Digital Commons Network^™

Automated Mycoplasma Genitalium Molecular Macrolide Resistance Detection And Nucleic Acid Target Semi-Quantitation: Patient Demographic Considerations, Josephine Moore, Trinity Krueger, Amanda Zapp, Stephen C Lavey, Kimber L Munson, Irene A Stafford, Michael E Newcomb, Brian Mustanski, Erik Munson

Faculty, Staff and Student Publications

Recent work has optimized parameters of a real-time reverse transcriptase PCR-based laboratory-developed test on the Panther Fusion system which detects Mycoplasma genitalium-specific macrolide resistance-associated mutations LDT (MRM-LDT) from primary swab and urine specimens. In this study, MRM-LDT was applied to a large multi-demographic study set to further characterize M. genitalium resistance in the United States. A total of 2,145 primary clinical specimens testing positive for M. genitalium 16S rRNA by transcription-mediated amplification (TMA) were initially titered by the same assay using serial 10-fold dilutions to determine relative target nucleic acid burden. Specimens were then processed for MRM-LDT. Findings were stratified …

Long-Term Exposure To Multiple Air Pollutants And Multi-Level Socioeconomic Status: Joint Effects On Age-Related Macular Degeneration, Subsequent Ocular Comorbidity, And Death In Middle-Aged And Older Adults, Yang Yang, Liangkai Chen, Qichen Liu, Min Mu, Jing Huang, Guangming Zhang, Qianqian Song

Faculty, Staff and Student Publications

Background: Both air pollution and socioeconomic status (SES) are recognized as significant determinants of health outcomes. However, no study has explored the combined effects of air pollutants and SES on (1) age-related macular degeneration (AMD) incidence; (2) trajectories from baseline to AMD, subsequent ocular comorbidity (OCMD), and mortality; and (3) life expectancy in middle-aged and older adults.

Methods: Using UK Biobank data, we created two composite air pollution scores (APS) and assessed SES at individual and neighborhood levels. OCMD was defined as glaucoma or cataract occurrence after AMD diagnosis. Cox proportional hazard regression models, multistate models, and life tables were …

Gut Virome Profile In New Onset Treatment Naïve Saudi Children With Ulcerative Colitis, Mohammad El Mouzan, Tor C Savidge, Ahmed Al Sarkhy, Shyam Badu, Badr Alsaleem, Mohammad Al Mofarreh, Abdullah Almasood, Asaad Assiri

Faculty, Staff and Students Publications

Background: Gut microbiome imbalance is well established in ulcerative colitis (UC) in Western populations. Significantly less is known about the gut virome and whether geography impacts the UC-associated microbiome. The aim of this study was to characterize gut bacteriophage changes, as well as to identify phage-bacterial associations that can serve as potential biomarkers of UC.

Methods: Twenty children with UC and 20 healthy controls were enrolled in the study. Inclusion criteria included newly diagnosed treatment-naïve children with UC with no antibiotic exposure for at least six months prior to sample collection. Deoxyribonucleic acid (DNA) was extracted from stool and rectal …

Involved But Not Essential: Cognitive Activity In Periventricular Nodules And Neuropsychological Outcomes Following Their Ablation, Yosefa A Modiano, Oscar Woolnough, Ryan M Mccormack, Kathryn Snyder, Ellery Wheeler, Samden D Lhatoo, Nuria Lacuey, Sandipan Pati, Katherine Harris, Jay Gavvala, Jessica A Johnson, Nitin Tandon

Faculty, Staff and Student Publications

Objective: Periventricular nodular heterotopia (PVNH) is a malformation of cortical development with high rates of epilepsy. The extent to which nodules participate in normal cerebral functions in addition to pathological processes is unclear. The authors assessed the functional utility (i.e., cognitive impacts) of surgically ablated epileptogenic PVNH tissue via comprehensive neuropsychological testing.

Methods: The sample included 32 patients with PVNH who underwent presurgical neuropsychological evaluation and a subsample of 16 patients who underwent MR-guided laser interstitial thermal therapy (MRgLITT) of nodules, with postsurgical neuropsychological testing. In 11 patients in whom intracranial recordings were performed, reading and naming tasks were tested …

Chronic Pain Is Associated With Greater Brain Entropy In The Prefrontal Cortex, Gianpaolo Del Mauro, Yiran Li, Jiaao Yu, Peter Kochunov, Landrew Samuel Sevel, Jeff Boissoneault, Shuo Chen, Ze Wang

Faculty, Staff and Student Publications

Chronic pain is a debilitating clinical condition and a severe public health issue that demands to be addressed. Neuroimaging-based techniques have been widely adopted to investigate the neural underpinnings of chronic pain. Despite the efforts the complex nature of pain experience as well as the heterogeneity of chronic pain have made the identification of neuroimaging-based biomarkers extremely challenging. In this study, resting-state fMRI-based brain entropy, a measure reflecting the "irregularity" of brain activity, was adopted as a biomarker of chronic pain by comparing individuals with chronic pain and healthy controls in a sample of middle-to-old-age participants (n > 30,000) drawn from …

