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Session Introduction: Translating Big Data Imaging Genomics Findings To The Individual: Prediction Of Risks And Outcomes In Neuropsychiatric Illnesses, Peter Kochunov, Li Shen, Zhongming Zhao, Paul M Thompson

Faculty, Staff and Student Publications

This PSB 2025 session is focused on opportunities, challenges and solutions for translating Big Data Imaging Genomic findings toward powering decision making in personalized medicine and guiding individual clinical decisions. It combines many of the scientific directions that are of interest to PSB members including Big Data analyses, pattern recognition, machine learning and AI, electronic health records and others.

Nrg Oncology White Paper On The Relative Biological Effectiveness In Proton Therapy, Harald Paganetti, Charles B Simone, Walter R Bosch, Daphne Haas-Kogan, David G Kirsch, Heng Li, Xiaoying Liang, Wei Liu, Anita Mahajan, Michael D Story, Paige A Taylor, Henning Willers, Ying Xiao, Jeffrey C Buchsbaum

Faculty, Staff and Student Publications

This position paper, led by the NRG Oncology Particle Therapy Work Group, focuses on the concept of relative biologic effect (RBE) in clinical proton therapy (PT), with the goal of providing recommendations for the next-generation clinical trials with PT on the best practice of investigating and using RBE, which could deviate from the current standard proton RBE value of 1.1 relative to photons. In part 1, current clinical utilization and practice are reviewed, giving the context and history of RBE. Evidence for variation in RBE is presented along with the concept of linear energy transfer (LET). The intertwined nature of …

Comprehensive Genomic Analysis Reveals Molecular Heterogeneity In Pediatric Alk-Positive Anaplastic Large Cell Lymphoma, Timothy I Shaw, Stanley Pounds, Xueyuan Cao, Jing Ma, Gustavo Palacios, John Mason, Sherrie Perkins, Gang Wu, Yiping Fan, Jian Wang, Xin Zhou, Alyssa Obermayer, Marsha C Kinney, Jacqueline Kraveka, Thomas Gross, John Sandlund, Jinghui Zhang, Charles Mullighan, Megan S Lim, Vasiliki Leventaki

Faculty, Staff and Student Publications

Anaplastic large cell lymphoma (ALCL) is a mature T-cell lymphoma that accounts for 10-15% of childhood lymphomas. Despite the observation that more than 90% of pediatric cases harbor the anaplastic lymphoma kinase (ALK) rearrangement resulting in aberrant ALK kinase expression, there is significant clinical, morphologic, and biological heterogeneity. To gain insights into the genomic aberrations and molecular heterogeneity within ALK-positive ALCL (ALK+ ALCL), we analyzed 46 pediatric ALK+ ALCLs by whole-exome sequencing, RNA sequencing, and DNA methylation profiling. Whole-exome sequencing found on average 25 SNV/Indel events per sample with recurring genetic events in regulators of DNA damage (TP53, MDM4), transcription …

Global Research Trends And Focus On Immunotherapy For Endometrial Cancer: A Comprehensive Bibliometric Insight And Visualization Analysis (2012–2024), Yachen Xu, Tao Wang, Xiaojing Liang, Jie Yang, Yuxiang Zhang, Shan Bao

Faculty, Staff and Student Publications

Background: This study conducted a novel systematic bibliometric and visualization analysis of global literature on immunotherapy for endometrial cancer (EC) to explore dynamic trends, research hotspots, and emerging topics, providing valuable references for future research.

Methods: Articles and reviews on EC immunotherapy published between 2012 and August 2024 were retrieved from the Web of Science Core Collection (WoSCC). Bibliometric tools, CiteSpace and VOSviewer, were used to analyze clustering patterns and research dynamics.

