Digital Commons Network^™

Consensus Recommendations For Hyperpolarized [1- 13c]Pyruvate Mri Multi-Center Human Studies, Shonit Punwani, Peder E Z Larson, Christoffer Laustsen, Jan Vandermeulen, Jan Henrik Ardenkjær-Larsen, Adam W Autry, James A Bankson, Jenna Bernard, Robert Bok, Lotte Bonde Bertelsen, Jenny Che, Albert P Chen, Rafat Chowdhury, Arnaud Comment, Charles H Cunningham, Duy Dang, Ferdia A Gallagher, Adam Gaunt, Yangcan Gong, Jeremy W Gordon, Ashley Grimmer, James Grist, Esben Søvsø Szocska Hansen, Mathilde Hauge Lerche, Richard L Hesketh, Jan-Bernd Hoevener, Ching-Yi Hsieh, Kayvan R Keshari, Sebastian Kozerke, Titus Lanz, Dirk Mayer, Mary Mclean, Jae Mo Park, Jim Slater, Damian Tyler, Jean-Luc Vanderheyden, Cornelius Von Morze, Fulvio Zaccagna, Vlad Zaha, Duan Xu, Daniel Vigneron

Faculty, Staff and Student Publications

MRI of hyperpolarized (HP) [1‐13C]pyruvate allows in vivo assessment of metabolism and has translated into human studies across diseases at 15 centers worldwide. To determine consensus on best practice for multi‐center studies for development of clinical applications. This paper presents the results of a two‐round formal consensus building exercise carried out by experts with HP [1‐13C]pyruvate human study experience. Twenty‐nine participants from 13 sites brought together expertise in pharmacy methods, MR physics, translational imaging, and data analysis with the goal of providing recommendations and best practice statements on conduct of multi‐center human studies of HP [1‐13C]pyruvate MRI. Overall, the group …

Correction: Inflammation Mediated By Gut Microbiome Promotes Immune Suppression And Lung Adenocarcinoma Progression, Zahraa Rahal, Yuejiang Liu, Fuduan Peng, Sujuan Yang, Mohamed A Jamal, Manvi Sharma, Hannah Moreno, Ashish V Damania, Matthew C Wong, Matthew C Ross, Ansam Sinjab, Tieling Zhou, Minyue Chen, Inti Tarifa Reischle, Jiping Feng, Chidera Chukwuocha, Elizabeth Tang, Camille Abaya, Jamie K Lim, Cheuk Hong Leung, Heather Y Lin, Nathaniel Deboever, Jack J Lee, Boris Sepesi, Don L Gibbons, Jennifer A Wargo, Junya Fujimoto, Linghua Wang, Joseph F Petrosino, Nadim J Ajami, Robert R Jenq, Seyed Javad Moghaddam, Tina Cascone, Kristi Hoffman, Humam Kadara

Faculty, Staff and Student Publications

No abstract provided.

Three-Dimensional Noise Characteristics Of Clinical Photon Counting Detector Ct, Humberto Monsivais, Xinming Liu, Frank Dong, Megan C Jacobsen, John Rong, Corey T Jensen, Ke Li

Faculty, Staff and Student Publications

Background: Since the introduction of whole-body photon-counting detector CT (PCD-CT) into clinical practice, extensive physics assessments have been conducted to elucidate its image quality advantages over energy-integrating detector CT (EID-CT) and to support its clinical adoption. However, evaluations of its three-dimensional (3D) noise power spectrum (NPS), which simultaneously quantifies in-plane and through-plane noise texture and magnitude, remain limited.

Purpose: To experimentally evaluate the 3D NPS of an NAEOTOM Alpha PCD-CT system and its dependence on scan mode, reconstruction image type, quantum iterative reconstruction (QIR) strength, mono-energy (keV) level, spiral pitch, and radiation dose.

