Digital Commons Network^™

Fam13a Polymorphism Is Associated With A Usual Interstitial Pneumonia Pattern In Patients With Systemic Sclerosis-Associated Interstitial Lung Disease, Elana J Bernstein, Francesco Boin, Brett Elicker, Yiming Luo, Yawen Ren, Meng Zhang, John Varga, Shervin Assassi

Faculty, Staff and Student Publications

Objectives: The MUC5B promoter single nucleotide polymorphism (SNP) rs35705950 has been associated with idiopathic pulmonary fibrosis (IPF) and RA-related interstitial lung disease (ILD), but not with SSc-ILD. We hypothesized that the MUC5B promoter polymorphism or other IPF susceptibility loci are associated with an increased risk for the uncommon SSc-usual interstitial pneumonia (UIP) endophenotype, rather than SSc-ILD in general.

Methods: We performed a cross-sectional study of SSc-ILD patients from four US Scleroderma Programs to investigate the frequency of MUC5B rs35705950 and 12 additional IPF susceptibility loci. SSc-ILD patients were stratified by high resolution chest CT (HRCT) imaging findings into UIP and …

Utilizing Functional Neuroimaging To Study Early Language Development, Halie A Olson, Trevor K M Day, Kelly J Hiersche, Brittany L Manning, Holly Bradley, Soujin Choi, Gavkhar Abdurokhmonova, Sarah A Mccormick, Amy L Conrad, Dustin Scheinost, Kelly A Vaughn

Faculty, Staff and Student Publications

Language develops rapidly over the infant and toddler period and has been a key area of research within the field of developmental cognitive neuroscience. Understanding the neural basis of early language development may help us predict delays or disorders, recommend early interventions, and provide a deeper mechanistic understanding of how the brain supports language learning. While the ontogeny of many cognitive functions can be studied in animal models, language development can only be studied in human children. Thus, functional neuroimaging is critical for uncovering the neural basis of language in early development. The purpose of this review is to take …

Social Media Listening Study To Understand The Journey And Unmet Needs Of Patients Living With Post-Stroke Spasticity, Stefano Carda, Jörg Wissel, Damon Hoad, Gerard E Francisco, Monica Verduzco-Gutierrez, Daniela Gallardo, Matteo Vacchelli, Jorge Jacinto

Faculty, Staff and Student Publications

Purpose: Stroke survivors may develop spasticity (post-stroke spasticity [PSS]) that can challenge activity and participation. Recognising the needs and expectations of people with PSS is crucial for enhancing care. This study is the first to employ social media listening to explore the experiences, unmet needs, and quality of life (QoL) of people with PSS.

Materials and methods: A subset of 417 patient-centric PSS-related posts published on major social media platforms was identified for analysis from 31 600 retrieved.

Results: Posts mainly discussed patient journey (centred around treatment options and management techniques), the impact of PSS on QoL, and patient interactions …

Navigating Health Literacy: Comparison Of Assessment Tools In A Surgical Safety-Net Population, Mokunfayo O Fajemisin, Stephanie Martinez Ugarte, Gabrielle E Hatton, Jackson G Burns, Lillian S Kao, Krislynn M Mueck

Faculty, Staff and Student Publications

Health literacy as measured by three validated assessment tools.

Refractory Hypoxemia In An Asymptomatic 6-Year-Old: It Is Not Always The Heart, Aymen Mirza, Bibek Bista, Vidhya Annavajjhala, Chinyere O'Connor

Faculty, Staff and Student Publications

No abstract provided.

