Medical Specialties Commons^™

Food Literacy Program Among Adults In A Primary Care Setting, Marie K. Williams

Student Scholarly Projects

Practice problem: The increase in preventable chronic diseases is associated with food illiteracy, which arises from a lack of understanding of nutritional value and dietary guidelines (Silva et al., 2023).

PICOT: (P) In adult primary care patients aged 30-75 years, (I) does the implementation of evidence-based food literacy program (C) compared to standard practice (O) improve food literacy (T) in eight weeks?

Evidence: Using a validated food literacy questionnaire effectively measures improvements in food literacy. Customized programs that fill knowledge gaps are essential for enhancing overall food literacy. Intervention: Customized educational tools were provided to participants based on their knowledge …

Imaging Efficacy And Safety Of Low Dose Intraventricular Tissue Plasminogen Activator In Aneurysmal Subarachnoid Hemorrhage: Case Series, Collin Liu, William W Wroe, Hussein A Zeineddine, Bryden Dawes, Michael Giordano, Aaron Mccabe, Ching-Jen Chen, Devin W Mcbride, Aaron M Gusdon, Huimahn A Choi, Spiros L Blackburn

Faculty, Staff and Student Publications

Introduction: Free hemoglobin's release into CSF from blood breakdown is a primary instigator of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Early clearance of subarachnoid blood with intrathecal (IT) fibrinolytics has shown potential to decrease incidence of DCI. However, the dosage of fibrinolytic needed is not known. We investigated the ability of low dose tissue plasminogen activator (tPA) to rapidly remove subarachnoid clot.

Material and methods: We performed a single center retrospective review of aSAH patients who received IT tPA. Dosing consistent with the CLEAR III trial for IVH was utilized-tPA (1 mg) administered every 8 h via …

Cancer Screening Uptake And Usual Source Of Care Among Hispanic Survivors Of Adolescent And Young Adult Cancer, Eunju Choi, Amy M Berkman, Clark R Andersen, John M Salsman, Andrea C Betts, Joel Milam, Kimberly A Miller, Susan K Peterson, Qian Lu, Christabel K Cheung, Lauren V Ghazal, J A Livingston, Michelle A T Hildebrandt, Susan K Parsons, David R Freyer, Michael E Roth

Faculty, Staff and Student Publications

Purpose: This study examines cancer screening rates and the usual source of care among Hispanic survivors of adolescent and young adult (AYA, aged 15-39) cancer, a group at increased risk for poor health outcomes, including secondary cancers.

Methods: National Health Interview Survey data were analyzed to identify Hispanic survivors of AYA cancer and Hispanic age- and sex-matched non-cancer controls. Breast, cervical, and colorectal screening (ever screened and up-to-date according to the U.S. Preventive Services Task Force recommendations) as well as reporting a usual source of care were compared among survivors and controls eligible for screening using multivariable logistic regressions.

Results: …

Minimal Ablative Margin Quantification Using Hepatic Arterial Versus Portal Venous Phase Ct For Colorectal Metastases Segmentation: A Dual-Center, Retrospective Analysis, Noreen S Siddiqi, Yuan-Mao Lin, Jessica Albuquerque Marques Silva, Gregor Laimer, Peter Schullian, Yannick Scharll, Alexandra M Dunker, Caleb S O'Connor, Kyle A Jones, Kristy K Brock, Reto Bale, Bruno C Odisio, Iwan Paolucci

Faculty, Staff and Student Publications

Objective: To compare the predictive value of minimal ablative margin (MAM) quantification using tumor segmentation on intraprocedural contrast-enhanced hepatic arterial (HAP) versus portal venous phase (PVP) CT on local outcomes following percutaneous thermal ablation of colorectal liver metastases (CRLM).

Methods: This dual-center retrospective study included patients undergoing thermal ablation of CRLM with intraprocedural preablation and postablation contrast-enhanced CT imaging between 2009 and 2021. Tumors were segmented in both HAP and PVP CT phases using an artificial intelligence-based auto-segmentation model and reviewed by a trained radiologist. The MAM was quantified using a biomechanical deformable image registration process. The area under the …

Survival-Inferred Fragility Of Statistical Significance In Phase Iii Oncology Trials, Alexander D Sherry, Yufei Liu, Pavlos Msaouel, Timothy A Lin, Alex Koong, Christine Lin, Joseph Abi Jaoude, Roshal R Patel, Ramez Kouzy, Molly B El-Alam, Avital M Miller, Mohannad Owiwi, Jonathan Ofer, David Bomze, Zachary R Mccaw, Tomer Meirson, Ethan B Ludmir