Methods: Repeated scans of a 20 cm …

First Experience With Third-Party Validations: A Robust Calibration And Qa Procedure For Proton Flash Delivery, Chih-Chiang Chang, Balaji Selvaraj, Xingyi Zhao, Jacob Rembish, Paige A Taylor, Alexander Bookbinder, Chingyun Cheng, J Isabelle Choi, Charles B Simone, Haibo Lin, Minglei Kang

Faculty, Staff and Student Publications

Background: Proton FLASH radiotherapy, delivering ultra-high dose rates, shows promise in reducing normal tissue toxicity while maintaining tumor control. However, accurate dosimetry and quality assurance (QA) for FLASH remain challenging due to the extreme dose rates involved. Developing reliable calibration and QA procedures is crucial for advancing FLASH towards clinical implementation.

Purpose: To present an effective routine calibration and QA procedure for proton FLASH delivery to ensure high-quality dosimetry performance for preclinical and clinical delivery.

Methods: A high temporospatial resolution strip ionization chamber array (SICA) detector was mounted to the treatment nozzle, which was calibrated using an Advanced Markus ion …

A Comparative Study Of Clinically Used Fast Monte Carlo Dose Engines For Proton Therapy, Sherif M Gadoue, Narayan Sahoo

Faculty, Staff and Student Publications

Background: Several fast Monte Carlo (MC) codes have been implemented and used to simulate proton transport and calculate patient doses in proton therapy. The resulting dose is typically compared to full MC codes, rather than other fast MC codes.

Purpose: The primary goal of this study was to compare the gamma pass rates (GPRs) of dose calculation from different fast MC codes to evaluate the accuracy of the computation and modeling among these codes.

Methods: Two GPU codes and one CPU MC code were commissioned to model our clinical proton beamline at University of Texas MD Anderson Cancer Center. The …

Natural History Of Primary Retroperitoneal Extra-Visceral Perivascular Epithelioid Cell Tumors (Pec): A Study From Transatlantic And Australasian Retroperitoneal Sarcoma Working Group (Tarpswg), Eyal Mor, Sameer Apte, Catherine Mitchell, Carolyn Nessim, Max Almond, Bruno Vincenzi, Jose Antonio Gonzalez Lopez, Lee Cranmer, Michael J Wagner, Aviram Nissan, Miguel Henriques Abreu, Markus Albertsmeier, Mathilda Knoblauch, Adam Barlow, Emily Z Keung, Giovanni Grignani, Jason L Hornick, Alessandro Gronchi, David E Gyorki

Faculty, Staff and Student Publications

Background: Perivascular epithelioid cell tumors (PEComa) are a rare family of mesenchymal tumors that include several subtypes. There are very limited data describing the natural history of patients with extra-visceral retroperitoneal PEComas of the retroperitoneum. The aim of this study is to describe the clinical features, treatment patterns, outcomes, and diagnostic challenges of primary extra-visceral retroperitoneal or abdominopelvic PEComa over the past decade.

Patients and methods: This is a retrospective analysis of all extra-visceral, non-renal, retroperitoneal, or abdominopelvic PEComas treated at participating centers over the past 10 years.

Results: A total of 77 patients from 13 centers were included. The …

Correction: Natural History Of Primary Retroperitoneal Extra-Visceral Perivascular Epithelioid Cell Tumors (Pec): A Study From Transatlantic And Australasian Retroperitoneal Sarcoma Working Group (Tarpswg), Eyal Mor, Sameer Apte, Catherine Mitchell, Carolyn Nessim, Max Almond, Bruno Vincenzi, Jose Antonio Gonzalez Lopez, Lee Cranmer, Michael J Wagner, Aviram Nissan, Miguel Henriques Abreu, Markus Albertsmeier, Mathilda Knoblauch, Adam Barlow, Emily Z Keung, Giovanni Grignani, Jason L Hornick, Alessandro Gronchi, David E Gyorki

Faculty, Staff and Student Publications

No abstract provided.

