Biomedical Informatics Commons^™

Repurposing Of The Macrolide Antibiotic Clarithromycin For The Prevention Of Lung Cancer, Shanshan Deng, Tabish Hussain, Thais F Bartelli, Manu M Sebastian, Melody Zarghooni, Walter V Velasco, Brandon Somerville, Linda Phan, Michelle I Savage, Yurong Song, John L Clifford, Humam Kadara, Florencia Mcallister, Powel H Brown, Seyed Javad Moghaddam, C Marcelo Aldaz

Faculty, Staff and Student Publications

Drug repurposing is the process of reusing existing pharmaceuticals for novel clinical purposes, which offers advantages such as streamlined clinical trial access and reduced drug development costs. Clarithromycin (CAM), a member of the macrolide antibiotics family, is a promising candidate for repurposing in cancer therapy due to its known preclinical and clinical immunomodulatory and anticancer properties. In the current study, we investigated whether CAM could be repurposed as a preventive treatment for KRAS-mutant lung cancer, a subtype of lung adenocarcinoma that is strongly associated with heavy smoking. CCSPCre; LSL-KrasG12D mice at an early stage of tumor development were treated with …

Proceedings From The Inaugural Conference On The Science Of Cancer Health Equity For Sexual And Gender Minority (Sgm) Communities, Charles S Kamen, Milena E Insalaco, Richard Brown, Chasity Burrows Walters, Shine Chang, Viktor Clark, Jason Domogauer, Lauren V Ghazal, Kelly Haviland, Forrest Hosea, Nelson Sanchez, Matthew B Schabath, Zul Surani, Gwendolyn P Quinn

Faculty, Staff and Student Publications

Purpose: Sexual and gender minority people (SGM) experience multiple cancer-related disparities, including higher rates of cancer risk factors, lower rates of cancer screening, higher lifetime risk of cancer, and unmet needs throughout cancer survivorship. Although many national organizations, including the National Cancer Institute (NCI) and the American Cancer Society (ACS), have emphasized the need for more cancer research among SGM communities, currently no consensus exists about the highest research priorities, promising research models, or mechanisms to support collaboration between geographically dispersed scientific teams.

Methods: To address this gap, we convened a three-day conference to focus on the "Science of Cancer …

Nci-Designated Cancer Centers' Policies And Practices With Regard To Alcohol And Cancer: A Call To Lead, Ernest T Hawk, Stephanie L Martch, Meghan Si, Sanjay Shete

Faculty, Staff and Student Publications

Background: Alcohol, a known carcinogen since 1988, increases risk of cancers of the mouth, pharynx, larynx, esophagus, liver, breast, and colorectum. More than one half of US adults consume alcohol whereas about two thirds are unsure whether or unaware that alcohol intake is linked to cancer risk.

Methods: Our objective was to survey awareness, beliefs, intentions, policies, practices, and goals/perceived responsibilities related to establishing/promoting actions to reduce alcohol-related cancer risks from leaders of 72 NCI-Designated Cancer Centers.

Results: Sixty-one percent responded. Forty-three percent either believed in or were uncertain about alcohol's purported health benefits. Nevertheless, 86% considered it part of …

Suvorexant For Alcohol Use Disorder And Post-Traumatic Stress Disorder: Study Protocol For A Phase Ii Randomized Clinical Trial, Lara A Ray, Steven J Nieto, Karen Miotto, Larissa Mooney, Richard Lebeau, Jin H Yoon, Joy M Schmitz, Ron Acierno, Nathaniel W Bailey, Jessica Jenkins, Jessica Vincent, Tracy Nolen, Shawn Hirsch, Alexis Williams, Scott D Lane

Faculty, Staff and Student Publications

Background: Alcohol use disorder (AUD) represents a highly prevalent, costly, and often untreated condition in the United States. Post-traumatic stress disorder (PTSD) represents a common comorbidity with AUD which worsens outcomes and decreases functional outcomes. Suvorexant (SUV) shows clear promise as a novel therapeutic candidate to treat AUD and PTSD.