Faculty, Staff and Student Publications

In phase III oncology trials, superiority is defined by statistical significance using P thresholds. However, this approach has been criticized because P is continuous. Here, we reconstruct patient-level data for 230 phase III oncology trials to model the robustness of statistical significance by estimating the survival-inferred fragility index (SIFI), defined as the smallest number of patients changing arms that alters the statistical significance interpretation. The median SIFI was 8 patients (IQR 4-19), representing 1.4% of enrollments (IQR 0.7%-3%). As a continuous statistic, P-but not the significance interpretation-was correlated with SIFI. Moreover, overall survival endpoints were more fragile than surrogate endpoints. …

Feasibility Of Manufacturing And Antitumor Activity Of Til For Advanced Endometrial Cancers, Yongliang Zhang, Kathleen N Moore, Amir A Jazaeri, Judy Fang, Ilabahen Patel, Andrew Yuhas, Patrick Innamarato, Nathan Gilbert, Joseph W Dean, Behzad Damirchi, Joe Yglesias, Rongsu Qi, Michelle R Simpson-Abelson, Erwin Cammaart, Sean R R Hall, Hequn Yin

Faculty, Staff and Student Publications

Lifileucel, a tumor-infiltrating lymphocyte (TIL) cell therapy approved for advanced melanoma, demonstrates promise for treating other solid tumors, including endometrial cancer (EC). The current study evaluates the feasibility of manufacturing TILs from EC tumors using Iovance’s proprietary 22-day Gen2 manufacturing process. Key parameters, including TIL yield, viability, immune phenotype, T-cell receptor clonality, and cytotoxic activity, were assessed. Of the 11 EC tumor samples processed at research scale, 10 (91%) successfully generated >1 × 109 viable TIL cells, with a median yield of 1.1 × 1010 cells and a median viability of 82.8%. Of the four EC tumor samples processed at …

Machine-Learning Driven Strategies For Adapting Immunotherapy In Metastatic Nsclc, Maliazurina B Saad, Qasem Al-Tashi, Lingzhi Hong, Vivek Verma, Wentao Li, Daniel Boiarsky, Shenduo Li, Milena Petranovic, Carol C Wu, Brett W Carter, Girish S Shroff, Tina Cascone, Xiuning Le, Yasir Y Elamin, Mehmet Altan, Simon Heeke, Ajay Sheshadri, Joe Y Chang, Percy P Lee, Zhongxing Liao, Don L Gibbons, Ara A Vaporciyan, J Jack Lee, Ignacio I Wistuba, Cara Haymaker, Seyedali Mirjalili, David Jaffray, Justin F Gainor, Yanyan Lou, Alessandro Di Federico, Federica Pecci, Mark Awad, Biagio Ricciuti, John V Heymach, Natalie I Vokes, Jianjun Zhang, Jia Wu

Faculty, Staff and Student Publications

Immune checkpoint inhibitors (ICIs), either as monotherapy (ICI-Mono) or combined with chemotherapy (ICI-Chemo), improves survival in advanced non-small cell lung cancer (NSCLC). However, prospective guidance for choosing between these options remains limited, and single-feature biomarkers like PD-L1 prove inadequate. We develop a machine learning model using clinicogenomic data from four cohorts (MD Anderson n = 750; Mayo Clinic n = 80; Dana-Farber n = 1077; Stand Up To Cancer n = 393) to predict individual benefit from adding chemotherapy. Benefit scores are calculated using five distinct functions derived from 28 genomic and 6 clinical features. Our integrated model, A-STEP (Attention-based …

The Histone H3 Lysine 36 Demethylase Kdm2a/Fbxl11 Controls Polycomb-Mediated Gene Repression And Germ Cell Development In Male Mice, Michael T Bocker, Grigorios Fanourgakis, Kristie Wetzel, Pavel A Komarov, Hélène Royo, Alexia Rohmer, Sunwoo Chun, Ching-Yeu Liang, Hubertus Kohler, Taiping Chen, Xiaohong Mao, Mark A Labow, Reginald A Valdez, Michael B Stadler, Dirk G De Rooij, Paola Capodieci, John Tallarico, Antoine H F M Peters, Thomas B Nicholson