Assessment Of Complement Cascade Components In Patients With Major Depressive Disorder, Brandi Quintanilla, Dede Greenstein, Ashutosh Tripathi, Alona Bartosh, Peixiong Yuan, Carlos A Zarate, Anilkumar Pillai

Faculty, Staff and Student Publications

Recent evidence suggests that the rapid-acting antidepressant ketamine has immune regulatory functions. The complement system is an important component of the innate immune response and plays a key role in synaptic plasticity. An increase in complement component 3 (C3) expression was previously found in the prefrontal cortex of individuals with depression. Given the complement system's role in depression and ketamine's potential anti-inflammatory properties, there is reason to suspect overlap between the complement system and ketamine's mechanism of action. This post-hoc study analyzed data from 39 individuals with major depressive disorder (MDD) and 25 healthy volunteers who previously participated in a …

Interconnections Of Insulin/Igf-1 Signaling And Autophagy Abnormalities In Alzheimer’S Disease, Wang Liao, Jinfeng Xuan, Woo-In Ryu, Mariana K Bormann, Yoon Lee, Haley Dion, Elizabeth Evangelista, Ruiyi Li, Lucas Trambaiolli, Jun Liu, Arthur J Siegel, Brent P Forester, Bruce M Cohen, Kai-Christian Sonntag

Faculty, Staff and Student Publications

Introduction: Impaired insulin (INS) and insulin-like growth factor 1 (IGF-1) signaling are features of both brain aging and late-onset Alzheimer's disease (LOAD). However, their exact underlying mechanisms and cause-and-effect linkages, including the downstream regulation of endocytosis and autophagy, are still not well understood.

Methods: We investigated INS/IGF-1 signaling and its connection with endocytic and autophagic processes in fibroblasts from LOAD patients and healthy young or old control individuals.

Results: Compared to control old-age cells, protein levels in the INS/IGF-1 signaling cascade were elevated in LOAD cells, but activation of AKT was reduced. The activation of the INS/IGF-1/AKT/FOXO1 or mTOR axes …

Ovarian Cancer Risk And Survival According To Tumor Sex Hormone Receptor Expression: An Ovarian Cancer Association Consortium And Ovarian Tumor Tissue Analysis Consortium Pooled Analysis, Zhuxuan Fu, Lauren Borho, Sarah E Taylor, Linda E Kelemen, Anna Defazio, Penelope M Webb, Martin Köbel, Nicola S Meagher, Renhua Na, Antonis C Antoniou, Alison H Brand, Catherine J Kennedy, Nikilyn Nevins, Paul D P Pharoah, Yurii B Shvetsov, Stacey J Winham, Jennifer Alsop, Matthias W Beckmann, Adelyn Bolithon, Jessica Boros, David D L Bowtell, James D Brenton, Michael E Carney, Anita Chudecka-Głaz, Linda S Cook, Cezary Cybulski, Peter A Fasching, Sian Fereday, Renée T Fortner, María J García, Ellen L Goode, Marc T Goodman, Jacek Gronwald, Arndt Hartmann, Brenda Y Hernandez, Estrid Høgdall, David G Huntsman, Allan Jensen, Mercedes Jimenez-Linan, Janine M Joseph, Beth Y Karlan, Ewa Kaznowska, Susanne K Kjaer, Tomasz Kluz, Jennifer M Koziak, Jenny Lester, Teri A Longacre, Maria Lycke, Valerie Mcguire, Kirsten B Moysich, Rachel A Murphy, Sandra Orsulic, Susan J Ramus, Cristina Rodríguez-Antona, Joseph H Rothstein, Spinder Samra, Weiva Sieh, Helen Steed, Karin Sundfeldt, Aline Talhouk, Jan Uciński, Chen Wang, Nicolas Wentzensen, Alice S Whittemore, Lynne R Wilkens, Thomas Songer, Maria Mori Brooks, Lu Tang, Francesmary Modugno

Faculty, Staff and Student Publications

Objective: Many epithelial ovarian cancer (EOC) risk factors relate to sex hormones. The association between these factors and the expression of androgen receptor (AR), estrogen receptor-α (ER), and progesterone receptor (PR) in tumors is unknown.