Cancer-Induced Nerve Injury Promotes Resistance To Anti-Pd-1 Therapy, Erez N Baruch, Frederico O Gleber-Netto, Priyadharsini Nagarajan, Xiayu Rao, Shamima Akhter, Tuany Eichwald, Tongxin Xie, Mohammad Balood, Adebayo Adewale, Shorook Naara, Hinduja N Sathishkumar, Shajedul Islam, William Mccarthy, Brandi J Mattson, Renata Ferrarotto, Michael K Wong, Michael A Davies, Sonali Jindal, Sreyashi Basu, Karine Roversi, Amin Reza Nikpoor, Maryam Ahmadi, Ali Ahmadi, Catherine Harwood, Irene Leigh, Dennis Gong, Paulino Tallón De Lara, Derrick L Tao, Tara M Davidson, Nadim J Ajami, Andrew Futreal, Kunal Rai, Veena Kochat, Micah Castillo, Preethi Gunaratne, Ryan P Goepfert, Sharia D Hernandez, Nikhil I Khushalani, Jing Wang, Stephanie S Watowich, George A Calin, Michael R Migden, Mona Yuan, Naijiang Liu, Yi Ye, William L Hwang, Paola D Vermeer, Nisha J D'Silva, Yuri L Bunimovich, Dan Yaniv, Jared K Burks, Javier Gomez, Patrick M Dougherty, Kenneth Y Tsai, James P Allison, Padmanee Sharma, Jennifer A Wargo, Jeffrey N Myers, Sebastien Talbot, Neil D Gross, Moran Amit

Faculty, Staff and Student Publications

Perineural invasion (PNI) is a well-established factor of poor prognosis in multiple cancer types1, yet its mechanism remains unclear. Here we provide clinical and mechanistic insights into the role of PNI and cancer-induced nerve injury (CINI) in resistance to anti-PD-1 therapy. Our study demonstrates that PNI and CINI of tumour-associated nerves are associated with poor response to anti-PD-1 therapy among patients with cutaneous squamous cell carcinoma, melanoma and gastric cancer. Electron microscopy and electrical conduction analyses reveal that cancer cells degrade the nerve fibre myelin sheets. The injured neurons respond by autonomously initiating IL-6- and type I interferon-mediated …

Imaging- And Tumor Biomarker-Based Multivariable Model For Early Prediction Of Pathologic Complete Response To Neoadjuvant Systemic Therapy In Triple-Negative Breast Cancer, Beatriz E Adrada, Mary S Guirguis, Lei Huo, Clinton Yam, Debu Tripathy, Rosalind Candelaria, Wei Yang, Miral Patel, Tanya Moseley, Gary J Whitman, Jessica W T Leung, Huong Le-Petross, Deanna L Lane, Nour Abuhadra, Jennifer Litton, Vicente Valero, Kelly K Hunt, Banu Arun, Rania Mohamed, Jia Sun, Anil Korkut, Sanaz Pashapoor, Jason White, Alastair Thompson, Peng Wei, Jingfei Ma, Stacy Moulder, Gaiane M Rauch

Faculty, Staff and Student Publications

Purpose: The response of triple-negative breast cancer (TNBC) to neoadjuvant therapy (NAT) varies widely. This study aimed to determine the performance of clinicopathologic biomarkers and volumetric changes on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting pathologic complete response (pCR) to NAT in patients with TNBC.

Patients and methods: This study included 264 patients with stage I to III TNBC enrolled in a prospective clinical trial. These patients underwent DCE-MRI at baseline and after two and/or after four cycles of dose-dense anthracycline and cyclophosphamide. Tumor volume (TV) was calculated by measuring three tumor dimensions at each time point. Clinicopathologic markers …

Chromosome 20q Gene Signature Associated With Colorectal Cancer Progression, Jennifer Carter Jones, Apurva M Hegde, Yu-Jing Huang, Ganiraju Manyam, Vibhuti Srivastava, Jee Hoo Song, Yulan Cheng, Ralf Krahe, Warapen Treekitkarnmongkol, Stephen J Meltzer, Scott Kopetz, Stanley R Hamilton, Hiroshi Katayama, Subrata Sen

