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Articles 4021 - 4050 of 159498
Full-Text Articles in Entire DC Network
Contemporary Opportunities And Potential Of Auger Electron-Emitting Theranostics, Seok-Yong Lee, H Charles Manning
Contemporary Opportunities And Potential Of Auger Electron-Emitting Theranostics, Seok-Yong Lee, H Charles Manning
Faculty, Staff and Student Publications
Recent breakthroughs in radiopharmaceutical (RP) therapy have emerged interest in employing Auger electron (AE)-emitting radionuclides as potential agents for precise theranostics. AE provides energy with exceptional localization due to their short tissue penetration range (TPR, < 10 nm), rendering them particularly effective for targeting nuclear DNA in tumor cells. In this context, AE-emitting radionuclide therapy (AE-emitting RLT) enables the targeted destruction of tumor cells while reducing harm to adjacent healthy tissue, a significant challenge in this field. Preclinical and early clinical investigations reveal the efficacy of AE-emitting RLTs in the theranostics of diverse malignancies, such as glioblastoma, prostate cancer, and neuroendocrine tumors. Notwithstanding these developments, challenges and limitations persist regarding dosimetry, delivery efficiency, and the treatment of radiotoxicity. A new paradigm is being developed to tackle the obstacles encountered by integrating molecular target markers (e.g., PARP) that function near the nucleus to improve the intranuclear delivery efficiency of AE-emitting radionuclides. Novel radiochemical methods such as these have facilitated the more stable and efficient labeling of biomolecules with AE-emitting radionuclides. Also, recent advances in DNA-molecular targeting, nanoparticles, nucleic acid/protein engineering, click- or bioorthogonal conjugation chemistry, and artificial intelligence (AI)-based structure modeling present concrete opportunities to overcome these limitations. Moreover, the integration of diagnostic imaging companion platforms employing theranostic radioisotope pairings facilitates real-time assessment of therapeutic efficacy and biodistribution, resulting in the formulation of enhanced treatment regimens. This review summarizes the prior development, recent advancements, barriers in clinical implementation, and future perspective of AE-emitting RLTs.
Nsd2 Inhibitors Rewire Chromatin To Treat Lung And Pancreatic Cancers, Jinho Jeong, Simone Hausmann, Hanyang Dong, Kacper Szczepski, Natasha M Flores, Andy Garcia Gonzalez, Liyang Shi, Xiaoyin Lu, Joanna Lempiäinen, Moritz Jakab, Liyong Zeng, Tourkian Chasan, Eric Bareke, Rui Dong, Emma Carlson, Reinnier Padilla, Dylan Husmann, Julia Thompson, Gerry A Shipman, Emily Zahn, Courtney A Barnes, Laiba F Khan, Liz Marie Albertorio-Sáez, Eva Brill, Vishnu Udayakumar Sunita Kumary, Matthew R Marunde, Danielle N Maryanski, Cheryl C Szany, Bryan J Venters, Carolina Lin Windham, Michal Eligiusz Nowakowski, Iwona Czaban, Mariusz Jaremko, Michael-Christopher Keogh, Kang Le, Michael J Soth, Benjamin A Garcia, Łukasz Jaremko, Jacek Majewski, Pawel K Mazur, Or Gozani
Nsd2 Inhibitors Rewire Chromatin To Treat Lung And Pancreatic Cancers, Jinho Jeong, Simone Hausmann, Hanyang Dong, Kacper Szczepski, Natasha M Flores, Andy Garcia Gonzalez, Liyang Shi, Xiaoyin Lu, Joanna Lempiäinen, Moritz Jakab, Liyong Zeng, Tourkian Chasan, Eric Bareke, Rui Dong, Emma Carlson, Reinnier Padilla, Dylan Husmann, Julia Thompson, Gerry A Shipman, Emily Zahn, Courtney A Barnes, Laiba F Khan, Liz Marie Albertorio-Sáez, Eva Brill, Vishnu Udayakumar Sunita Kumary, Matthew R Marunde, Danielle N Maryanski, Cheryl C Szany, Bryan J Venters, Carolina Lin Windham, Michal Eligiusz Nowakowski, Iwona Czaban, Mariusz Jaremko, Michael-Christopher Keogh, Kang Le, Michael J Soth, Benjamin A Garcia, Łukasz Jaremko, Jacek Majewski, Pawel K Mazur, Or Gozani
Faculty, Staff and Student Publications
NSD2 catalyses the epigenetic modification H3K36me2 (refs. 1,2) and is a candidate convergent downstream effector of oncogenic signalling in diverse malignancies3–5. However, it remains unclear whether the enzymatic activity of NSD2 is therapeutically targetable. Here we characterize a series of clinical-grade small-molecule catalytic NSD2 inhibitors (NSD2i) and show that the pharmacological targeting of NSD2 constitutes an epigenetic dependency with broad therapeutic efficacy in KRAS-driven preclinical cancer models. NSD2i inhibits NSD2 with single-digit nanomolar half-maximal inhibitory concentration potency and high selectivity over related methyltransferases. Structural analyses reveal that the specificity of NSD2i for NSD2 …