Faculty, Staff and Student Publications

KDM2A/FBXL11 is a Jumonji-domain containing lysine demethylase catalyzing the removal of mono- and di-methyl modifications of histone H3 lysine 36 (H3K36me1/2). While Kdm2a is required for mouse embryogenesis, its role in adult physiology has been largely unexplored. Using conditional deletion approaches, we demonstrate that Kdm2a deficiency leads to testicular atrophy and male infertility. Although spermatogonial stem cells remain unaffected, proliferating and differentiating spermatogonia exhibit delayed cell cycle progression and apoptosis. RNA-sequencing of purified spermatogonia and spermatocytes reveals Kdm2a-dependent repression of over 750 genes during spermatogonial differentiation. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) demonstrates increased H3K36me2 levels at CpG-rich gene promoters …

The Microtubule-Severing Enzyme Spastin Regulates Spindle Dynamics To Promote Chromosome Segregation In Trypanosoma Brucei, Thiago Souza Onofre, Qing Zhou, Ziyin Li

Faculty, Staff and Student Publications

Microtubule-severing enzymes play essential roles in diverse cellular processes, including mitosis and cytokinesis, by modulating microtubule dynamics. In the early branching Trypanosoma brucei, microtubule-severing enzymes are involved in cytokinesis and flagellum length control, but none of them have been found to regulate mitosis. Here we report the characterization of the microtubule-severing enzyme spastin in the procyclic form of T. brucei. We demonstrate that spastin severs microtubule in vitro and overexpression of spastin disrupts spindle microtubules in vivo in trypanosomes, leading to defective chromosome segregation. Knockdown of spastin impairs spindle integrity and disrupts chromosome alignment and segregation. We further show that …

Timing Of Nodal Metastasis In Patients With Eyelid Sebaceous Carcinoma And Implications For Surveillance And Survival, Tracy Lu, Casey Anthony, Xinyang Jiang, Jing Ning, Ryan Goepfert, Bita Esmaeli

Faculty, Staff and Student Publications

Background/aims: Sebaceous carcinoma (SC) is a rare cancer with periocular predilection. Studies focused on patterns and timing of nodal metastasis are scarce.Our aim is to report patterns of regional nodal metastasis in patients with eyelid SC, including results of sentinel lymph node biopsy (SLNB).

Methods: All consecutive patients with eyelid SC treated during 1999-2023 were retrospectively reviewed.All subjects had standard of care surgery for eyelid SC and regional lymph node evaluation using physical examination and ultrasonography (US) at baseline and during the surveillance period. 38 patients with negative findings on US had SLNB to rule out microscopic metastasis.The frequency and …

An Alternative Neural Basis Underlying Leptin Resistance, Hongli Li, Cunjin Su, Yuanzhong Xu, Mette Q Ludwig, Jon Davis, Qingchun Tong

Faculty, Staff and Student Publications

Overconsumption of a palatable Western diet, a condition linked to central leptin resistance, contributes extensively to the current obesity epidemic. In this context, intensive efforts have focused on detailing the molecular mechanisms underlying leptin resistance. Here, we demonstrate that chronic inhibition of hypothalamic arcuate GABAergic neurons (ArcGABA) effectively reduced diet-induced obesity (DIO). Interestingly, palatable food exposure increased the activity level of ArcGABA neurons, which do not express the leptin receptor (non-LepR neurons; nonresponsive to leptin). Chronic activation of ArcGABA non-LepR neurons led to massive obesity, which was associated with normal leptin-induced pSTAT3 signaling but phenotypic leptin resistance; i.e., high leptin …

Longitudinal Analysis Of Gut Microbiome And Metabolome Correlates Of Response And Toxicity With Idecabtagene Vicleucel, Satabdi Saha, Lubna Rehman, Abdur Rehman, Faezeh Darbaniyan, Donna M Weber, Melody Becnel, Mahmoud Gaballa, Sheeba K Thomas, Hans C Lee, Chia-Chi Chang, Reetakshi Arora, Meghan Menges, Salvatore Corallo, Marco L Davila, Frederick L Locke, Mark R Tanner, Sattva S Neelapu, Elizabeth J Shpall, Christopher R Flowers, Robert Z Orlowski, Robert R Jenq, Michael D Jain, Christine Peterson, Doris K Hansen, Neeraj Y Saini, Krina K Patel

Faculty, Staff and Student Publications

Increasing evidence suggests that the gut microbiome may influence the responses and toxicities associated with chimeric antigen receptor T-cell (CAR-T) therapy. We conducted whole-genome shotgun sequencing on stool samples (N = 117) collected at various times from patients with multiple myeloma (n = 33) who underwent idecabtagene vicleucel (ide-cel) anti-B-cell maturation antigen CAR-T therapy. We observed a significant decrease in bacterial diversity after ide-cel infusion, along with significant differences in the bacterial composition linked to therapy response and toxicities. Specifically, we found significant enrichment of Flavonifractor plautii, Bacteroides thetaiotaomicron, Blautia fecis, and Dysosmobacter species in ide-cel responders. A notable finding …

