Digital Commons Network^™

Occupational Health Equity: A Call To Consider Social-Structural Factors In Injury Prevention Research, Shannon Guillot-Wright, Elizabeth S Mcclure, Marizen R Ramirez, Alexis Grimes Trotter, David B Richardson

Faculty, Staff and Student Publications

Occupational health equity scholarship has been growing over the past decade, including social-structural determinants of health research that centres the voices and experiences of historically marginalised communities. In our commentary, we focus on the intersection of work-related and non-work-related factors and how they impact the health of workers, their families and their communities through community-engaged research. Case studies include the implementation of mobile clinics that are developed alongside communities, community organising to examine and reduce health disparities among racially segregated workers, the development of research instruments and measures to study racism and discrimination, and a focus on how the distribution …

Next-Gen Tools In Cancer Neuroscience, Vera Thiel, Debpali Sur, Caroline C Picoli, Tamara Mcerlain, Katalina Couto, David J Simon, Yuan Pan, Karen Olivia Dixon, Rajan P Kulkarni, Sebastien Talbot, Alexander Birbrair

Faculty, Staff and Student Publications

The emerging field of cancer neuroscience is rapidly evolving, driven by novel technologies and tools. These include advances in single-cell and spatial transcriptomics; genetic mouse models paired with automated high-throughput; and innovative optical electrophysiological approaches, optogenetics, chemogenetics, engineered viruses, and new methods for visualizing neuronal activity. Collectively, these technologies are revolutionizing how we investigate, manipulate, and characterize distinct components that contribute to the nervous system-cancer interface. In the present review, we discuss the key technologies that are closing the gap between oncology and neuroscience, highlighting the innovations that are propelling the cancer neuroscience field forward.

Rna/Dna-Binding Protein Tdp43 Regulates Dna Mismatch Repair Genes With Implications For Genome Stability, Vincent E Provasek, Albino Bacolla, Suganya Rangaswamy, Manohar Kodavati, Joy Mitra, Issa O Yusuf, Vikas H Malojirao, Velmarini Vasquez, Gavin W Britz, Guo-Min Li, Zuoshang Xu, Sankar Mitra, Ralph M Garruto, John A Tainer, Muralidhar L Hegde

Faculty, Staff and Student Publications

TDP43 is an RNA/DNA-binding protein increasingly recognized for its role in neurodegenerative conditions, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). As characterized by its aberrant nuclear export and cytoplasmic aggregation, TDP43 proteinopathy is a hallmark feature in over 95% of ALS/FTD cases, leading to detrimental cytosolic aggregates and a reduction in nuclear functionality in neurons. Building on our prior work linking TDP43 proteinopathy to the accumulation of DNA double-strand breaks (DSBs) in neurons, the present investigation uncovers a novel regulatory relationship between TDP43 and DNA mismatch repair (MMR) gene expression. Here, we show that TDP43 depletion or overexpression …

Sars-Cov-2 Nsp13 Interacts With Tead To Suppress Hippo-Yap Signaling, Fansen Meng, Jong Hwan Kim, Chang-Ru Tsai, Jeffrey D Steimle, Jun Wang, Yufeng Shi, Rich G Li, Bing Xie, Vaibhav Deshmukh, Shijie Liu, Xiao Li, James F Martin

Faculty, Staff and Students Publications

The Hippo pathway controls organ development, homeostasis, and regeneration primarily by modulating YAP/TEAD-mediated gene expression. Although emerging studies report Hippo-YAP dysfunction after viral infection, it is largely unknown in the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we analyzed RNA sequencing data from human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and SARS-CoV-2-infected human lung samples, and observed a decrease in YAP target gene expression. In screening SARS-CoV-2 nonstructural proteins, we found that nonstructural protein 13 (NSP13), a conserved coronavirus helicase, inhibits YAP transcriptional activity independent of the upstream Hippo kinases LATS1/2. Consistently, introducing NSP13 into mouse cardiomyocytes suppresses …

Atrial Fibroblast-Derived Macrophage Migration Inhibitory Factor Promotes Atrial Macrophage Accumulation In Postoperative Atrial Fibrillation, Joshua A Keefe, Jose Alberto Navarro-Garcia, Shuai Zhao, Mihail G Chelu, Xander Ht Wehrens

Faculty, Staff and Students Publications

New study: Blocking MIF protein prevents irregular heartbeats after surgery by reducing harmful immune cell buildup in the atria.