Method: We linked epidemiologic, AR/ER/PR tumor expression, and survival data from 19 studies in the Ovarian Cancer Association Consortium (OCAC; 4762 cases, 20,888 controls) and the Ovarian Tumor Tissue Analysis (OTTA) consortium (5737 cases). We estimated odds ratios (ORs) and 95 % confidence intervals (CIs) between hormonally-linked factors and tumor AR/ER/PR expression using polytomous logistic regression. We assessed survival by AR/ER/PR tumor expression overall and …

Βiv Spectrin Abundancy, Cellular Distribution And Sensitivity To Akt/Gsk3 Regulation In Schizophrenia, Jessica Di Re, Michela Marini, Syed Ibrar Hussain, Aditya K Singh, Akshaya Venkatesh, Musaad A Alshammari, Tahani K Alshammari, Abdul-Rizaq Ali Hamoud, Ali Sajid Imami, Zahra Haghighijoo, Nickolas Fularcyzk, Laura Stertz, Derek Hawes, Angela Mosebarger, Jordan Jernigan, Claire Chaljub, Ralda Nehme, Consuelo Walss-Bass, Anton Schulmann, Marquis P Vawter, Robert Mccullumsmith, Robert D Damoiseaux, Agenor Limon, Demetrio Labate, Michael F Wells, Fernanda Laezza

Faculty, Staff and Student Publications

Schizophrenia (SCZ) is a complex psychiatric disorder with unclear biological mechanisms. Spectrins, cytoskeletal proteins linked to neurodevelopmental disorders, are regulated by the AKT/GSK3 pathway, which is implicated in SCZ. However, the impact of SCZ-related dysregulation of this pathway on spectrin expression and distribution remains unexplored. Here, we show that βIV spectrin protein levels were reduced in neurons of the dorsolateral prefrontal cortex in SCZ postmortem samples compared to healthy control (HC) from the Human Brain Collection Core (HBCC). To investigate potential links between βIV spectrin and the AKT/GSK3 pathway, we analyzed the PsychEncode dataset, revealing elevated SPTBN4 and AKT2 mRNA …

Targeting Cdk2 And Other Novel Cell Cycle Targets For Breast Cancer Therapy, Mei-Kuang Chen, Linjie Luo, Nicole Massoumi, Khandan Keyomarsi

Faculty, Staff and Student Publications

Introduction: The dysregulation of cyclin-dependent kinases (CDKs) is a key driver of cancer progression, making them attractive therapeutic targets. In CDK4/6 inhibitor (CDK4/6i)-resistant breast cancer, targeting CDK2 offers a promising approach. CDK2 is frequently hyperactivated due to cyclin E1 overexpression or retinoblastoma protein loss, acting as a mechanism that sustains proliferation despite CDK4/6 inhibition. CDK2 inhibitors (CDK2i) show strong anti-tumor activity, particularly in combination with CDK4/6i or immune checkpoint inhibitors.

Areas covered: This review explores the biological roles of CDK2 and its regulatory mechanisms. The review highlights the latest advancements in CDK2i, their mechanisms of action, and their potential in …

Long-Term Cytoreduction Outcomes With Or Without Heated Intraperitoneal Chemotherapy For Colorectal Peritoneal Metastases, Michael G White, Paula Marincola Smith, Neal Bhutiani, Beth Helmink, Norman Galbraith, Scott Kopetz, Michael Overman, Paul Mansfield, Keith Fournier, Abhineet Uppal

Faculty, Staff and Student Publications

Background: Patients with peritoneal metastases from colorectal adenocarcinoma (CRC) benefit from cytoreductive surgery (CRS). However, the role of heated intraperitoneal chemotherapy (HIPEC) remains unclear. We studied associations between HIPEC, peritoneal disease-free survival (PDFS), and overall survival (OS) in patients with CRC undergoing CRS.

Study design: All patients with CRC undergoing CRS between 2008 and 2023 were retrospectively identified at our center. Patient clinicodemographic factors were determined by chart review. OS and PDFS were evaluated using the Kaplan-Meier method. Associations between clinical factors and survival were determined using Cox proportional hazard models.

Results: A total of 147 patients were identified with …

Pathologist-Read Vs Ai-Driven Assessment Of Tumor-Infiltrating Lymphocytes In Melanoma, Thazin N Aung, Matthew Liu, David Su, Saba Shafi, Ceren Boyaci, Sanna Steen, Nikolaos Tsiknakis, Joan Martinez Vidal, Nigel Maher, Goran Micevic, Samuel X Tan, Matthew D Vesely, Saeed Nourmohammadi, Yalai Bai, Dijana Djureinovic, Pok Fai Wong, Katherine Bates, Nay N N Chan, Niki Gavirelatou, Mengni He, Sneha Burela, Robert Barna, Martina Bosic, Konstantin Bräutigam, Irineu Illabochaca, Zhou Chenhao, Joao Gama, Bianca Kreis, Reka Mohacsi, Nir Pillar, Joao Pinto, Christos Poulios, Maria Angeliki Toli, Evangelos Tzoras, Yadriel Bracero, Francesca Bosisio, Gábor Cserni, Alis Dema, Francesco Fortarezza, Mercedes Solorzano Gonzalez, Irene Gullo, Francisco Javier Queipo Gutiérrez, Ezgi Hacihasanoglu, Viktor Jovic, Bianca Lazar, Maria Olinca, Christina Neppl, Rui Caetano Oliveira, Federica Pezzuto, Daniel Gomes Pinto, Vanda Plotar, Ovidiu Pop, Tilman Rau, Kristijan Skok, Wenwen Sun, Ezgi Dicle Serbes, Wiebke Solass, Olga Stanowska, Marcell Szasz, Krzysztof Szymonski, Franziska Thimm, Danielle Vignati, Alon Vigdorovits, Victor Prieto, Tobias Sinnberg, James Wilmott, Shawn Cowper, Jonathan Warrell, Yvonne Saenger, Johan Hartman, Jasmine Plummer, Iman Osman, David L Rimm, Balazs Acs