Benzodioxane-Benzamides Targeting Bacterial Cell Division Protein Ftsz Potentially Disrupt Slma-Mediated Nucleoid Occlusion And Reversible Biomolecular Condensation, Marta Sobrinos-Sanguino, Inés Barros-Medina, Lorenzo Suigo, Alessia Lanzini, Ermanno Valoti, William Margolin, Valentina Straniero, Begoña Monterroso, Silvia Zorrilla

Faculty, Staff and Student Publications

New strategies are urgently needed against antimicrobial resistance, a major health threat, and the different mechanisms regulating the bacterial cell division machinery offer multiple opportunities for developing novel therapeutics. FtsZ, an essential protein of this process, is targeted by multiple small molecules, and benzodioxane-benzamides (BDOBs) are among the most potent inhibitors in several bacterial species. BDOBs mechanisms are however poorly understood, particularly their impact on FtsZ's interplay with partners and ability to assemble phase-separated biomolecular condensates potentially involved in stress sensing. We show that certain BDOBs shielded FtsZ against depolymerization induced by the nucleoprotein complexes of SlmA, which inhibit Z-ring …

Breakwater Phase Iii: Results For Encorafenib And Cetuximab Plus Mfolfox6 In First-Line Braf V600e-Mutant Metastatic Colorectal Cancer, Scott Kopetz, Josep Tabernero, Elena Élez

Faculty, Staff and Student Publications

The BREAKWATER Phase III study investigated encorafenib and cetuximab plus mFOLFOX6 versus chemotherapy with or without bevacizumab for the treatment of patients with previously untreated BRAF V600E – mutant metastatic colorectal cancer. The study showed significantly improved objective response rate by blinded independent central review, and significantly longer progression-free survival by blinded independent central review and overall survival in patients treated with first-line encorafenib and cetuximab plus mFOLFOX6 compared with chemotherapy with or without bevacizumab. The safety profiles were consistent with those known for each agent. These results led to the approval of encorafenib and cetuximab plus mFOLFOX6 for the …

Tubulin Regulates Stability And Localization Of Stmn2 By Binding Preferentially To Its Soluble Form, Xiang Deng, Gary A Bradshaw, Marian Kalocsay, Timothy Mitchison

Faculty, Staff and Student Publications

The small, tubulin-binding protein STMN2 is highly expressed in neurons and is implicated in amyotrophic lateral sclerosis. STMN2 degrades rapidly and accumulates at axotomy sites, suggesting fast turnover is crucial for its neuroprotective function. We show that STMN2 was primarily degraded by the ubiquitin-proteasome system. Its membrane-targeting N-terminal domain promoted fast turnover, whereas its tubulin-binding domain promoted stabilization. Proximity labeling and imaging showed that tubulin binding reduced STMN2 targeting to trans-Golgi network membranes. Pull-down assays showed that tubulin binds preferentially to soluble over membrane-bound STMN2. Our observations suggest that STMN2 interconverts between a soluble, tubulin-bound form and a membrane-bound, tubulin-free …

Smags-Lasso: A Novel Feature Selection Method For Sensitivity Maximization In Early Cancer Detection, Hamid Khoshfekr Rudsari, Sara Khorami-Sarvestani, Johannes F Fahrmann, James P Long, Samir Hanash, Kim-Anh Do, Ehsan Irajizad

Faculty, Staff and Student Publications

Background: Sensitivity and specificity are foundational metrics for cancer detection tools. However, most machine learning algorithms prioritize overall accuracy during optimization, which fails to align with clinical priorities of early detection. We aim to develop a feature selection machine learning algorithm while maximizing sensitivity at a given specificity.

Methods: We developed SMAGS-LASSO, a machine learning algorithm that combines our developed Sensitivity Maximization at a Given Specificity (SMAGS) framework with L1 regularization for feature selection. This approach simultaneously optimizes sensitivity at user-defined specificity thresholds while performing feature selection. SMAGS-LASSO utilizes a custom loss function with L1 regularization and multiple parallel optimization …

Knowledge Mapping And Visualized Analysis Of Research Progress In Onconephrology: A Bibliometric Analysis, Yiwei Wang, Shuling Fan, Wei Wang

Faculty, Staff and Student Publications

Objectives: Onconephrology is an expanding subspecialty focused on the management of cancer patients with renal injury. This study used a comprehensive bibliometric analysis to emphasize the need for cooperation between oncologists and nephrologists, exploring current trends and future research areas in onconephrology.

