Digital Commons Network^™

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, Dimitris Karnabatidis, 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, …

Novel Volumetric Modulated Arc Therapy Approach For Lattice Radiation Therapy For Bulky Liver Tumors, Christine V Chung, Saurabh S Nair, Meena S Khan, Callistus I Nguyen, Rachael M Martin-Paulpeter, Laurence E Court

Faculty, Staff and Student Publications

Purpose: Lattice radiation therapy (LRT) is a type of spatially fractionated radiation therapy that has emerged as an effective treatment approach for bulky solid tumors. RapidArc Dynamic (RAD) is a novel beam delivery approach that may be advantageous for LRT. The purpose of this in silico study was to evaluate and compare a novel RAD-based LRT approach (RAD-LRT) with conventional volumetric modulated arc therapy (VMAT)-based LRT (VMAT-LRT).

Methods: Twenty patients with bulky liver tumors treated with RT were retrospectively identified. VMAT-LRT and RAD-LRT plans were generated for all patients. Lattice spheres were placed in a standardized hexagonal pattern with alternating …

Consolidation Alk Tyrosine Kinase Inhibitors Versus Durvalumab Or Observation After Chemoradiation In Unresectable Stage Iii Alk-Positive Nsclc, Amin H Nassar, Ritujith Jayakrishnan, Jamie Feng, Frances Shepherd, Elio Adib, Jessica J Lin, Steven H Lin, Kaushal Parikh, Arthi Sridhar, Purnima Shakya, Thomas J Dilling, David Kaldas, Jhanelle E Gray, Anastasiya Lobachov, Jair Bar, Heike Luders, Christian Grohe, Shruti Gupta, Ticiana Leal, Bailey Fitzgerald, Fionnuala Crowley, Yu Fujiwara, Thomas U Marron, Molly Wilgucki, Joshua Reuss, Luxi Chen, Kamya Sankar, Jacqueline V Aredo, Joel W Neal, Heather A Wakelee, Rohit Thummalapalli, Helena Yu, Ryan Whitaker, Ana Velazquez, Meera Ragavan, Alessio Cortellini, David J Kwiatkowski, Abdul Rafeh Naqash, Sarah B Goldberg, So Yeon Kim

Faculty, Staff and Student Publications

Introduction: Patients with advanced ALK-positive NSCLC typically have poor response to immunotherapy; the benefit of consolidation durvalumab in patients with unresectable stage III ALK-positive NSCLC remains unclear. Herein, we compare the efficacy and safety of consolidation ALK tyrosine kinase inhibitor (TKI) versus durvalumab or observation after concurrent chemoradiation.

Methods: We conducted a retrospective study using a multicenter study of 17 institutions globally. Patients with unresectable stage III ALK-positive NSCLC treated between 2015 and 2022 were included. Patients received ALK TKI, durvalumab, or observation after concurrent chemoradiation. Real-world progression-free survival (rwPFS) and overall survival (OS) were estimated using Kaplan-Meier method. Treatment-related …

The Impact Of Post-Remission Granulocyte Colony-Stimulating Factor Use In The Phase 3 Studies Of Venetoclax Combination Treatments In Patients With Newly Diagnosed Acute Myeloid Leukemia, Courtney D Dinardo, Keith W Pratz, Panayiotis Panayiotidis, Xudong Wei, Vladimir Vorobyev, Inho Kim, Grace Ku, Catherine L Miller, Meng Zhang, Fernando Tatsch, Jalaja Potluri, Xenia Schmidt, Christian Récher

Faculty, Staff and Student Publications

No abstract provided.

