman, Lisa B Leypoldt, Jacob Laubach, Francesca Gay, Xavier Leleu, Thierry Facon, Philippe Moreau, Meletios A Dimopoulos, Hartmut Goldschmidt, Elias K Mai, Michele Cavo, Katja C Weisel, Jesus G Berdeja, Robert Z Orlowski, Meral Beksaç, Aurore Perrot, Joseph Mikhael, Thomas Martin

Faculty, Staff and Student Publications

Introduction: The addition of the anti-CD38 monoclonal antibody isatuximab to standard therapies is transforming the care of patients with newly diagnosed multiple myeloma (NDMM), as previously seen in the relapsed/refractory setting. This is particularly important for patients with NDMM as early treatment with effective, well tolerated therapies may ensure better clinical outcomes.

Areas covered: Here, we examine recent results from pivotal Phase 3 and 2 clinical trials that demonstrate efficacy and safety of isatuximab across multiple combinations, for both transplant-ineligible and transplant-eligible NDMM patients. We then evaluate long-term outcomes from the IKEMA and ICARIA-MM trials as well as real-world evidence …

The Role Of Speech And Language Therapists (Slts) In International Stroke Teams: A Systematic Review, Marina Charalambous, John E Pierce, Georgia Pastou, Erasmia Kola, Sean I Savitz

Faculty, Staff and Student Publications

Background: Current published guidelines suggest that speech and language therapists (SLTs) should be part of stroke teams, but their involvement and roles according to country income are unknown.

Aims: This review aims to (1) investigate the level of involvement of SLTs in acute stroke management, rehabilitation, and long-term care, and (2) examine whether the roles and contributions of SLTs in stroke care vary according to a country's income level.

Methods: A systematic review methodology was conducted by an expert librarian and three independent researchers based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This systematic review …

Geographic Disparities In Access To Outpatient Stroke Rehabilitation In Texas, Joseph Wozny, Melissa Howard, Susan Doherty, Yenan Zhu, Kalyani Sonawane, Dorothea Parker, Lisa W Thomas, Bukola Azeez, Ndi Chukwumerije, Susan Varghese, Nicholas Hoang, Suja S Rajan, Charles Green, Vahed Maroufy, Trudy Millard Krause, Sean I Savitz

Faculty, Staff and Student Publications

Background: Outpatient rehabilitation plays a vital role in providing post-discharge care for stroke survivors' optimum recovery. Geographic variability in access to post-stroke rehabilitation care in rural areas is poorly understood.

Methods: This study used Medicare claims from 2016 to 2019 to estimate incidence of stroke discharges home and compared rehabilitation utilization rates after discharge from acute hospitalization in the state of Texas. We also examined spatial accessibility to post-discharge outpatient rehabilitation centers between rural and urban areas. We supplemented claims results with a survey to better understand locations where outpatient rehabilitation clinics provided services to stroke patients.

Results: After discharge …

Serum Metabolome Profiling In Patients With Mild Cognitive Impairment Reveals Sex Differences In Lipid Metabolism, Rocio Diaz Escarcega, Vijay Kumar M J, Vasilia E Kyriakopoulos, Guadalupe J Ortiz, Aaron M Gusdon, Huihui Fan, Pedram Peesh, Maria P Blasco Conesa, Gabriela Delevati Colpo, Hilda W Ahnstedt, Lucy Couture, Stella H Kim, Miriam Hinojosa, Christine M Farrell, Sean P Marrelli, Akihiko Urayama, Bhanu P Ganesh, Paul E Schulz, Louise D Mccullough, Andrey S Tsvetkov

Faculty, Staff and Student Publications

Alzheimer's disease (AD) affects more women than men. Although women live longer than men, it is not longevity alone, but other factors, including metabolic changes, that contribute to the higher risk of AD in women. Metabolic pathways have been implicated in AD progression, but studies to date examined targeted pathways, leaving many metabolites unmeasured. Sex is often a neglected biological variable, and most metabolomic studies were not designed to investigate sex differences in metabolomic profiles. Here, we performed untargeted metabolomic profiling of sera from male and female patients with mild cognitive impairment (MCI), a common precursor to AD, and matched …