Methods: Relevant literature on onconephrology published between 1 January 2000 and 27 April 2024 was retrieved from the Science Citation Index Expanded of the Web of Science Core Collection, followed by manual screening. Bibliometric analyses were performed using CiteSpace, VOSviewer, and Bibliometrix software.

Results: A total of 1,853 publications, including 1,647 articles and 206 reviews, by 11,606 authors …

Secretory Iga Dysfunction Underlies Poor Prognosis In Fusobacterium-Infected Colorectal Cancer, Ilseok Choi, Kyung-A Kim, Sang Cheol Kim, Donghwan Park, Ki Taek Nam, Jun Hyung Cha, Seungbyn Baek, Junha Cha, Hye-Yeong Jo, Minsun Jung, Melody Y Zeng, Irina Matei, Susan Bullman, Joong Bae Ahn, Yoon Dae Han, Han Sang Kim, Insuk Lee

Faculty, Staff and Student Publications

Fusobacterium nucleatum (Fn) is commonly enriched in colorectal cancer (CRC) and associated with poor outcomes, though its mechanisms remain unclear. Our study investigated how Fn affects the tumor microenvironment through single-cell transcriptomic analyses of 42 CRC patient tissues, comparing Fn-positive and Fn-negative tumors. We discovered that Fn impairs IgA plasma cell development and secretory IgA (sIgA) production by disrupting communication with tumor-associated macrophages. Additional experiments in germ-free mice, together with our re-analysis of a publicly available single-cell RNA-seq data set from a CRC mouse model with an intact gut microbiome–both models having been orally gavaged with Fn–jointly validated the causal …

Extracellular Domain Shedding Of Trop2 Activates Egfr Signaling To Drive Prostate Cancer Metastasis, Shiqin Liu, En-Chi Hsu, Merve Aslan, Fernando Garcia-Marques, Michelle Shen, Alifiani B Hartono, Francisco Solano, Kewei Le, Hyeonji Hwang, Chung S Lee, Abel Bermudez, Rosalie Nolley, Donna M Peehl, James D Brooks, Michael A Liss, Sharon J Pitteri, Tanya Stoyanova

Faculty, Staff and Student Publications

UNLABELLED: Metastasis is the main cause of prostate cancer-associated deaths, highlighting the urgent need to determine the mechanisms underlying prostate cancer progression. TROP2 (also known as tumor-associated calcium signal transducer 2) is an oncogenic transmembrane surface protein that is highly expressed in metastatic prostate cancer. Naturally occurring cleavage of TROP2 leads to a release of the TROP2 extracellular domain (TECD) into the extracellular environment. In this study, we identified an important functional role of TECD in prostate cancer metastasis. TECD was detectable in media from prostate cancer cells and serum from patients with clinically significant prostate cancer. Although shed TECD …

Acculturation, Values, And Acculturative Stress For Autistic Latino Emerging Adults And Spanish-Speaking Parents Participating In The ¡Iniciando! La Adultez Program, Antonio F Pagán, Miriam Ortiz, Erin Bernal, Katherine A Loveland, Ana Esparza, Cecilia Montiel-Nava, Ron Acierno

Faculty, Staff and Student Publications

Latino families with emerging adults diagnosed with Autism Spectrum Disorder (ASD) face unique challenges during the transition to adulthood, influenced by cultural values, acculturation, and systemic barriers. Acculturation and acculturative stress are particularly relevant in this population, as they navigate cultural adaptation while maintaining traditional values like familismo (family) and respeto (respect). These dynamics are further complicated by disparities in access to resources and culturally responsive interventions. This study explores the interplay of cultural values, acculturation, and acculturative stress among Latino emerging adults with ASD and their Spanish-speaking parents participating in a culturally adapted and translated intervention. Using a cross-sectional …

Differential Microrna Profiling Of Blood L1cam And Bulk Extracellular Vesicles In Bipolar Disorder, Gabriel R Fries, Salahudeen Mirza, Jun Wang, Camila N C Lima, Wei Zhang, Marcela Carbajal Tamez, Giselli Scaini, Jair C Soares, Joao Quevedo

Faculty, Staff and Student Publications

Objective: This preliminary study aimed to identify microRNA (miRNA) signatures associated with bipolar disorder (BD) by profiling blood-derived extracellular vesicles (EVs) of both putative neuronal origin and from all sources.