Deciphering The Mycn-Driven Metabolic Microenvironment Of Neuroblastoma, Amber Wolf, Davide Leardini, Lingzhi Li, Riccardo Masetti, Costas A Lyssiotis, Eveline Barbieri

Faculty, Staff and Students Publications

Oncogenic MYCN drives aggressive disease in many cancers including neuroblastoma (NB). Metabolic reprogramming is essential to support cancer cell homeostasis and survival under nutrient- and oxygen-deprived conditions. MYCN directly reprograms many nodes of tumor-intrinsic metabolism, which have significant repercussions on the cells of the tumor microenvironment (TME), resulting in complex intercellular metabolic circuits that contribute to the immunosuppressive microenvironment of NB. These metabolic circuits are also regulated by the organismal and cellular circadian clock and host diet to further impact the TME and NB oncogenesis. This review discusses the mechanisms by which MYCN regulates the metabolic crosstalk between tumor, TME, …

Understanding Cancer Survivorship Care Needs Using Amazon Reviews: Content Analysis, Algorithm Development, And Validation Study, Liwei Wang, Qiuhao Lu, Rui Li, Taylor B Harrison, Heling Jia, Ming Huang, Heidi Dowst, Rui Zhang, Hoda Badr, Jungwei W Fan, Hongfang Liu

Faculty, Staff and Students Publications

Background: Complementary therapies are being increasingly used by cancer survivors. As a channel for customers to share their feelings, outcomes, and perceived knowledge about the products purchased from e-commerce platforms, Amazon consumer reviews are a valuable real-world data source for understanding cancer survivorship care needs.

Objective: In this study, we aimed to highlight the potential of using Amazon consumer reviews as a novel source for identifying cancer survivorship care needs, particularly related to symptom self-management. Specifically, we present a publicly available, manually annotated corpus derived from Amazon reviews of health-related products and develop baseline natural language processing models using deep …

Adsl Deficiency Is A Secondary Mitochondrial Disease Affecting Organelle Homeostasis And Erk2/Akt Signaling In A Linear Genotype-Phenotype Relation, Matteo Bordi, Beatrice Testa, Claudia Compagnucci, Fiorella Colasuonno, Francesca Cipressa, Elisabetta Betterini, Andrea Mancini, Claudia Carsetti, Illari Salvatori, Caterina Ferraina, Ming Yang, Rossella De Cegli, Eugenio Del Prete, Chiara Veroni, Salvatore Rizza, Sofia Mauri, Elena Ziviani, Marina Macchiaiolo, Davide Vecchio, Filippo Maria Panfili, Teresa Rizza, Gerrit Weber, Rosalba Carrozzo, Alberto Ferri, Silvia Campello, Andrea Ballabio, Christian Frezza, Gianluca Cestra, Marco Tartaglia, Andrea Bartuli, Francesco Cecconi

Duncan NRI Faculty and Staff Publications

Adenylosuccinate lyase deficiency (ADSLd) is a rare autosomal recessive purine metabolism disorder with several clinical manifestations. While toxic substrate accumulation is a known hallmark, no additional molecular mechanisms have been established. Here, we show that ADSLd is associated with mitochondrial dysfunction, including increased fragmentation, impaired respiration, and reduced ATP production. The severity of mitochondrial impairment correlates with ADSLd pathology, especially in mitochondria-dependent tissues. We also identify defects in mitochondrial dynamics and transport linked to ERK2 and AKT suppression. Notably, overexpressing constitutively active ERK2 or supplementing purine intermediates partially rescues the mitochondrial phenotype. These findings suggest an alternative disease mechanism and …

A Picture Puzzle Approach To Microbes, Infectious Diseases, History And Art, Adarsh Bhimraj

History of Medicine Seminar

Topics covered in this session:

• What is proper attire for doctors to wear?
• Why read history?
• Picture Puzzles