Novel Use And Value Of Contrast-Enhanced Susceptibility-Weighted Imaging Morphologic And Radiomic Features In Predicting Extremity Soft Tissue Undifferentiated Pleomorphic Sarcoma Treatment Response, Raul F Valenzuela, Elvis De Jesus Duran Sierra, Mathew A Canjirathinkal, Behrang Amini, Ken-Pin Hwang, Jingfei Ma, Keila E Torres, R Jason Stafford, Wei-Lien Wang, Robert S Benjamin, Andrew J Bishop, John E Madewell, William A Murphy, Colleen M Costelloe

Faculty, Staff and Student Publications

Purpose: Undifferentiated pleomorphic sarcomas (UPSs) demonstrate therapy-induced hemosiderin deposition, granulation tissue formation, fibrosis, and calcification. We aimed to determine the treatment-assessment value of morphologic tumoral hemorrhage patterns and first- and high-order radiomic features extracted from contrast-enhanced susceptibility-weighted imaging (CE-SWI).

Materials and methods: This retrospective institutional review board-authorized study included 33 patients with extremity UPS with magnetic resonance imaging and resection performed from February 2021 to May 2023. Volumetric tumor segmentation was obtained at baseline, postsystemic chemotherapy (PC), and postradiation therapy (PRT). The pathology-assessed treatment effect (PATE) in surgical specimens separated patients into responders (R; ≥90%, n = 16), partial responders …

The Impact Of A Small-Group Mammography Video Discussion On Promoting Screening Uptake Among Nonadherent Chinese American Immigrant Women: A Randomized Controlled Trial, Naomi Q P Tan, Grace X Ma, Annette E Maxwell, Roger L Brown, Kathy Zhou, Alice Loh, Lucy Young, Robert J Volk, Qian Lu, Judy Huei-Yu Wang

Faculty, Staff and Student Publications

Background: The objective of this study was to evaluate the efficacy of an in-person, small-group mammography video discussion (SMVD) intervention on mammography uptake among nonadherent Chinese American immigrant women.

Methods: Women (N = 956) were randomized into either an SMVD group, where Chinese-speaking community health workers (CHWs) used an effective, culturally appropriate video to discuss mammography, or a video-only group, which viewed the cultural video sent by mail. Outcomes were mammography uptake at 6 months and 21 months postintervention.

Results: Women in both groups increased mammography uptake, and an outcome analysis revealed no group differences (adjusted odds ratio [AOR], 1.18; …

Development Of An H&E On-Block Staining Technique For Collagen Detection In Cryo-Fluorescence Tomography Imaging Of Frozen Breast Tissue Samples, Erin P Snoddy, Tien T Tang, Natalie Fowlkes, Thomas Huynh, Kari J Brewer Savannah, Alejandro Contreras, Gregory Reece, Kristy K Brock

Faculty, Staff and Student Publications

Hematoxylin and eosin (H&E) staining is widely considered to be the gold-standard diagnostic tool for histopathology evaluation. However, the fatty nature of some tissue types, such as breast tissue, presents challenges with cryo-sectioning, often resulting in artifacts that can make histopathologic interpretation and correlation with other imaging modalities virtually impossible. We present an optimized on-block H&E staining technique that improves contrast for identifying collagenous stroma during cryo-fluorescence tomography (CFT) sectioning. In this prospective study, we embedded four breast specimens with confirmed ligaments from a bilateral mastopexy in an optimal cutting temperature block. Two of the samples were processed on a …

Knowledge-Based Planning For Fully Automated Radiation Therapy Treatment Planning Of 10 Different Cancer Sites, Christine V Chung, Meena S Khan, Adenike Olanrewaju, Mary Pham, Quyen T Nguyen, Tina Patel, Prajnan Das, Michael S O'Reilly, Valerie K Reed, Anuja Jhingran, Hannah Simonds, Ethan B Ludmir, Karen E Hoffman, Komeela Naidoo, Jeannette Parkes, Ajay Aggarwal, Lauren L Mayo, Shalin J Shah, Chad Tang, Beth M Beadle, Julie Wetter, Gary Walker, Simon Hughes, Vinod Mullassery, Stephen Skett, Christopher Thomas, Lifei Zhang, Son Nguyen, Raymond P Mumme, Raphael J Douglas, Hana Baroudi, Laurence E Court

Faculty, Staff and Student Publications

Purpose: Radiation treatment planning is highly complex and can have significant inter- and intra-planner inconsistency, as well as variability in planning time and plan quality. Knowledge-based planning (KBP) is a tool that can be used to efficiently produce high-quality, consistent, clinically acceptable plans, independent of planner skills and experience. In this study, we created and validated multiple clinically acceptable and fully automatable KBP models, with the goal of creating VMAT plans without user intervention.