Results: A total of 861 articles were contributed by 5,331 authors from 1,392 institutions across 58 countries or regions, involving 1,823 keywords. China demonstrated outstanding performance in this …

Long-Term Symptom Burden In A Young, Ambulatory Cohort After The Omicron Outbreak In China, Simeng Ren, Yumeng Tan, Hongkun Xu, Mian Wang, Rumei Xiang, Jiayue Jin, Baojin Han, Jiaheng Shi, Jingyu Zhang, Jinliang Yang, Xin Tian, Ying Li, Jiaojiao Chen, Wenzheng Zhang, Jingqi Yang, Xin Shelley Wang, Qiuling Shi, Jie Liu

Faculty, Staff and Student Publications

Introduction: At the end of 2022, an outbreak of the Omicron BF.7 and BA.5.2 subvariants of SARS-CoV-2 occurred in China. In this prospective cohort study, we investigated the pattern of development of major symptom burden and influencing factors in infected Chinese patients.

Methods: First-time infected outpatients were enrolled from December 7, 2022, to January 11, 2023 (N = 355). The prevalence of symptoms was monitored by a repeated patient-reported quantitative symptom survey over nine months.

Results: At the onset of the infection, the most prevalent symptoms (score ≥1 on a 0-10 numeric rating scale) were fatigue (91.8%), cough (91.8%), …

Characterization Of Additive Gene-Environment Interactions For Colorectal Cancer Risk, Claire E Thomas, Yi Lin, Michelle Kim, Eric S Kawaguchi, Conghui Qu, Caroline Y Um, Brigid M Lynch, Bethany Van Guelpen, Kostas Tsilidis, Robert Carreras-Torres, Franzel J B Van Duijnhoven, Lori C Sakoda, Peter T Campbell, Yu Tian, Jenny Chang-Claude, Stéphane Bézieau, Arif Budiarto, Julie R Palmer, Polly A Newcomb, Graham Casey, Loic Le Marchandz, Marios Giannakis, Christopher I Li, Andrea Gsur, Christina Newton, Mireia Obón-Santacana, Victor Moreno, Pavel Vodicka, Hermann Brenner, Michael Hoffmeister, Andrew J Pellatt, Robert E Schoen, Niki Dimou, Neil Murphy, Marc J Gunter, Sergi Castellví-Bel, Jane C Figueiredo, Andrew T Chan, Mingyang Song, Li Li, D Timothy Bishop, Stephen B Gruber, James W Baurley, Stephanie A Bien, David V Conti, Jeroen R Huyghe, Anshul Kundaje, Yu-Ru Su, Jun Wang, Temitope O Keku, Michael O Woods, Sonja I Berndt, Stephen J Chanock, Catherine M Tangen, Alicja Wolk, Andrea Burnett-Hartman, Anna H Wu, Emily White, Matthew A Devall, Virginia Díez-Obrero, David A Drew, Edward Giovannucci, Akihisa Hidaka, Andre E Kim, Juan Pablo Lewinger, John Morrison, Jennifer Ose, Nikos Papadimitriou, Bens Pardamean, Anita R Peoples, Edward A Ruiz-Narvaez, Anna Shcherbina, Mariana C Stern, Xuechen Chen, Duncan C Thomas, Elizabeth A Platz, W James Gauderman, Ulrike Peters, Li Hsu

Faculty, Staff and Student Publications

Background: Colorectal cancer (CRC) is a common, fatal cancer. Identifying subgroups who may benefit more from intervention is of critical public health importance. Previous studies have assessed multiplicative interaction between genetic risk scores and environmental factors, but few have assessed additive interaction, the relevant public health measure.

Methods: Using resources from CRC consortia, including 45,247 CRC cases and 52,671 controls, we assessed multiplicative and additive interaction (relative excess risk due to interaction, RERI) using logistic regression between 13 harmonized environmental factors and genetic risk score, including 141 variants associated with CRC risk.