Belumosudil Reduces Oral Chronic Graft-Versus-Host Disease Tissue Inflammation And Fibrosis: A Rockstar Companion Study, Rubina Sharma, Noa G Holtzman, Iskra Pusic, Corey Cutler, Nathaniel Treister, Rohtesh S Mehta, Amin S Alousi, Nadarajah Vigneswaran, Ayesha Javaid, Francis Boksa, Drashty P Mody, Ana C Costa-Da-Silva, Olivier Schueller, Sandrine Macé, Yu Yao, Ran Ji, Beifang Hu, Kathy Marshall, Bruce R Blazar, Stephanie J Lee, Steven Z Pavletic, Jacqueline W Mays

Faculty, Staff and Student Publications

Belumosudil (KD025), an oral, selective, Rho-associated, coiled-coil-containing protein kinase 2 (ROCK2) inhibitor, is approved for third-line treatment of chronic graft-versus-host disease (cGVHD). Previous studies demonstrated that ROCK2 inhibition reduces blood interleukin-17 (IL-17) activity and promotes regulatory T-cell (Treg cell) recovery. However, these studies did not evaluate immune responses within cGVHD-affected tissues. This study assessed tissue-level immune dynamics in 20 patients with oral cGVHD from the phase 2 ROCKstar trial, before and after 6 months of belumosudil treatment, focusing on key effector sites (oral mucosa [OM], minor salivary glands [MSGs], and skin) and the peripheral blood. After belumosudil treatment, reduction in …

Detection Of Oncogenic Fusions In Colorectal Cancer Using A Partner-Agnostic Next-Generation Sequencing Approach, Andrew J Pellatt, Reagan M Barnett, Sante Gnerre, Kristin Edwards, Jason A Willis, Michael J Overmann, Kanwal Raghav, Christine M Parseghian, Arvind Dasari, M Pia Morelli, Alisha Bent, Madhulika Eluri, Nicholas Hornstein, Leylah M Drusbosky, Scott Kopetz, Van K Morris

Faculty, Staff and Student Publications

Background: Gene fusions exist with low prevalence in colorectal cancer (CRC), and the clinical utility of fusion testing in advanced CRC remains unclear. We sought to identify oncogenic fusions in patients with advanced CRC using a fusion partner-agnostic circulating tumor DNA (ctDNA) assay to better understand their clinical relevance.

Methods: We performed a retrospective analysis using de-identified data from 18,558 patients with advanced CRC who underwent ctDNA next-generation sequencing with Guardant360® from 2017 to 2022. These samples were subsequently reanalyzed with a partner-agnostic bioinformatics method to identify both clonal and non-clonal fusions. We analyzed for associations between fusions and MSI-H …

Mouse Metastable Epialleles Are Extremely Rare, Chathura J Gunasekara, Uditha Maduranga, Taylor Zhang, Jonathan N Wells, Maria S Baker, Eleonora Laritsky, Yumei Li, Cristian Coarfa, Yi Zhu, Robert A Waterland

Faculty, Staff and Students Publications

Metastable epialleles (MEs) are genomic loci at which epigenetic marks are established stochastically during early embryonic development and maintained during subsequent differentiation and throughout life, leading to stable epigenetic and phenotypic variation among genetically identical individuals. Although MEs were first described in mice over 20 years ago, the extent of epigenetic metastability in the mouse genome remains unknown. We present the first unbiased genome-wide screen for MEs in mice. Using deep whole-genome bisulfite sequencing across tissues derived from the three embryonic germ layers in isogenic C57BL/6J mice, we identified only 29 MEs, precisely localizing them and documenting their rarity. Consistent …

A Cancer Education Needs Assessment: Informing Middle-Aged Female Patients About The Relationships Between Obesity And Women’S Health Concerns In The Reproductive System, Breast, And Endometrial Health, Batul Mirza