Methods: Ten KBP models were configured using high quality clinical plans from a single institution. They were then honed to be part of a fully automatable …

Tissue And Imaging Biomarkers Of Response To Neoadjuvant Nivolumab Or Nivolumab Plus Ipilimumab In Patients With Resectable Hepatocellular Carcinoma, Michael Lapelusa, Shadi Chamseddine, Hop Sanderson Tran Cao, Lianchun Xiao, Elshad Hasanov, Priya Bhosale, Hesham M Amin, Yehia I Mohamed, Betul Gok Yavuz, Yara Sakr, Li Xu, Ian Hu, Sunyoung S Lee, Divya Sakamuri, Sonali Jindal, Van Nguyen, Michael A Curran, Ryan Sun, Asif Rashid, Dan Gabriel Duda, Padmanee Sharma, Aliya Qayyum, Ahmed Omar Kaseb

Faculty, Staff and Student Publications

Introduction: Perioperative immunotherapy has shown promise in some patients with early-stage hepatocellular carcinoma (HCC). This study examined tissue and imaging biomarkers associated with pathologic response in a phase II clinical trial in patients with resectable HCC.

Methods: Analysis included 18 patients with biopsy-proven resectable HCC treated with neoadjuvant nivolumab plus ipilimumab or nivolumab alone in a phase II clinical trial at MD Anderson Cancer Center (NCT03222076). Liver MRE (to measure tissue fibrosis) and biopsies (to evaluate immune activation markers) were obtained serially pretreatment and after completing neoadjuvant immunotherapy. A major pathologic response (MPR) was defined as tumor necrosis …

Characterizing Spatial Immune Architecture In Metastatic Melanoma Using High-Dimensional Multiplex Imaging, Joel Eliason, Santhoshi Krishnan, Yasunari Fukuda, Matias A Bustos, Dan Winkowski, Sungnam Cho, Akshay Basi, Regan Baird, Elizabeth A Grimm, Michael A Davies, Dave S B Hoon, Arvind Rao, Jared K Burks, Suhendan Ekmekcioglu

Faculty, Staff and Student Publications

Introduction: Immune checkpoint inhibitors (ICIs) have significantly improved survival for patients with metastatic melanoma, yet many experienceresistance due to immunosuppressive mechanisms within the tumor immune microenvironment (TIME). Understanding how the spatial architecture of immune and inflammatory components changes across disease stages may reveal novel prognostic biomarkers and therapeutic targets.

Methods: We performed high-dimensional spatial profiling of two melanoma tissue microarrays (TMAs), representing Stage III (n = 157) and Stage IV (n = 248) metastatic tumors. Using imaging mass cytometry (IMC) and multiplex immunofluorescence (mIF), we characterized the phenotypic, functional, and spatial properties of the TIME. Cellular neighborhoods were …

Case Report: Durable Remission After Abscopal Effect Following Transcatheter Hepatic Arterial Embolization In A Patient With Mucosal Melanoma Refractory To Immunotherapy, Lynsey M Claus, Hannah E Kostan, Marshall E Hicks, Rony Avritscher, Michael A Davies

Faculty, Staff and Student Publications

Mucosal melanoma, a rare subtype of melanoma affecting mucosal surfaces, presents significant challenges in diagnosis and treatment, particularly due to its low programmed death-ligand 1 (PD-L1) expression and reduced response to immune checkpoint inhibitors (ICIs). This case report describes a 58-year-old woman with metastatic nasal mucosal melanoma initially resistant to neoadjuvant ipilimumab and nivolumab. After undergoing hepatic transcatheter arterial embolization, she experienced an unexpected abscopal effect, where distant metastases showed near-complete resolution despite prior lack of response to immunotherapy. The patient's disease initially progressed despite two cycles of ICI treatment, and further immunotherapy with nivolumab and relatimab did not improve …