Methods: This study features a promising compound (i.e., suvorexant), the application of a well-established human laboratory paradigm (i.e., alcohol cue reactivity), and a novel early efficacy laboratory model (i.e., practice quit attempt) to provide a cost/time-efficient evaluation of safety and initial efficacy of suvorexant for AUD with comorbid PTSD. Additionally, …

Exploring Sex Differences In Stroke Outcomes: A Comprehensive Analysis From The Span 1 Trial, Anjali Chauhan, Eunyoung Angela Lee, Rakesh B Patel, Mariia Kumskova, Enrique C Leira, Anil Chauhan, Yanrong Shi, Suyi Cao, Raymond C Koehler, Krishnan M Dhandapani, Mohammad Badruzzaman Khan, Pradip K Kamat, Ali Arbab, David C Hess, Alison L Herman, Ligia Boisserand, Lauren H Sansing, Andreia Morais, Xuyan Jin, Sanem Aykan, Takahiko Imai, Cenk Ayata, Karisma A Nagarkatti, Jessica Lamb, Márcio A Diniz, Patrick D Lyden, Jaroslaw Aronowski, Louise D Mccullough

Faculty, Staff and Student Publications

Background: Stroke is a sexually dimorphic disease, with different risk factors, incidence, outcomes, and treatment responses in men and women. While sex differences have been documented in preclinical studies, these findings often come from single-site studies with small sample sizes and require validation across diverse research settings.

Methods: We used data from the SPAN (Stroke Preclinical Assessment Network), a randomized, placebo-controlled, blinded, multilaboratory trial, to determine if sex differences in neurological outcomes are present in preclinical stroke models. We analyzed data from 665 stroke animals treated with saline, including young mice, diet-induced obese mice, aging mice, young rats, and spontaneously …

Cd8+ T Cells In The Tumor Microenvironment Modulate The Response To Endocrine Therapy In Breast Cancer, Fabiana Napolitano, Yunguan Wang, Dhivya R Sudhan, Paula I Gonzalez-Ericsson, Luigi Formisano, Nisha Unni, Shahbano Shakeel, James Z Zhu, Khushi Ahuja, Lei Guo, María Rosario Chica-Parrado, Yuki Matsunaga, Pamela Luna, Chang-Ching A Lin, Yasuaki Uemoto, Kyung-Min Lee, Hongli Ma, Nathaniel J Evans, Alberto Servetto, Saurabh Mendiratta, Spencer D Barnes, Roberto Bianco, Yisheng V Fang, Lin Xu, Jeon Lee, Tao Wang, Justin M Balko, Gordon B Mills, Marilyne Labrie, Ariella B Hanker, Carlos L Arteaga

Faculty, Staff and Student Publications

The role of the tumor immune microenvironment (TIME) in modulating responses to antiestrogen therapy in hormone receptor-positive (HR+) breast cancers remains unclear. We analyzed pre- and on-treatment biopsies from patients with HR+ breast cancer treated with letrozole to induce estrogen deprivation (ED). Stromal tumor-infiltrating lymphocytes, assessed by H&E staining, and immune-related gene sets, including IFN-γ signaling genes, measured by RNA-Seq, were increased in ED-resistant tumors. Cyclic immunofluorescence and spatial transcriptomics revealed an abundance of CD8+ T cells and enhanced antigen processing and immune gene signatures in ED-resistant tumors. In this group, the expression of CXCL9, CXCL10, and CXCL11 - chemokine …

Women's Preferences For Home-Based Self-Sampling Or Clinic-Based Testing For Cervical Cancer Screening, Joël Fokom Domgue, Monalisa Chandra, Olajumoke Oladoyin, Manali Desai, Robert Yu, Sanjay Shete

Faculty, Staff and Student Publications

Importance: While home-based self-sampling for cervical cancer screening is an evidence-based strategy proven to increase screening access and uptake, it is not currently recommended in the US despite recent Food and Drug Administration approval of the first at-home self-sampling device. Little nationally representative research has examined preference for and drivers of home-based self-sampling over clinic-based testing (the standard of care).

Objective: To assess women's perspectives about, reasons for considering, and factors associated with preferring at-home self-sampling for cervical cancer screening.