Faculty, Staff and Student Publications

Importance: Tumor-infiltrating lymphocytes (TILs) are a provocative biomarker in melanoma, influencing diagnosis, prognosis, and immunotherapy outcomes; however, traditional pathologist-read TIL assessment on hematoxylin and eosin-stained slides is prone to interobserver variability, leading to inconsistent clinical decisions. Therefore, development of newer TIL scoring approaches that produce more reliable and consistent readouts is important.

Objective: To evaluate the analytical and clinical validity of a machine learning algorithm for TIL quantification in melanoma compared with traditional pathologist-read methods.

Design, setting, and participants: This multioperator, global, multi-institutional prognostic study compared TIL scoring reproducibility between traditional pathologist-read methods and an artificial intelligence (AI)-driven approach. The …

Adtnorm: Robust Integration Of Single-Cell Protein Measurement Across Cite-Seq Datasets, Ye Zheng, Daniel P Caron, Ju Yeong Kim, Seong-Hwan Jun, Yuan Tian, Florian Mair, Kenneth D Stuart, Peter A Sims, Raphael Gottardo

Faculty, Staff and Student Publications

Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) enables paired measurement of surface protein and mRNA expression in single cells using antibodies conjugated to oligonucleotide tags. Due to the high copy number of surface protein molecules, sequencing antibody-derived tags (ADTs) allows for robust protein detection, improving cell-type identification. However, variability in antibody staining leads to batch effects in the ADT expression, obscuring biological variation, reducing interpretability, and obstructing cross-study analyses. Here, we present ADTnorm, a normalization and integration method designed explicitly for ADT abundance. Benchmarking against 14 existing scaling and normalization methods, we show that ADTnorm accurately aligns populations …

Mutation Dynamics From Diagnosis To Relapse In Acute Myeloid Leukemia With Chromosomal 7 Deletions, Eitan Kugler, Enes Dasdemir, Alex Bataller, Bofei Wang, Courtney D Dinardo, Naval Daver, Musa Yilmaz, Nicholas J Short, Gautam Borthakur, Tapan M Kadia, Koji Sasaki, Danielle Hammond, Alexandre Bazinet, Ehsan Irajizad, Beenu Thakral, Sherry Pierce, Patrick Reville, Farhad Ravandi, Hussein A Abbas

Faculty, Staff and Student Publications

Monosomy 7 and 7q deletions (-7/del(7q)) are the most common adverse cytogenetic event in acute myeloid leukemia (AML), linked to high relapse rates. We analyzed 115 AML patients with -7/del(7q) who achieved remission after induction therapy to characterize the mutational landscape from diagnosis to relapse. Median overall survival (OS) was 10.4 months, with improved survival in patients without TP53 mutation (13.04 vs. 8.6 months) or complex karyotype (12.4 vs. 8.6 months). TP53 mutations were most frequent (67% of cases at diagnosis) and persisted in 97% of patients at relapse. At time of relapse, patients with TP53 mutations had fewer co-occurring …

Blood Bacterial Dna Signatures In A Prospective Cohort Of Patients With Masld Cirrhosis, Suet-Ying Kwan, Lillian I Dolapchiev, Caren I Sanchez, Tiffany L Calderone, Jessica I Sanchez, Megha B Bhongade, Ahmed El Sabagh, Darrel W Cleere, Nakul Gupta, Prasun K Jalal, David W Victor, Laura Beretta

Faculty, Staff and Student Publications

Background: Predictive biomarkers are needed to identify individuals with metabolic dysfunction-associated steatotic liver disease (MASLD), at high risk for HCC. Our study aimed to determine whether the detection of circulating bacterial DNA could be associated with HCC development in MASLD patients with liver cirrhosis.

Methods: We developed a multicenter prospective cohort of patients with cirrhosis undergoing surveillance for HCC by contrast-enhanced magnetic resonance imaging. In a nested cohort study, we performed 16S rRNA sequencing of cell-free DNA extracted from 343 longitudinal plasma samples collected from 151 MASLD patients with cirrhosis. Among the 151 patients, 25 developed HCC during follow-up.