Nampt Inhibition Uncovers Therapeutic Vulnerabilities To Venetoclax And Chemotherapy In Acute Myelogenous Leukemia, John R Sanchez, Chaomei Liu, Vishakha Pawar, Yanqing Huang, Daisy Diaz-Rohena, Jyotsana Singh, Priya Koppikar, Tzung-Huei Lai, Lisa St John, Vinay Puduvalli, Jeffrey Molldrem, Palaniraja Thandapani, Nitin Jain, Rosa Lapalombella, Deepa Sampath
Nampt Inhibition Uncovers Therapeutic Vulnerabilities To Venetoclax And Chemotherapy In Acute Myelogenous Leukemia, John R Sanchez, Chaomei Liu, Vishakha Pawar, Yanqing Huang, Daisy Diaz-Rohena, Jyotsana Singh, Priya Koppikar, Tzung-Huei Lai, Lisa St John, Vinay Puduvalli, Jeffrey Molldrem, Palaniraja Thandapani, Nitin Jain, Rosa Lapalombella, Deepa Sampath
Faculty, Staff and Student Publications
Acute myeloid leukemia (AML) cells depend on nicotinamide adenine dinucleotide (NAD
Freeze-Dried, Not Frozen: Lyophilized Mesenchymal Stromal Cell-Derived Extracellular Vesicles And Therapeutic Function In Neuroinflammatory Models, Janet R Ashley, Aidan M Collier, Scott D Olson, Charles S Cox
Freeze-Dried, Not Frozen: Lyophilized Mesenchymal Stromal Cell-Derived Extracellular Vesicles And Therapeutic Function In Neuroinflammatory Models, Janet R Ashley, Aidan M Collier, Scott D Olson, Charles S Cox
Faculty, Staff and Student Publications
Background: Mesenchymal stromal cell (MSC)-derived extracellular vesicles (EVs) offer a promising acellular therapy for immune modulation, but clinical translation is hindered by variability and storage constraints. Lyophilization (freeze-drying) could enable shelf-stable EV therapeutics, although its effects on biological activity remain incompletely defined.
Study design: We compared the immunomodulatory effects of frozen and lyophilized EVs from bone marrow (BM), adipose tissue (AD), and umbilical cord (UC) MSCs using lipopolysaccharide-stimulated rodent splenocytes and microglial models and human peripheral blood mononuclear cells (PBMCs). Variables included batch scale (small vs large), cytokine priming, and MSC source. Tumor necrosis factor alpha (TNF-α) secretion was measured …
Management Of Retropharyngeal Lymph Node Metastases In Thyroid Cancer, Isabelle Fournier, Ashwini Venkata Bandi, Sarah Hamidi, Priyanka Iyer, Naifa L Busaidy, Maria E Cabanillas, Ramona Dadu, Mimi I Hu, Steven G Waguespack, Ugur Nur Basmaci, Michelle D Williams, Mena Mansour, Maria Gule Monroe, Neil D Gross, Ryan P Goepfert, Nancy D Perrier, Victoria Banuchi, Jennifer R Wang, Anastasios Maniakas, Mark E Zafereo
Management Of Retropharyngeal Lymph Node Metastases In Thyroid Cancer, Isabelle Fournier, Ashwini Venkata Bandi, Sarah Hamidi, Priyanka Iyer, Naifa L Busaidy, Maria E Cabanillas, Ramona Dadu, Mimi I Hu, Steven G Waguespack, Ugur Nur Basmaci, Michelle D Williams, Mena Mansour, Maria Gule Monroe, Neil D Gross, Ryan P Goepfert, Nancy D Perrier, Victoria Banuchi, Jennifer R Wang, Anastasios Maniakas, Mark E Zafereo
Faculty, Staff and Student Publications
Background: Retropharyngeal lymph node (RPLN) metastases in thyroid cancer are rare, with optimal management underreported.
Methods: Retrospective study of consecutive thyroid cancer patients with RPLN metastases treated at MD Anderson Cancer Center between 2000 and 2024.
Results: One hundred and sixty-seven patients (75% differentiated, 21% medullary, 4% poorly differentiated thyroid cancer) were divided into three groups: active surveillance (AS) (13%), surgery (56%), and nonsurgical treatment (31%). In the AS group (median follow-up 2.3 years), RPLN metastases grew a median 3% (range: 0-56) or 0.02 cm (range: 0-0.7) per year. Surgical therapy included transcervical (73%), transoral robotic (14%), transoral (12%), and …
Evaluation Of Organ-Specific Relative Biological Effectiveness Of Proton Therapy Using Radiation-Induced Pneumonitis As An Endpoint, Li Liao, Ting Xu, Mei Chen, Tingshi Su, Narayan Sahoo, Xiaorong Zhu, Steven J Frank, Quynh-Nhu Nguyen, Zhongxing Liao, Xiaodong Zhang
Evaluation Of Organ-Specific Relative Biological Effectiveness Of Proton Therapy Using Radiation-Induced Pneumonitis As An Endpoint, Li Liao, Ting Xu, Mei Chen, Tingshi Su, Narayan Sahoo, Xiaorong Zhu, Steven J Frank, Quynh-Nhu Nguyen, Zhongxing Liao, Xiaodong Zhang
Faculty, Staff and Student Publications
Background and purpose: Proton therapy has become widely used for non-small cell lung cancer (NSCLC) due to its ability to spare normal tissue. However, the commonly assumed relative biological effectiveness (RBE) of 1.1 may underestimate the therapy's true biological effects on lung, potentially leading to a higher than expected incidence of radiation-induced pneumonitis (RP). In this retrospective study, we evaluated the variability of organ-specific RBE of proton therapy using RP grade 2 or higher (RP2+) as an endpoint.
