Digital Commons Network^™

Dominantly Inherited Muscle Disorders: Understanding Their Complexity And Exploring Therapeutic Approaches, Andrew R Findlay

2020-Current year OA Pubs

Treatments for disabling and life-threatening hereditary muscle disorders are finally close to becoming a reality. Research has thus far focused primarily on recessive forms of muscle disease. The gene replacement strategies that are commonly employed for recessive, loss-of-function disorders are not readily translatable to most dominant myopathies owing to the presence of a normal chromosome in each nucleus, hindering the development of novel treatments for these dominant disorders. This is largely due to their complex, heterogeneous disease mechanisms that require unique therapeutic approaches. However, as viral and RNA interference-based therapies enter clinical use, key tools are now in place to …

Network-Level Enrichment Provides A Framework For Biological Interpretation Of Machine Learning Results, Jiaqi Li, Ari Segel, Xinyang Feng, Jiaxin Cindy Tu, Andy Eck, Kelsey T King, Babatunde Adeyemo, Nicole R Karcher, Likai Chen, Adam T Eggebrecht, Muriah D Wheelock

2020-Current year OA Pubs

Machine learning algorithms are increasingly being utilized to identify brain connectivity biomarkers linked to behavioral and clinical outcomes. However, research often prioritizes prediction accuracy at the expense of biological interpretability, and inconsistent implementation of ML methods may hinder model accuracy. To address this, our paper introduces a network-level enrichment approach, which integrates brain system organization in the context of connectome-wide statistical analysis to reveal network-level links between brain connectivity and behavior. To demonstrate the efficacy of this approach, we used linear support vector regression (LSVR) models to examine the relationship between resting-state functional connectivity networks and chronological age. We compared …

Effect Of Universal Masking On Non-Severe Acute Respiratory Syndrome Coronavirus 2 Healthcare-Associated Respiratory Viral Infections, Satish Munigala, Patrick R Ching, Helen Wood, R J Waken, Josephine Fox, Heather Gasama, Robert Russell, Melanie L Yarbrough, David K Warren

2020-Current year OA Pubs

BACKGROUND: Respiratory viral infections are common and are a major cause of morbidity and mortality. We evaluated the impact of universal masking implemented during the coronavirus disease 2019 (COVID-19) pandemic on other healthcare-associated respiratory viral infections (HA-RIs) in an academic medical center.

METHODS: A retrospective cohort study was performed among all inpatients aged ≥18 years admitted between 1 May 2019 and 30 June 2022. Universal masking was implemented in May 2020 at our hospital and state-level mask mandates had been lifted by May 2021. We evaluated and compared the HA-RI rates, adjusted for monthly community-onset viral infections, during the premasking …

15-Gene Expression Profile And Prame As Integrated Prognostic Test For Uveal Melanoma: First Report Of Collaborative Ocular Oncology Group Study No. 2 (Coog2.1), J William Harbour, Kisha D Piggott, Et Al.

2020-Current year OA Pubs

PURPOSEValidated and accurate prognostic testing is critical for precision medicine in uveal melanoma (UM). Our aims were to (1) prospectively validate an integrated prognostic classifier combining a 15-gene expression profile (15-GEP) and

Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis Attenuates Disparity In Outcomes Between Use Of Matched Or Mismatched Unrelated Donors, Brian C Shaffer, Ramzi Abboud, Et Al.

2020-Current year OA Pubs

PURPOSEAccess to allogeneic hematopoietic cell transplantation (HCT) remains limited among persons of non-European ancestry if human leukocyte antigen (HLA) matching is required. We evaluated whether post-transplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis improved HCT outcomes with HLA-matched unrelated donor (MUD) and mismatched unrelated donor (MMUD) HCT when compared with calcineurin inhibitor (CNI)-based prophylaxis.METHODSThree-year overall survival (OS) and GVHD-free, relapse-free survival (GRFS) were compared between adult recipients undergoing initial MUD or single HLA locus MMUD HCT with either PTCy- or CNI-based prophylaxis who were reported to the Center for International Blood and Marrow Transplant Research between 2017 and 2021.RESULTSIncluded were 10,025 …

Accessibility Of And Barriers To Long-Term Follow-Up Care For Childhood Cancer Survivors, Jiaoyang Cai, Sara Malone, Nickhill Bhakta, Ching-Hon Pui, Jing Chen, Shaoyan Hu, Hui Jiang, Xiuli Ju, Fen Zhou, Melissa M Hudson, Yin Ting Cheung

2020-Current year OA Pubs

IMPORTANCE: Childhood cancer survivorship programs and long-term follow-up (LTFU) practices are inadequate in most regions of China.