Design, setting, and participants: This population-based cross-sectional study used data from the 2024 Health Interview National Trends Survey (HINTS 7), …

Osimertinib Activates A Tgf-Β2-Dependent Secretory Program That Drives Lung Adenocarcinoma Progression, Madhurima Ghosh, Chao Wu, Abhishek Kumar, Monique Nilsson, John V Heymach, Weina Zhao, Jiang Yu, Xin Liu, Na Ding, Shike Wang, Guan-Yu Xiao, Angelo Chen, Kate Grimley, William K Russell, Chad J Creighton, Xiaochao Tan, Jonathan M Kurie

Faculty, Staff and Student Publications

EGFR-mutant lung adenocarcinomas (LUADs) that are vulnerable to the EGFR antagonist osimertinib (Osi) eventually relapse, owing in part to the emergence of drug-tolerant persister (DTP) cells that arise through epigenetic mechanisms. Intratumoral DTP cells can herald a worse clinical outcome, but the way in which DTP cells influence LUAD progression remains unclear. Osi-resistant (OR) cells exhibit typical DTP cell features, including a propensity to undergo senescence and epithelial-mesenchymal transition (EMT), which can activate heightened secretory states. Therefore, we postulated that OR cells influence LUAD progression through paracrine mechanisms. To test this hypothesis, we utilized congenic pairs of EGFR-mutant LUAD cell …

Dispersion-Enhanced Nitrogen-Centered Photocatalysis Of The Direct Hydrogen Atom Transfer, Jiasong Zhang, Kaitong Zhuang, Ramon Trevino, Babu Raj Dhungana, Huiying Sun, Shuyu Yin, Yuting Li, Jacob A Sanchez, Xiaoyu Xia, Ramy Elerian, Yao Sun, Seth O Fremin, Chao Huang, Min He, Maosheng Cheng, Oleg V Larionov, Shengfei Jin

Faculty, Staff and Student Publications

The development of structurally distinct and modular photocatalysts for direct hydrogen atom transfer (HAT) has emerged as a key frontier in radical-mediated C-H functionalization of strong carbon-hydrogen bonds. Despite the largely untapped potential across the fields of organic synthesis, medicinal chemistry, and materials science, few classes of direct HAT photocatalysts are currently known, and the approaches to enhancing their photocatalytic activity remain underdeveloped. We report herein the development of nitrogen-centered direct HAT photocatalysts based on the acridine framework, which leverage a C9-ortho-biaryl substituent for enhancing the photocatalytic activity through stabilizing dispersion interactions with the substrate as the key steering effect. …

The Impact Of Vascular Management On Postoperative Complications In Patients Undergoing Surgery For Retroperitoneal Leiomyosarcoma, Neha Malik, Seokhun Kim, Christopher P Scally, Emily Z Keung, Heather Lillemoe, Keila E Torres, Kelly K Hunt, Sophia Khan, Christina L Roland, Heather G Lyu

Faculty, Staff and Student Publications

Background: Retroperitoneal leiomyosarcomas are aggressive malignancies. Complete surgical resection with negative margins is crucial to decrease the risk of recurrence but can be risky due to vascular involvement. The aim of our study was to evaluate the different approaches to IVC and renal vein management and their impact on postoperative complications.

Methods: We performed a retrospective review of patients who underwent surgery for retroperitoneal leiomyosarcoma with IVC and/or renal vein involvement at our institution from 2016 to 2024. Patients were stratified by intraoperative vascular management, including ligation only versus varying forms of vascular reconstruction. Postoperative complications, including bleeding, transfusions, the …

Transcriptomics And Metabolomics Analysis Reveal Cell Subpopulations Of Trophoblast Cells Associated With Preeclampsia, Xiaojun Zhu, Ying Jiang, Lilin Wang, Peiyue Jiang, Zixing Zhong, Hetong Li, Caihong Zheng, Lujiao Chen, Juan Wei, Xishi Lin, Peng Ding, Zehua Dong, Xiaosheng Wang, Qiong Luo