Materials and methods: Data from 270 NSCLC patients across two clinical trials were analyzed, with 134 given photon therapy and 136 given …
Applications And Challenges Of Utilizing Digital Pathology And Ai-Enabled Workflows In Clinical Trials, Manu Sebastian, Harsh Batra, Monika Lamba Saini, Staci Kearney, Lorcan Sherry, Serge Alexanian, Michael Cohen, William Weber, Joe Lennerz, Anil V Parwani
Applications And Challenges Of Utilizing Digital Pathology And Ai-Enabled Workflows In Clinical Trials, Manu Sebastian, Harsh Batra, Monika Lamba Saini, Staci Kearney, Lorcan Sherry, Serge Alexanian, Michael Cohen, William Weber, Joe Lennerz, Anil V Parwani
Faculty, Staff and Student Publications
This is a comprehensive review on current utilization and challenges of digital pathology adoption in clinical trials and aims to provide a broad view on its impact on pathology review processes in clinical trials. It provides an overview of current pathology review practices in clinical trials and unique advantages digital pathology adoption can offer. The key areas including existing workflows, use case scenarios in different disease areas in clinical trials, including but not limited to patient identification and pre-screening, and regulatory aspects have been described with relevance. In addition, the review delves into the integration of genomics, AI, image analysis, …
Reconsidering The Definition Of Triple-Negative Breast Cancer In The Immune Checkpoint Inhibitor Era: An Optimal Cut-Off Value For Hormone Receptor Percentage Of Her2-Negative Invasive Breast Cancer, Takeo Fujii, Toshiaki Iwase, Yu Shen, Jami Fukui, Naoto T Ueno
Reconsidering The Definition Of Triple-Negative Breast Cancer In The Immune Checkpoint Inhibitor Era: An Optimal Cut-Off Value For Hormone Receptor Percentage Of Her2-Negative Invasive Breast Cancer, Takeo Fujii, Toshiaki Iwase, Yu Shen, Jami Fukui, Naoto T Ueno
Faculty, Staff and Student Publications
The optimal cut-off values of estrogen receptor (ER) and progesterone receptor (PgR) expression to define the positivity of ER and PgR have been under discussion for over a decade but remain controversial. The American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) and the St. Gallen International Expert Consensus recommended that breast cancers with ≥1% of ER or PgR expression should be considered hormone receptor (HR)-positive tumors but ER/PR expression of 1% to 10% should be reported as HR-low positive; however, among HER2-negative disease, data on the overall benefit of adjuvant endocrine therapies for patients with HR-low positive disease is …
T Cells Modulate The Development And Maintenance Of Painful Paclitaxel-Induced Peripheral Neuropathy In Rnu Rats, Ahmed Olalekan Bakare, Gerard Limerick, Vasudha Goel, Ratan K Banik, Lei Zheng, Andrew J Shepherd, Kristine Glunde, Qin Zheng, Eellan Sivanesan
T Cells Modulate The Development And Maintenance Of Painful Paclitaxel-Induced Peripheral Neuropathy In Rnu Rats, Ahmed Olalekan Bakare, Gerard Limerick, Vasudha Goel, Ratan K Banik, Lei Zheng, Andrew J Shepherd, Kristine Glunde, Qin Zheng, Eellan Sivanesan
Faculty, Staff and Student Publications
The role of T cells in chemotherapy-induced peripheral neuropathy (CIPN) is complex and shaped by biological and experimental factors, including sex, hormonal status, genetic background, and cancer model. This complexity has contributed to inconsistent findings among studies, limiting therapeutic progress. In this study, we investigate how T cells contribute to painful paclitaxel (PTX)-induced peripheral neuropathy (PIPN). Adult male T cell-competent (RNU+/−) and T cell-deficient (RNU−/−) rats were subcutaneously inoculated with tumor cells and subsequently treated with intraperitoneal PTX (8 mg/kg total dose). Reflexive (mechanical, heat, cold) and non-reflexive (burrowing, gait) pain behaviors were assessed from baseline through week 6. Immunohistochemistry …
The Lysine Demethylase Kdm4c Is An Oncogenic Driver And Regulates Erk Activity In Kras-Mutant Pancreatic Ductal Adenocarcinoma, Menna-T-Allah Shaheen, Sarah Dhebat, Kimal I Rajapakshe, Bidyut Ghosh, Benson Chellakkan Selvanesan, Shariq S Ansari, Cara L Haymaker, Dorsay Sadeghian, Huamin Wang, Ching-Fei Li, Haoqiang Ying, Anirban Maitra