MUSC Theses and Dissertations

Obesity significantly impacts women’s health, particularly among middle-aged women, by increasing the risk of hormone-sensitive cancers such as breast, endometrial, and reproductive system cancers. This study examines the educational needs of this demographic group regarding obesity-related cancer risks and explores effective intervention strategies. Obesity-induced mechanisms – hormonal imbalances, chronic inflammation, and insulin resistance – drive cancer susceptibility, emphasizing the need for targeted health education. The study employs a qualitative design, which includes interviews with subject matter experts (SMEs) and surveys of middle-aged women. The goal is to assess awareness, perceived barriers, and preferred learning methods. Findings suggest that with many …

Image-Based Inference Of Tumor Cell Trajectories Enables Large-Scale Cancer Progression Analysis, Yang Liu, Ling Cai, Ruichen Rong, Shidan Wang, Liwei Jia, Peiran Quan, Qin Zhou, Guanghua Xiao, Yang Xie

Faculty, Staff and Student Publications

Current approaches to estimating cell trajectories, tumor progression dynamics, and cell population diversity of tumor microenvironment often depend on single-cell RNA sequencing, which is costly and resource intensive. To address this limitation, we developed an artificial intelligence (AI) model that leverages cell morphology features and histological spatial organization to classify tumor cell differentiation status, infer cell dynamic trajectories, and quantify tumor progression from hematoxylin and eosin (H&E)-stained whole-slide images. In three independent lung adenocarcinoma cohorts, our AI-based model accurately predicted cell differential status and provided quantifiable measures of tumor progression that were prognostic of patient survival. Spatial transcriptomic integrative analyses …

A Two-Stage Dual-Task Learning Strategy For Early Prediction Of Pathological Complete Response To Neoadjuvant Chemotherapy For Breast Cancer Using Dynamic Contrast-Enhanced Magnetic Resonance Images, Bowen Jing, Jing Wang

Faculty, Staff and Student Publications

Early prediction of treatment response can facilitate personalized treatment for breast cancer patients. Studies on the I-SPY 2 clinical trial demonstrate that multi-time point dynamic contrast-enhanced magnetic resonance (DCEMR) imaging improves the accuracy of predicting pathological complete response (pCR) to chemotherapy. However, previous image-based prediction models usually rely on mid- or post-treatment images to ensure the accuracy of prediction, which may outweigh the benefit of response-based adaptive treatment strategy. Accurately predicting the pCR at the early time point is desired yet remains challenging. To improve prediction accuracy at the early time point of treatment, we proposed a two-stage dual-task learning …

Truncated Ntrk2 Is Induced In Cap1 Endothelial Cells During Mouse Lung Injury-Repair, Celine Shuet Lin Kong, Mitheera V, Jezreel Pantaleón-García, Scott E Evans, Jichao Chen

Faculty, Staff and Student Publications

Pulmonary capillary endothelial cells (ECs) consist of two populations, CAP1 and CAP2; how each population reacts to diverse tissue injury is incompletely understood. Using single-cell multiome and mouse genetics, we characterize the induction and function of a truncated isoform of Ntrk2, Ntrk2-T1, in multiple lung injury models. Upon Sendai parainfluenza infection, Ntrk2-T1 is broadly induced in CAP1s after the initial interferon response, associated with increased intronic chromatin accessibility, and persists for weeks. Ntrk2-T1 ECs arise from CAP1s but not CAP2s-traced by

Ifn-Β Production Promotes Metabolic Rewiring And Protection Against Oxidative Stress In Hepatitis Delta Virus-Infected Hepatocyte Cultures, Olga A Khomich, Patrick Giavalisco, Romain Parent, George S Krasnov, Peter Tessarz, Philip Meuleman, Rani Burm, Natalia F Zakirova, Jennifer Molle, Enkhtuul Batbold, Eyal Gottlieb, Fabien Zoulim, Alexander V Ivanov, Birke Bartosch

Faculty, Staff and Student Publications

Type I interferons are secreted in response to various stimuli and are used as a treatment for many diseases, including infections with the hepatitis B virus (HBV) and its satellite virus, hepatitis delta (HDV). HDV significantly aggravates HBV-mediated liver damage and is - in contrast to HBV - a strong inducer of interferon responses, including IFN-β. As the role of IFN- β in liver metabolism is so far ill explored, we studied its impact on hepatocyte metabolism in HDV-infected cultures. Transcriptome analysis, isotope tracing and functional tests on differentiated, HDV-infected hepatocytes showed reduction of mitochondrial TCA cycle and respiratory activity …

Patient-Centered, Theory-Based, Online Intervention To Promote A Physically Active Lifestyle For People With Multiple Sclerosis: Protocol For A Randomized Controlled Trial, Chungyi Chiu, Vaishnavi Sridharan, Mojtaba Khaliji, Md Refat Uz Zaman Sajib, Xiaotian Gao, Kathleen Zackowski

Children’s Nutrition Research Center Staff Publications

Background: People with multiple sclerosis (MS) experience life challenges due to the nature of disease progression. Although an active lifestyle has been shown effective for symptom and relapse management, most people with MS lead a sedentary lifestyle and do not reach the recommended physical activity (PA) guidelines.