"I Just Really Felt Like I Was Heard For The First Time": Survivor Experiences With An Adult Forensic Interviewing Model, Morgan E Pettyjohn, Aly Kramer Jacobs, Khara Breeden, Bethany L Backes, Leila Wood

Faculty, Staff and Student Publications

Adult forensic interviewing (AFI) collects evidence for the investigation and prosecution of interpersonal violence in a trauma-informed setting. The present study uses mixed methods evaluation data from an AFI program in the U.S. to assess survivors' perceptions of safety and the utility of participating in these interviews. Most participants felt the process was beneficial to their personal lives and criminal justice system engagement by: (a) allowing them to share their stories in more detail, (b) supporting their healing journeys, and (c) helping them feel safer through resource referral. AFI is a promising practice that warrants continued research.

Robust Detection Of Watermarks For Large Language Models Under Human Edits, Xiang Li, Feng Ruan, Huiyuan Wang, Qi Long, Weijie J Su

Faculty, Staff and Student Publications

Watermarking has offered an effective approach to distinguishing text generated by large language models (LLMs) from human-written text. However, the pervasive presence of human edits on LLM-generated text dilutes watermark signals, thereby significantly degrading detection performance of existing methods. In this paper, by modeling human edits through mixture model detection, we introduce a new method in the form of a truncated goodness-of-fit test for detecting watermarked text under human edits, which we refer to as Tr-GoF. We prove that the Tr-GoF test achieves optimality in robust detection of the Gumbel-max watermark in a certain asymptotic regime of substantial text modifications …

Impacts Of The Conductive Networks On Solid-State Battery Operation, Shimao Deng, Yixian Wang, Tianxiao Sun, Wenlong Li, Mingyuan Ge, Jian Wang, Peter Cloetens, Piero Pianetta, David Mitlin, Yijin Liu

Faculty, Staff and Student Publications

The micromorphology of composite cathodes is known to play a vital role in determining all‐solid‐state battery (ASSB) performance. However, much of our current understanding is derived from empirical observations, lacking a deeper mechanistic foundation. The “rocking chair” concept of battery chemistry requires maintaining charge neutrality, emphasizing the necessity of examining electrode micromorphology from the perspective of conductive networks. This study systematically investigates the microscopic electrochemical impacts of conductive network micromorphology by varying the Li+‐to‐e− channel ratio in cathodes comprising LiNbO3‐coated LiNi0.8Co0.1Mn0.1O2, Li6PS5Cl, and carbon fibers. Utilizing multiscale synchrotron‐based spectro‐microscopy, we unravel that unbalanced Li+ and e− conducting channels intensify charge …

Repeat Selective Dorsal Rhizotomy For Residual Spasticity: Illustrative Case, Elizabeth Ledbetter, Aloysia L Schwabe, Heather Sgro, Sarah Slocum, Nisha Gadgil

Faculty, Staff and Students Publications

Background: Selective dorsal rhizotomy (SDR) is typically a one-time surgical procedure supported by intense rehabilitation to improve ambulatory capability in children with spastic cerebral palsy (CP).

Observations: The authors present the unique case of a teenager with spastic diplegic CP who had undergone L2-S1 SDR as a child and presented with residual focal spasticity in the right plantar flexors. He underwent revision SDR at the right L5 and S1 levels in addition to decompression of canal stenosis. Postoperatively, he had notable improvement in his gait with relief of preoperative right knee and foot pain, improved ease of ambulation, and improved …

Bridging The Cost-Effectiveness Gap In Cardiovascular Disease Prevention For Statin-Intolerant Patients, Jerrin S Philip, Christie M Ballantyne

Faculty, Staff and Students Publications

No abstract provided.