The Lysine Demethylase Kdm4c Is An Oncogenic Driver And Regulates Erk Activity In Kras-Mutant Pancreatic Ductal Adenocarcinoma, Menna-T-Allah Shaheen, Sarah Dhebat, Kimal I Rajapakshe, Bidyut Ghosh, Benson Chellakkan Selvanesan, Shariq S Ansari, Cara L Haymaker, Dorsay Sadeghian, Huamin Wang, Ching-Fei Li, Haoqiang Ying, Anirban Maitra
Faculty, Staff and Student Publications
Deregulation of proteins involved in chromatin regulation is common in pancreatic ductal adenocarcinoma (PDAC). Lysine demethylase 4C (KDM4C) is one of the chromatin-modifying proteins frequently overexpressed across multiple solid cancers and is linked to chromatin instability, increased cell proliferation, and enhanced stem cell–like behavior. We observed upregulation of KDM4C protein in a panel of human PDAC cell lines and patient samples compared with nonneoplastic controls. CRISPR/Cas9-mediated deletion of KDM4C in human and murine PDAC cells reduced proliferation, clonogenicity, and increased survival of orthotopically implanted murine PDAC allografts. Transcriptomic and proteomic analyses revealed that loss of KDM4C in both human and …
Clinical And Molecular Characteristics Of Patients With Young-Onset And Average-Onset Pancreatic Adenocarcinoma, Adriana C Gamboa, Kever A Lewis, Laura R Prakash, Zhouxuan Li, Wei Qiao, Dan Zhao, Mark W Hurd, Mahmoud Yousef, Naruhiko Ikoma, Michael P Kim, Jeffrey E Lee, Jessica E Maxwell, Ching-Wei D Tzeng, Matthew H G Katz, Rebecca A Snyder
Clinical And Molecular Characteristics Of Patients With Young-Onset And Average-Onset Pancreatic Adenocarcinoma, Adriana C Gamboa, Kever A Lewis, Laura R Prakash, Zhouxuan Li, Wei Qiao, Dan Zhao, Mark W Hurd, Mahmoud Yousef, Naruhiko Ikoma, Michael P Kim, Jeffrey E Lee, Jessica E Maxwell, Ching-Wei D Tzeng, Matthew H G Katz, Rebecca A Snyder
Faculty, Staff and Student Publications
Purpose: The incidence of young-onset pancreatic cancer (YO-PC) has risen over the past two decades, yet its molecular characteristics and long-term outcomes remain poorly defined.
Methods: We retrospectively evaluated patients with PC treated at a tertiary referral center from 2016 to 2022 who had available molecular data. Patients were classified as YO-PC (≤50 years) or average-onset PC (AO-PC, >50 years). A subset analysis examined outcomes in those who underwent curative-intent pancreatectomy. Primary end points included overall survival (OS) and recurrence-free survival (RFS).
Results: Among 511 patients, 10.9% had YO-PC (n = 56; median age 44 years). Patients with YO-PC more …
Case Report: Management Of A Challenging Case Presenting With Dysphagia After Thyroidectomy Requiring Administration Of Liquid 131i Via Mic-Key Low-Profile Tube—A Multidisciplinary Approach, Ahmed Ebada Salem, Sandra Ramirez, Brian R Weston, Akram Hussein, Simone Krebs
Case Report: Management Of A Challenging Case Presenting With Dysphagia After Thyroidectomy Requiring Administration Of Liquid 131i Via Mic-Key Low-Profile Tube—A Multidisciplinary Approach, Ahmed Ebada Salem, Sandra Ramirez, Brian R Weston, Akram Hussein, Simone Krebs
Faculty, Staff and Student Publications
Radioactive iodine (RAI) therapy with 131-iodine (131I) remains a cornerstone in the postoperative management of differentiated thyroid carcinoma (DTC). The standard route of administration is oral, typically in capsule form and less commonly as a liquid. However, in patients with severe dysphagia and compromised airway, traditional oral 131I delivery may be contraindicated due to the risk of aspiration and radioactivity contamination. These scenarios present unique clinical challenges that necessitate deviation from conventional protocols. While liquid 131I may be administered through the mouth or via nasogastric or percutaneous gastrostomy tubes, there is currently no standardized approach, and potential risks, such as …
Preliminary Examination Of Orexin Receptor Antagonism With Suvorexant In Individuals With Methamphetamine Use Disorder: A Case Series Study, Heather Webber, Jessica Badawi, Douglas Calvillo, Jin Yoon, Michael Weaver, Scott Lane, Joy Schmitz
Preliminary Examination Of Orexin Receptor Antagonism With Suvorexant In Individuals With Methamphetamine Use Disorder: A Case Series Study, Heather Webber, Jessica Badawi, Douglas Calvillo, Jin Yoon, Michael Weaver, Scott Lane, Joy Schmitz
Faculty, Staff and Student Publications
No abstract provided.