Faculty, Staff and Student Publications

Amplification of human chromosome 20q has been reported as the most frequently recurring genetic abnormality associated with large scale changes in mRNA and protein levels in sporadic colorectal carcinomas. While some studies have found 20q amplification to be consistent between primary and metastatic samples from the same patient with a role in the development of metastasis and worse patient prognosis, others have reported association with improved overall survival for a subset of these patients with colorectal cancer (CRC). To fine map the Minimal Common Regions (MCRs) of amplification on chromosome 20q and identify the candidate genes playing roles in progression …

Grpa-Prs: A Risk Stratification Method To Identify Genetically-Regulated Pathways In Polygenic Diseases, Xiaoyang Li, Brisa S Fernandes, Andi Liu, Jingchun Chen, Xiangning Chen, Zhongming Zhao, Yulin Dai

Faculty, Staff and Student Publications

Introduction: Polygenic risk score (PRS) assesses genetic risk for diseases, yet some high-risk individuals avoid illness while low-risk individuals develop it. We hypothesize that unknown counterfactors may reverse PRS predictions, offering insights into disease mechanisms and interventions.

Methods: We developed a novel framework to identify genetically-regulated pathways (GRPas) using PRS-based stratification in Alzheimer's disease (AD) and schizophrenia (SCZ) cohorts. We calculated PRS models, stratified individuals by risk and diagnosis, and analyzed differential GRPas. For AD, analyses were further conducted with and without apolipoprotein E (APOE) effects, and across APOE haplotype.

Results: In AD, we identified several well-known AD-related pathways, including …

Relationship Between Quantitative Mri Ute T2* Of Acl Autografts And Bmi-Normalized Knee Laxity Within The First Year After Acl Reconstruction, Alonso Figueroa, Tomasz Bugajski, Dillon Humpal, Manickam Kumaravel, Walter Lowe, Payam Zandiyeh

Faculty, Staff and Student Publications

Background: The anterior cruciate ligament reconstruction (ACLR) graft undergoes a remodeling process that affects its structural properties. Ultrashort echo time T2* (UTE-T2*) imaging has been instrumental in examining this process. However, more research is needed on the postoperative relationship between UTE-T2* of the graft and its mechanical properties.

Purpose: To longitudinally examine ACL graft changes after ACLR using UTE-T2* decay coefficients and knee laxity and explore their relationship.

Study design: Case series; Level of evidence, 4.

Methods: A total of 31 patients who underwent ACLR had magnetic resonance imaging of their knees at 1, 6, and 12 months after surgery …

Bipolar Spinal Correction Reduces Transfusion Rate And Hospital Stay Compared With Traditional Posterior Spinal Fusion In Children With Scoliosis Secondary To Cerebral Palsy, Kristopher Lundine, Matthias Lu, Timothy C Borden, Samuel Yoon, Mia Percival, Michael B Johnson

Faculty, Staff and Student Publications

Purpose: Patients with neuromuscular scoliosis due to Cerebral Palsy (CP) are complex due to their curve severity and associated medical comorbidities. Spinal fusion is associated with high risk of peri-operative complications and large blood loss requiring allogenic red blood cell (RBC) transfusion. In June 2017, our tertiary paediatric institution implemented a new minimally-invasive approach for the treatment of neuromuscular scoliosis, Bipolar Spinal Correction (Bipolar), a technique first published by Miladi et al. in 2018. This study represents an analysis of the initial experience of this technique to see if it achieves the goal of minimally invasive surgery by decreasing surgical …

Irf6 Regulates Adherens Junction Proteins And Inflammatory Cytokines In Salivary Acinar Cells And Its Expression Is Elevated In Sjӧgren’S Syndrome, Vi Pham, Antonio Hernandes Chaves Neto, Julia Zheng, Mary Elmeniawi, Krishna Kumar Kookal, Muhammad F Walji, Mary C Farach-Carson, Walid D Fakhouri

Faculty, Staff and Student Publications

Objective: To investigate the mechanism of Interferon Regulatory Factor 6 (IRF6) function in regulating adherens junction proteins and inflammatory cytokines in human salivary acinar cells and Sjögren's syndrome biopsies.

Design: We used mouse model, salivary cell lines, and human salivary gland (SG) biopsies to investigate IRF6 function in SG cellular integrity and immunomodulation.