Meeting Highlights The 4th Marie Skłodowska-Curie Symposium On Cancer Research And Care: Mechanisms Of Support For Regional & International Collaborations, Pawel Kalinski, Kathleen M Kokolus, Indu Ahluwalia, Mihaela Balu, Łukasz Balwicki, Brygida Baran, Loretta Beine, Mikhail Berezin, Ioana Berindan-Neagoe, Andriy Beznosenko, Blanka Borowiec, Szabolcs Bozsányi, Jonathan Bramson, Brian Czerniecki, Rūta Everatt, Wojciech Fendler, Peter Forsyth, Jeffrey E Gershenwald, Maciej Goniewicz, Khurshid Guru, Andrew Hyland, Smitha James, Iva Kirac, Pawel Koczkodaj, Leszek Kotula, Maciej Łuba, Iwona Ługowska, Elizabeth Luke, Cristian Lungulescu, Sandro Matosevic, Kaushal Nanavati, Michael Nemeth, Karolina Nowak, Katia Noyes, Mark Parascandola, Waldemar Priebe, Piotr Rutkowski, Mukund Seshadri, Christine E Sheffer, Ioana-Miruna Stanciu, Joanna Stanson, Telisa Stewart, Edita Sužiedėlienė, Kęstutis Sužiedėlis, Iryna Tanasiichuk, Anda M Vlad, Wei-Zen Wei, Dylan Williams, Malgorzata Wojtowicz, Tomasz Zdrojewski

Faculty, Staff and Student Publications

The Marie Skłodowska-Curie Symposia on Cancer Research and Care (MSCS-CRC) promote collaborations between cancer researchers and care providers in the United States, Canada and Central and Eastern European Countries (CEEC) to accelerate the development of new cancer therapies, new strategies for early detection and prevention, and improve cancer care and the quality of life for patients and their families. The 4th MSCS-CRC (September 25-27, 2024, Buffalo, New York) brought together 147 participants from the US, Canada, Croatia, Czechia, Lithuania, Poland, Romania and Ukraine, and involved representatives of the US Centers for Disease Control and Prevention (CDC), National Cancer Institute (NCI) …

Comparison Of Deep Learning Schemes In Grading Non-Alcoholic Fatty Liver Disease Using B-Mode Ultrasound Hepatorenal Window Images With Liver Biopsy As The Gold Standard, Petros Drazinos, Ilias Gatos, Paraskevi F Katsakiori, Stavros Tsantis, Efstratios Syrmas, Stavros Spiliopoulos, Dimitris Karnabatidis, Ioannis Theotokas, Pavlos Zoumpoulis, John D Hazle, George C Kagadis

Faculty, Staff and Student Publications

Background/introduction: To evaluate the performance of pre-trained deep learning schemes (DLS) in hepatic steatosis (HS) grading of Non-Alcoholic Fatty Liver Disease (NAFLD) patients, using as input B-mode US images containing right kidney (RK) cortex and liver parenchyma (LP) areas indicated by an expert radiologist.

Methods: A total of 112 consecutively enrolled, biopsy-validated NAFLD patients underwent a regular abdominal B-mode US examination. For each patient, a radiologist obtained a B-mode US image containing RK cortex and LP and marked a point between the RK and LP, around which a window was automatically cropped. The cropped image dataset was augmented using up-sampling, …

Safety And Activity Of Ctx130, A Cd70-Targeted Allogeneic Crispr-Cas9-Engineered Car T-Cell Therapy, In Patients With Relapsed Or Refractory T-Cell Malignancies (Cobalt-Lym): A Single-Arm, Open-Label, Phase 1, Dose-Escalation Study, Swaminathan P Iyer, R Alejandro Sica, P Joy Ho, Anca Prica, Jasmine Zain, Francine M Foss, Boyu Hu, Amer Beitinjaneh, Wen-Kai Weng, Youn H Kim, Michael S Khodadoust, Auris O Huen, Leah M Williams, Anna Ma, Elaine Huang, Avanti Ganpule, Shashwat Deepali Nagar, Parin Sripakdeevong, Erika L Cullingford, Sushant Karnik, Mary-Lee Dequeant, Janki N Patel, Xinyi Shirley He, Ziliang Li, Qiuling Ally He, Joy H Mendonez, Alissa Keegan, Steven M Horwitz

Faculty, Staff and Student Publications

Background: Effective treatment options are scarce for relapsed or refractory T-cell lymphoma. This study assesses the safety and activity of CTX130 (volamcabtagene durzigedleucel), a CD70-directed, allogeneic chimeric antigen receptor (CAR) immunotherapy manufactured from healthy donor T cells, in patients with relapsed or refractory T-cell lymphoma.