Anticonvulsant Use In Older Age Bipolar Disorder In A Global Sample From The Global Aging And Geriatric Experiments In Bipolar Disorder Project: Utilisation D'Anticonvulsivants Pour Le Traitement Des Troubles Bipolaires Du Sujet Âgé Auprès D'Un Échantillon Mondial Provenant Du Projet Gage-Bd, Katie C Bodenstein, Myriam Lesage, Paola Lavin, Sigfried Schouws, Melis Orhan, Alexandra Beunders, Osvaldo P Almeida, Kursat Altinbas, Vicent Balanzá-Martínez, Izabela G Barbosa, Hilary P Blumberg, Farren B S Briggs, Cynthia V Calkin, Orestes V Forlenza, Brent Forester, Ariel G Gildengers, Benno C M Haarman, Tomas Hajek, Beny Lafer, Paula V Nunes, Benoit Mulsant, Andrew T Olagunju, Regan E Patrick, Joquim Radua, Kaylee Sarna, Christian Simhandl, Jair C Soares, Ashley N Sutherland, Nicole Fiorelli, Antonio L Teixeira, Shangying Tsai, Eduard Vieta, Joy Yala, Lisa Eyler, Annemiek Dols, Martha Sajatovic, Soham Rej

Faculty, Staff and Student Publications

Background:

Anticonvulsants are an essential treatment for bipolar disorder; however, there is relatively little known about their use in older age bipolar disorder (OABD). In this paper, which leverages a large international dataset, we aim to 1) describe the use of anticonvulsants in OABD compared to younger age bipolar disorder (YABD; ages < 50 years old) and 2) explore any demographic/clinical correlates.

Methods:

A secondary analysis was conducted on the international data from the Global Aging and Geriatric Experiments in Bipolar Disorder project. The main objective was to report the prevalence of anticonvulsant use in OABD over 50 years old (mean age = 62.27) and the most prescribed anticonvulsant. Additional …

Benefit Of Icosapent Ethyl Across Types And Sizes Of Myocardial Infarction In Reduce-It, Chen Gurevitz, Deepak L Bhatt, Robert P Giugliano, Ph Gabriel Steg, Michael Miller, Eliot A Brinton, Terry A Jacobson, Steven B Ketchum, Armando Lira Pineda, Ralph T Doyle, Gabriella Giugliano, R Preston Mason, Jean-Claude Tardif, Fabrice M A C Martens, Christie M Ballantyne, Matthew J Budoff, C Michael Gibson

Faculty, Staff and Students Publications

Aims: We studied the efficacy and safety of icosapent ethyl (IPE) 4g daily in reducing the risk of myocardial infarction (MI) across different MI subtypes and sizes, among REDUCE-IT high-risk patients with hypertriglyceridemia.

Methods: REDUCE-IT was a phase 3b, double-blind multicenter trial. Patients with established CVD or diabetes who were treated with statins and had moderate hypertriglyceridemia were randomized to receive IPE 4g daily or placebo. The current analysis focused on MI subtypes (fatal MI, nonfatal MI, ST-segment elevation MI (STEMI), non-STEMI (NSTEMI)), as well as MI size (measured by multiples of troponin upper limit of normal) and MI-related complications. …

Cerebellar Dysfunction In A Mouse Model Of Childhood-Onset Manganese-Induced Dystonia Parkinsonism, Alexander N Rodichkin, Amanda M Brown, Pavani Devabathini, Jennifer L Mcglothan, Si Chen, Ajith Pattammattel, Yong S Chu, Tao Lin, Daniel D Pontow, Karam Abilmouna, Ritishka Kapoor, Sarah E Hardin, Yulia Pushkar, Roy V Sillitoe, Tomás R Guilarte

Duncan NRI Faculty and Staff Publications

Humans with pathogenic variants of the manganese (Mn) transporter gene SLC39A14 exhibit highly elevated brain Mn concentrations and childhood-onset dystonia-parkinsonism. Here we show that Slc39a14-knockout (KO) mice, a preclinical model of the disease with elevated Mn concentrations in the CB, express deficits in physiological tremor implicating cerebellar (CB) dysfunction. Imaging of intracellular Mn in Purkinje cells (PCs) using synchrotron-based X-ray fluorescence microscopy confirmed highly elevated Mn concentrations in the PCs of Slc39a14-KO mice. To determine biological pathways altered in the CB of Slc39a14-KO mice relative to wildtype (WT), we performed RNA sequencing and discovered significant upregulation of pathways and genes …