Results: There was no evidence of multiplicative interaction …

Optimization Of Proximity Labeling In Endothelial Cells: Overcoming Endogenous Biotin Interference And Cost Barriers, Ying Jiang, Kuizhi Qu, Mengjun Dai, Yan-Ning Rui, Zhen Xu

Faculty, Staff and Student Publications

Proximity labeling has become a powerful technique for mapping protein-protein interactions under physiologically relevant conditions, with TurboID offering high enzymatic activity and rapid labeling. However, its application in endothelial systems has been limited, partly due to the presence of endogenous biotin in specialized media, which reduces labeling specificity. Here, we optimized TurboID-mediated proximity labeling in brain microvascular endothelial cells by addressing two key challenges: endogenous biotin interference and cost-effective depletion. We discovered that endothelial cell medium contains substantial biotin levels, which saturate TurboID labeling and obscure the effects of exogenous biotin. Using High Capacity NeutrAvidin

Structured Personalized Oxygen And Supportive Therapies For Dyspnea In Oncology (Spot-On): A Personalized Randomized Clinical Trial Protocol, David Hui, Min Ji Kim, Saji Thomas, Gautam Sachdev, Sanjay Shete, Nisha Rathi, Nicole Hensch, Vera De La Cruz, Amy Ontai, Donald A Mahler, Jie Li, Eduardo Bruera

Faculty, Staff and Student Publications

Background: Low-flow supplemental oxygen (LFSO), high-flow nasal cannula (HFNC), and non-invasive ventilation (NIV) are often used for palliation of dyspnea in hospitalized patients. However, it is unclear how patients prefer to use these modalities and how they can be personalized for optimal dyspnea relief. The objective of this randomized clinical trial is to compare the effect of a personalized respiratory therapist (RT)-led intervention, termed SPOT-ON, and enhanced usual care on dyspnea intensity in both hypoxemic and non-hypoxemic hospitalized patients with cancer.

Methods: In this two-arm, parallel group, partially blinded, waitlist-controlled randomized clinical trial, hospitalized patients with advanced cancer and at …

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 …

Improved Survival And Decreased Cancer Deaths In Young Adults With Cancer After Passage Of The Affordable Care Act Dependent Coverage Expansion, Michael Roth, Clark R Andersen, Amy Berkman, Stuart Siegel, Branko Cuglievan, J Andrew Livingston, Michelle Hildebrandt, Jaime Estrada, Archie Bleyer

Faculty, Staff and Student Publications

Background: The Patient Protection and Affordable Care Act (ACA) allowed Americans aged 19-25 years to remain on their parents' health insurance plans until age 26 years (the Dependent Care Expansion [DCE]). Have those with cancer diagnoses benefited?

Methods: The ACE DCE 7-year age range of 19-25 years was compared for changes in cancer survival and mortality before and after enactment of the ACA with groups that were younger and older (in 7-year age spans: ages 12-18 and 26-32 years, respectively). Cancer death data for the entire United States were obtained from the Centers for Disease Control and Prevention, and relative …

Utility Of Pre-Procedural [99mtc]Tcmaa Spect/Ct Multicompartment Dosimetry For Treatment Planning Of 90y Glass Microspheres In Patients With Hepatocellular Carcinoma: Comparison Of Anatomic Versus [99mtc]Tcmaa-Based Segmentation, Marnix Lam, Etienne Garin, Paul Haste, Alban Denys, Brian Geller, S Cheenu Kappadath, Cuneyt Turkmen, Daniel Y Sze, Hamad Saleh Alsuhaibani, Ken Herrmann, Marco Maccauro, Murat Cantasdemir, Matthew Dreher, Kirk D Fowers, Vanessa Gates, Riad Salem

Faculty, Staff and Student Publications

Purpose: Pre-treatment [99mTc]TcMAA-based radioembolization treatment planning using multicompartment dosimetry involves the definition of the tumor and normal tissue compartments and calculation of the prescribed absorbed doses. The aim was to compare the real-world utility of anatomic and [99mTc]TcMAA-based segmentation of tumor and normal tissue compartments.