OBJECTIVE: To understand the clinician and caregiver perceptions of LTFU care and to identify barriers to adherence to LTFU care in mainland China.

DESIGN, SETTING, AND PARTICIPANTS: This survey study had a 2-phase sequential mixed-methods approach, consisting of a cross-sectional survey followed by semistructured interviews. Participants included oncology clinicians recruited through an educational seminar on LTFU and caregivers recruited through convenience sampling. Data were collected from November 2022 to September 2023.

MAIN OUTCOMES AND MEASURES: The clinician survey and interview focused on the …

Perioperative Antibiotic Prophylaxis Duration In Patients Undergoing Cystectomy With Urinary Diversion: A Randomized Clinical Trial, Maria C Thurnheer, Astrid Schürmann, Markus Huber, Jonas Marschall, Patrick Y Wuethrich, Fiona C Burkhard

2020-Current year OA Pubs

IMPORTANCE: Perioperative antibiotic prophylaxis (PAP) reduces the incidence of surgical site infections (SSIs). Guidelines recommend 24 hours or less of PAP for cystectomy with urinary diversion; however, evidence specifying optimal PAP duration for this surgery is lacking, and prolonged administration of PAP is common practice.

OBJECTIVE: To establish noninferiority of 24-hour PAP vs extended-duration PAP in preventing SSIs within 90 days after cystectomy with urinary diversion.

DESIGN, SETTING, AND PARTICIPANTS: This single-center, noninferiority randomized clinical trial was performed from April 18, 2018, to August 18, 2022, in patients aged older than 18 years undergoing elective open cystectomy with urinary diversion. …

Rehabilitation Transition Program To Improve Community Participation Among Stroke Survivors: A Randomized Clinical Trial, Rebecca M Bollinger, Melissa J Krauss, Emily K Somerville, Brianna M Holden, Gabrielle Blenden, Holly Hollingsworth, Audrey A Keleman, Alexandre Carter, Timothy D Mcbride, Abigail R Barker, Yan Yan, Susan L Stark

2020-Current year OA Pubs

IMPORTANCE: Interventions are needed to support the long-term needs of stroke survivors when they transition from inpatient rehabilitation to home, where they face new home and community environmental barriers.

OBJECTIVE: To compare the efficacy of a novel, enhanced rehabilitation transition program with attentional control to improve community participation and activity of daily living (ADL) performance and to reduce environmental barriers in the home and community after stroke.

DESIGN, SETTING, AND PARTICIPANTS: This phase 2b, parallel randomized clinical trial assessed patients 50 years or older who had experienced an acute ischemic stroke or intracerebral hemorrhage, were independent in ADLs before stroke, …

Leveraging Gpt-4 For Identifying Cancer Phenotypes In Electronic Health Records: A Performance Comparison Between Gpt-4, Gpt-3.5-Turbo, Flan-T5, Llama-3-8b, And Spacy's Rule-Based And Machine Learning-Based Methods, Kriti Bhattarai, Inez Y Oh, Jonathan Moran Sierra, Jonathan Tang, Philip R O Payne, Zach Abrams, Albert M Lai

2020-Current year OA Pubs

OBJECTIVE: Accurately identifying clinical phenotypes from Electronic Health Records (EHRs) provides additional insights into patients' health, especially when such information is unavailable in structured data. This study evaluates the application of OpenAI's Generative Pre-trained Transformer (GPT)-4 model to identify clinical phenotypes from EHR text in non-small cell lung cancer (NSCLC) patients. The goal was to identify disease stages, treatments and progression utilizing GPT-4, and compare its performance against GPT-3.5-turbo, Flan-T5-xl, Flan-T5-xxl, Llama-3-8B, and 2 rule-based and machine learning-based methods, namely, scispaCy and medspaCy.

MATERIALS AND METHODS: Phenotypes such as initial cancer stage, initial treatment, evidence of cancer recurrence, and affected …

Dean's Update, October 2024, Neil W. Schluger

SOM Dean's Research Newsletter

No abstract provided.

Impact Of Electronic Resources On Research Productivity Of Scholars In Universities Of Jamshoro, Sindh, Ali Ahmed Jamali, Shamshad Ahmed Dr.