Results: In Irf6-null mice, we observed myoepithelial cell detachment from acinar cells of major SGs, and the acini were remarkably disorganized compared to wild-type littermates. At the molecular level, the acinar differentiation markers E-cadherin and MIST1 were markedly reduced in Irf6-null embryonic SG, while the proinflammatory cytokines, …

Morphometric Analysis Of Spina Bifida After Fetal Repair Shows New Subtypes With Associated Outcomes, L K Mann, S Pandiri, N Agarwal, H Northrup, K S Au, E Grundberg, E P Bergh, M T Austin, R Patel, B Miller, S Zhu, J S Feinberg, D Lai, K Tsao, S A Fletcher, R Papanna

Faculty, Staff and Student Publications

Objectives: The binary classification of spina bifida lesions as myelomeningocele (with sac) or myeloschisis (without sac) belies a spectrum of morphologies. This study aimed to characterize types of spina bifida lesion and correlate them with preoperative presentation and postoperative outcome.

Methods: This was a secondary analysis of a prospective cohort of patients referred for fetal spina bifida who underwent fetoscopic repair between 2020 and 2023 at a single center. We evaluated lesion morphology on high-resolution intraoperative images and videos to categorize lesions based on placode exposure and nerve root stretching. The reproducibility of lesion classification was assessed using the Kappa …

Lesion Absorbed Dose-Response Relationship In Patients With Metastatic Castration-Resistant Prostate Cancer Undergoing [177lu]Lu-Psma-617 Radiopharmaceutical Therapy, Milan Grkovski, Simone S Krebs, Joseph A O'Donoghue, Jonathan Kuten, Audrey Mauguen, Parnian Shobeiri, Daniel Lafontaine, Maria Thor, Finn Augensen, Josef J Fox, Neeta Pandit-Taskar, Mark P Dunphy, Lisa Bodei, John L Humm, Heiko Schöder

Faculty, Staff and Student Publications

The relationship between lesion absorbed dose (AD) and response in patients with metastatic castration-resistant prostate cancer undergoing [177Lu]Lu-PSMA-617 radiopharmaceutical therapy (RPT) remains poorly understood. The objective of this work was to investigate the AD-response relationship at both the patient and lesion levels.

Methods: Sixty-five patients underwent serial SPECT/CT imaging after receiving 7.31 ± 0.27 GBq of [177Lu]Lu-PSMA-617. Single-time-point (STP) (Hänscheid approximation at 72 h) and multiple-time-point voxelwise dosimetry were performed. Patient response was evaluated by changes in serum prostate-specific antigen level before and after cycle 1 of RPT. The response of individual lesions was evaluated by the change in the …

Alterations In Region-Specific Gray Matter Volume Underlying Callous Unemotional Traits In Adolescents, Johannah Bashford-Largo, Ru Zhang, R James R Blair, Karina S Blair, Jaimie Elowsky, Matthew Dobbertin, Ahria J Dominguez, Melissa Hatch, Tyler Patrick, Sahil Bajaj

Faculty, Staff and Student Publications

Background: Callous-unemotional (CU) traits during adolescence, for example, shallow affect or lack of remorse, have been shown to be a risk marker for antisocial behavior. Only a few studies have investigated structural brain alterations underlying CU traits, and findings are inconclusive. The study examines CU symptomatology and gray matter volume (GMV) associations.

Methods: Structural brain MRI data were collected from a sample of 578 adolescents (60% male) with a mean age of 14.85 years (SD = 2.30; range = 10-19 years). CU traits were indexed via the Inventory for Callous Unemotional Traits (ICU). Region-wise volumetric parameters were obtained following parcellation …

Family History Of Substance Use And Stressful Life Events Impact Adolescent Maturation Of Cerebral White Matter, Yizhou Ma, Ashley Acheson, Corneliu Bolbocean, Mustafa N Mithaiwala, Si Gao, Neda Jahanshad, Paul M Thompson, Bhim M Adhikari, Xiaoming Du, A Ankeeta, Alia Warner, Antonio F Pagán, L Elliot Hong, Peter Kochunov