Evolving Molecular Subtypes Of Gastric Cancer: From Past Classifications To Present Consensus And Future Directions For Precision Therapy, Ju-Seog Lee
Faculty, Staff and Student Publications
Gastric cancer is a biologically heterogeneous disease. The advent of high-throughput multi-omic technologies has revolutionized our understanding of gastric cancer by deconstructing this heterogeneous entity into distinct and more homogeneous molecular subtypes. Early classifications based on gene expression, methylation, and histology have laid the groundwork for multi-omic frameworks proposed by The Cancer Genome Atlas and Asian Cancer Research Group, which established the foundation of modern molecular taxonomy. Subsequent integrative efforts, particularly the Consensus Genomic Subtypes (Super 6) model, have unified this collected information into clinically relevant subtypes that bridge prognostic stratification with treatment strategies. Established biomarkers such as human epidermal …
Bop2-Te: Bayesian Optimal Phase 2 Design For Jointly Monitoring Efficacy And Toxicity With Application To Dose Optimization, Kai Chen, Heng Zhou, J Jack Lee, Ying Yuan
Bop2-Te: Bayesian Optimal Phase 2 Design For Jointly Monitoring Efficacy And Toxicity With Application To Dose Optimization, Kai Chen, Heng Zhou, J Jack Lee, Ying Yuan
Faculty, Staff and Student Publications
We propose a Bayesian optimal phase 2 design for jointly monitoring efficacy and toxicity, referred to as BOP2-TE, to improve the operating characteristics of the BOP2 design proposed by Zhou et al. (2017). BOP2-TE utilizes a Dirichlet-multinomial model to jointly model the distribution of toxicity and efficacy endpoints, making go/no-go decisions based on the posterior probability of toxicity and futility. In comparison to the original BOP2 and other existing designs, BOP2-TE offers the advantage of providing rigorous type I error control in cases where the treatment is toxic and futile, effective but toxic, or safe but futile, while optimizing …
Prickle4 Drives Microenvironmental Remodeling And Resistance To Parp Inhibition In Idh-Mutant Glioma, Ju Yang, Hua Yang, Yifan Yuan, Chenyang Zhang, Ziwei Fu, Yanyan Chen, Yinghong Xiong, Shuyu Chen, Kexin Ling, Ying Liu, Jason T Huse, Bo Chen, Timothy A Chan, Zengxin Qi, Zhao Zhang, Xiuping Liu, Yuxiang Wang
Prickle4 Drives Microenvironmental Remodeling And Resistance To Parp Inhibition In Idh-Mutant Glioma, Ju Yang, Hua Yang, Yifan Yuan, Chenyang Zhang, Ziwei Fu, Yanyan Chen, Yinghong Xiong, Shuyu Chen, Kexin Ling, Ying Liu, Jason T Huse, Bo Chen, Timothy A Chan, Zengxin Qi, Zhao Zhang, Xiuping Liu, Yuxiang Wang
Faculty, Staff and Student Publications
Mutations in isocitrate dehydrogenase (IDH) genes sensitize gliomas to PARP inhibition (PARPi) by inducing epigenetic reprogramming of DNA damage repair circuits. However, tumors treated with PARPi eventually relapse despite initial responsiveness. In this study, it is demonstrated that the anti-angiogenic agent lenvatinib synergizes effectively with PARPi, resulting in substantial tumor regression and significantly extended survival. Genomic analysis of tumors reveals that PARPi induces widespread transcriptomic changes that are predominantly pro-inflammatory, thereby promoting tumor angiogenesis. Prickle4, a planar cell polarity protein, is identified as a critical mediator of PARPi-induced neovascularization. Targeting Prickle4 effectively overcomes PARPi resistance in these tumors. Collectively, these …
A Gut-Activated Nhr-86-Cyp Pathway Mediates The Neuroprotective Effects Of Enterococcus Faecium Probiotics In A Nematode Model Of Amyotrophic Lateral Sclerosis, Yu Sang, Jie Ren, Alejandro Aballay
A Gut-Activated Nhr-86-Cyp Pathway Mediates The Neuroprotective Effects Of Enterococcus Faecium Probiotics In A Nematode Model Of Amyotrophic Lateral Sclerosis, Yu Sang, Jie Ren, Alejandro Aballay
Faculty, Staff and Student Publications
Neurodegenerative diseases are often associated with oxidative stress, and while probiotics may influence neuronal health, the underlying mechanisms remain poorly understood. Using the sod-1 A4VM amyotrophic lateral sclerosis (ALS) model in Caenorhabditis elegans, we investigated the protective effects of the probiotic Enterococcus faecium against oxidative stress-induced neurodegeneration. Animals fed E. faecium showed reduced motor neuron degeneration under oxidative stress compared to those maintained on a standard Escherichia coli diet. Transcriptome analysis revealed a significant enrichment of oxidoreductase genes, including cytochrome P450 (cyp) genes. RNAi-mediated knockdown of cyp genes impaired E. faecium-mediated neuroprotection, and this loss correlated with increased reactive oxygen …
Endogenous Processes Underlying Clock-Like Mutational Signatures, Teresa Druck, Rami I Aqeilan, C Marcelo Aldaz, Nicola Zanesi, Kay Huebner
Endogenous Processes Underlying Clock-Like Mutational Signatures, Teresa Druck, Rami I Aqeilan, C Marcelo Aldaz, Nicola Zanesi, Kay Huebner
Faculty, Staff and Student Publications