Protecting Organs-At-Risk In Cancer Therapies Through Temporary Organ Displacement: A Comprehensive Review, Rance B Tino, Michael Li, Amirreza Heshmat, Ayush Suresh, Anasimone Guillaume, Bruno C Odisio

Faculty, Staff and Student Publications

Radiation therapy (RT) and locoregional ablation are cornerstones of modern oncology, yet their therapeutic potential is frequently limited by the challenge of sparing healthy organs-at-risk (OARs) from treatment-related complications. Temporary organ displacement (TOD) techniques directly address this issue by creating a physical separation using 'spacers' during treatment, thereby minimizing collateral damage while enhancing therapeutic precision. The clinical benefits, including improved tumor control, reduced morbidity, and enhanced survival, are documented across malignancies of the head and neck, thorax, abdomen, and pelvis. To create a unified framework for this evolving field, this comprehensive review provides a systematic classification of TOD techniques based …

Rethinking Parkinson's Disease Genetics In The Precision Medicine Era: Why Genomic Diversity Matters?, Camilla Teixeira Pinheiro Gusmão, Giselli Scaini, Everton Ferreira De Souza, Rafael Antônio Vicente Lacerda, Matheus De Almeida Costa, João Quevedo

Faculty, Staff and Student Publications

No abstract provided.

Autophagy Cargo Profiles In Skeletal Muscle During Starvation And Exercise, Mohd Farhan, Shangze Lyu, Trezze P Nguyen, Dakai Zhang, Hong Liang, Yu A An, Hongyuan Yang, Guangwei Du, Yang Liu

Faculty, Staff and Student Publications

Autophagy is a cellular process to clear unwanted and dysfunctional cellular cargoes, which are sequestered in autophagosomes before their delivery to lysosomes for degradation. Autophagy cargo selection, mediated by cargo receptors, varies across cell types and conditions. Understanding the cargo features is essential for elucidating autophagy's function in specific physiological or pathological contexts. Here, we present a simple and rapid method for isolating LC3B-positive autophagosomes from the tissues of GFP-LC3 transgenic mice, a widely used autophagy reporter model, without relying on the complex ultracentrifugation steps required by traditional methods. When combined with quantitative proteomics, this approach enables efficient in vivo …

Corrigendum To Exosomal Mirna Confers Chemo Resistance Via Targeting Cav1/P-Gp/M2-Type Macrophage Axis In Ovarian Cancer, Pinar Kanlikilicer, Recep Bayraktar, Merve Denizli, Mohammed H Rashed, Cristina Ivan, Rahul Mitra, Emine Bayraktar, Xinna Zhang, Cristian Rodriguez-Aguayo, Amr Ahmed El-Arabey, Nermin Kahraman, Seyda Baydogan, Ozgur Ozkayar, Michael L Gatza, Bulent Ozpolat, George A Calin, Anil K Sood, Gabriel Lopez-Berestein

Faculty, Staff and Student Publications

No abstract provided.

Role Of Posterior Carbon Fiber Implants In Spine Tumor Surgery, Christopher A Alvarez-Breckenridge, Robert North, Claudio Tatsui, Naresh Kumar, Sheng-Fu Lo, Jeremy Reynolds, Ilya Laufer, Jorrit Jan Verlaan, Ziya Gokaslan, Alessandro Luzzati, Riccardo Cecchinato, John Shin, Francis Hornicek, Alexander Disch, Matthew Goodwin, Rory Goodwin, Arjun Sahgal, Alessandro Gasbarrini, Stefano Boriani

Faculty, Staff and Student Publications

Study design: Narrative Review.

Objective: The management of spinal tumors requires a multi-disciplinary approach including surgery, radiation, and systemic therapy. Surgical approaches typically require posterior segmental instrumentation to maintain long-term spinal stability. Carbon fiber reinforced pedicle screws (CFRP) are increasingly used in the oncologic setting due to reductions in both imaging artifacts and radiotherapy perturbations compared to titanium implants. We performed a review of the literature and highlight advantages and future areas of study for CFRP.

Methods: We performed a systematic review of the literature using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and identified 10 articles …

Combined Inhibition Of Lysine-Specific Demethylase 1 And Kinase Signaling As A Preclinical Treatment Strategy In Glioblastoma, Lea M Stitzlein, Deokhwa Nam, Faith A Hernandez, Kareena H Patel, Alaina Poche, Katie Impelman, Heping Wang, Jing Wang, Samantha Gadd, Wafik Zaky, Oren Becher, Richard W Dudley, Frederick F Lang, Gangadhara R Sareddy, Joya Chandra

Faculty, Staff and Student Publications

Background: Lysine-specific demethylase 1 (LSD1) is overexpressed in glioblastoma, contributing to tumor growth and treatment resistance. LSD1 inhibitors have shown preclinical promise but have had limited clinical development for glioblastoma. Given the frequent kinase pathway alterations seen in glioblastoma, the interplay between LSD1 inhibition and kinase signaling pathways was investigated.