Faculty, Staff and Student Publications

Family history (FH) of substance use disorders (SUDs) and stressful life events (SLEs) are known risk factors for SUDs in adolescents and young adults. Cross‐sectional studies suggest that FH and SLEs affect adolescent white matter (WM) development and form abnormal WM patterns. Here, we examined the effects of FH, SLEs and their interaction on WM integrity in youths in the Adolescent Cognitive Brain Development (ABCD) study at baseline and 2‐ and 4‐year follow‐ups. ABCD youths (N = 8939, age ± SD = 9.9 ± 0.6 years, 4302 female) completed baseline diffusion tensor imaging, of which 5661 repeated the scan …

Associations Of High Attenuation Area-Related Proteomic Biomarkers With Fibrotic Or Subpleural Interstitial Lung Abnormalities, John S Kim, Catherine L Debban, Daniel E Guzman, Riley T Hannan, Mary Salvatore, Claire Mcgroder, David Zhang, Anna J Podolanczuk, Daniel A Duprez, Shwu-Fan Ma, Yong Huang, Jeffrey M Sturek, Stephen S Rich, Jerome I Rotter, Rajat Deo, Ruth F Dubin, Janelle Vu Pugashetti, Jennifer M Wang, Meilan K Han, Justin M Oldham, Imre Noth, Prescott G Woodruff, Victor E Ortega, Julie C Fanburg-Smith, Edward B Stelow, Christopher A Moskaluk, Eric A Hoffman, Christine Kim Garcia, Russell P Bowler, Peter Ganz, R Graham Barr, Ani Manichaikul

Faculty, Staff and Student Publications

No abstract provided.

Improving Data-Driven Gated (Ddg) Pet And Ct Registration In Thoracic Lesions: A Comparison Of Ai Registration And Ddg Ct, Tinsu Pan, M Allan Thomas, Yang Lu, Dershan Luo

Faculty, Staff and Student Publications

Purpose: Misregistration between CT and PET can result in mis-localization and inaccurate quantification of the tracer uptake in PET. Data-driven gated (DDG) CT can correct registration and quantification but requires a radiation dose of 1.3 mSv and 1 min of acquisition time. AI registration (AIR) does not require an additional CT and has been validated to improve registration and reduce the 'banana' misregistration artifacts around the diaphragm. We aimed to compare a validated AIR and DDG CT in registration and quantification of avid thoracic lesions misregistered in DDG PET scans.

Methods: Thirty PET/CT patient data (23 with 18F-FDG, 4 with …

Growth Plate Skeletal Stem Cells And Their Actions Within The Stem Cell Niche, Natalie Kiat-Amnuay Cheng, Shion Orikasa, Noriaki Ono

Faculty, Staff and Student Publications

The growth plate is a specialized cartilage structure near the ends of long bones that orchestrates longitudinal bone growth during fetal and postnatal stages. Within this region reside a dynamic population of growth plate skeletal stem cells (gpSSCs), primarily located in the resting zone, which possess self-renewal and multilineage differentiation capacity. Recent advances in cell-lineage tracing, single-cell transcriptomics, and in vivo functional studies have revealed distinct subpopulations of gpSSCs, which are defined by markers such as parathyroid hormone-related protein (PTHrP), CD73, axis inhibition protein 2 (Axin2), forkhead box protein A2 (FoxA2), and apolipoprotein E (ApoE). These stem cells interact intricately …

Occupational Health Equity: A Call To Consider Social-Structural Factors In Injury Prevention Research, Shannon Guillot-Wright, Elizabeth S Mcclure, Marizen R Ramirez, Alexis Grimes Trotter, David B Richardson

Faculty, Staff and Student Publications

Occupational health equity scholarship has been growing over the past decade, including social-structural determinants of health research that centres the voices and experiences of historically marginalised communities. In our commentary, we focus on the intersection of work-related and non-work-related factors and how they impact the health of workers, their families and their communities through community-engaged research. Case studies include the implementation of mobile clinics that are developed alongside communities, community organising to examine and reduce health disparities among racially segregated workers, the development of research instruments and measures to study racism and discrimination, and a focus on how the distribution …