An Open Trial For Transdiagnostic Behavior Therapy For Primary Care (Tbt-Pc) In Veterans With Symptoms Of Depression And Anxiety, Daniel F Gros, Stephanie Hart, Michelle Pompei, Ron Acierno

Faculty, Staff and Student Publications

Transdiagnostic psychotherapies were developed to address multiple diagnostic presentations via a single, easier-to-implement protocol. However, despite advances, these protocols are largely limited to longer formats designed for mental health settings. The present study investigated a version of Transdiagnostic Behavior Therapy (TBT-PC) that was adapted for primary care settings. Forty-one participants with emotional disorders received 6 sessions of TBT-PC, with symptoms of depression and anxiety assessed at baseline, immediate post-treatment, and at 3-month follow-up. Medium treatment effects for symptoms of depression and anxiety were evidenced at post-treatment and sustained at follow-up. Treatment feasibility was supported by excellent attendance, treatment completion, and …

Combined Annual Modulation Dark Matter Search With Cosine-100 And Anais-112, N Carlin, J Y Cho, J J Choi, S Choi, A C Ezeribe, L E França, C Ha, I S Hahn, S J Hollick, S B Hong, E J Jeon, H W Joo, W G Kang, M Kauer, B H Kim, H J Kim, J Kim, K W Kim, S H Kim, S K Kim, W K Kim, Y D Kim, Y H Kim, Y J Ko, D H Lee, E K Lee, H Lee, H S Lee, H Y Lee, I S Lee, J Lee, J Y Lee, M H Lee, S H Lee, S M Lee, Y J Lee, D S Leonard, N T Luan, V H A Machado, B B Manzato, R H Maruyama, R J Neal, S L Olsen, H K Park, H S Park, J C Park, J S Park, K S Park, K Park, S D Park, R L C Pitta, H Prihtiadi, S J Ra, C Rott, K A Shin, D F F S Cavalcante, M K Son, N J C Spooner, L T Truc, L Yang, G H Yu, J Amaré, J Apilluelo, S Cebrián, D Cintas, I Coarasa, E García, M Martínez, Y Ortigoza, A Ortiz De Solórzano, T Pardo, J Puimedón, M L Sarsa, C Seoane

Faculty and Staff Publications

The annual modulation signal, claimed to be consistent with dark matter as observed by DAMA/LIBRA in a sodium-iodide based detector, has persisted for over two decades. COSINE-100 and ANAIS-112 were designed to test the claim directly using the same target material. COSINE-100, located at Yangyang Underground Laboratory in South Korea, and ANAIS-112, located at Canfranc Underground Laboratory in Spain, have been taking data since 2016 and 2017, respectively. Each experiment published its respective results independently. In this Letter, we present the results of an annual modulation search as a test of the signal observed by DAMA/LIBRA with the first three …

Epac1 Deletion Attenuates Müller Glial Pathological Activation And Mitigates Retinal Neurodegeneration In Ischemia-Induced Retinopathy, Shuizhen Shi, Fan Xia, Zhongqiao Lu, Erick Palacios, Fang Mei, Massoud Motamedi, Xiaodong Cheng, Hua Liu, Wenbo Zhang

The Brown Foundation: Institute of Molecular Medicine

Introduction: Ischemia-induced retinopathies, such as retinopathy of prematurity and proliferative diabetic retinopathy, are major causes of vision loss. Both pathological neovascularization and neuronal damage contribute to vision impairment in these conditions, yet current therapies primarily target neovascularization and may further compromise neuronal health.

Objectives: Cyclic AMP (cAMP) is a widely recognized second messenger regulating diverse physiological and pathological processes. Exchange protein directly activated by cAMP (Epac) is a recently identified effector of cAMP signaling. This study aimed to investigate the role of Epac1 in ischemia-induced retinopathy and elucidate its underlying mechanisms using a mouse model of oxygen-induced retinopathy (OIR).