Faculty, Staff and Student Publications

Placental abnormalities are central to preeclampsia (PE), yet the cellular and molecular mechanisms underlying this dysfunction remain unclear. We applied a multi-layered, integrative approach to investigate placental tissue from patients with PE and matched controls. Single-cell RNA sequencing (scRNA-seq; GSE173193) and bulk RNA sequencing (bulk RNA-seq; GSE203507) datasets were obtained from the Gene Expression Omnibus. The scRNA-seq dataset included two PE and two control samples, whereas the bulk RNA-seq dataset focused on eight early-onset PE and five uncomplicated term births. Trophoblast subpopulations were identified via scRNA-seq, and pseudotime analysis was used to trace differentiation trajectories. Differential expression and pathway enrichment …

Proceedings Of The Second Artificial Intelligence In Primary Immunodeficiency (Aipi) Meeting, Jacques G Rivière, Lisa Bastarache, Luiza C Campos, Gerard Carot-Sans, Aaron Chin, Rumi Chunara, Charlotte Cunningham-Rundles, Lorenzo Erra, Jocelyn Farmer, Nicolas Garcelon, Elena Hsieh, Helen Leavis, Seungwon Lee, Liangying Liu, Maaike Kusters, Brian C Lloyd, Alexandra K Martinson, Rachel Mester, Justin B Moore, Despina Moshous, Jordan S Orange, Nefatia Parrish, Sarah Henrickson Parker, Bogdan Pasaniuc, Xiao P Peng, Martine Pergent, Jordi Piera-Jiménez, Jessica Quinn, Sidharth Ramesh, Kirk Roberts, Peter N Robinson, Guergana Savova, Christopher Scalchunes, Markus G Seidel, Rachel Simoneau, Pere Soler-Palacin, Kathleen E Sullivan, Marielle Van Gijn, Chung-Il Wi, Dawei Zhou, Vanessa Tenembaum, Manish J Butte, Nicholas L Rider

Faculty, Staff and Student Publications

The use of artificial intelligence (AI) in inborn errors of immunity offers transformative potential in diagnostics and disease management but faces multiple challenges that were discussed at the second Artificial Intelligence in Primary Immunodeficiency conference, held in New York City (March 19-22, 2025). The conference addressed 7 themes: predictive diagnostic algorithms, health equity, industry collaboration, advanced computational tools like large language models, patient-led AI initiatives, multiomics integration, and implementation science. Discussions highlighted the growing impact of AI on diagnostics, genomics, and health systems, emphasizing the need for high-quality, diverse datasets and ethical safeguards to ensure equitable application. Participants stressed that …

Scper: A Rigorous Computational Approach To Determine Cellular Subtypes In Tumors Aligned With Cancer Phenotypes From Total Rna Sequencing, Bingrui Li, Xiaobo Zhou, Raghu Kalluri

Faculty, Staff and Student Publications

Single-cell RNA sequencing (scRNA-seq) is a powerful technique for understanding cellular diversity, but processing large patient cohorts to identify phenotype-associated cell populations remains challenging. Here, scPER (Estimating cell Proportions using single-cell RNA-seq Reference), a rigorous approach combining adversarial autoencoder and extreme gradient boosting to estimate tumor microenvironment cell compositions and identify phenotype-associated subclusters for bulk RNA-seq samples. Integrating scRNA-seq datasets from diverse studies, scPER constructed comprehensive reference panels and disentangled confounders from true signals. scPER achieved superior accuracy in cellular proportion estimation compared to CIBERSORTx, BayesPrism, Scaden, MuSiC, SCDC, DeSide and ReCIDE. It showed high accuracy in predicting metastatic melanoma …

Investigation Of Teratogenic Concerns In The Coronavirus Disease Of 2019 Era, Kate Richardson, Emily C Daykin, Kathleen Shields, S Shahrukh Hashmi, Lorrie Harris-Sagaribay, Molly Daniels, Myla Ashfaq

Faculty, Staff and Student Publications

Background: MotherToBaby (MTB) is a teratogen information service that provides information about exposures during pregnancy and breastfeeding to the public and healthcare providers. During the Coronavirus Disease of 2019 (COVID-19) pandemic, MTB received an influx of queries regarding the teratogenicity of the virus and the vaccine. The purpose of this study was to assess the frequency and type of exposures asked about prior to the onset of the COVID-19 pandemic through March 2022 and to evaluate the demographics of individuals who made inquiries.