Materials and methods: Included patients had HCC treated by glass [90Y]yttrium microspheres, ≥ 1 tumor, ≥ 3 cm diameter and [99mTc]TcMAA SPECT/CT imaging before treatment. Segmentation was performed retrospectively using dedicated dosimetry software: (1) anatomic (diagnostic CT/MRI-based), and (2) [99mTc]TcMAA threshold-based (i.e., using an activity-isocontour threshold). CT/MRI was co-registered with [99mTc]TcMAA SPECT/CT. Logistic regression and …

Hsa-Mir-214-3p Inhibits Breast Cancer Cell Growth And Improves The Tumor Immune Microenvironment By Downregulating B7h3, Yan Lu, Kang Wang, Yuanhong Peng, Meng Chen, Lin Zhong, Luji Huang, F U Cheng, Xindan Sheng, Xin Yang, Manzhao Ouyang, George A Calin, Zhiwei He

Faculty, Staff and Student Publications

BACKGROUND: Immune checkpoint inhibitors play an important role in the treatment of solid tumors, but the currently used immune checkpoint inhibitors targeting programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), and cytotoxic T-lymphocyte antigen-4 (CTLA-4) show limited clinical efficacy in many breast cancers. B7H3 has been widely reported as an immunosuppressive molecule, but its immunological function in breast cancer patients remains unclear.

METHODS: We analyzed the expression of B7H3 in breast cancer samples using data from the Cancer Genome Atlas Program (TCGA) and the Gene Expression Omnibus (GEO) databases. MicroRNAs were selected using the TarBase, miRTarBase, and miRBase databases. …

Consensus Guidelines For Delineation Of Clinical Target Volumes For Intensity Modulated Radiation Therapy For Intact Cervical Cancer: An Update, Emma C Fields, Walter R Bosch, Kevin V Albuquerque, Rohini Bhatia, Junzo Chino, Brandon Dyer, Beth Erickson, Denise Fabian, David Gaffney, Scott Glaser, Kathy Han, Lara Hathout, I-Chow Hsu, Naresh Jegadeesh, Jenna Kahn, Elizabeth Kidd, Ann Klopp, Eric Leung, Lilie Lin, Michelle Ludwig, Tianjun Ma, Loren Mell, Jyoti Mayadev, Ivy Petersen, Lorraine Portelance, Dominique Rash, Neil Taunk, Akila Viswanathan, Aaron Wolfson, Catheryn Yashar, Anamaria Yeung, Emi Yoshida, Christine M Fisher

Faculty, Staff and Student Publications

Purpose: Accurate target delineation is essential when using intensity modulated radiation therapy for intact cervical cancer. In 2011, the Radiation Therapy Oncology Group published a consensus guideline using magnetic resonance imaging (MRI). The current project expands on the previous atlas by including computed tomography (CT)-based contours, contours with MRI and positron emission tomography (PET) registrations, the addition of common and complex scenarios, and incorporating information on simulation and treatment planning techniques.

Methods and materials: Twenty-eight experts in gynecologic radiation oncology contoured 3 cases, first on a noncontrast CT simulation scan and then with registered diagnostic scans. The cases included (1) …

The Primary Cilia: Orchestrating Cranial Neural Crest Cell Development, Hiroyuki Yamaguchi, Matthew D Meyer, William B Barrell, Maryam Faisal, Rebecca Berdeaux, Karen J Liu, Yoshihiro Komatsu

Faculty, Staff and Student Publications

Primary cilia (hereafter "cilia") are microtubule-based antenna-like organelles projecting from the surface of vertebrate cells. Cilia can serve as cellular antennae controlling cell growth and differentiation. Absent or dysfunctional cilia frequently lead to craniofacial anomalies known as craniofacial ciliopathies. However, the detailed pathological mechanisms of craniofacial ciliopathies remain unclear. This perspective discusses our current understanding of the role of cilia in cranial neural crest cells. We also describe potential mechanisms of ciliogenesis in cranial neural crest cells, which may contribute to unraveling the complex pathogenesis of craniofacial ciliopathies.