Methods: …

Prenatal Metabolomics Analysis And Fetal Congenital Anomalies And Genetic Conditions: A Review Of Current Literature, Sarah Araji, Onur Turkoglu, Mohamad Ali Maktabi, Tracy Ashby, Ignatia B Van Den Veyver

Library Staff Publications

Fetal congenital anomalies and genetic disorders complicate 3%-5% of pregnancies and can have a significant impact on pregnancy outcomes. Precise and individualized prenatal diagnosis is crucial for effective counseling and management. The identification of new biomarkers holds promise for enhancing prenatal screening, diagnosis, and prognostic counseling in affected pregnancies. Recently, metabolomics has emerged as a potential adjunct in the interpretation of genetic variants identified through genome-wide sequencing for rare genetic conditions. To assess the potential of metabolomic profiling as a functional assay capable of providing deeper insights into the pathological processes and genetic findings associated with prenatal congenital anomalies, we …

Metabolic Shifts In Murine Inner Ears Mimicking Erythrocytes And Plasma Reveal Diagnostics And Early Predictors For Age-Related Hearing Loss, Qi Guo, Zhenjiang Li, Cheng Luo, Changhan Chen, Xi Long, Yidan Wang, Qingfen Qiang, Fang Yu, Wuping Liu, Yujin Zhang, Rodney E Kellems, Yang Xia

Faculty, Staff and Student Publications

Age-related hearing loss (ARHL) is a major public health concern, driven by the interplay of multiple factors. Here, we reveal spatiotemporal metabolic shifts in murine inner ears mirroring erythrocytes and plasma. Isotope-labeled glucose tracing demonstrates a metabolic rerouting favoring glycolysis over the pentose phosphate pathway, alongside downregulation of the tricarboxylic acid cycle, indicating impaired energy production and redox homeostasis. Accumulation of medium- and long-chain acylcarnitines further exacerbates lipotoxicity. Notably, age-dependent depletion of arginine, lysine, proline, and glycine disrupts the arginine-polyamine-urea cycle. Translationally, UK Biobank plasma metabolomics links omega-6 fatty acids, linoleic acid, glycine, and albumin to ARHL resilience, while branched-chain …

Protocol For Non-Invasive Pulsed-Doppler Evaluation Of Blood Flow In The Mouse Ophthalmic Artery, Radwa Awad, Emil Martin, Anilkumar K Reddy, Iraida Sharina

Faculty, Staff and Student Publications

The number of reliable and non-invasive techniques to characterize ocular blood flow is limited. Here, we present a protocol for identifying a soft tissue window in the orbital aperture using pulsed-Doppler ultrasonography to offer real-time, non-invasive blood flow velocity monitoring in the mouse ophthalmic artery. We describe steps for preparing a mouse, positioning the ultrasound probe, and acquiring and recording signals. We then detail procedures for analyzing results using a workstation equipped with Doppler flow velocity software. For complete details on the use and execution of this protocol, please refer to Sharina et al.

Human Cerebral Organoids Model Tumor Initiation And Infiltration In An Autologous Astrocyte-Supported Setting, Esther Schickel, Tamara Bender, Leon Kaysan, Simone Hufgard, Margot Mayer, David R Grosshans, Christiane Thielemann, Insa S Schroeder

Faculty, Staff and Student Publications

Efforts to efficiently target brain tumors are constrained by the dearth of appropriate models to study tumor behavior toward treatment approaches as well as potential side effects to the surrounding normal tissue. We established a reproducible cerebral organoid model of brain tumorigenesis in an autologous setting by overexpressing

Gait Analysis In Rett Syndrome: Integrating Linear And Nonlinear Techniques, Dacia Martinez Diaz, Brock Futrell, Bernhard Suter, Charles S Layne

Faculty, Staff and Students Publications

Rett syndrome is a rare neurodevelopmental disorder that significantly impairs bipedal postural control and walking ability. This study quantifies the gait characteristics of 22 females with Rett syndrome (divided into 3 age groups) and compares them with age-matched neurotypical females. Bilateral sagittal plane joint angles of the hip, knee, and ankle were analyzed. Measures included joint range of motion, stride time, peak angular velocity, angle-angle diagrams, phase portrait areas, and asymmetries. Results revealed reduced joint range of motion and angular velocity in individuals with Rett syndrome, as well as greater asymmetries in gait parameters reflecting disruptions in bilateral coordination. Phase …