Objective: This study aims to test the preliminary efficacy of a codeveloped, online self-management intervention based on the health action process approach (HAPA) adapted for people with MS to cultivate a physically active lifestyle.

Methods: The 8-week intervention program was developed using community-based participatory research based on the HAPA. The program includes increasing …

Nrg Oncology Liver Proton Sbrt And Hypofractionated Radiation Therapy: Current Treatment Technical Assessment And Practice Patterns, Minglei Kang, Paige A Taylor, Jiajian Shen, Jun Zhou, Jatinder Saini, Theodore S Hong, Kristin Higgins, Wei Liu, Ying Xiao, Charles B Simone, Liyong Lin

Faculty, Staff and Student Publications

No abstract provided.

Efficacy Of A Novel Bcl-Xl Degrader, Dt2216, In Preclinical Models Of Jak2-Mutated Post-Mpn Aml, Zhe Wang, Anna Skwarska, Gowri Poigaialwar, Sovira Chaudhry, Alba Rodriguez-Meira, Pinpin Sui, Emmanuel Olivier, Yannan Jia, Varun Gupta, Warren Fiskus, Cassandra L Ramage, Guangrong Zheng, Alexandra Schurer, Kira Gritsman, Eirini P Papapetrou, Kapil Bhalla, Daohong Zhou, Adam J Mead, Raajit K Rampal, Jeffrey W Tyner, Hussein A Abbas, Naveen Pemmaraju, Qi Zhang Tatarata, Marina Konopleva

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) that evolves from myeloproliferative neoplasm (MPN) is known as post-MPN AML. Current treatments do not significantly extend survival beyond 12 months. B-cell lymphoma-extra large (BCL-xL) has been found to be overexpressed in leucocytes from patients with MPN, making it a potential therapeutic target. We investigated the role of BCL-xL in post-MPN AML and tested the efficacy of DT2216, a platelet-sparing BCL-xL proteolysis-targeting chimera, in preclinical models of post-MPN AML. We found that BCL2L1, the gene encoding BCL-xL, is expressed at higher levels in patients with post-MPN AML than in those with de novo AML. Single-cell multiomics …

Altered Patterning Of Neural Activity In A Neuropathology, Clarissa Hoffman, Jingheng Cheng, Rodrigo Morales, Daoyun Ji, Yuri Dabaghian

Faculty, Staff and Students Publications

The dynamics of neural circuits and their role in mediating cellular and organismal phenomena remain poorly understood, despite numerous efforts to dissect these processes through precise instantaneous measurements or longer-time averages and approximations. We use an alternative approach: we investigate these dynamics at the system's mesoscale by analyzing spike trains and waveforms. These extended activity patterns carry robust, tractable information, are highly responsive to physiological specifics, and enable detailed tracking of circuit behavior. In particular, this methodology allows for characterizing the functionality of tau-pathology-afflicted hippocampal circuits and identifying circuit-level abnormalities that are missed by through traditional analyses. In healthy mice, …

Serum Metabolomic Profiling Of Incident Type 2 Diabetes Mellitus In The Multi-Ethnic Study Of Atherosclerosis And Rotterdam Study, Xuanwei Jiang, Fang Zhu, Gonçalo Graça, Xihao Du, Jinjun Ran, Fariba Ahmadizar, Alexis C Wood, Yanqiu Zhou, Denise M Scholtens, Ali Farzaneh, M Arfan Ikram, Alan Kuang, Carel W Le Roux, Meghana D Gadgil, Marilyn C Cornelis, Kent D Taylor, Xiuqing Guo, Mohsen Ghanbari, Laura J Rasmussen-Torvik, Russell P Tracy, Alain G Bertoni, Jerome I Rotter, David M Herrington, Philip Greenland, Maryam Kavousi, Victor W Zhong

Children’s Nutrition Research Center Staff Publications

Objective: This study aimed to investigate serum metabolomic biomarkers associated with incident type 2 diabetes mellitus (T2DM) and evaluate their performance in improving T2DM risk prediction.