Results: …

Long-Term Transfusion Independence With Luspatercept Versus Epoetin Alfa In Erythropoiesis-Stimulating Agent-Naive, Lower-Risk Myelodysplastic Syndromes In The Commands Trial, Guillermo Garcia-Manero, Valeria Santini, Amer M Zeidan, Rami S Komrokji, Veronika Pozharskaya, Shelonitda Rose, Karen Keeperman, Yinzhi Lai, Sameer Kalsekar, Barkha Aggarwal, Dimana Miteva, David Valcárcel, Pierre Fenaux, Jake Shortt, Matteo Giovanni Della Porta, Uwe Platzbecker

Faculty, Staff and Student Publications

Introduction: The efficacy of erythropoiesis-stimulating agents (ESAs) for transfusion-dependent (TD) anemia in lower-risk myelodysplastic syndromes (LR-MDS) is limited. Luspatercept achieved significantly greater rates of red blood cell (RBC) transfusion independence (TI) versus epoetin alfa (an ESA) in the phase 3 COMMANDS trial. This analysis assessed long-term RBC-TI, cumulative response, and safety with luspatercept in COMMANDS.

Methods: Eligible patients aged ≥ 18 years, with ESA-naive, RBC TD LR-MDS were randomized 1:1 to receive luspatercept (1.0 mg/kg, titration to 1.75 mg/kg permitted) or epoetin alfa (450 IU/kg, titration to 1050 IU/kg). Disease assessment was carried out at week 24 (day 169) and …

Hyalinization-Based Pathologic Response And Immune Infiltration Following Neoadjuvant Radiotherapy With Or Without Immune-Checkpoint Blockade In Localized Undifferentiated Pleomorphic Sarcoma, R S Traweek, M Zoghbi, R Lazcano, B M Cope, A J Bishop, A Farooqi, D Mitra, A K Yoder, B A Guadagnolo, D R Ingram, K Wani, D Shamsutdinova, A J Lazar, W-L Wang, C P Scally, E Z Keung, K E Torres, K K Hunt, R Ratan, J A Livingston, M S Nakazawa, D M Araujo, S Patel, V Ravi, A P Conley, M A Zarzour, N Somaiah, C L Roland, E F Nassif Haddad

Faculty, Staff and Student Publications

BACKGROUND: Standard-of-care treatment of localized undifferentiated pleomorphic sarcoma (UPS) involves preoperative radiotherapy (RT) and surgery. Combination of RT with immune-checkpoint blockade (ICB) represents a promising new strategy.

METHODS: Our primary objective was to assess survival outcomes and pathologically documented response in patients receiving RT with or without ICB or chemotherapy.

RESULTS: In a retrospective cohort of 68 patients with primary or locally recurrent UPS who received neoadjuvant RT with or without ICB, the ICB group had greater tumor hyalinization than the non-ICB group (89% compared with 30%, P = 0.018). In the non-ICB group, 19/37 patients (51%) achieved hyalinization-based pathologic …

Dynamic Contrast-Enhanced Mri Processing Comparison For Distinguishing True Progression From Pseudoprogression In High-Grade Glioma, Ahmad Amer, Shehbaz Ansari, Apollo Krayyem, Suprateek Kundu, Swapnil Khose, Halyna Pokhylevych, Susana Calle, Chirag B Patel, Zixi Yang, Ho-Ling Anthony Liu, Jason M Johnson

Faculty, Staff and Student Publications

Background: Treatment-related changes may occur due to radiation and temozolomide in glioblastoma and can mimic tumor progression on conventional MRI. DCE-MRI enables quantification of the extent of blood-brain barrier (BBB) disruption, providing information about areas of suspicious postcontrast T1 enhancement. We compared DCE-MRI processing methods for distinguishing true disease progression from pseudoprogression in high-grade gliomas (HGGs).

Methods: We identified 110 patients with HGG treated with surgery and chemoradiation who underwent DCE-MRI to further interrogate areas of new/increasing enhancement. All patients had confirmatory surgery/biopsy with pathology-confirmed progression or pseudoprogression. Scans were performed at 3T and analyzed using nordicICE. The MCA, SSS, …

Kap1 Promotes Gastric Adenocarcinoma Progression By Activating Hippo/Yap1 Signaling Via Binding To Hnrnpab, Shumei Song, Yibo Fan, Gengyi Zou, Longfei Huo, Janani Kumar, Yuan Li, Ruiping Wang, Enyu Dai, Jiankang Jin, Ailing W Scott, Shan Shao, Melissa Pool Pizzi, Jody V Vykoukal, Hiroyuki Katayama, Samir Hanash, George A Calin, Xing Zhang, Min Gyu Lee, Zhenning Wang, Yuan-Hung Lo, Qiong Gan, Rebecca E Waters, Feng Yin, Linghua Wang, Xiaodong Cheng, Jaffer A Ajani, Shilpa S Dhar