Method: In two parallel studies of individuals with BD and controls (CON), we characterized miRNA expression profiles of blood EVs selected for L1CAM, a putative marker of neuronal origin (n = 20 BD/20 CON), as well as bulk EVs (n = 21 BD/20 CON). For each study, analyses identified miRNAs differentially expressed between groups, followed by functional interrogation and testing for associations with clinical features.

Results: Results of …

Neighborhood-Level Social Vulnerability, Race And Ethnicity, And Stage At Diagnosis: A Population-Based Study Of 12,957 Patients With Oral Cavity Cancer, Guillermo A Tortolero, Erich M Sturgis, Jose-Miguel Yamal, Melissa F Peskin, Cici Bauer, Caitlin C Murphy

Faculty, Staff and Student Publications

Background: Oral cavity cancer (OCC) is marked by racial and ethnic disparities. We examined these differences in OCC stage at diagnosis and whether neighborhood-level social vulnerability, a measure of susceptibility to hardship at the census-tract level, modifies disparities.

Methods: We identified adults newly diagnosed with OCC (1995 to 2020) from the Texas Cancer Registry. We estimated the association between stage at diagnosis and race and ethnicity using logistic regression and assessed effect modification by neighborhood-level social vulnerability.

Results: The sample included 12,957 reported OCC cases, 77% non-Hispanic White, 6% non-Hispanic Black, and 14% Hispanic patients, and 47.4% late stage at …

Real-World First-Line Outcomes Of Alectinib And Brigatinib In Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer: A Nationwide South Korean Cohort Study Using The Health Insurance Review And Assessment Data, Hee Jun Kim, Eunyoung Angela Lee, Jin-Hee Park, Hyun Woo Lee

Faculty, Staff and Student Publications

Background: Lung cancer remains the leading cause of cancer-related mortality worldwide. Anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) presents unique clinical challenges, including frequent central nervous system (CNS) metastases. At present, comparative real-world data on ALK inhibitors remain limited. This study aimed to compare real-world progression-free survival (PFS) and overall survival (OS) among patients with ALK-positive NSCLC treated with first-line alectinib or brigatinib using nationwide South Korean data.

Methods: This retrospective cohort study analyzed anonymized data from South Korea's Health Insurance Review and Assessment Service, covering January 2007 to December 2023. Patients diagnosed with ALK-positive NSCLC (ICD-10: C34x) …

Stage- And Smoking-Associated Microrna Expression In Lung Adenocarcinoma, Min Huang, Yimin Ge, Huiqin Chen, Caimiao Wei, David Cogdell, Cristina Ivan, Meng Chen, Wei Zhang, George A Calin, Ming Guo

Faculty, Staff and Student Publications

Background: Altered expression of microRNAs (miRNAs) is implicated in lung carcinogenesis, but little research has investigated the association of miRNA alterations with lung cancer stage or smoking status. To identify such alterations in lung adenocarcinoma, we conducted miRNA profiling.

Methods: Lung adenocarcinoma specimens and paired nonneoplastic lung tissues from 58 patients who had received no preoperative therapy and underwent tumor resection from 1991 to 2006 were collected from tumor tissue banks. Thirty (52%) of the tumors were stage I and 28 (48%) stage II or higher. Twenty-five (43%) patients were nonsmokers and 33 (57%) were smokers. To identify miRNAs of …

Early Determination Of The Dorsal-Ventral Axis In Endochondral Ossification In Mice, Sixun Wu, Hirotaka Matsumoto, Jumpei Morita, Mina Yamabe, Azumi Noguchi, Shinsuke Ohba, Noriaki Ono, Yuki Matsushita