Methods: Data from MTB contacts (2018-2022) were accessed through a data-sharing agreement. The data were cleaned and …

Development And Implementation Of An Mri-Only Simulation, Planning, And Treatment Workflow For Prostate Radiotherapy Using Synthetic Ct On Mr-Linac, Reza Reiazi, Yao Ding, Sarath Vijayan, Jinzhong Yang, Ergys Subashi, Yao Zhao, Belinda M Lee, Hunter L Emory, Vi T Dinh, Greg L Swiedom, Jie Deng, Mu-Han Lin, Peter Balter, Rajat J Kudchadker, Elaine E Cha, Seungtaek Choi, Yusung Kim, Eun Young Han, Surendra Prajapati

Faculty, Staff and Student Publications

Purpose: We evaluated the feasibility of a magnetic resonance (MR)-only simulation, planning, and treatment (MROSPT) workflow for prostate cancer patients using synthetic computed tomography (sCT) generated from magnetic resonance imaging (MRI) data. By validating sCT-based dose calculations, we aimed to streamline radiotherapy workflows, eliminate the need for CT simulation, and enable reliable clinical implementation of MR-based radiotherapy for MR-linac (MRL).

Methods: We developed a comprehensive workflow encompassing the entire process from initial consultation to treatment delivery. After developing the workflow, a retrospective dosimetric validation study was performed on nine men with prostate cancer. They underwent CT and MRI simulations, and …

Inferring High-Fat Dietary Patterns From Electronic Health Record Data Using Machine Learning, Ya-Yun Yeh, Hsin-Yueh Lin, Jingchuan Guo, Ramon C Sun, Sizun Jiang, Jiang Bian, Hao Dai

Faculty, Staff and Student Publications

Objectives: Electronic health records (EHRs) rarely capture dietary detail, limiting diet-disease research. We aimed to develop machine learning (ML) computable phenotypes to identify high-fat diet (HFD) using variables typically available in EHRs.

Materials and methods: We used National Health and Nutrition Examination Survey (NHANES) 1999-2020 data, where 24-h dietary recall served as ground truth. Dietary fat intake was summarized into a score (0-30) based on percent energy from fat, carbohydrate, and protein; lower scores indicated HFD. We defined HFD at cutoffs of 10, 15, and 20, and trained ML models (Extreme Gradient Boosting, logistic regression, random forest) using EHR-compatible variables …

Implanting Microelectrode Arrays In The Bottom Of The Central Sulcus Targeting Somatosensory Area 3a For Restoration Of Proprioception, Tyler R Johnson, Sarah Moralle, Ziling Luo, Dawn M Taylor

Faculty, Staff and Student Publications

Objective: The long-term goal of this work is to develop a sensorimotor brain-machine interface (BMI) in which intended movements are decoded from the motor cortex and proprioceptive feedback is delivered via intracortical microstimulation of Brodmann's area 3a. A vital step toward this goal is to demonstrate in rhesus macaques a novel surgical approach for the precise and safe implantation of custom-length microelectrode arrays into area 3a at the bottom of the central sulcus.

Methods: Preoperative planning combined high-resolution 7-T MR and CT imaging to generate 3D models of the cortices of 2 subjects. These models were used to fabricate 3D-printed …

Hootation: A Gui And Api Library For Ontology Validation And Verbalization., Muhammad Amith, Xubing Hao, Warren Manuel, Manqi Li, Shun Rao, Kirk Roberts, Hua Xu, Yang Gong, Frank Manion, Cui Tao, Licong Cui

Faculty, Staff and Student Publications

Ontology verbalization refers to the process of translating formal axioms into natural language expressions. The primary objective is to facilitate the review and validation of ontology content by subject matter experts without requiring extensive technical expertise. While previous approaches based on templates or controlled grammar have been effective, they often face limitations in scalability, fluency, and adaptability. To address these issues, we developed Hootation, an open-source software system that supports ontology verbalization through both a graphical user interface and an API library. The tool implements rule-based translation of OWL2 axioms and further incorporates optional Large Language Model (LLM) components for …