Blue-Shifted Ancyromonad Channelrhodopsins For Multiplex Optogenetics, Elena G Govorunova, Oleg A Sineshchekov, Hai Li, Yueyang Gou, Hongmei Chen, Shuyuan Yang, Yumei Wang, Stephen Mitchell, Alyssa Palmateer, Leonid S Brown, François St-Pierre, Mingshan Xue, John L Spudich

Duncan NRI Faculty and Staff Publications

Light-gated ion channels from protists (channelrhodopsins or ChRs) are optogenetic tools widely used for controlling neurons and cardiomyocytes. Multiplex optogenetic applications require spectrally separated molecules, which are difficult to engineer without disrupting channel function. Scanning numerous sequence databases, we identified three naturally blue-shifted ChRs from ancyromonads. They form a separate branch on the phylogenetic tree and contain residue motifs characteristic of anion ChRs (ACRs). However, only two conduct chloride, whereas the closely related Nutomonas longa homolog generates inward cation currents in mammalian cells under physiological conditions, significantly exceeding those by previously known tools with similar spectral maxima (peak absorption at …

Can Handoffs Bridge The Interprofessional Divide To Build A Team?, Aubrey Samost-Williams, Eric J Thomas

Faculty, Staff and Student Publications

No abstract provided.

Cetuximab Increases Lgr5 Expression And Augments Lgr5-Targeting Antibody-Drug Conjugate Efficacy In Patient-Derived Colorectal Cancer Models, Peyton C High, Zhengdong Liang, Cara Guernsey-Biddle, Shraddha Subramanian, Yueh-Ming Shyu, Adela M Aldana, Yukimatsu Toh, Kendra S Carmon

The Brown Foundation: Institute of Molecular Medicine

Colorectal cancer (CRC) remains the second-leading cause of cancer-associated deaths, indicating an urgent need for improved therapeutic options. We previously generated antibody-drug conjugates (ADCs) targeting the cancer stem-like cell marker leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5). However, tumor relapse due to LGR5 downregulation and suboptimal payload selection warrants strategies to improve ADC efficacy. Here, we report that cetuximab, an epidermal growth factor receptor (EGFR)-targeting monoclonal antibody indicated for RASWT metastatic CRC, augments LGR5 expression independent of RAS/PIK3CA mutation status and promotes EGFR-LGR5 interactions. Furthermore, we describe the development of LGR5 ADCs incorporating a camptothecin-derived payload that is well tolerated …

Connecting Innovation And Trust Through Translational Sciences – A Need For A Community Focus And Effective Education Strategiess, Filipa Godoy-Vitorino, Michelle Borrero, Josué Pérez-Santiago, Rubén García-García, Candelaria Gomez-Manzano

Faculty, Staff and Student Publications

Report of a conference held in Puerto Rico, this article highlights how interdisciplinary translational science-anchored in education, public trust, and equity-can accelerate innovation in cancer therapy while empowering underserved communities through inclusive training, collaboration, and research participation.

Disparities In Liver Transplantation For Metabolic Dysfunction-Associated Steatohepatitis-Associated Hepatocellular Carcinoma, David W Victor, Sudha Kodali, Mazen Noureddin, Elizabeth W Brombosz, Analisa Lopez, Tamneet Basra, Edward A Graviss, Duc T Nguyen, Ashish Saharia, Ashton A Connor, Maen Abdelrahim, Yee Lee Cheah, Caroline J Simon, Mark J Hobeika, Constance M Mobley, R Mark Ghobrial

Faculty, Staff and Students Publications

Background: Metabolic dysfunction-associated steatohepatitis (MASH) is increasingly common, as is hepatocellular carcinoma (HCC) in the background of MASH. Liver transplantation (LT) provides superior long-term survival for patients with unresectable MASH-HCC, but not all patients have equal access to transplant. MASH-HCC disproportionately affects Hispanic patients, but minorities are less likely to undergo LT for HCC. Additionally, females also undergo LT at lower rates than males.

Aim: To investigate whether race/ethnicity and sex affect LT waitlist outcomes.

Methods: Records of adults with MASH-HCC in the United States Organ Procurement and Transplantation Network database listed for LT between 1/2015 and 12/2021 were analyzed. …