Exploring The Role Of Reward Functioning In The Overlap Of Post-Traumatic Stress And Cocaine Use Disorder, Kate Hull, Hanaan Bing-Canar, Krista Miloslavich, Christopher Holden, Aneet Ahluwalia, Scott D Lane, Joy M Schmitz, Margaret C Wardle

Faculty, Staff and Student Publications

Background: Posttraumatic stress disorder (PTSD) symptoms are common in people with cocaine use disorder (CUD), and even sub-threshold PSTD symptoms result in worse treatment outcomes. Difficulties with reward functioning may drive this comorbidity. Impairments in reward functioning are prominent in both PTSD and CUD and contribute to development of substance use problems after trauma. There are three distinct reward processes that may be involved in the PTSD/CUD overlap: consummatory reward (ability to experience pleasure), motivational reward (willingness to exert effort for rewards), and reward learning (adapting behavior based on reward history). Here we test whether impairments in these reward functions …

Clinical Criteria For Limbic-Predominant Age-Related Tdp-43 Encephalopathy, David A Wolk, Peter T Nelson, Liana Apostolova, Konstantinos Arfanakis, Patricia A Boyle, Cynthia M Carlsson, Nick Corriveau-Lecavalier, Penny Dacks, Bradford C Dickerson, Kimiko Domoto-Reilly, Brittany N Dugger, Rebecca Edelmayer, David W Fardo, Michel J Grothe, Timothy J Hohman, David J Irwin, Gregory A Jicha, David T Jones, Claudia H Kawas, Edward B Lee, Karen Lincoln, Gladys E Maestre, Elizabeth C Mormino, Chiadi U Onyike, Ronald C Petersen, Gil D Rabinovici, Rosa Rademakers, Rema Raman, Katya Rascovsky, Robert A Rissman, Emily Rogalski, Philip Scheltens, Reisa A Sperling, Hyun-Sik Yang, Lei Yu, Henrik Zetterberg, Julie A Schneider

Faculty, Staff and Student Publications

Limbic predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is highly prevalent in late life and a common co-pathology with Alzheimer's disease neuropathologic change (ADNC). LATE-NC is a slowly progressive, amnestic clinical syndrome. Alternatively, when present with ADNC, LATE-NC is associated with a more rapid course. With the emergence of anti-amyloid therapeutics, discrimination of LATE-NC from ADNC is critical and will lead to greater clinical recognition of amnestic patients without ADNC. Furthermore, co-pathology with LATE-NC may influence outcomes of these therapeutics. Thus there is a need to identify patients during life with likely LATE-NC. We propose criteria for clinical diagnosis of …

Exposure Therapy Consortium: Outcomes Of The Proof-Of-Principle Study, Jasper A J Smits, Jonathan S Abramowitz, Rebecca A Anderson, Joanna J Arch, Daniel Badeja, Snir Barzilay, Amanda N Belanger, Thomas Borchert, Emma Bryant, Alane S Burger, Laura J Dixon, Christina D Dutcher, Hayley E Fitzgerald, Bronwyn M Graham, Anke Haberkamp, Stefan G Hofmann, Jürgen Hoyer, Jonathan D Huppert, David Johnson, Baraa Q Kabha, Alex Kirk, Jürgen Margraf, Peter M Mcevoy, Bryan Mcspadden, Jill Newby, Michael W Otto, Santiago Papini, E Marie Parsons, Andre Pittig, Roxana Pittig, Winfried Rief, Svenja Schaumburg, Kiara R Timpano, Lena Waltemate, Andre Wannemüller, Cornelia Weise, Exposure Therapy Consortium

Faculty, Staff and Student Publications

Background: This paper reports on the outcomes of a proof-of-principle study for the Exposure Therapy Consortium, a global network of researchers and clinicians who work to improve the effectiveness and uptake of exposure therapy. The study aimed to test the feasibility of the consortium's big-team science approach and test the hypothesis that adding post-exposure processing focused on enhancing threat reappraisal would enhance the efficacy of a one-session large-group interoceptive exposure therapy protocol for reducing anxiety sensitivity.