Rna/Dna-Binding Protein Tdp43 Regulates Dna Mismatch Repair Genes With Implications For Genome Stability, Vincent E Provasek, Albino Bacolla, Suganya Rangaswamy, Manohar Kodavati, Joy Mitra, Issa O Yusuf, Vikas H Malojirao, Velmarini Vasquez, Gavin W Britz, Guo-Min Li, Zuoshang Xu, Sankar Mitra, Ralph M Garruto, John A Tainer, Muralidhar L Hegde

Faculty, Staff and Student Publications

TDP43 is an RNA/DNA-binding protein increasingly recognized for its role in neurodegenerative conditions, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). As characterized by its aberrant nuclear export and cytoplasmic aggregation, TDP43 proteinopathy is a hallmark feature in over 95% of ALS/FTD cases, leading to detrimental cytosolic aggregates and a reduction in nuclear functionality in neurons. Building on our prior work linking TDP43 proteinopathy to the accumulation of DNA double-strand breaks (DSBs) in neurons, the present investigation uncovers a novel regulatory relationship between TDP43 and DNA mismatch repair (MMR) gene expression. Here, we show that TDP43 depletion or overexpression …

Robust Detection Of Watermarks For Large Language Models Under Human Edits, Xiang Li, Feng Ruan, Huiyuan Wang, Qi Long, Weijie J Su

Faculty, Staff and Student Publications

Watermarking has offered an effective approach to distinguishing text generated by large language models (LLMs) from human-written text. However, the pervasive presence of human edits on LLM-generated text dilutes watermark signals, thereby significantly degrading detection performance of existing methods. In this paper, by modeling human edits through mixture model detection, we introduce a new method in the form of a truncated goodness-of-fit test for detecting watermarked text under human edits, which we refer to as Tr-GoF. We prove that the Tr-GoF test achieves optimality in robust detection of the Gumbel-max watermark in a certain asymptotic regime of substantial text modifications …

Anticonvulsant Use In Older Age Bipolar Disorder In A Global Sample From The Global Aging And Geriatric Experiments In Bipolar Disorder Project: Utilisation D'Anticonvulsivants Pour Le Traitement Des Troubles Bipolaires Du Sujet Âgé Auprès D'Un Échantillon Mondial Provenant Du Projet Gage-Bd, Katie C Bodenstein, Myriam Lesage, Paola Lavin, Sigfried Schouws, Melis Orhan, Alexandra Beunders, Osvaldo P Almeida, Kursat Altinbas, Vicent Balanzá-Martínez, Izabela G Barbosa, Hilary P Blumberg, Farren B S Briggs, Cynthia V Calkin, Orestes V Forlenza, Brent Forester, Ariel G Gildengers, Benno C M Haarman, Tomas Hajek, Beny Lafer, Paula V Nunes, Benoit Mulsant, Andrew T Olagunju, Regan E Patrick, Joquim Radua, Kaylee Sarna, Christian Simhandl, Jair C Soares, Ashley N Sutherland, Nicole Fiorelli, Antonio L Teixeira, Shangying Tsai, Eduard Vieta, Joy Yala, Lisa Eyler, Annemiek Dols, Martha Sajatovic, Soham Rej

Faculty, Staff and Student Publications

Background:

Anticonvulsants are an essential treatment for bipolar disorder; however, there is relatively little known about their use in older age bipolar disorder (OABD). In this paper, which leverages a large international dataset, we aim to 1) describe the use of anticonvulsants in OABD compared to younger age bipolar disorder (YABD; ages < 50 years old) and 2) explore any demographic/clinical correlates.