Methods: Glioblastoma stem cell (GSC) lines and normal human astrocytes (NHAs) were treated with catalytic LSD1 inhibitors, NCD38 and bomedemstat, and the LSD1 scaffolding inhibitor, seclidemstat alone and in combination with kinase inhibitors, including osimertinib, afatinib, and ulixertinib. The effect on cell viability, proliferation, and neurosphere formation was assessed, and …

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, Sherrie Perkins, 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 …

Examining The Presence And Effects Of Coherence And Fragmentation In The Gulf Of Maine Fishery Management Network, Derek Katznelson, Antonia Sohns, Dongkyu Kim, Evelyn Roozee, William R Donner, Jasper R De Vries, Gordon M Hickey

Faculty, Staff and Student Publications

Natural resource management networks cohere due to mutual dependencies and fragment, in part, due to the perceived risks of interaction. However, research on these networks has tended to accept coherence a priori rather than problematizing dependence, and few studies exist on interorganizational risk perception. This article presents the results of a study operationalizing these concepts and measuring the distribution of three types of dependence (capital, legitimacy, and regulatory) and two types of perceived risk (performance and sanction) among nearly fifty stakeholder groups and organizations participating in the management of fisheries in the binational Gulf of Maine. The analysis reveals an …

Rationale And Design For A Phase Iiib Trial Of First-Line Tremelimumab Plus Durvalumab Versus Pembrolizumab, In Combination With Chemotherapy, In Patients With Non-Squamous Metastatic Non-Small-Cell Lung Cancer And Mutations Or Co-Mutations In Stk11, Keap1, Or Kras: The Triton Study, Ferdinandos Skoulidis, Hossein Borghaei, Edward B Garon, Ticiana A Leal, Jacob Kaufman, Eric Nadler, Solange Peters, Biagio Ricciuti, Ashish Gautam, Ugochinyere Emeribe, Luisa Luciani-Silverman, John V Heymach

Faculty, Staff and Student Publications

Background: Metastatic non-small-cell lung cancers (mNSCLC) harboring mutations in STK11 or KEAP1 are associated with an immunosuppressive tumor microenvironment and reduced responsiveness to PD-(L)1 inhibitor-based therapy, which is particularly notable when these genes are co-mutated with each other or with KRAS. Patients with these mNSCLC subtypes may benefit from combinations including cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors, aimed at enhancing immune responses.

Objectives: TRITON is an ongoing study comparing tremelimumab plus durvalumab and chemotherapy with pembrolizumab plus chemotherapy as first-line treatment for patients with non-squamous mNSCLC and mutations or co-mutations in STK11, KEAP1, or KRAS.

Design: Phase …

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, Joshua A Bauer, 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 …

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

Faculty, Staff and Student Publications

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

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

Results: After discharge …

Approach To Determining Etiology Of Hypophosphatemia In A Patient With Coexisting Phosphaturic Mesenchymal Tumor And Fibrous Dysplasia, Madhuri D Patil, Sintawat Wangsiricharoen, Alexander J Lazar, Bryan Moon, John E Madewell, Theresa A Guise

Faculty, Staff and Student Publications

Dysregulated FGF23 production is a demonstrated cause of hypophosphatemia and osteomalacia. Diseases associated with these conditions include phosphaturic mesenchymal tumor (PMT) causing tumor induced osteomalacia, various forms of rickets, and fibrous dysplasia (FD). Coexistence of 2 conditions that can increase FGF23 concentrations is rare. We report a case of a 79-yr-old man who presented with rib and right flank pain. Imaging revealed bone lesions in the right iliac wing, left supra-acetabular area, and L4 vertebral body. Biopsies showed a right iliac PMT and left supra-acetabular FD. Cryoablation of both lesions resolved the phosphaturia with normalization of phosphorus level. Coexistence 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, Amanda N Belanger, 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) …