Faculty, Staff and Student Publications

Gastric adenocarcinoma (GAC) remains a significant global health challenge, with over a million new cases annually. Peritoneal carcinomatosis (PC), detected in ∼20 % of cases at diagnosis and ∼45 % later, is uniformly fatal, with limited treatment options. This study investigated the role of KAP1 in GAC progression, focusing on its interaction with YAP1 and cancer stemness traits. Analysis of over 596 primary GACs and 72 PC samples revealed that high nuclear KAP1 expression correlates with poor prognosis. KAP1 knockdown reduced oncogenic activity and stemness traits in GAC cells. Mechanistically, KAP1 positively regulates YAP1 transcription by binding to its promoter …

Risk Of Early Death After Acute Leukemia Diagnosis Among Adolescents And Young Adults, Amy M Berkman, Clark R Andersen, Vidya Puthenpura, Nicholas J Short, Kelly Merriman, Mahesh Swaminathan, Branko Cuglievan, David Mccall, Courtney Dinardo, Cesar Nunez, Nitin Jain, Tapan Kadia, Ghayas Issa, Amber Gibson, Miriam B Garcia, J Andrew Livingston, Susan Parsons, Michelle A T Hildebrandt, Michael E Roth

Faculty, Staff and Student Publications

Background: Advances in care have led to improvements in survival for adolescents and young adults (AYAs) diagnosed with cancer; however, the risk of early death remains high for certain cancers, particularly acute leukemias. Risk factors for early death in AYAs diagnosed with acute leukemia have not been well studied.

Methods: The Surveillance, Epidemiology, and End Results registry was used to assess risk of early death (within 2 months of diagnosis) in AYAs diagnosed with acute leukemia (n = 16 153). Early death proportion, by year, for AYAs diagnosed between 2006 and 2020 was described. Associations between incidence of early death …

A Follow-Up Study On The Novel Use Of Contrast-Enhanced Susceptibility-Weighted Imaging For Extremity Desmoid Fibromatosis Response Assessment, Raul F Valenzuela, Elvis Duran-Sierra, Mathew Antony, Behrang Amini, Sam Lo, Keila E Torres, Ken-Pin Hwang, Jingfei Ma, R Jasson Stafford, Ravin Ratan, John E Madewell, Dejka Araujo, William A Murphy, Colleen M Costelloe

Faculty, Staff and Student Publications

Desmoid tumors are rare mesenchymal neoplasms characterized by a clonal proliferation of fibroblasts and myofibroblasts. Using the novel contrast-enhanced susceptibility-weighted imaging (CE-SWI) for characterizing desmoid tumors can enhance the separation between fibrous T2-hypointense and cellular T1-enhancing components. We aim to evaluate the effectiveness of the CE-SWI signal, volumetric, and radiomics-derived features in assessing desmoid treatment response. This IRB-approved study included 17 single-lesion extremity desmoid fibromatosis patients who underwent standard-of-care MRI, including CE-SWI, from March 2021 to February 2024. Measurements of maximum diameter, volume, and the modified Choi (m-Choi: tumor/muscle T2 ratio) were computed based on CE-SWI and T2-STIR volumetric tumor …

Autologous T Cell Therapy For Prame, Martin Wermke, Dejka M Araujo, Manik Chatterjee, Apostolia M Tsimberidou, Tobias A W Holderried, Amir A Jazaeri, Ran Reshef, Carsten Bokemeyer, Winfried Alsdorf, Katrin Wetzko, Peter Brossart, Katrin Aslan, Linus Backert, Sebastian Bunk, Jens Fritsche, Swapna Gulde, Silvana Hengler, Norbert Hilf, Mohammad B Hossain, Jens Hukelmann, Mamta Kalra, Delfi Krishna, M Alper Kursunel, Dominik Maurer, Andrea Mayer-Mokler, Regina Mendrzyk, Ali Mohamed, Karine Pozo, Arun Satelli, Marilena Letizia, Heiko Schuster, Oliver Schoor, Claudia Wagner, Hans-Georg Rammensee, Carsten Reinhardt, Harpreet Singh-Jasuja, Steffen Walter, Toni Weinschenk, Jason J Luke, Cedrik M Britten

Faculty, Staff and Student Publications

In contrast to chimeric antigen receptor T cells, T cell receptor (TCR)-engineered T cells can target intracellular tumor-associated antigens crucial for treating solid tumors. However, most trials published so far show limited clinical activity. Here we report interim data from a first-in-human, multicenter, open-label, 3 + 3 dose-escalation/de-escalation phase 1 trial studying IMA203, an autologous preferentially expressed antigen in melanoma (PRAME)-directed TCR T cell therapy in HLA-A*02+ patients with PRAME+ recurrent and/or refractory solid tumors, including melanoma and sarcoma. Primary objectives include the evaluation of safety and tolerability and the determination of the maximum tolerated dose (MTD) and/or recommended dose …

Hernia Recurrence Risk Matters More Than Mesh Type To Patients Undergoing Ventral Hernia Repair, Stephanie Martinez Ugarte, Mokunfayo O Fajemisin, Chelsea J Guy-Frank, Dalya M Ferguson, Jonah J Stulberg, Lillian S Kao, Julie L Holihan

Faculty, Staff and Student Publications

Introduction: Patients' perceptions about synthetic mesh for ventral hernia repair (VHR) may stem from a lack of knowledge of risks. We assessed patients' threshold for accepting the risk of hernia recurrence to avoid synthetic mesh.