Methods: The study involved a multi-site cluster-randomized controlled trial comparing exposure with post-processing (ENHANCED), exposure without post-processing (STANDARD), and a stress management intervention (CONTROL) …

Moderately Hypofractionated, Preoperative Radiotherapy In Patients With Soft Tissue Sarcomas (Hyport-Sts): Updated Local Control, Late Toxicities, And Patient-Reported Outcomes, Andrew J Bishop, Devarati Mitra, Ahsan Farooqi, David M Swanson, Caroline Hempel, Tiara Willis, Chris Pearlnath, Wei-Lien Wang, Ravin Ratan, Neeta Somaiah, Robert S Benjamin, Keila E Torres, Kelly K Hunt, Christopher P Scally, Emily Z Keung, Robert L Satcher, Justin E Bird, Patrick P Lin, Bryan S Moon, Valerae O Lewis, Christina L Roland, B Ashleigh Guadagnolo

Faculty, Staff and Student Publications

Background: Moderately hypofractionated, preoperative radiotherapy in patients with soft tissue sarcomas (HYPORT-STS; ClinicalTrials.gov identifier NCT03819985) investigated a radiobiologically equivalent, moderately hypofractionated course of preoperative radiotherapy (RT) 15 × 2.85 Gy in patients with soft tissue sarcoma (STS). Here, the authors report longer term follow-up to update local control and report late toxicities, as well as functional and patient-reported outcomes.

Methods: HYPORT-STS was a single-center, open-label, single-arm, prospective phase 2 clinical trial that enrolled 120 eligible adult patients with localized STS of the extremities or superficial trunk between 2018 and 2021. Patients received a 3-week course of preoperative RT followed …

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 …

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 …

Incidence Of Bacterial Blood Stream Infections In Patients With Acute Gvhd, Whitney Wallis, Alison M Gulbis, Tao Wang, Catherine J Lee, Akshay Sharma, Kirsten M Williams, Taiga Nishihori, Tim Prestidge, Lohith Gowda, Michael Byrne, Maxwell M Krem, Margaret L Macmillan, Carrie L Kitko, Joseph Pidala, Stephen R Spellman, Stephanie J Lee, Amin M Alousi

Faculty, Staff and Student Publications

Bacterial bloodstream infections (BSI) can be a substantial contributor to complications of GVHD treatment. The aim of this study was to determine the risk for BSI from neutrophil engraftment through day 100 post transplant in patients with acute GVHD (AGVHD) based on organ involvement and severity. Patients (n = 4064) who underwent an allogeneic hematopoietic stem cell transplant (HCT) reported to the CIBMTR registry were analyzed. Grade II-IV AGVHD occurred in 1607 (39.5%) patients and was associated with a greater day-100 incidence of post engraftment BSI than with grade 0/I (24.9 vs. 15.3%). Patients with grade III/IV AGVHD had the …

Long-Term Follow-Up Of A Phase 2 Study Of All-Trans Retinoic Acid, Arsenic Trioxide, And Gemtuzumab Ozogamicin In Acute Promyelocytic Leukemia, Wei-Ying Jen, Jennifer Marvin-Peek, Hagop M Kantarjian, Yesid Alvarado, Gautam Borthakur, Elias Jabbour, William Wierda, Tapan M Kadia, Naval G Daver, Courtney D Dinardo, Nicholas J Short, Nitin Jain, Alessandra Ferrajoli, Steven Kornblau, Musa Yilmaz, Maro Ohanian, David Mccue, Jan Burger, Danielle Hammond, Keyur Patel, Ghayas C Issa, Naveen Pemmaraju, Koji Sasaki, Abhishek Maiti, Hussein A Abbas, Kelly Chien, Koichi Takahashi, Fadi Haddad, Prithviraj Bose, Lucia Masarova, Guillermo Montalban-Bravo, Mahesh Swaminathan, Mark Brandt, Sherry Pierce, Guillermo Garcia-Manero, Farhad Ravandi

Faculty, Staff and Student Publications

Background: All-trans retinoic acid (ATRA) and arsenic trioxide (ATO) combinations have produced excellent outcomes in patients with standard-risk acute promyelocytic leukemia (APL). Herein, the authors update their long-term results with the regimen of ATO-ATRA and gemtuzumab ozogamicin (GO) in standard-risk and high-risk APL.