Methods:

A secondary analysis was conducted on the international data from the Global Aging and Geriatric Experiments in Bipolar Disorder project. The main objective was to report the prevalence of anticonvulsant use in OABD over 50 years old (mean age = 62.27) and the most prescribed anticonvulsant. Additional …

Bayesian Clustering Prior With Overlapping Indices For Effective Use Of Multisource External Data, Xuetao Lu, J Jack Lee

Faculty, Staff and Student Publications

The use of external data in clinical trials offers numerous advantages, such as reducing enrollment, increasing study power, and shortening trial duration. In Bayesian inference, information in external data can be transferred into an informative prior for future borrowing (i.e. prior synthesis). However, multisource external data often exhibits heterogeneity, which can cause information distortion during the prior synthesizing. Clustering helps identifying the heterogeneity, enhancing the congruence between synthesized prior and external data. Obtaining optimal clustering is challenging due to the trade-off between congruence with external data and robustness to future data. We introduce two overlapping indices: the overlapping clustering index …

Infusion Of Blood From Young And Old Mice Modulates Amyloid Pathology, Matias Pizarro, Ruben Gomez-Gutierrez, Ariel Caviedes, Catalina Valdes, Ute Woehlbier, Cristian Vargas, Mauricio Hernandez, Claudia Duran-Aniotz, Rodrigo Morales

Faculty, Staff and Student Publications

Alzheimer's disease (AD) is a neurodegenerative disease characterized by the accumulation of misfolded proteins in the brain. Recently, the impact of blood components in the progression of this disease has come to attention. This study investigates the effects of infusing blood from young and old wild-type mice into transgenic mice that model AD brain amyloidosis. Impaired memory and Aβ accumulation were observed in mice infused with blood from old donors. A proteomic analysis in the brain of these mice identified alterations in components related to synaptogenesis and the endocannabinoid system. The α2δ2 protein, associated with neuronal calcium regulation, was validated …

The Glutaminase Activity Of Asns Fuels Glutamine Metabolism In Leukemia, Wai-Kin Chan, Lin Tan, Sara A Martinez, Di Du, Thomas D Horvath, Michael Pontikos, Leona A Rusling, Yulun Chiu, Bao Q Tran, Susan B Rempe, Sergei Sukharev, John N Weinstein, Philip L Lorenzi

Faculty, Staff and Student Publications

Not available.

Nmr-Based Metabolomic Profiling For Brain Cancer Diagnosis And Treatment Guidance, Julia R Zickus, José S Enriquez, Paytience Smith, Bill T Sun, Muxin Wang, Aldo Morales, Pratip K Bhattacharya, Shivanand Pudakalakatti

Faculty, Staff and Student Publications

Nuclear magnetic resonance (NMR) spectroscopy is a routinely used analytical tool for studying chemical entities of varying molecular sizes, ranging from approximately 20 Da to ~45 kDa, and in some cases even larger. Over the past two decades, the use of NMR spectroscopy has significantly expanded to the study of metabolomics. In this medium-sized review, the application of NMR-based metabolomics in the diagnosis, therapeutic intervention, and guidance of therapy for various types of brain cancer is discussed.

Innate And Adaptive Immune Features Associated With Immune-Related Adverse Events, Shaheen Khan, Venkat S Malladi, Mitchell S Von Itzstein, Hong Mu-Mosley, Farjana J Fattah, Yang Liu, Mary E Gwin, Jason Y Park, Suzanne M Cole, Sheena Bhalla, Jay Lohrey, David Hsiehchen, Angela Moses, Tao Wang, Yaming Xue, Angela B Mobley, J David Farrar, Marjaan Imam, Michelle Wu, Quan-Zhen Li, Edward K Wakeland, Yang Xie, Jeffrey A Sorelle, David E Gerber

Faculty, Staff and Student Publications

Background: While highly efficacious for numerous cancers, immune checkpoint inhibitors (ICIs) can cause unpredictable and potentially severe immune-related adverse events (irAEs), underscoring the need to understand irAE biology.

Methods: We used a multidimensional approach incorporating single-cell RNA sequencing, mass cytometry, multiplex cytokine assay, and antinuclear antibody (ANA) profiling to characterize the peripheral immune landscape of patients receiving ICI therapy according to irAE development.

Results: Analysis of 162 patients revealed that individuals who developed clinically significant irAEs exhibited a baseline proinflammatory, autoimmune-like state characterized by a significantly higher abundance of CD57+ T and natural killer (NK) T cells, plasmablasts, proliferating and …