Methods: Untargeted proton nuclear magnetic resonance (1H NMR) spectroscopy-based metabolomics analyses were conducted in the Multi-Ethnic Study of Atherosclerosis (MESA; n = 3460; discovery cohort) and The Rotterdam Study (RS; n = 1556; replication cohort). Multivariable cause-specific hazards models were used to analyze the associations between 23 571 serum metabolomic spectral variables and incident T2DM. Replicated metabolites required an false discovery rate-adjusted P < .01 in MESA, P < .05 in RS, and consistent direction of association. Pathway and network analyses were conducted to elucidate biological mechanisms underlying T2DM development. The utility of the replicated metabolites in improving T2DM risk prediction was assessed based on the Framingham Diabetes Risk Score. A 2-sample Mendelian randomization was conducted to assess causal associations.

Results: Nineteen metabolites were significantly associated with incident T2DM. Pathway analyses …

Facts And Hopes: Toward The Next Quantum Leap In Melanoma, Keith T Flaherty, Andrew E Aplin, Michael A Davies, Nir Hacohen, Meenhard Herlyn, Dave Hoon, Patrick Hwu, Michal Lotem, James Mulé, Jennifer A Wargo, David E Fisher

Faculty, Staff and Student Publications

Outcomes from advanced melanoma, the deadliest of the skin cancers arising from melanocytes and capable of widely metastasizing, have greatly improved, with death rates decreasing for patients with American Joint Committee on Cancer stage 4 melanoma by 3% to 5% annually over the past 10 years. This improvement is a result of advances in both targeted therapy and immunotherapy. BRAF and MEK inhibitors for advanced melanoma have led the way for targeted cancer strategies and first-in-class approvals for immune checkpoint blockers targeting CTLA4, PD-1, and LAG3; T-cell engager therapy targeting the antigen gp100; and tumor-infiltrating lymphocyte therapy. All of these …

Technology Roadmap Of Micro/Nanorobots, Xiaohui Ju, Chuanrui Chen, Cagatay M Oral, Semih Sevim, Ramin Golestanian, Mengmeng Sun, Negin Bouzari, Xiankun Lin, Mario Urso, Jong Seok Nam, Yujang Cho, Xia Peng, Fabian C Landers, Shihao Yang, Azin Adibi, Nahid Taz, Raphael Wittkowski, Daniel Ahmed, Wei Wang, Veronika Magdanz, Mariana Medina-Sánchez, Maria Guix, Naimat Bari, Bahareh Behkam, Raymond Kapral, Yaxin Huang, Jinyao Tang, Ben Wang, Konstantin Morozov, Alexander Leshansky, Sarmad Ahmad Abbasi, Hongsoo Choi, Subhadip Ghosh, Bárbara Borges Fernandes, Giuseppe Battaglia, Peer Fischer, Ambarish Ghosh, Beatriz Jurado Sánchez, Alberto Escarpa, Quentin Martinet, Jérémie Palacci, Eric Lauga, Jeffrey Moran, Miguel A Ramos-Docampo, Brigitte Städler, Ramón Santiago Herrera Restrepo, Gilad Yossifon, James D Nicholas, Jordi Ignés-Mullol, Josep Puigmartí-Luis, Yutong Liu, Lauren D Zarzar, C Wyatt Shields, Longqiu Li, Shanshan Li, Xing Ma, David H Gracias, Orlin Velev, Samuel Sánchez, Maria Jose Esplandiu, Juliane Simmchen, Antonio Lobosco, Sarthak Misra, Zhiguang Wu, Jinxing Li, Alexander Kuhn, Amir Nourhani, Tijana Maric, Ze Xiong, Amirreza Aghakhani, Yongfeng Mei, Yingfeng Tu, Fei Peng, Eric Diller, Mahmut Selman Sakar, Ayusman Sen, Junhui Law, Yu Sun, Abdon Pena-Francesch, Katherine Villa, Huaizhi Li, Donglei Emma Fan, Kang Liang, Tony Jun Huang, Xiang-Zhong Chen, Songsong Tang, Xueji Zhang, Jizhai Cui, Hong Wang, Wei Gao, Vineeth Kumar Bandari, Oliver G Schmidt, Xianghua Wu, Jianguo Guan, Metin Sitti, Bradley J Nelson, Salvador Pané, Li Zhang, Hamed Shahsavan, Qiang He, Il-Doo Kim, Joseph Wang, Martin Pumera