Library Philosophy and Practice (e-journal)

The aim of this study was to analyze the relationship between electronic resources and the research productivity of scholars at universities in Jamshoro, Sindh. The important role of electronic resources in enhancing research productivity has been widely acknowledged. The purpose of this study was to look objectively at the impact of electronic resources on the research productivity of scholars in universities of Jamshoro, Sindh. The level of awareness, usage frequency, dependency, purposes, satisfaction level, and challenges and their impact on research productivity are the main areas of this study. A survey approach to data collection was used with the help …

Ict Skills And Electronic Information Resources Utilization Among Undergraduate Sandwich Students In Nigerian Universities, Adesola Victoria Alade

Library Philosophy and Practice (e-journal)

This study investigated ICT skills and electronic information resource (EIRs) utilization among undergraduate sandwich students in Nigerian universities. The study employed a descriptive survey design. Six hundred sandwich students in 4 public universities in South-west Nigeria were randomly selected for the study. A close-ended questionnaire was used for data collection. Descriptive and inferential statistics were used for data analysis. The study found that the students have a high level of ICT skills and low EIR utilization. The challenges the students encounter in using EIRs include a lack of required ICT skills to search the Internet, and inadequate ICT professionals in …

Fall 2024 Gsbms Alumni Connections, New York Medical College

Graduate School of Biomedical Sciences

• NYMC to Celebrate Visionary Public Health Leaders at Annual Founder’s Dinner
• Teeing Off for Tomorrow’s Scholars at the Golf Outing
• New Medical School Linkage Agreement for GSBMS Students
• GSBMS Greets Incoming Students for the New Academic Year
• NYMC Research Well Represented at Touro Research Day
• Entries for Love at NYMC

Transcription And Post-Translational Mechanisms: Dual Regulation Of Adiponectin-Mediated Occludin Expression In Diabetes, Yanru Duan, Demin Liu, Huahui Yu, Shihan Zhang, Yihua Xia, Zhiyong Du, Yanwen Qin, Yajing Wang, Xin-Liang Ma, Huirong Liu, Yunhui Du

Department of Emergency Medicine Faculty Papers

BACKGROUND: Occludin, a crucial component of tight junctions, has emerged as a promising biomarker for the diagnosis of acute ischemic disease, highlighting its significant potential in clinical applications. In the diabetes, Occludin serves as a downstream target gene intricately regulated by the adiponectin (APN) signaling pathway. However, the specific mechanism by which adiponectin regulates Occludin expression remains unclear.

METHODS AND RESULTS: Endothelial-specific Ocln knockdown reduced APN-mediated blood flow recovery after femoral artery ligation and nullified APN's protection against high-fat diet (HFD)-triggered apoptosis and angiogenesis inhibition in vivo. Mechanically, we have meticulously elucidated APN's regulatory role in Occludin expression through a …

Assessing The Effectiveness Of Law Enforcement Strategies In Combating E-Crime Using Ai, Mohammad Ahmad Alkhazraji

Theses

The rise of e-crime, particularly international online scams, has presented significant challenges to law enforcement agencies around the world. Scams have become transnational, exploiting the internet's interconnectivity to deceive victims from different countries. Law enforcement agencies have a severe uphill battle in trying to combat these types of crimes because of technological and jurisdictional limitations and resource accessibility. This research has analyzed the effectiveness of current policing against international online scams, focusing on the challenges encountered thus far and possible solutions. The critical research objectives revolve around assessing law enforcement agencies' present strategies, identifying the main barriers that these agencies …

Chemometric Processing Of Ecstasy Tablet Thermal Profiles Using Machine Learning Methods, Ali Arif Ibrahim

Theses

Ecstasy is an amphetamine-type substance scientifically known as MDMA (3,4- methylenedioxymethamphetamine) that belongs to a group of illicit drugs called “club drugs” that are widespread and distributed illegally (Maione et al., 2016). Its ever-growing popularity and variety in multiple forms, shapes, and colors complicates the identification and tracking process to law enforcement and forensic analysts. The current study focused on integrating data analytics and advanced chemometric methods to Differential Scanning Calorimetry (DSC) to analyze the thermal profiles of ecstasy tablets. This approach aims to discriminate between tablets linked to different suspects and origins through thermal profiling, which will provide law …