Visit-Level Quality Measurement Reveals Missed Opportunities And Overuse In Preventive Oral Health Care, Bunmi Tokede, Suhasini Bangar, Swaroop Gantela, Ryan Brandon, Alfa Yansane, Donald B Rindal, Don Worley, Joel White, Joanna Mullins, Ana Neumann, Todd Johnson, Nicholas Skourtes, Gregory Olson, Janelle Urata, Heather Weidner, Katie Lamberger, Aaron Truong, Heiko Spallek, Elsbeth Kalenderian, Muhammad F Walji

Faculty, Staff and Student Publications

Background: Traditional annual dental quality measures fail to capture real-time care delivery and can mask critical gaps in patient-specific treatment. The authors developed and implemented visit-level adaptations of established caries quality measures to enable actionable, point-of-care assessment.

Methods: The authors conducted a retrospective analysis of 1.09 million dental visits across 400,000 patients (2021-2023) at 4 US institutions using axiUm (Henry Schein Corp) or Epic (Epic Systems) electronic health records. The authors transformed 2 annual measures involving caries risk assessment and risk-based preventive treatment into visit-level metrics using a 2 × 2 matrix framework: action due and performed, due and not …

Phase 1b Pilot Study Of Itacitinib With Alemtuzumab In Patients With T-Cell Prolymphocytic Leukemia, Tapan M Kadia, Akhil Jain, Caitlin R Rausch, Alex Bataller, Farhad Ravandi, Elias Jabbour, Wei Qiao, Gautam Borthakur, Nicholas Short, Guillermo Montalban-Bravo, Andres E Quesada, Jan Burger, Alessandra Ferrajoli, William Wierda, Chitra Hosing, Hagop Kantarjian

Faculty, Staff and Student Publications

T-cell prolymphocytic leukemia (T-PLL) is a mature T-cell neoplasm with an aggressive clinical course. Overall prognosis is poor, and treatment relies on alemtuzumab because of inadequate response to conventional chemotherapy. Three-quarters of cases harbor activating mutations in the JAK-STAT pathway (JAK1, JAK3, STAT5B, IL2RG). We report safety and efficacy from a phase 1B study evaluating the combination of the JAK1 inhibitor itacitinib with alemtuzumab. Patients (N = 15) were aged >18 years, with treatment-naïve (n = 8) or relapsed/refractory (n = 7) T-PLL with adequate organ function, European Cooperative Oncology Group Performance Status ≤2, and …

First Report Of Response To Tarlatamab In A Patient With Histologic-Transformed Sclc From Alk-Rearranged Nsclc: Case Report, Kaiwen Wang, Ceylan Altintas Taslic, Patricia De Groot, Mitchell A Parma, Alvaro Guimaraes Paula, Melody Caranto, Komal Shah, Mukulika Bose, Cole Ruoff, Loukia G Karacosta, Lauren A Byers, Carl M Gay, Jianjun Zhang, John V Heymach, Bingnan Zhang

Faculty, Staff and Student Publications

Small cell transformation has been described as a resistance mechanism to targeted therapy treated in patients with EGFR-mutated NSCLC and less often reported with those with other actionable oncogenic alterations, including ALK-rearranged NSCLC. Given lack of standard-of-care treatments for patients with actionable oncogenic alteration NSCLC transformed to SCLC, this remains a challenge and unmet need for treating these patients.

Here, we present a case of a patient with ALK-rearranged NSCLC with transformation to SCLC, who has progressed on several lines of therapies and successfully treated with tarlatamab to elicit and maintain clinical benefit, including intracranial response.

Fireproof: Intricacies Of Microglial Biology, Wei Cao

Faculty, Staff and Student Publications

No abstract provided.