Faculty, Staff and Student Publications

Endochondral ossification is a highly coordinated process involving distinct progenitor cell populations within the mesenchymal condensation and subsequent cartilage anlage and perichondrium, all of which drive skeletal formation. Cell-type specific lineage tracing conducted to understand fetal bone development has revealed various fates of early skeletal cells. However, the underlying continuous and precise cellular dynamics of fetal skeletal cells, particularly along the dorsoventral axis, remain unclear. Here, we show that spatiotemporally specific skeletal progenitor cells in the early developmental stage contribute to the dorsal-ventral axis in a manner that is strictly determined during initial developmental stages. Lineage-tracing experiments using Fgfr3-creER and …

Recombination Suppression Drives Expansion Of The Drosophila Dot Chromosome, Timothy J Stanek, Wilson Leung, Christopher D Shaffer, Ishtar Olaveja, Annabelle Laughlin, Jaquelyn Hester, Darwin Garrido, Emily K Oh, Maria Volski, Nistha Panda, Mia Mo, Ethan Cordes, Martin Dalling, Kacie Kershaw, Malcolm Arnott, Stephen Daly, Silvia Garcia Valenzuela, Paige Thompson, Kayla L Hastert, Destiny Sabb, Kathryn Karpinski, Meher Naaz Arora, Nicholas Rius, Larissa Lobello, Sebastian Jaramillo, Omkar Sonavane, Alice Herrmann, Laura K Reed, Sarah C R Elgin, Cindy Arrigo, Christopher E Ellison

Faculty, Staff and Student Publications

Genome size varies widely, even among closely related species, yet much less is known about chromosome size variation. Here we use the fourth chromosome of Drosophila, also known as the "Muller F element" or "dot chromosome", as a model to investigate chromosome-specific size expansion. The F element of most Drosophila species is small (∼1.3 Mb) and almost entirely heterochromatic, yet harbors approximately 80 protein-coding genes. Here, we study D. kikkawai, D. takahashii, D. ananassae, and D. bipectinata, whose F elements are 2- to 15-fold larger in size compared to D. melanogaster. Through manual gene curation and comparative genomic analysis, we …

Developmental Stage-Dependent Transcriptomic Responses To Neonatal Intraventricular Hemorrhage, Elizabeth Wallace-Anthony, Miriam Zamorano, Hemendra J Vekaria, Braden B Oldham, Kiara P Umpornpun, Scott D Olson, Stefano Berto, Brandon A Miller

Faculty, Staff and Student Publications

Neonatal intraventricular hemorrhage (IVH) is a major complication of preterm birth, yet how developmental stage influences the brain's response to injury remains unclear. We performed single-nucleus RNA sequencing on rat brains 24 h after IVH at postnatal day 2 (PND2) or day 5 (PND5) to define transcriptional responses across cell types. We identified 42 distinct cell populations and found that PND5 brains exhibited a markedly stronger immune and inflammatory response to IVH, with a threefold increase in differentially expressed genes compared to PND2. Microglia were the most perturbed cell type at both stages, showing increased oxidative stress and polarization toward …

Radiologist-Validated Automatic Lumbar T1-Weighted Spinal Mri Segmentation Tool Via An Attention U-Net Algorithm, Aryan Kalluvila, Ethan Wang, Michael C Hurley, Colbey Freeman, Jason M Johnson

Faculty, Staff and Student Publications

Background/Objectives: Spinal MRI segmentation has become increasingly important with the prevalence of disc herniation and vertebral injuries. Artificial intelligence can help orthopedic surgeons and radiologists automate the process of segmentation. Currently, there are few tools for T1-weighted spinal MRI segmentation, with most focusing on T2-weighted imaging. This paper focuses on creating an automatic lumbar spinal MRI segmentation tool for T1-weighted images using deep learning.