Methods: Patients ≥18 y old with prior or upcoming VHR viewed a one-time video decision aid describing recurrence risk with biologic versus synthetic mesh. Patients chose between these options using a probability trade-off (PTO) technique, varying hernia recurrence rate with biologic mesh. Based on randomized trials, the recurrence rate using synthetic mesh was 9%. The PTO score was the recurrence rate (0%-100%) at which patients …

Outcomes And Toxicity Following 3 Or More Definitive Courses Of Thoracic Radiation Therapy For Non-Small Cell Lung Cancer, Abigael Odwuor, Percy Lee, Joe Y Chang, Saumil Gandhi, Zhongxing Liao, Steven H Lin, Aileen Chen, Quynh-Nhu Nguyen, Michael S O'Reilly, Stephen G Chun, Julianna Bronk, David Qian, Matthew S Ning

Faculty, Staff and Student Publications

Purpose: Salvage re-irradiation is increasingly utilized to manage non-small cell lung cancer (NSCLC) locoregional recurrence or new lung primaries in previously treated areas. There is sparse information on efficacy and toxicity profile. We report a large experience of patients treated with multiple courses of definitive radiation for new and recurrent NSCLC.

Methods and materials: Medical records of patients who underwent ≥ 3 definitive thoracic radiation therapy (RT) courses for new or recurrent NSCLC at our cancer center from 2012 through 2021 were retrospectively reviewed following institutional review board approval. Toxicity was graded per Common Terminology Criteria for Adverse Events (CTCAE) …

Crem Is A Regulatory Checkpoint Of Car And Il-15 Signalling In Nk Cells, Hind Rafei, Rafet Basar, Sunil Acharya, Yu-Sung Hsu, Pinghua Liu, Deqiang Zhang, Toszka Bohn, Qingnan Liang, Vakul Mohanty, Ranjan Upadhyay, Ping Li, Pravin Phadatare, Merve Dede, Donghai Xiong, Huihui Fan, Corry Mathew Jones, Sebastian Kunz, May Daher, Ana Karen Nunez Cortes, Mayra Shanley, Bin Liu, Sadie Mae Moseley, Chenyu Zhang, Dexing Fang, Pinaki Banerjee, Nadima Uprety, Ye Li, Rejeena Shrestha, Xinhai Wan, Hong Shen, Vernikka Woods, April Lamour Gilbert, Seema Rawal, Jinzhuang Dou, Yukun Tan, Jeong-Min Park, Francia Reyes Silva, Alexander Biederstädt, Mecit Kaplan, Xin Ru Jiang, Inci Biederstädt, Bijender Kumar, Silvia Tiberti, Madison Moore, Jingling Jin, Ryan Z Yang, Luis Muniz-Feliciano, Samuel Rosemore, Paul Lin, Gary M Deyter, Natalie Wall Fowlkes, Abhinav K Jain, David Marin, Anirban Maitra, Ken Chen, Tobias Bopp, Elizabeth J Shpall, Katayoun Rezvani

Faculty, Staff and Student Publications

Chimeric antigen receptor (CAR) natural killer (NK) cell immunotherapy offers a promising approach against cancer1-3. However, the molecular mechanisms that regulate CAR-NK cell activity remain unclear. Here we identify the transcription factor cyclic AMP response element modulator (CREM) as a crucial regulator of NK cell function. Transcriptomic analysis revealed a significant induction of CREM in CAR-NK cells during the peak of effector function after adoptive transfer in a tumour mouse model, and this peak coincided with signatures of both activation and dysfunction. We demonstrate that both CAR activation and interleukin-15 signalling rapidly induce CREM upregulation in NK cells. Functionally, CREM …

Aortopexy With Plication Of Kommerell Diverticulum Is An Effective Alternative To Diverticulum Resection And Reimplantation Of The Aberrant Left Subclavian Artery For Surgical Management Of Vascular Rings In Children, Adegbemisola Aregbe Perkins, Ana-Lucia Tomescu, Christopher J Knott-Craig, Umar Boston, Thomas Spentzas, Karthik Vaidyanathan Ramakrishnan

Faculty, Staff and Student Publications

Background

Right aortic arch with an aberrant left subclavian artery arising from a Kommerell diverticulum is the most common form of vascular ring. We report the outcomes of plication and pexy of the diverticulum in addition to division of the left-sided ligamentum to treat this lesion in children.