The Influence Of The Microbiome On Radiotherapy And Dna Damage Responses, Aadil Sheikh, Michael A Curran

Faculty, Staff and Student Publications

Colorectal cancer (CRC) is one of the most prevalent cancers in terms of diagnosis and mortality. Radiotherapy (RT) remains a mainstay of CRC therapy. As RT relies on DNA damage to promote tumor cell death, the activity of cellular DNA damage repair pathways can modulate cancer sensitivity to therapy. The gut microbiome has been shown to influence intestinal health and is independently associated with CRC development, treatment responses and outcomes. The microbiome can also modulate responses to CRC RT through various mechanisms such as community structure, toxins and metabolites. In this review we explore the use of RT in the …

Key Considerations For Combination Therapy In Alzheimer’S Clinical Trials: Perspectives From An Expert Advisory Board Convened By The Alzheimer’S Drug Discovery Foundation, Jeffrey Cummings, Michael Gold, Mark Mintun, Michael Irizarry, Andrew Von Eschenbach, Donald Berry, Kaycee Sink, Jaren Landen, Miia Kivipelto, Michael Grundman, Steven E Arnold, Allan Green, Katherine Partrick, Laura Nisenbaum, Aaron Burstein, Howard Fillit

Faculty, Staff and Student Publications

There is growing consensus in the Alzheimer's community that combination therapy will be needed to maximize therapeutic benefits through the course of the disease. However, combination therapy raises complex questions and decisions for study sponsors, from preclinical research through clinical trial design to regulatory, statistical, and operational considerations. In January 2024, the Alzheimer's Drug Discovery Foundation convened an expert advisory board to discuss the key considerations in each of these areas. Experts agreed on the need to prioritize a combination therapy approach that encompasses a wide range of targets associated with aging and the underlying biology of Alzheimer's disease. Progress …

Evaluation Of Quantum Contouring Algorithms For Treatment Planning On Mr Abdominal Images, Rachel Glenn, Tucker Netherton, Adrian Celaya, Mohamed Eltaher, Beatrice Riviere, David Fuentes

Faculty, Staff and Student Publications

Introduction: Quantum computing is increasingly being investigated for integration into medical radiology and healthcare applications worldwide. Given its potential to enhance clinical care and medical research, there is growing interest in evaluating its practical applications in clinical workflows.

Methods: We developed an evaluation of quantum computing-based auto-contouring methods to introduce medical physicists to this emerging technology. We implemented existing quantum algorithms as prototypes tailored for specific quantum hardware, focusing on their application to auto-contouring in medical imaging. The evaluation was performed using a medical resonance imaging (MRI) abdominal dataset, comprising 102 patient scans.

Results: The quantum algorithms were applied to …

Knowledge-Based Planning For Fully Automated Radiation Therapy Treatment Planning Of 10 Different Cancer Sites, Christine V Chung, Meena S Khan, Adenike Olanrewaju, Mary Pham, Quyen T Nguyen, Prajnan Das, Valerie K Reed, Anuja Jhingran, Hannah Simonds, Ethan B Ludmir, Karen E Hoffman, Komeela Naidoo, Jeannette Parkes, Ajay Aggarwal, Lauren L Mayo, Shalin J Shah, Chad Tang, Beth M Beadle, Julie Wetter, Gary Walker, Simon Hughes, Vinod Mullassery, Stephen Skett, Christopher Thomas, Lifei Zhang, Son Nguyen, Raymond P Mumme, Raphael J Douglas, Hana Baroudi, Laurence E Court