Methods: An Attention U-Net was employed as the main algorithm because the architecture has shown success in other segmentation applications. Segmentation loss functions were compared, focusing on the difference between BCE and MSE loss. Two board-certified …

Outcomes After Flow Diversion For Ruptured Blood Blister-Like And Dissecting Aneurysms: A Single-Center Series, William W Wroe, Hussein A Zeineddine, Si Y Yu, Bridger H Freeman, Richard S Cook, Charles M Christensen, Peng Roc Chen, Sunil A Sheth, Spiros L Blackburn

Faculty, Staff and Student Publications

Background

Flow diverter (FD) use has become a popular method for treating intracranial aneurysms, but evidence in acutely ruptured blood blister-like and dissecting morphologies is limited. Furthermore, there is little evidence regarding the role of short-term follow-up imaging to assess aneurysm stability. This study is a single-center retrospective review of dissecting aneurysms treated by FD, with an analysis of short-term follow-up angiograms to guide post-treatment management.

Methods

Our single-center retrospective review included all patients from 2016 to 2024 with spontaneous subarachnoid hemorrhage from blood blister-like and dissecting aneurysms who underwent treatment with an FD. Outcomes included re-rupture, treatment failure, re-treatment, …

Benchmarking Dna Foundation Models For Genomic And Genetic Tasks, Haonan Feng, Lang Wu, Bingxin Zhao, Chad Huff, Jianjun Zhang, Jia Wu, Lifeng Lin, Peng Wei, Chong Wu

Faculty, Staff and Student Publications

The rapid evolution of DNA foundation models promises to revolutionize genomics, yet comprehensive evaluations are lacking. Here, we present a comprehensive, unbiased benchmark of five models (DNABERT-2, Nucleotide Transformer V2, HyenaDNA, Caduceus-Ph, and GROVER) across diverse genomic and genetic tasks including sequence classification, gene expression prediction, variant effect quantification, and topologically associating domain (TAD) region recognition, using zero-shot embeddings. Our analysis reveals that mean token embedding consistently and significantly improves sequence classification performance, outperforming other pooling strategies. Model performance varies among tasks and datasets; while general purpose DNA foundation models showed competitive performance in pathogenic variant identification, they were less …

Human Plasma Proteomic Profile Of Clonal Hematopoiesis, Zhi Yu, Amélie Vromman, Ngoc Quynh H Nguyen, Art Schuermans, Linke Li, Thiago Rentz, Tetsushi Nakao, Shamsudheen K Vellarikkal, Md Mesbah Uddin, Abhishek Niroula, Gabriel Griffin, Michael C Honigberg, Amy E Lin, Christopher J Gibson, Daniel H Katz, Usman A Tahir, Shi Fang, Jacqueline S Dron, Michael Pan, Sara Haidermota, Shriienidhie Ganesh, Tajmara Antoine, Joshua Weinstock, Thomas R Austin, Ramachandran S Vasan, Gina M Peloso, Whitney Hornsby, Peter Ganz, Joann E Manson, Bernhard Haring, Charles Kooperberg, Alexander P Reiner, Joshua C Bis, Bruce M Psaty, Yuan-I Min, Adolfo Correa, Leslie A Lange, Wendy S Post, Jerome I Rotter, Stephen S Rich, James G Wilson, Benjamin L Ebert, Bing Yu, Christie M Ballantyne, Josef Coresh, Vijay G Sankaran, Alexander G Bick, Siddhartha Jaiswal, Robert E Gerszten, Nhlbi Trans-Omics For Precision Medicine, Peter Libby, Rajat M Gupta, Pradeep Natarajan

Faculty, Staff and Student Publications

Plasma proteomic profiles associated with subclinical somatic mutations in blood cells may offer insights into downstream clinical consequences. Here we explore these patterns in clonal hematopoiesis of indeterminate potential (CHIP), which is linked to several cancer and non-cancer outcomes, including coronary artery disease (CAD). Among 61,833 participants (3881 with CHIP) from TOPMed and UK Biobank (UKB) with blood-based DNA sequencing and proteomic measurements (1,148 proteins by SomaScan in TOPMed and 2917 proteins by Olink in UKB), we identify 32 and 345 proteins from TOPMed and UKB, respectively, associated with CHIP and most prevalent driver genes (DNMT3A, TET2, and ASXL1). These …