Wellcome Trust scientists have shown that “mutational signatures” in specific nucleotide contexts accumulate in genomes of mammalian tissues, providing clues to underlying causes of specific signatures. Analysis of cancer genomes has identified more than 50 single‐base substitution (SBS) signatures, with SBS1, SBS5, and SBS40 linked to aging and present in normal tissues. SBS1 results from cytosine demethylation, whereas SBS5 and SBS40 arise from unknown endogenous mechanisms. We hypothesized that loss of fragile‐site genes drives these two signatures. FHIT, located at FRA3B, is frequently deleted in cancers, and Fhit‐deficient mouse tissues exhibit a mutation profile resembling human SBS5. Data mining of …
Preclinical Ischemic Stroke Multicenter Trials (Prism) Collective Statement: Opportunities, Challenges, And Recommendations For A New Era, Cenk Ayata, Philip M Bath, Anna M Planas, Stuart M Allan, Johannes Boltze, Ryan P Cabeen, Claire L Gibson, Marilyn J Cipolla, Marcio A Diniz, Stefano Fumagalli, Fahmeed Hyder, Raymond C Koehler, Arthur Liesz, Sarah K Mccann, Tim Magnus, Louise D Mccullough, Emily S Sena, Simone Beretta, Jaroslaw Aronowski, Francesca Bosetti, Clinton B Wright, Patrick D Lyden, Lauren H Sansing
Preclinical Ischemic Stroke Multicenter Trials (Prism) Collective Statement: Opportunities, Challenges, And Recommendations For A New Era, Cenk Ayata, Philip M Bath, Anna M Planas, Stuart M Allan, Johannes Boltze, Ryan P Cabeen, Claire L Gibson, Marilyn J Cipolla, Marcio A Diniz, Stefano Fumagalli, Fahmeed Hyder, Raymond C Koehler, Arthur Liesz, Sarah K Mccann, Tim Magnus, Louise D Mccullough, Emily S Sena, Simone Beretta, Jaroslaw Aronowski, Francesca Bosetti, Clinton B Wright, Patrick D Lyden, Lauren H Sansing
Faculty, Staff and Student Publications
Preclinical stroke research faces a critical translational gap, with animal studies failing to reliably predict clinical efficacy. To address this, the field is moving toward rigorous, multicenter preclinical randomized controlled trials (mpRCTs) that mimic phase 3 clinical trials in several key components. This collective statement, derived from experts involved in mpRCTs, outlines considerations for designing and executing such trials. mpRCTs offer advantages such as increased sample sizes, robust statistical design, incorporation of heterogeneity, and standardized protocols, but they face challenges in finding the right balance between standardization and heterogeneity, appropriate stroke model selection, and outcome measures, as well as the …
Dog Waste Creates A Preference-Performance Mismatch For Urban Dung Beetles, Erin L. Mccullough, Beatrice M. Altopp, Daniel F. Kellogg, Madelyn S. Mcinnis, Luna J. Pagan
Dog Waste Creates A Preference-Performance Mismatch For Urban Dung Beetles, Erin L. Mccullough, Beatrice M. Altopp, Daniel F. Kellogg, Madelyn S. Mcinnis, Luna J. Pagan
Biology
Urban environments expose animals to novel conditions that may favor behavioral flexibility but can create preference-performance mismatches when attractive resources are associated with reduced reproductive success. Dung beetles are often considered dietary generalists, yet little is known about how they respond to altered food availability in human-dominated habitats. We combined field surveys and laboratory experiments using two domestic dung types to examine diet preference, maternal provisioning, and offspring performance in the urban dung beetle Onthophagus orpheus. Beetles strongly preferred dog dung over cow dung, and offspring reared on dog dung developed faster and emerged as larger adults. Despite these apparent …
Herbivore Identity And Species Richness Shape Fruit Chemical And Quality Responses To Foliar Herbivory, Xavier Ozowara, Taylor M. Sloey, Susan R. Whitehead
Herbivore Identity And Species Richness Shape Fruit Chemical And Quality Responses To Foliar Herbivory, Xavier Ozowara, Taylor M. Sloey, Susan R. Whitehead
Biological Sciences Faculty Publications
The cascading consequences of foliar herbivory on fruit chemistry and quality remain relatively underexplored, with most existing studies focusing on the effects of only one or two attackers. In this study, we examine how increasing herbivore species richness during foliar herbivory alters strawberry (Fragaria × ananassa Duch) fruit quality and phenolic chemistry. We conducted a greenhouse experiment with single species feeding and different combinations of feeding by three generalist lepidopteran species: Spodoptera frugiperda, Heliothis virescens, Helicoverpa zea. Species fed on leaves for 72 h as fruits ripened, and fully ripe fruits were harvested 72 h after …
Microbiota Characterization Of Zostera Marina Seeds At Early Stage Development, Gina Chaput, Torrie Hanley, Jonathan A. Eisen, E. Maggie Sogin, A. Randall Hughes, Cynthia G. Hays
Microbiota Characterization Of Zostera Marina Seeds At Early Stage Development, Gina Chaput, Torrie Hanley, Jonathan A. Eisen, E. Maggie Sogin, A. Randall Hughes, Cynthia G. Hays
Biology Faculty Publications
Understanding seagrass seed microbiomes is crucial for developing microbial-mediated methods to improve germination in restoration efforts. Here, we used 16S rRNA gene and ITS2 amplicon sequencing to characterize the bacterial and fungal communities of seeds from the model seagrass, Zostera marina.