Exploring Ngc 2287: An Investigation Of Open Cluster Membership, Rotation, And A Curiously Bifurcated Main Sequence, Benjamin J. Ramsey

Theses

The study of stellar clusters is integral to our understanding of many areas of astrophysics because of the role they play as astrophysical benchmarks. Thanks to shared characteristics (in particular, age and chemical composition) of their members, open star clusters represent essential subjects to address contemporary problems in stellar structure, formation, and evolution. The rich open cluster NGC 2287 (the Little Beehive) is young (age~200 Myr), relatively nearby (D~735 pc), and suffers little intervening extinction, making it ripe for further study. The cluster is particularly noteworthy for displaying a rotationally bifurcated upper main sequence. We are investigating the membership and …

Resistance To Acetyl Coenzyme A Carboxylase (Accase) Inhibitor In Lolium Multiflorum: Effect Of Multiple Target-Site Mutations, Gulab Rangani, Ana Claudia Langaro, Shilpi Agrawal, Reiofeli Algodon Salas-Perez, Juan Camilo Velasquez, Christopher E. Nelson, Nilda Roma-Burgos

Crop, Soil and Environmental Sciences Faculty Publications and Presentations

Italian ryegrass (Lolium multiflorum Lam.) is a persistent weed species that poses significant management challenges in key agricultural crops such as wheat, corn, cotton, and soybean. This study investigated the prevalence of resistance to ACCase inhibitor herbicides, specifically diclofop and pinoxaden, among field-collected Italian ryegrass populations. The survey revealed widespread resistance to diclofop and emerging cross-resistance to pinoxaden. To elucidate the physiological mechanism of ACCase herbicide resistance, we investigated mutations in the carboxyl-transferase (CT) domain of the ACCase enzyme, a critical region for herbicide sensitivity. Using dCAPS assays and CT domain sequencing, several known resistance-conferring mutations were detected in …

Oxyfluorfen Use In Combination With Clomazone Or Quinclorac, Jason K. Norsworthy, Casey H. Arnold, Thomas R. Butts, Chad W. Shelton

Crop, Soil and Environmental Sciences Faculty Publications and Presentations

Oxyfluorfen is a herbicide that inhibits protoporphyrinogen IX oxidase and has shown significant potential in its ability to control barnyardgrass. Oxyfluorfen is categorized as a Group 14 herbicide by the Herbicide Resistance Action Committee (HRAC)/Weed Science Society of America (WSSA). Despite its current lack of labeling for use on rice in the mid-southern United States due to its potential to cause crop injury, the introduction of a trait in rice that confers resistance to oxyfluorfen could provide producers with an effective alternative site of action for weed control. Field experiments were conducted during the 2021 and 2022 growing seasons near …

Clomazone And Oxyfluorfen Combinations In A Flooded Rice System, Jason K. Norsworthy, Casey H. Arnold, Thomas R. Butts, Trenton L. Roberts, Chad W. Shelton

Crop, Soil and Environmental Sciences Faculty Publications and Presentations

Rice producers battle herbicide-resistant weeds worldwide while producing rice for ≥50% of the world’s population. Oxyfluorfen can provide rice producers with an alternative site of action for barnyardgrass control, as there are no documented cases of grass weeds being resistant to the herbicide in the mid-southern United States. Oxyfluorfen is anticipated to be labeled in the Roxy Rice Production System and may be sold as a clomazone/oxyfluorfen premixture; hence, experiments were conducted in 2021 and 2022 to evaluate preemergence-applied clomazone/oxyfluorfen ratios compared to clomazone alone on silt loam and clay soils. All ratios of the herbicides caused less than 7% …

Characterization Of A Carbon Fiber Based Broadband Microwave Absorber, Ha Tran, Branimir Pejcinovic, Robert Doneker, Kent Thompson, Adithya Ramachandran

Electrical and Computer Engineering Faculty Publications and Presentations

This paper reports the development and characterization of a novel ultra-wideband microwave absorber material (MAM) based on vertically aligned carbon fibers and ferrite beads. This specific material combination and manufacturing process allows MAM design that is thin, lightweight, and broadband. The material is prepared using a flocking process in which its components are electrostatically deposited on top of an adhesive substrate. Distinct material properties of the substrate and materials layers require characterization done with two separated layers. The microwave absorption characteristics are studied first by rectangular waveguide measurements at X and Ku bands that yield complex electric permittivity and magnetic …