Developing Ehealth Interventions To Improve Diabetes Management In Emerging Adulthood: Qualitative Formative Study, April Idalski Carcone, Deepika Baskar, Aishah Mahmood, Karen Macdonell, Susan Eggly, Samiran Ghosh, Colleen Buggs-Saxton, Steven J Ondersma, Deborah A Ellis

Faculty, Staff and Student Publications

Background: Emerging adulthood is a high-risk period during which many with type 1 diabetes demonstrate suboptimal diabetes management and glycemic control. There is a need for effective, scalable interventions designed specifically for this population. Technology-based approaches are readily accessible to this age group. Furthermore, interventions consistent with self-determination theory-which posits that the fulfillment of psychological needs for autonomy, self-efficacy, and relatedness promotes intrinsic motivation for change-may resonate well with emerging adults' developmental needs for establishing independence and autonomy, and growing their social network.

Objective: This study aimed to enhance the potential relevance, sustainability, and efficacy of 3 self-determination theory-informed mobile …

Met Overexpression Is Associated With Superior Immunotherapy Benefit In Advanced Non-Small Cell Lung Cancer, Hui Li, Lingzhi Hong, Pedro Rocha, Rafael Bach, Luisa M Solis Soto, Waree Rinsurongkawong, Bingnan Zhang, Haniel A Araujo, Yasir Y Elamin, Mehmet Altan, Claudio A Arrechedera, Jianling Zhou, Khaja B Khan, Wei Lu, Elliana Young, Carl M Gay, Tina Cascone, Lauren A Byers, Ferdinandos Skoulidis, George Blumenschein, Frank V Fossella, Anne Tsao, Marcelo V Negrao, Natalie Vokes, Jia Wu, Hai T Tran, Ignacio I Wistuba, J Jack Lee, Don L Gibbons, Ara A Vaporciyan, John V Heymach, Xiuning Le, Jianjun Zhang

Faculty, Staff and Student Publications

Background/objectives: MET overexpression is common in non-small cell lung cancer (NSCLC). The correlation between MET overexpression and immune checkpoint inhibitor (ICI) efficacy in NSCLC is underexplored.

Methods: In this retrospective observational cohort study, we curated a dataset of 279 stage IV NSCLC patients who received ICI treatment and had MET expression assessed by CLIA-certified immunohistochemistry (IHC) assay. MET expression was graded on a scale from 0 to 3+, with overexpression defined as 2+ or 3+. Clinicopathological features associated with MET expression were assessed using logistic regression. Overall survival (OS) and progression-free survival (PFS) were evaluated via Kaplan-Meier analysis and the …

Improving Diagnostic Accuracy In Preoperative Glioma Classification: Performance Of Knowledge-Enhanced Large Language Models Compared With Radiologists, Shuang Li, Xin Fang, Yuqi Jin, Yujiao Deng, Wei Hu, Bing Wu, Xiaobo Zhou, Guotai Wang, Kang Li, Qiang Yue

Faculty, Staff and Student Publications

Accurate preoperative MRI classification of gliomas is essential but challenging due to complex radiological features and inter-observer variability. This study evaluated three large language models (LLMs) for VASARI-based glioma classification compared to radiologist interpretations. We retrospectively analyzed 150 histopathologically confirmed gliomas (43 circumscribed astrocytic, 53 high-grade diffuse, 54 low-grade diffuse gliomas) using standardized MRI protocols. Three radiologists extracted VASARI features, while three LLMs (GPT-4, Claude3.5-Sonnet, Claude3.0-Opus) analyzed these features using standard input-output or knowledge-enhanced prompting incorporating diagnostic guidelines. Knowledge-enhanced prompting consistently outperformed standard prompting, improving diagnostic consistency (intra-model agreement: Sonnet κ = 0.91, Opus κ = 0.92, GPT-4 κ = …