Methods: This single-arm, open-label, phase 1 study was done at ten medical centres across the USA, Australia, and Canada in patients (aged ≥18 years) with relapsed or refractory peripheral T-cell lymphoma or cutaneous T-cell lymphoma, who had received at least one or at least two previous systemic therapy lines, respectively, and had an Eastern Cooperative …

Cord Blood-Derived Ink T Cells As A Platform For Allogeneic Car T Cell Therapy, Maison Grefe, Abel Trujillo-Ocampo, Jelita Clinton, Hong He, Ling Yu, Dan Li, Qing Ma, Elizabeth J Shpall, Jeffrey J Molldrem, Jin S Im

Faculty, Staff and Student Publications

CD1d-restricted invariant Natural Killer (iNK) T cells are a suitable candidate for allogeneic Chimeric Antigen Receptor (CAR) T cell therapy as they do not cause graft-versus-host disease (GvHD) due to the monomorphic nature of CD1d proteins. However, the phenotypic and functional heterogeneity of iNK T cells from adult donors (AD) may lead to the inconstant CAR-iNK T cell products. Cord blood-derived (CB) iNK T cells, in contrast, exhibit inter-donor homogeneity in phenotype including uniform CD4 expression and are enriched in memory iNK T cell populations. Thus, we evaluated the preclinical therapeutic potential of iNK T cells derived from cord blood …

Weighted Hypoxemia Index: An Adaptable Method For Quantifying Hypoxemia Severity, Diane C Lim, Cheng-Bang Chen, Ankita Paul, Yujie Wang, Jinyoung Kim, Soonhyun Yook, Emily Y Kim, Edison Q Kim, Anup Das, Medhi Wangpaichitr, Virend K Somers, Chi Hang Lee, Phyllis C Zee, Toshihiro Imamura, Hosung Kim

Faculty, Staff and Student Publications

Objective: To quantitate hypoxemia severity.

Methods: We developed the Weighted Hypoxemia Index to be adapted to different clinical settings by applying 5 steps to the oxygen saturation curve: (1) Identify desaturation/resaturation event [Formula: see text] by setting the upper threshold; (2) Exclude events as artifact by setting a lower threshold; (3) Calculate weighted area for each [Formula: see text] as [Formula: see text]; (4) Calculate a normalization factor [Formula: see text] for each subject; (5) Calculate the Weighted Hypoxemia Index as the summation of all weighted areas multiplied by [Formula: see text]. We assessed the Weighted Hypoxemia Index predictive value …

Stat3 Inhibition In Combination With Cd47 Blockade Inhibits Osteosarcoma Lung Metastasis, Pradeep Shrestha, Rejeena Shrestha, You Zhou, Rafal Zielinski, Waldemar Priebe, Eugenie S Kleinerman

Faculty, Staff and Student Publications

Background: New therapies are urgently needed for patients with osteosarcoma (OS). STAT3 and CD47 are potential therapeutic target in OS. Here we investigated the therapeutic activity of the orally bioavailable STAT3 inhibitor, WP1066, and anti-CD47 antibody using OS mouse models.

Methods: Cytotoxic effect of WP1066 against OS cell lines and its immunomodulatory effects were evaluated in vitro. Experimental metastasis and orthotopic syngeneic mouse models were used to investigate the therapeutic efficacy of WP1066 and anti-CD47 antibody. Further flow cytometric analysis was performed.

Results: STAT3 was constitutively activated in multiple human and mouse OS cell lines. WP1066 suppressed STAT3 activation …

Predicting Sinonasal Inverted Papilloma Attachment Using Machine Learning: Current Lessons And Future Directions, Sean P Mckee, Xiaomin Liang, William C Yao, Brady Anderson, Jumah G Ahmad, David Z Allen, Salman Hasan, Andy J Chua, Chinmay Mokashi, Samia Islam, Amber U Luong, Martin J Citardi, Luca Giancardo

Faculty, Staff and Student Publications

Background: Hyperostosis is a common radiographic feature of inverted papilloma (IP) tumor origin on computed tomography (CT). Herein, we developed a machine learning (ML) model capable of analyzing CT images and identifying IP attachment sites.

Methods: A retrospective review of patients treated for IP at our institution was performed. The tumor attachment site was manually segmented on CT scans by the operating surgeon. We used a nnU-Net model, a state-of-the-art deep learning-based segmentation algorithm that automatically configures image preprocessing, network architecture, training, and post-processing to identify the IP attachment site. The model was trained and evaluated using a 5-fold cross …