Epidural Interlay Graft For Pituitary Surgery: A 4-Year Institutional Experience, Rita Snyder, Sungho Lee, Prazwal Athukuri, Emmeline Monique Tan Ngo, Meha Goyal Fox, Samer Fakhri, Masayoshi Takashima, Bahar Kapoor Force, Susan Leanne Samson, Kathleen Kelly Gallagher, Daniel Yoshor, Ali Jalali

Faculty, Staff and Students Publications

Objective  Sellar repair techniques with varying complexity and effectiveness have been employed to reduce the incidence of postoperative cerebrospinal fluid (CSF) leaks following endoscopic transsphenoidal pituitary surgery. This study describes our institutional experience with a minimalistic, highly effective approach to sellar repair.

Methods  The authors performed a retrospective review of consecutive cases of transsphenoidal pituitary surgery performed at our institution. All included subjects underwent sellar repair with an epidural interlay graft. Relationships between patient and tumor characteristics, incidence of CSF leak, adjunct repair techniques, and endocrine outcomes were examined.

Results  Three hundred and thirty-four (334) cases were included. Intraoperative CSF …

“The Truth Should Not Be Hidden”: Experiences And Recommendations Of Individuals Making Npe Discoveries Through Genetic Genealogy Databases, Olivia Schuman, Caroline Beit, Jill Oliver Robinson, Whitney Bash Brooks, Amy L Mcguire, Christi Guerrini

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Fueled by direct-to-consumer (DTC) genetic testing and genetic-relative finder services, some participants in genetic genealogy databases are making "not parent expected" (NPE) discoveries. To better understand experiences of this phenomenon, we surveyed a large cohort of users of genetic relative finder (GRF) services concerning their experiences after an NPE discovery.

Methods: Using thematic analysis, we analyzed responses from a cohort of GRF users (n = 646) to open-ended survey items to understand these experiences and their recommendations for DTC genetic testing companies and other GRF users.

Results: We found that individuals had both positive and negative emotional experiences related …

A Method For Rapid And Reliable Quantification Of Vegf-Cell Binding Activity, Prabuddha Waduge, Avinash Kaur, Wei Li

Faculty, Staff and Students Publications

Vascular endothelial growth factor (VEGF) is a pleiotropic growth factor that binds a broad spectrum of cell types and regulates diverse cellular processes, including angiogenesis, growth and survival. However, it is technically difficult to quantify VEGF-cell binding activity because of reversible nature of ligand-receptor interactions. Here we used T7 bacteriophage display to quantify and compare binding activity of three human VEGF-A (hVEGF) isoforms, including hVEGF111, 165 and 206. All three isoforms bound equally well to immobilized aflibercept, a decoy VEGF receptor. hVEGF111-Phage exhibited minimal binding to immobilized heparan sulfate, whereas hVEGF206-Phage and hVEGF165-Phage had the highest and intermediate binding to …

Distinct Landscape And Clinical Implications Of Therapy-Related Clonal Hematopoiesis, Koichi Takahashi, Daisuke Nakada, Margaret Goodell

Faculty, Staff and Student Publications

Therapy-related clonal hematopoiesis (t-CH) is defined as clonal hematopoiesis detected in individuals previously treated with chemotherapy and/or radiation therapy. With the increased use of genetic analysis in oncological care, the detection of t-CH among cancer patients is becoming increasingly common. t-CH arises through the selective bottleneck imposed by chemotherapies and potentially through direct mutagenesis from chemotherapies, resulting in a distinct mutational landscape enriched with mutations in DNA damage-response pathway genes such as TP53, PPM1D, and CHEK2. Emerging evidence sheds light on the mechanisms of t-CH development and potential strategies to mitigate its emergence. Due to its unique characteristics that predominantly …

Behavioral Screening Reveals A Conserved Residue In Y-Box Rna-Binding Protein Required For Associative Learning And Memory In C Elegans, Ashley N Hayden, Katie L Brandel, Edward W Pietryk, Paul R Merlau, Priyadharshini Vijayakumar, Emily J Leptich, Elizabeth S Gaytan, Meredith I Williams, Connie W Ni, Hsiao-Tuan Chao, Jill A Rosenfeld, Rachel N Arey