A Phase 1/2 Study Of Ds-1594 Menin Inhibitor In Relapsed/Refractory Acute Leukemias, Jayastu Senapati, Marina Konopleva, Ghayas C Issa, Elias Jabbour, Tapan Kadia, Courtney Dinardo, Gautam Borthakur, Naveen Pemmaraju, Nicholas J Short, Musa Yilmaz, Indraneel Deshmukh, Joie Alvarez, Sanam Loghavi, Guilin Tang, Hussein A Abbas, Michael Andreeff, Kapil Bhalla, Narasimha M Midde, Nabil Said, Amy Noyalis, Derek E Mires, Jing Ning, Lianchun Xiao, Farhad Ravandi, Guillermo Garcia-Manero, Hagop M Kantarjian, Naval G Daver

Faculty, Staff and Student Publications

Several menin inhibitors are in development targeting menin dependent leukemias, however available preclinical results show variable level of activity. We report the phase 1 portion (to establish a recommended phase 2 dose [RP2D]) and pharmacokinetic analysis of a phase 1/2 first-in-human clinical trial of DS-1594b menin inhibitor. Eligible patients included adults (≥ 18 years of age) with relapsed/refractory (R/R) acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) including but not restricted to those with KMT2A-rearrangement (r) or NPM1 mutation. Seventeen patients at a median of age 56 years (range, 19-82 years) were treated, 15 (88%) had R/R AML, and …

Brain Power Comparison Between Microgravity And Head-Down Tilt Bed Rest: An Electroencephalography Approach, María Sevilla-García, Adrián Quivira-Lopesino, Pablo Cuesta, Sandra Pusil, Ricardo Bruña, Patrique Fiedler, Fernando Maestu, Ana Maria Cebolla, Guy Cheron, Katharina Brauns, Alexander C Stahn, Michael E Funke

Faculty, Staff and Student Publications

This study examines neurophysiological changes in microgravity by comparing EEG data from two ground analog 60-day head-down tilt bed rest (HDBR) experiments (ESA/DLR “Cocktail” and “RSL”) and the NEUROSPAT experiment in space. The primary objective was to determine whether HDBR could effectively model spaceflight’s impact on the human brain’s EEG signal. In the HDBR dataset, increases in relative delta (2–4 Hz) (p <  0.01) and theta (4–8 Hz) (p <  0.001) power bands were observed during a two-month HDBR experiment, predominantly in the left temporal and parieto-occipital regions. Conversely, the NEUROSPAT dataset showed a significant increase in beta (12–30 Hz) (p <  0.05) power in the left somatosensory cortex during in-flight conditions, suggesting a potential adaptation to disrupted proprioceptive input and motor control in microgravity. The contrasting findings between the two datasets indicate that while HDBR can simulate some aspects of microgravity, it may not serve as a model for all central nervous system changes, especially those related to proprioception and motor functions. This highlights the need for further research, including larger sample sizes, consistent EEG recording conditions, and integration of additional physiological and cognitive markers to fully understand the effects of prolonged microgravity.

Soluble Immune Factor Profiles In Blood And Csf Associated With Lrrk2 Mutations And Parkinson's Disease, Roshni Jaffery, Yuhang Zhao, Sarfraz Ahmed, Jackson G Schumacher, Jae Ahn, Leilei Shi, Yujia Wang, Yukun Tan, Jiayin Zhang, Ken Chen, Hussein Tawbi, Jian Wang, Michael A Schwarzschild, Weiyi Peng, Xiqun Chen

Faculty, Staff and Student Publications

Mutations in LRRK2, a leading genetic cause of Parkinson's disease (PD), are linked to immune dysregulation, but the immune profiles in the periphery and central nervous system (CNS) remain incompletely defined. This study utilized a large cohort of serum samples (n = 651) and matched CSF samples (n = 129) from LRRK2 mutation carriers and non-carriers, with and without PD, to assess immune regulators using Luminex immunoassay. After correction for multiple comparisons, LRRK2 mutations were associated with significantly elevated serum levels of SDF-1 alpha and TNF-RII, while CSF markers such as BAFF, CD40L, and IL-27 were nominally reduced. Regardless of …