Faculty, Staff and Student Publications

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

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

Sex And Apoe Ε4 Allele Differences In Longitudinal White Matter Microstructure In Multiple Cohorts Of Aging And Alzheimer's Disease, Amalia Peterson, Aditi Sathe, Dimitrios Zaras, Yisu Yang, Alaina Durant, Niranjana Shashikumar, Michael E Kim, Chenyu Gao, Nazirah Mohd Khairi, Zhiyuan Li, Tianyuan Yao, Yuankai Huo, Logan Dumitrescu, Katherine A Gifford, Jo Ellen Wilson, Francis E Cambronero, Shannon L Risacher, Lori L Beason-Held, Yang An, Konstantinos Arfanakis, Guray Erus, Christos Davatzikos, Duygu Tosun, Arthur W Toga, Paul M Thompson, Elizabeth C Mormino, Mohamad Habes, Di Wang, Panpan Zhang, Kurt Schilling, Marilyn Albert, Walter Kukull, Sarah A Biber, Bennett A Landman, Sterling C Johnson, Julie Schneider, Lisa L Barnes, David A Bennett, Angela L Jefferson, Susan M Resnick, Andrew J Saykin, Timothy J Hohman, Derek B Archer

Faculty, Staff and Student Publications

Introduction: The effects of sex and apolipoprotein E (APOE)-Alzheimer's disease (AD) risk factors-on white matter microstructure are not well characterized.

Methods: Diffusion magnetic resonance imaging data from nine well-established longitudinal cohorts of aging were free water (FW)-corrected and harmonized. This dataset included 4741 participants (age = 73.06 ± 9.75) with 9671 imaging sessions over time. FW and FW-corrected fractional anisotropy (FAFWcorr) were used to assess differences in white matter microstructure by sex and APOE ε4 carrier status.

Results: Sex differences in FAFWcorr in projection tracts and APOE ε4 differences in FW limbic and occipital transcallosal tracts were most pronounced.

Discussion: …

Selective Inhibition Of Canonical Stat3 Signaling Suppresses K-Ras Mutant Lung Tumorigenesis And Reinvigorates Anti-Tumor Immunity, Michael J Clowers, Zahraa Rahal, Sung-Nam Cho, Avantika Krishna, Bo Yuan, T Kris Eckols, Samuel Liu, Stephen Peng, Marco Ramos-Castaneda, Annamarie L Thompson, Carlos Ignacio Rodriguez Reyna, Katherine E Larsen, Maria T Grimaldo, Shanshan Deng, Nastaran Karimi, Cody Chou, Walter V Velasco, Melody Zarghooni, Sayan Alekseev, Luisa M Solis Soto, Edwin J Ostrin, Humam Kadara, Suhendan Ekmekcioglu, David J Tweardy, Seyed Javad Moghaddam

Faculty, Staff and Student Publications

Introduction: K-ras mutant lung adenocarcinoma (KM-LUAD) is a difficult-to-treat cancer subtype in which chronic inflammation pervades the tumor immune microenvironment (TIME). Pro-inflammatory pathways dampen the response to treatments, including immune checkpoint inhibitors, necessitating therapies that target this inflammatory signaling network in the TIME. One of the lynchpins of chronic inflammation in KM-LUAD is signal transducer and activator of transcription 3 (STAT3).

Methods: Here, we tested the anti-tumor and early immunotherapeutic efficacy of TTI-101, a selective small-molecule inhibitor of canonical STAT3 signaling, in a K-rasG12D mutant lung cancer mouse model (CC-LR).

Results: Treatment of CC-LR mice with TTI-101 resulted in reduced …

Isotonic Phase I Cancer Clinical Trial Design Utilizing Patient-Reported Outcomes, Nolan A Wages, Ruitao Lin

Faculty, Staff and Student Publications

This article considers the concept of designing Phase I clinical trials using both clinician- and patient-reported outcomes to adaptively allocate study participants to tolerable doses and determine the maximum tolerated dose (MTD) at the study conclusion. We describe a new isotonic patient-reported outcome (PRO-ISO) Phase I design with the flexibility of allocating patients to lower, more tolerable regimens if a large number of PRO-DLT events are seen at higher doses. We conduct simulation studies of the operating characteristics of the design and compared them to the patient-reported outcomes continual reassessment method (PRO-CRM). We illustrate that the PRO-ISO makes appropriate dose …

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, William Wierda, 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: …

Fraud In Genetic Testing: Swindling The System, Rachel Notestine, Claire N Singletary, Meagan Choates, Stephanie Gandomi, Molly Daniels, Quinn Stein

Faculty, Staff and Student Publications

Purpose: Health care fraud comprises a sizable portion of United States health care expenditure and inflicts undue burden on payors, patients, and the health care system overall. The genetic testing industry is rapidly growing, which propagates opportunities for health care fraud. Although federal organizations have highlighted it as an issue, there is limited research exploring genetic testing fraud.