Faculty, Staff and Students Publications

RNA-binding proteins (RBPs) regulate translation and plasticity which are required for memory. RBP dysfunction has been linked to a range of neurological disorders where cognitive impairments are a key symptom. However, of the 2,000 RBPs in the human genome, many are uncharacterized with regards to neurological phenotypes. To address this, we used the model organism C. elegans to assess the role of 20 conserved RBPs in memory. We identified eight previously uncharacterized memory regulators, three of which are in the C. elegans Y-Box (CEY) RBP family. Of these, we determined that cey-1 is the closest ortholog to the mammalian Y-Box …

Meta-Analysis Comparing Oral Anticoagulant Monotherapy Versus Dual Antithrombotic Therapy In Patients With Atrial Fibrillation And Stable Coronary Artery Disease, Mushood Ahmed, Areeba Ahsan, Aimen Shafiq, Raheel Ahmed, Mahboob Alam, Pierre Sabouret, Jamal S Rana, Gregg C Fonarow

Faculty, Staff and Students Publications

BACKGROUND: Oral anticoagulants (OACs) are routinely used for the management of atrial fibrillation (AF) while antiplatelet agents are used in coronary artery disease (CAD). However, data regarding the comparative clinical outcomes of OAC monotherapy versus dual antithrombotic therapy (anticoagulant plus antiplatelet agent) in patients with AF and stable CAD are limited.

METHODS: A comprehensive search of major databases including PubMed/MEDLINE, Cochrane Library, and Embase was performed from inception to September 1, 2024 to identify randomized control trials (RCTs) that compared OAC monotherapy with dual antithrombotic therapy in patients with AF and stable CAD. The risk ratios (RRs) were estimated with …

Multivalent Protein-Nucleic Acid Interactions Probed By Composition-Gradient Multiangle Light Scattering, Josephine C Ferreon, Natee Kongchan, Phoebe S Tsoi, Kyoung-Jae Choi, Sophia Kenrick, Joel Neilson, Allan Chris M Ferreon

Faculty, Staff and Students Publications

Many RNA-binding proteins, such as TDP-43 or CELF1, interact multivalently with nucleic acid repetitive elements. The molecular stoichiometry of protein to nucleic acid is often difficult to assess, particularly by standard electrophoretic mobility shift assays (EMSAs). Here, we investigate the use of composition-gradient multiangle light scattering (CG-MALS) for quantifying binding affinity and stoichiometry for two RNA-binding proteins with their nucleic acid partners of varied sequence and length: TDP43's N-terminal RNA recognition motifs with both TG/GU-repeat ssDNA and ssRNA, respectively, and CELF1's two N-terminal RNA recognition motifs with (TG/UGUU/GU) repeats and an experimentally defined cognate GU-rich element (GRE). Our CG-MALS data …

Holistic Methodologies For Fusing The Material And The Ideological: Tracing The Sociotechnical Imaginaries That Enable The World’S Fastest Supercomputer, Sarah Read, Jordan Firth

English Faculty Publications and Presentations

When the Aurora supercomputer launches at Argonne National Laboratory it will operate at the exascale and be one of the fastest supercomputers in the world. We have been invited by Argonne to do field work to understand both the day-to-day processes that maintain supercomputing (e.g. user documentation, government reporting, user testing) and the sociotechnical national imaginaries [11], –in particular the increasingly tense global competition between the US and China in the supercomputing race–that shaped the development of Aurora. This article proposes our work-in-progress methodological approach that accounts for both higher-level imaginaries and the everyday practices of supercomputing. We also describe …

Editorial Expression Of Concern: Role Of Brca1 In Heat Shock Response, Yong Xian Ma, Saijun Fan, Jingbo Xiong, Ren-Qi Yuan, Qinghui Meng, Min Gao, Itzhak D Goldberg, Suzanne A Fuqua, Richard G Pestell, Eliot M Rosen

Faculty, Staff and Students Publications

Background

Despite significant improvements in the outcome of Estrogen Receptor (ER) α-positive breast cancer (BC) following the use of endocrine therapies, resistance remains a major challenge. Clinical studies proved that obesity, in addition to promote BC progression, is associated with a reduced efficacy to these treatments, but mechanisms remain unclear.

Methods

We used co-culture systems followed by validation through an ‘ex vivo’ model of human mammary obese (Ob) adipocytes and obese endocrine-resistant metastatic Patient-Derived Organoids (PDOs). Transcriptomics with MixOmics-MINT and MetaCore Functional Tools along with lentiviral and pharmacological approaches provide insights into mechanisms. Clinical relevance was investigated using public datasets, …