Outcomes Of Therapy-Related Non-Core Binding Factor Acute Myeloid Leukemia With Venetoclax-Based Therapies, Jayastu Senapati, Jennifer Croden, Guillermo Garcia-Manero, Koichi Takahashi, Naval G Daver, Tapan M Kadia, Gautam Borthakur, Nicholas James Short, Elias Jabbour, Fadi Haddad, Jennifer Marvin-Peek, Hussein A Abbas, Prithviraj Bose, Guilin Tang, Sanam Loghavi, Elizabeth J Shpall, Jeremy Ramdial, Uday R Popat, Richard E Champlin, Farhad Ravandi, Hagop M Kantarjian, Courtney D Dinardo

Faculty, Staff and Student Publications

Prognosis in therapy‐related acute myeloid leukemia (T‐AML) remains poor, but understanding outcomes with venetoclax (VEN)‐based therapy is relevant. We retrospectively analyzed 317 adult patients with newly diagnosed T‐AML focusing on lower intensity therapy (LIT) VEN‐containing regimens. Patients with an antecedent myeloid disorder before AML diagnosis were excluded. The median age was 69 years (range 21–92); 50% evaluated patients had a complex karyotype, and 40% evaluated patients had a TP53 mutation. Composite complete response rates were higher with LIT + VEN compared to LIT (58% vs. 40%, P = 0.003) but were similar in intensive chemotherapy (IC) + VEN versus IC …

Circulating Fatty Acid Binding Protein 4 (Fabp-4) Concentrations And Mortality In Individuals With Colorectal Cancer In The European Prospective Investigation Into Cancer And Nutrition Study, Thu Thi Pham, Katharina Nimptsch, Krasimira Aleksandrova, Mazda Jenab, Veronika Fedirko, Anja Olsen, Anne Tjønneland, Claire Cadeau, Gianluca Severi, Matthias B Schulze, Renée Turzanski Fortner, Verena Katzke, Claudia Agnoli, Carlotta Sacerdote, Rosario Tumino, Simona Signoriello, Camino Trobajo-Sanmartín, Jesús-Humberto Gómez, María-Dolores Chirlaque, Maria-Jose Sánchez, Marta Crous-Bou, Anne May, Alicia Heath, Dagfinn Aune, Elisabete Weiderpass, Tobias Pischon

Faculty, Staff and Student Publications

Human fatty acid binding protein‐4 (FABP‐4), a protein elevated in obesity that promotes colon cancer cell invasiveness and metastasis, may be associated with higher mortality in individuals with colorectal cancer (CRC) and may serve as a mediator of the obesity–mortality association in these individuals. We used a causal diagram to inform covariate selection and applied Cox proportional hazards models to estimate hazard ratios (HRs) for CRC‐specific, non‐CRC‐specific, and all‐cause mortality by FABP‐4 levels measured in baseline blood samples from 1371 incident CRC cases from the European Prospective Investigation into Cancer and Nutrition cohort. Competing risk analyses were adapted for CRC …

Hypoglossal Neuropathy In The Pathogenesis Of Fibrosis-Related Late-Radiation Associated Dysphagia: A Correlative Analysis Utilizing Electromyography To Explore The Frequency Of Clinical And Subclinical Neuropathy In A Pilot Dysphagia Trial, Holly Mcmillan, Christine Okoro, Sheila Buoy, Karin Woodman, Nicolaas Anderson, Clifton Fuller, Stephen Y Lai, Katherine Hutcheson

Faculty, Staff and Student Publications

Background: Late radiation-associated dysphagia (late-RAD) commonly presents in patients with signs of hypoglossal neuropathy, with hallmark clinical features including lingual atrophy, deviation, and fasciculation. Gold-standard electromyography (EMG) has not been used to explore the frequency of hypoglossal neuropathy in patients with late-RAD.

Methods: Exploratory post hoc secondary analysis of MANTLE trial (NCT03612531) was completed. The presence of cranial nerve XII (CN XII) neuropathy was classified by (1) features of clinical assessment as well as (2) intramuscular genioglossus EMG pre-MANTLE intervention in disease-free HNC survivors ≥ 2 years post-radiotherapy (RT) with grade ≥ 2 fibrosis and dysphagia.