Methods: A retrospective review of federal websites, news articles, and a legal database resulted in 42 cases of fraud involving outpatient genetic testing published between February 2019 and December 2023. These cases were analyzed for themes via inductive conventional content analysis.

Results: …

Role Of Mir-204 In Controlling Metabolic Functions Of The Subretinal Microglia, Yan Chen, Sarah E Bounds, Neloy Kundu, James Regun Karmoker, Yin Liu, Jiyang Cai

Faculty, Staff and Student Publications

Rationale: MicroRNA-204 (miR-204) is one of the most abundant miRNA species in the retinal pigment epithelium (RPE) and RPE-derived extracellular vesicles (EVs). Knockout (KO) of miR-204 leads to dysfunction and degeneration of both the RPE and the retina. In addition to previously reported retinal pathologies, we observed the accumulation of lipid-laden subretinal microglia in miR-204 KO mice. This study aimed to identify potential molecular targets of miR-204 involved in microglia lipid processing and to determine whether RPE-derived EVs can improve the function of miR-204-deficient retinal microglia.

Methods: Lipid accumulation in microglia was detected by staining with LipidTox, a fluorescent dye …

Correction: New Insights Into The Mechanisms Of Electroconvulsive Therapy In Treatment-Resistant Depression, Ana C Ruiz, Abdul Haseeb, William Baumgartner, Edison Leung, Giselli Scaini

Faculty, Staff and Student Publications

This corrects the article "New insights into the mechanisms of electroconvulsive therapy in treatment-resistant depression", 1614076.

Hepatic Metabolic Signature And Its Association With The Response To Immunotherapy In Hepatocellular Carcinoma, Hyewon Park, Sowon Park, Kena Park, Sun Young Yim, Ju-Seog Lee

Faculty, Staff and Student Publications

Introduction: Increased metabolic activity is frequently observed in hepatocellular carcinoma (HCC). However, the impact of this increased metabolic activity on the efficacy of current treatments, such as the combination immunotherapy using atezolizumab and bevacizumab for HCC, remains unknown.

Methods: Gene expression data from mouse livers representing hepatic metabolic activity and HCC patient tumor tissues were used to identify a transcriptomic signature for high metabolic activity in HCC tumors. The hepatic metabolic signature (HMS) was used to categorize HCC patients treated with atezolizumab plus bevacizumab or sorafenib from the IMbrave150 clinical trial into high-or low-metabolic groups, using multiple statistical approaches to …

A Phase Ib/Ii Trial Of Neoadjuvant Neratinib Added To Standard Therapy In Patients With Her2-Positive Or Hr-Positive/Her2-Negative Inflammatory Breast Cancer (Including Stage Iii And Iv Disease), Bora Lim, Angela Marx, Megumi Kai, Angela Alexander, Roland Bassett, Jie Willey, Azadeh Nasrazadani, Mohammad M Mohammad, Jianhua Zhang, Anthony Lucci, Susie X Sun, Michael C Stauder, Gary J Whitman, Huong Le-Petross, Vicente Valero, Wendy A Woodward, Rachel M Layman

Faculty, Staff and Student Publications

Background: Inflammatory breast cancer (IBC) is rare but aggressive, characterized by the rapid onset of diffuse skin erythema, edema, tenderness, induration, and fast metastasis. Both hormone receptor positive (HR+) and human epidermal receptor 2 positive (HER2+) are associated with inferior response after neoadjuvant systemic therapy (NAST) compared to non-IBC. Despite multimodal treatment approaches, the 3-year overall survival rate for stage III IBC remains low at approximately 74%, around 10% lower than the 83% for non-IBC.

Objectives: To evaluate whether the addition of neratinib, an irreversible pan-ErbB receptor small molecule tyrosine kinase inhibitor, improves the rate of pathological complete response in …