Digital Commons Network^™

Dynamic Imaging Of Blood Coagulation Within The Hematoma Of Patients With Acute Hemorrhagic Stroke, Muhammad E Haque, Seth B Boren, James Mills, Kerry G Schneider, Maria Parekh, Stuart M Fraser, Ivo Bach, Praveen Hariharan, Pamela J Zelnick, Felix S Guerra Castanon, Asim Naveed, Muhammad Tariq, Octavio D Arevalo, Khader M Hasan, Miguel Escobar, Xiurong Zhao, Clark Sitton, Ponnada A Narayana, James C Grotta, Jaroslaw Aronowski, Sean I Savitz

Faculty, Staff and Student Publications

BACKGROUND: The dynamics of blood clot (combination of Hb [hemoglobin], fibrin, and a higher concentration of aggregated red blood cells) formation within the hematoma of an intracerebral hemorrhage is not well understood. A quantitative neuroimaging method of localized coagulated blood volume/distribution within the hematoma might improve clinical decision-making.

METHODS: The deoxyhemoglobin of aggregated red blood cells within extravasated blood exhibits a higher magnetic susceptibility due to unpaired heme iron electrons. We propose that coagulated blood, with higher aggregated red blood cell content, will exhibit (1) a higher positive susceptibility than noncoagulated blood and (2) increase in fibrin polymerization-restricted localized diffusion, …

New Horizons In Hyperpolarized13c Mri, Myriam M Chaumeil, James A Bankson, Kevin M Brindle, Shdema Epstein, Ferdia A Gallagher, Martin Grashei, Caroline Guglielmetti, Joshua D Kaggie, Kayvan R Keshari, Stephan Knecht, Christoffer Laustsen, Andreas B Schmidt, Daniel Vigneron, Yi-Fen Yen, Franz Schilling

Faculty, Staff and Student Publications

Hyperpolarization techniques significantly enhance the sensitivity of magnetic resonance (MR) and thus present fascinating new directions for research and applications with in vivo MR imaging and spectroscopy (MRI/S). Hyperpolarized 13C MRI/S, in particular, enables real-time non-invasive assessment of metabolic processes and holds great promise for a diverse range of clinical applications spanning fields like oncology, neurology, and cardiology, with a potential for improving early diagnosis of disease, patient stratification, and therapy response assessment. Despite its potential, technical challenges remain for achieving clinical translation. This paper provides an overview of the discussions that took place at the international workshop "New Horizons …

E-Cadherin Loss Drives Diffuse-Type Gastric Tumorigenesis Via Ezh2-Mediated Reprogramming, Gengyi Zou, Yuanjian Huang, Shengzhe Zhang, Kyung-Pil Ko, Bongjun Kim, Jie Zhang, Vishwa Venkatesan, Melissa P Pizzi, Yibo Fan, Sohee Jun, Na Niu, Huamin Wang, Shumei Song, Jaffer A Ajani, Jae-Il Park

Faculty, Staff and Student Publications

Diffuse-type gastric adenocarcinoma (DGAC) is a deadly cancer often diagnosed late and resistant to treatment. While hereditary DGAC is linked to CDH1 mutations, the role of CDH1/E-cadherin inactivation in sporadic DGAC tumorigenesis remains elusive. We discovered CDH1 inactivation in a subset of DGAC patient tumors. Analyzing single-cell transcriptomes in malignant ascites, we identified two DGAC subtypes: DGAC1 (CDH1 loss) and DGAC2 (lacking immune response). DGAC1 displayed distinct molecular signatures, activated DGAC-related pathways, and an abundance of exhausted T cells in ascites. Genetically engineered murine gastric organoids showed that Cdh1 knock-out (KO), KrasG12D, Trp53 KO (EKP) accelerates tumorigenesis with immune evasion …

Protective Effects Of The Postbiotic Lactobacillus Plantarum Md35 On Bone Loss In An Ovariectomized Mice Model, Ju-Yeong Myeong, Hye-Yeon Jung, Hyo-Seok Chae, Hyang Hyun Cho, Don-Kyu Kim, You-Jee Jang, Jae-Il Park