Methods: This was a phase 2 trial of patients with newly diagnosed APL. Induction comprised ATRA 45 mg/m2 and ATO 0.15 mg/kg daily. GO 6-9 mg/m2 was added for high-risk patients and for standard-risk patients who developed leukocytosis >10 × 109/L. Consolidation consisted of four courses of ATO-ATRA, with GO for patients who had PML::RARA persistence.

Results: …

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 …

The Tripod-Llm Reporting Guideline For Studies Using Large Language Models, Jack Gallifant, Majid Afshar, Saleem Ameen, Yindalon Aphinyanaphongs, Shan Chen, Giovanni Cacciamani, Dina Demner-Fushman, Dmitriy Dligach, Roxana Daneshjou, Chrystinne Fernandes, Lasse Hyldig Hansen, Adam Landman, Lisa Lehmann, Liam G Mccoy, Timothy Miller, Amy Moreno, Nikolaj Munch, David Restrepo, Guergana Savova, Renato Umeton, Judy Wawira Gichoya, Gary S Collins, Karel G M Moons, Leo A Celi, Danielle S Bitterman

Faculty, Staff and Student Publications

Large language models (LLMs) are rapidly being adopted in healthcare, necessitating standardized reporting guidelines. We present transparent reporting of a multivariable model for individual prognosis or diagnosis (TRIPOD)-LLM, an extension of the TRIPOD + artificial intelligence statement, addressing the unique challenges of LLMs in biomedical applications. TRIPOD-LLM provides a comprehensive checklist of 19 main items and 50 subitems, covering key aspects from title to discussion. The guidelines introduce a modular format accommodating various LLM research designs and tasks, with 14 main items and 32 subitems applicable across all categories. Developed through an expedited Delphi process and expert consensus, TRIPOD-LLM emphasizes …

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 …

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, …

Prevalence Of Carotid Ultrasound Screening In Survivors Of Childhood Cancer: A Report From The Childhood Cancer Survivor Study, Yolanda Bryce, Jillian A Whitton, Kayla L Stratton, Wendy M Leisenring, Eric J Chow, Gregory Armstrong, Brent Weil, Bryan Dieffenbach, Rebecca M Howell, Kevin C Oeffinger, Paul C Nathan, Emily S Tonorezos

Faculty, Staff and Student Publications

Introduction: Many childhood cancer survivors are at risk for cardiovascular disease and stroke. The North American Children's Oncology Group long-term follow-up guidelines recommend carotid ultrasound in cancer survivors 10 years after neck radiation therapy (RT) ≥40 Gy. The use of carotid ultrasound in this population has not been described.

Methods: Survivors of childhood cancer diagnosed 1970-1999 (N = 8693) and siblings (N = 1989) enrolled in the Childhood Cancer Survivor Study were asked if they had ever had a carotid ultrasound. Prevalence of carotid ultrasound was evaluated. Prevalence ratios (PR) and 95% confidence intervals (CIs) were evaluated in multivariate Poisson …

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 …

Acute Myeloid Leukemia Management And Research In 2025, Hagop M Kantarjian, Courtney D Dinardo, Tapan M Kadia, Naval G Daver, Jessica K Altman, Eytan M Stein, Elias Jabbour, Charles A Schiffer, Amy Lang, Farhad Ravandi

Faculty, Staff and Student Publications

The first 5 decades of research in acute myeloid leukemia (AML) were dominated by the cytarabine plus anthracyclines backbone, with advances in strategies including allogeneic hematopoietic stem cell transplantation, high-dose cytarabine, supportive care measures, and targeted therapies for the subset of patients with acute promyelocytic leukemia. Since 2017, a turning point in AML research, 12 agents have received regulatory approval for AML in the United States: venetoclax (BCL2 inhibitor); gemtuzumab ozogamicin (CD33 antibody-drug conjugate); midostaurin, gilteritinib, and quizartinib (fms-like tyrosine kinase 3 inhibitors); ivosidenib, olutasidenib, and enasidenib (isocitrate dehydrogenase 1 and 2 inhibitors); oral azacitidine (a partially absorbable formulation); CPX351 …