Methods

Forty-four patients were included in the study; 22 patients underwent division of the ligamentum arteriosum alone, while the other half underwent plication and/or pexy of the Kommerell diverticulum in addition to division of the ligamentum. The primary outcome of interest was reintervention for persistent symptoms following the initial operation. The other …

Polaris: Encorafenib Plus Binimetinib For People With Braf V600-Mutant Melanoma With Brain Metastasis, Alexander M Menzies, Michael A Davies

Faculty, Staff and Student Publications

POLARIS was a study to evaluate different doses of encorafenib plus binimetinib for people with BRAF V600-mutant melanoma with brain metastasis. The first part, known as the safety lead-in, looked at a high dose of encorafenib (300 mg twice daily) combined with standard binimetinib (45 mg twice daily); in the phase 2 part, patients were given the standard dose of encorafenib (450 mg once daily) plus binimetinib. In the safety lead-in, many patients were unable to tolerate the high dose of encorafenib plus binimetinib. Despite recruitment challenges in POLARIS, in the 13 enrolled patients with unresectable metastatic BRAF V600-mutant melanoma …

History Of Hypoxia Exposure Aids Future Cell Invasion According To Cell Type And Collagen Density, José A Almeida, Diego B Avila, Gregory D Longmore, Amit Pathak

2020-Current year OA Pubs

In cancer progression, tumor microenvironments (TME) progressively become denser and hypoxic, and cell migrate toward higher oxygen levels as they invade across the tumor-stromal boundary. Although cell invasion dependence on optimal collagen density is well appreciated, it remains unclear whether past oxygen conditions alter future invasion phenotype of cells. Here, we show that normal human mammary epithelial cells (MCF10A) and leader-like human breast tumor cells (BT549) undergo higher rates of invasion and collagen deformation after past exposure to hypoxia, compared with normoxia controls. Upon increasing collagen density by ∼50%, cell invasion under normoxia reduced, as expected due to the increased …

Association Of Statin Use On Survival Outcomes Of Patients With Early-Stage Her2-Positive Breast Cancer In The Aphinity Trial, Christian Maurer, Elisa Agostinetto, Lieveke Ameye, Matteo Lambertini, Samuel Martel, Noam Ponde, Mariana Brandão, Francesca Poggio, Arlindo Ferreira, Rachel Schiff, Carmine De Angelis, Richard D Gelber, Susan Dent, Christoph Thomssen, Martine Piccart, Evandro De Azambuja

Faculty, Staff and Students Publications

Purpose: There is evidence that statins might improve the outcome of patients with breast cancer. The role of statins in patients with early HER2-positive breast cancer is unknown. Therefore, we explored the association between statin use and survival outcomes in early HER2-positive breast cancer patients in the phase III APHINITY trial (adjuvant pertuzumab/trastuzumab).

Methods: All patients (intent-to-treat population, n = 4804) were included (6.2 years median follow-up database). The primary objective was to investigate the association of statin use on invasive disease-free survival (IDFS), distant relapse-free interval (DRFI), and overall survival (OS). Patients who received statins at baseline, or started …

The Long-Term Effects Of Chemotherapy On Normal Blood Cells, Emily Mitchell, My H Pham, Anna Clay, Rashesh Sanghvi, Nicholas Williams, Sandra Pietsch, Joanne I Hsu, Nina Friesgaard Øbro, Hyunchul Jung, Aditi Vedi, Sarah Moody, Jingwei Wang, Daniel Leonganmornlert, Michael Spencer Chapman, Ellie Dunstone, Anna Santarsieri, Alex Cagan, Heather E Machado, E Joanna Baxter, George Follows, Daniel J Hodson, Ultan Mcdermott, Gary J Doherty, Inigo Martincorena, Laura Humphreys, Krishnaa Mahbubani, Kourosh Saeb Parsy, Koichi Takahashi, Margaret A Goodell, David Kent, Elisa Laurenti, Peter J Campbell, Raheleh Rahbari, Jyoti Nangalia, Michael R Stratton

Faculty, Staff and Student Publications

Several chemotherapeutic agents act by increasing DNA damage in cancer cells, triggering cell death. However, there is limited understanding of the extent and long-term consequences of collateral DNA damage in normal tissues. To investigate the impact of chemotherapy on mutation burdens and the cell population structure of normal tissue, we sequenced blood cell genomes from 23 individuals aged 3-80 years who were treated with a range of chemotherapy regimens. Substantial additional somatic mutation loads with characteristic mutational signatures were imposed by some chemotherapeutic agents, but the effects were dependent on the drug and blood cell types. Chemotherapy induced premature changes …