Investigating The Potential Neurotoxic Effects Of Cell-Free Factors By Batrachochytrium Dendrobatidis On Locomotion In Xenopus Laevis, Anna Lennon, Laura K. Reinert, Louise A. Rollins-Smith, Will Best, Chase T. Kinsey Phd
Investigating The Potential Neurotoxic Effects Of Cell-Free Factors By Batrachochytrium Dendrobatidis On Locomotion In Xenopus Laevis, Anna Lennon, Laura K. Reinert, Louise A. Rollins-Smith, Will Best, Chase T. Kinsey Phd
Funded Scholarship
Chytridiomycosis is a contributor to amphibian population declines. Diseased amphibians show symptoms of lethargy and loss of righting reflexes, likely due to ion imbalance across the skin. However, it is possible developing zoosporangia release toxins that affect neuromuscular activity. Using Xenopus laevis as a model, we hypothesized that locomotor performance would be affected by injection of Bd supernatant factors. X. laevis were injected and then filmed performing a swimming escape response with high-speed cameras at 4 hours, 24 hours, and 1- week post-injection. Average maximum swimming velocity and escape latency were digitized using high speed video. Despite no difference in …
Comparison Of Enrichment Interaction Duration Between Male And Female Panthera Leo Leo, Maegen G. Meldrum
Comparison Of Enrichment Interaction Duration Between Male And Female Panthera Leo Leo, Maegen G. Meldrum
Undergraduate Honors Thesis Projects
African lion (Panthera leo leo) populations have declined significantly over the past century within their natural habitats, increasing the importance of effective management strategies for individuals in human care. Environment enrichment is a critical tool for promoting species typical behavior in human care; however, enrichment practices are often generalized and may not account for sex-specific differences. This study examined how sex, enrichment types, behaviors, and time of day influenced enrichment interaction duration in a small pride of African lions (n = 4) housed at the Columbus Zoo and Aquarium. Two enrichment types were evaluated: cognitive/occupational (CO, a manipulable barrel) …
Tick Lipocalin Triggers Mammalian Igfbp-3-Mediated Apoptosis In Macrophages And Keratinocytes, Krittika Nandy, P. P. Mahesh, Lichao Liu, Daniel E. Sonenshine, Hameeda Sultana, Girish Neelakanta
Tick Lipocalin Triggers Mammalian Igfbp-3-Mediated Apoptosis In Macrophages And Keratinocytes, Krittika Nandy, P. P. Mahesh, Lichao Liu, Daniel E. Sonenshine, Hameeda Sultana, Girish Neelakanta
Biological Sciences Faculty Publications
Ticks secrete several molecules, including lipocalins, in their saliva during blood feeding on a vertebrate host. In this study, we provide novel evidence on the role of Ornithodoros turicata americanus tick lipocalin (Otlip) in modulating cytokine expression and in triggering apoptosis in mammalian macrophages and keratinocytes. The cytokine array analysis revealed significantly increased secretion of insulin-like growth factor-binding protein 3 (IGFBP3) from murine macrophage cell line upon treatment with recombinant Otlip protein (rGST-Otlip) when compared to the secretion noted from cells treated with a control protein (rGST). Similar observation with cytokine protein array analysis was noted when murine macrophages were …
Microarray Analysis Of Human Abdominal Aortic Aneurysm With Emphasis On Cardiovascular Genes Revealed Differentially Expressed Genes, Song Lu, Li Ping Li, John V. White, Xiaoying Zhang, Ifeyinwa Nwaneshiudu, Adaobi Nwaneshiudu, Nectaria Ntaoula, John Gaughan, Dimitri S. Monos, Wan-Lu Lin, Charalambos C. Solomides, Emilia L. Oleszak, Chris D. Platsoucas
Microarray Analysis Of Human Abdominal Aortic Aneurysm With Emphasis On Cardiovascular Genes Revealed Differentially Expressed Genes, Song Lu, Li Ping Li, John V. White, Xiaoying Zhang, Ifeyinwa Nwaneshiudu, Adaobi Nwaneshiudu, Nectaria Ntaoula, John Gaughan, Dimitri S. Monos, Wan-Lu Lin, Charalambos C. Solomides, Emilia L. Oleszak, Chris D. Platsoucas
Biological Sciences Faculty Publications
Background/Aim: We examined gene expression profiles in abdominal aortic aneurysm (AAA) lesions vs. normal aortas by cDNA microarray and real-time quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR).
Materials and Methods: Phosphorus (32P)-labeled cDNA from AAA specimens (mean AAA size 6.65 cm) and normal aortas were hybridized with a 588-gene microarray primarily of the cardiovascular system. The results were validated by qRT-PCR.