Results: All …

Impact Of Treatment Interruption On Outcomes In Head And Neck Cancer: Nrg/Rtog Secondary Analysis, Laila A Gharzai, Emily Morris, Matthew J Schipper, Kelley M Kidwell, Phuc Felix Nguyen-Tân, David I Rosenthal, Maura L Gillison, Richard C Jordan, Adam S Garden, Shlomo A Koyfman, Jimmy J Caudell, Dukagjin M Blakaj, Neal E Dunlap, Greg A Krempl, John M Longo, Christopher U Jones, Michael F Gensheimer, Thomas J Galloway, Lyudmila Demora, Quynh-Thu Le, Jennifer L Shah, Krithika Suresh, Michelle Mierzwa

Faculty, Staff and Student Publications

Importance: Historical evidence demonstrated that delays or interruptions in radiotherapy (RT) are associated with poorer oncologic outcomes in head and neck squamous cell carcinoma (HNSCC). Substantial concerns arose during the COVID-19 pandemic, when treatment schedules were frequently disrupted.

Objective: To determine the association of RT interruptions with locoregional failure (LRF) and overall survival (OS).

Design, setting, and participants: This retrospective review and secondary analysis of 3 randomized clinical trials (NRG/RTOG 0129, 0522, and 1016) included patients enrolled in the trials who were treated with RT. Patients with HNSCC were grouped as (1) p16-positive oropharynx (p16+ OPSCC) and (2) p16-negative oropharynx …

Identification Of Raptor And Gli1 As Usp37 Substrates Highlight Its Context-Specific Function In Medulloblastoma Cells, Ashutosh Singh, Donghang Cheng, Amanda R Haltom, Yanwen Yang, Tara Dobson, Rashieda Hatcher, Veena Rajaram, Vidya Gopalakrishnan

Faculty, Staff and Student Publications

The USP37 gene encodes a deubiquitylase (DUB), which catalyzes the proteolytic removal of ubiquitin moieties from proteins to modulate their stability, cellular localization or activity. Its expression is downregulated in a subgroup of medulloblastomas driven by constitutive activation of sonic hedgehog (SHH) signaling. Patients with SHH-driven medulloblastomas with elevated expression of the RE1 silencing transcription factor (REST) and reduced expression of USP37 have poor outcomes. In previous studies, we showed sustained proliferation of SHH-medulloblastoma cells due to blockade of terminal cell cycle exit and neuronal differentiation stemming from a failure in USP37-dependent stabilization of its target, the cyclin-dependent kinase inhibitor …

Introducing A New Frontier In The Journal Of Pediatric Rehabilitation Medicine: An Interdisciplinary Approach Throughout The Lifespan: The Pediatric Brain Injury Section, Michael Green, Glendaliz Bosques, Kimberly Davis, Brenda Eagan-Johnson, Carty Husted

Faculty, Staff and Student Publications

No abstract provided.

Acta2 Pathogenic Variants Activating Heat Shock Factor 1 And Increasing Cholesterol Biosynthesis In Smooth Muscle Cells Predispose To Early Onset Atherosclerosis, Maura L Boerio, Abhijnan Chattopadhyay, Xue-Yan Duan, Aamuktha Karla, Ernesto Calderon Martinez, Amelie Pinard, Andrew K Morse, Darshan Reddy, Sree Dharma, Walter Velasco-Torrez, Julien Marcadier, Siddharth K Prakash, Sherene Shalhub, Julie De Backer, Richmond Jeremy, Shaine A Morris, Anji T Yetman, Alan C Braverman, Dianna M Milewicz

Faculty, Staff and Student Publications

Background: ACTA2 pathogenic variants predispose to thoracic aortic disease, and a subset of variants lead to early onset atherosclerotic cardiovascular disease (ASCVD). The molecular pathway linking misfolded SMA (α-smooth muscle actin) monomers to augmented atherosclerosis-associated smooth muscle cell phenotypic modulation can be modeled in vitro by stably expressing the ACTA2 p.R149C variant in Acta2-/- smooth muscle cells.

Methods: The Montalcino Aortic Consortium patient registry was used to identify cases with ACTA2 pathogenic/likely pathogenic missense variants. These patients were surveyed, and medical records were reviewed, to identify cases with early onset ASCVD. The variants for these cases, as well as …

Composite Mantle Cell Lymphoma And Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Diagnostic And Therapeutic Challenge, Matthew T Ye, Yaling Yang, M James You

Faculty, Staff and Student Publications

No abstract provided.