Faculty, Staff and Student Publications

Inspired by Richard Feynman’s 1959 lecture and the 1966 film Fantastic Voyage, the field of micro/nanorobots has evolved from science fiction to reality, with significant advancements in biomedical and environmental applications. Despite the rapid progress, the deployment of functional micro/nanorobots remains limited. This review of the technology roadmap identifies key challenges hindering their widespread use, focusing on propulsion mechanisms, fundamental theoretical aspects, collective behavior, material design, and embodied intelligence. We explore the current state of micro/nanorobot technology, with an emphasis on applications in biomedicine, environmental remediation, analytical sensing, and other industrial technological aspects. Additionally, we analyze issues related to …

The Integrated Stress Response Pathway Coordinates Translational Control Of Multiple Immune Checkpoints In Lung Cancer, Shayna Thomas-Jardin, Shruthy Suresh, Ariana Arce, Nicole Novaresi, Qing Deng, Emily Stein, Lisa Thomas, Cheryl Lewis, Chul Ahn, Bret M Evers, Esra A Akbay, Maria E Salvatierra, Wei Lu, Khaja Khan, Luisa M Solis Soto, Ignacio I Wistuba, John D Minna, Kathryn A O'Donnell

Faculty, Staff and Student Publications

The integrated stress response (ISR) is an adaptive pathway hijacked by cancer cells to survive cellular stresses in the tumor microenvironment. ISR activation potently induces PD-L1, leading to suppression of antitumor immunity. In this study, we sought to uncover additional immune checkpoint proteins regulated by the ISR to elucidate mechanisms of tumor immune escape. The ISR coordinately induced cluster of differentiation 155 (CD155) and PD-L1, enhancing translation of both immune checkpoint proteins through bypass of inhibitory upstream open reading frames in their 5' untranslated regions. Analysis of primary human lung tumors identified a significant correlation between expression of PD-L1 and …

Ctdna Analysis In Erbb2-Amplified Colorectal Cancer: Biomarker Analysis Of The Mypathway Trial, Funda Meric-Bernstam, Kanwal Pratap Singh Raghav, Christopher J Sweeney, Charles Swanton, David R Spigel, Ron Bose, Howard A Burris, Claire F Friedman, Carin R Espenschied, Jessica M Grindheim, Julia Malato, Katja Schulze, Richard Price, Razelle Kurzrock

Faculty, Staff and Student Publications

Purpose: A combination of two HER2-directed antibodies, pertuzumab and trastuzumab (P + T), has antitumor activity in HER2-positive colorectal cancer. Although liquid biopsies are increasingly being used in clinical oncology, the association between tumor and ctDNA ERBB2 status and ctDNA monitoring for early response and resistance are unknown.

Patients and methods: Eighty-five patients with ERBB2-amplified and/or -overexpressed colorectal cancer were treated with P + T in the MyPathway trial; 42 had ctDNA testing at cycle (C) 1 day (D) 1, and 38 had longitudinal plasma tested for ctDNA. We analyzed the ctDNA versus tissue ERBB2 concordance, genomic co-alterations, and ctDNA …

Met Pathway Inhibition Increases Chemo-Immunotherapy Efficacy In Small Cell Lung Cancer, Raúl Del Rey-Vergara, Miguel Alejandro Galindo-Campos, Pedro Rocha, Marina Carpes, Carlos Martínez, Laura Masfarré, Silvia Menéndez, Fabricio Quimis, Adrià Rossell, Albert Iñañez, Sandra Pérez-Buira, Federico Rojo, Ramon Gimeno, Dolores Isla, Jon Zugazagoitia, Cristina Martí Blanco, Rosario García-Campelo, Alberto Moreno-Vega, Luis León-Mateos, Ángel Callejo Mellén, Kwon-Sik Park, Simon Heeke, John V Heymach, Álvaro Taus, Luis Paz-Ares, Ana Rovira, Edurne Arriola

Faculty, Staff and Student Publications

The introduction of immunotherapy as a first-line treatment for advanced small cell lung cancer (SCLC) represents significant progress, yet there remains an opportunity to further improve patient outcomes. Hepatocyte growth factor (HGF) receptor (MET) pathway activation promotes epithelial-mesenchymal transition, driving chemoresistance and potentially impairing the efficacy of immunotherapy. In SCLC mouse models, adding MET inhibition to chemo-immunotherapy (anti-PD-L1) reduces tumor growth, extends survival, and reshapes the tumor microenvironment by decreasing suppressive myeloid cell infiltration and enhancing the immune response. Analysis of pretreatment human SCLC tumor samples reveals that myeloid-enriched immune infiltrates may contribute to chemo-immunotherapy resistance. Elevated serum HGF levels …