Results: A total of 35 out of the 588 genes were differentially expressed, with either log2 ratio of AAAs/controls ≥1 (upregulated; 20 genes) or ≤−1 (downregulated; 15 genes) in AAA lesions vs. normal aorta, and 25 of these were significantly …
Challenging And Diagnosing Structured Population Models By Testing Predictions From Stochastic Demography, Stephen P. Ellner, Robin E. Snyder, Daniel T. Blumstein, Dylan Z. Childs, Joshua C. Fowler, Christina M. Hernández, Julien G. A. Martin, María Paniw, Yngvild Vindenes
Challenging And Diagnosing Structured Population Models By Testing Predictions From Stochastic Demography, Stephen P. Ellner, Robin E. Snyder, Daniel T. Blumstein, Dylan Z. Childs, Joshua C. Fowler, Christina M. Hernández, Julien G. A. Martin, María Paniw, Yngvild Vindenes
Biological Sciences Faculty Publications
1. Structured population models are parameterized to accurately project expected population sizes, stage/state distributions and population growth rates, but they also predict the variation in outcomes among individuals, such as the variance and skewness of lifetime reproductive output (LRO) and lifespan, the probability of never reproducing, and many other life-history metrics.
2. Testing such predictions about individual outcomes can be very useful model 'stress tests', because they depend on how components of the model (e.g. submodels for survival and fecundity) interact over multiple time steps, not just on the accuracy of the submodels. Because data on among-individual variation is rarely …
Optimal Control Analysis Of Malaria Transmission In The Presence Of Insecticide Resistance And Climate Variability In Kenya, Lorna Chepkemoi, Titus Okello Orwa, Samuel Mwalili, Rachel Waema Mbogo, Steeven Belvinos Affognon, Daisy Salifu, Henri E.Z. Tonnang
Optimal Control Analysis Of Malaria Transmission In The Presence Of Insecticide Resistance And Climate Variability In Kenya, Lorna Chepkemoi, Titus Okello Orwa, Samuel Mwalili, Rachel Waema Mbogo, Steeven Belvinos Affognon, Daisy Salifu, Henri E.Z. Tonnang
All Peer-Reviewed Publications
Malaria remains a major public health concern in Kenya, where changing climatic conditions, insecticide resistance, and mosquito behavioral adaptations continue to challenge control efforts. This study develops and analyzes a climate-sensitive malaria transmission model that incorporates mosquito behavior, insecticide resistance, and vector–human ecological dynamics to identify optimal control strategies for the Kenyan context. The model’s well-posedness was established, the basic reproduction number (R0) computed using the next-generation matrix method, and the stability of equilibrium points assessed. Spatial analysis of R0 was performed using temperature and rainfall raster data to map transmission risk across Kenya under varying insecticide use scenarios. Results …
Behavioral And Electrophysiological Responses Of Fall Armyworm Larval Parasitoid Coccygidium Luteum To Maize And Companion Plant Volatiles, Emmanuel Peter, Sevgan Subramanian, Abdullahi Yusuf, Samira A. Mohamed, Baldwyn Torto, Emily A. Martin, Amanuel Tamiru
Behavioral And Electrophysiological Responses Of Fall Armyworm Larval Parasitoid Coccygidium Luteum To Maize And Companion Plant Volatiles, Emmanuel Peter, Sevgan Subramanian, Abdullahi Yusuf, Samira A. Mohamed, Baldwyn Torto, Emily A. Martin, Amanuel Tamiru
All Peer-Reviewed Publications
Companion cropping and biological control are among the best agronomic practices recommended for ecologically sustainable management of the invasive fall armyworm (FAW), Spodoptera frugiperda J.E. Smith (Lepidoptera: Noctuidae). Companion plants may suppress the FAW population by repelling the pest, disrupting host-plant location and recruiting biocontrol agents such as parasitoids. These interactions are primarily mediated by plant-derived volatile organic compounds (VOCs). Understanding parasitoids’ responses to VOCs emitted by companion plants enables selection of suitable cultivars to enhance biological control and design appropriate intercropping systems for effective FAW management. This study investigated behavioral and electrophysiological responses of a key FAW larval parasitoid, …
Taxonomy, Distribution And Ecology, Biology, Nutritional Composition, And Conservation Status Of Critically Endangered Lake Chala Tilapia Oreochromis Hunteri (Günther, 1889): Implications For Aquaculture Development, Jonathan Munguti, Mavindu Muthoka, Domitila Kyule, Esther Magondu, Jacob O. Iteba, Kevin Obiero, Paul Orina, Menaga Meenakshisundaram, Tanga M. Chrysantus
Taxonomy, Distribution And Ecology, Biology, Nutritional Composition, And Conservation Status Of Critically Endangered Lake Chala Tilapia Oreochromis Hunteri (Günther, 1889): Implications For Aquaculture Development, Jonathan Munguti, Mavindu Muthoka, Domitila Kyule, Esther Magondu, Jacob O. Iteba, Kevin Obiero, Paul Orina, Menaga Meenakshisundaram, Tanga M. Chrysantus
All Peer-Reviewed Publications
Oreochromis hunteri Günther, 1889, commonly known as Lake Chala tilapia, is an endemic cichlid restricted to the small crater lake, Lake Chala, on the border of Kenya and Tanzania. This review synthesizes existing knowledge on the taxonomy, and phylogenetic placement, distribution and ecology, and biology including nutritional composition, and conservation status of O. hunteri and identifies knowledge gaps to assess its potential for aquaculture development. The knowledge gaps include its reproductive biology, population structure, and adaptive capacity to environmental and climatic variability. As the type species of the genus Oreochromis, O. hunteri is a unique, genetically isolated lineage within a …