Faculty, Staff and Student Publications

Postmenopausal osteoporosis is caused by estrogen deficiency, which impairs bone homeostasis, resulting in increased osteoclastic resorption without a corresponding increase in osteoblastic activity. Postbiotics have several therapeutic properties, including anti-obesity, anti-diabetic, anti-inflammatory, and anti-osteoporotic effects. However, the beneficial effects of the postbiotic MD35 of Lactobacillus plantarum on bone have not been studied. In this study, we demonstrated that the postbiotic L. plantarum MD35, isolated from young radish water kimchi, influences osteoclast differentiation in mouse bone marrow-derived macrophage (BMM) culture. In addition, it was effective protecting against estrogen deficiency-induced bone loss in ovariectomized (OVX) mice, an animal model of postmenopausal osteoporosis. …

Systemic Neutrophil Gelatinase-Associated Lipocalin Alterations In Chronic Pancreatitis: A Multicenter, Cross-Sectional Study, Kristyn Gumpper-Fedus, Kaylin Chasser, Valentina Pita-Grisanti, Molly Torok, Timothy Pfau, Thomas A Mace, Rachel M Cole, Martha A Belury, Stacey Culp, Phil A Hart, Somashekar G Krishna, Luis F Lara, Mitchell L Ramsey, William Fisher, Evan L Fogel, Chris E Forsmark, Liang Li, Stephen Pandol, Walter G Park, Jose Serrano, Stephen K Van Den Eeden, Santhi Swaroop Vege, Dhiraj Yadav, Darwin L Conwell, Zobeida Cruz-Monserrate, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Student Publications

Introduction: Chronic pancreatitis (CP) is a progressive fibroinflammatory disorder lacking therapies and biomarkers. Neutrophil gelatinase-associated lipocalin (NGAL) is a proinflammatory cytokine elevated during inflammation that binds fatty acids (FAs) such as linoleic acid. We hypothesized that systemic NGAL could serve as a biomarker for CP and, with FAs, provide insights into inflammatory and metabolic alterations.

Methods: NGAL was measured by immunoassay, and FA composition was measured by gas chromatography in plasma (n = 171) from a multicenter study, including controls (n = 50), acute and recurrent acute pancreatitis (AP/RAP) (n = 71), and CP (n = 50). Peripheral blood mononuclear …

Influenza Incidence, Lineages, And Vaccine Effectiveness Estimates In Lima, Peru, 2023, Juan Gonzalo Acevedo-Rodriguez, Carlos Zamudio, Noah Kojima, Fiorella Krapp, Pablo Tsukayama, Victor Giancarlo Sal Y Rosas Celi, Dante Baldeon, Carmen Stefany Neciosup-Vera, Carlos Medina, Elsa Gonzalez-Lagos, Laura Castro, Ashley Fowlkes, Eduardo Azziz-Baumgartner, Eduardo Gotuzzo

Faculty, Staff and Student Publications

No abstract provided.

Does A Reduction In Receiving Assistance With Daily Activities Among Older Adults In Mexico Indicate An Increase In Unmet Needs Or A Decrease In Needs For Care?, Brian Downer, Rafael Samper-Ternent, Philip Cantu, Matthew Miller, Rebeca Wong

Faculty, Staff and Student Publications

OBJECTIVES: The percentage of older adults in Mexico with difficulty completing activities of daily living (ADL) who receive assistance from family appears to be decreasing. We compared 2 birth cohorts of older adults in Mexico to investigate whether this trend reflects an increase in unmet caregiving needs or a decrease in the need for care.

METHODS: We selected Mexican Health and Aging Study participants aged 60-76 in 2001 (n = 4,805) and 2018 (n = 6,494). ADL tasks were dressing, walking, bathing, getting in and out of bed, and toileting. Participants who reported difficulty with an ADL were asked if …

Final Report Of The Phase Ii Next/Cns-Gct-4 Trial: Gempox Followed By Marrow-Ablative Chemotherapy For Recurrent Intracranial Germ Cell Tumors, Margaret Shatara, Megan Blue, Joseph Stanek, Yin A Liu, Daniel M Prevedello, Pierre Giglio, Vinay K Puduvalli, Sharon L Gardner, Jeffrey C Allen, Kenneth K Wong, Marvin D Nelson, Floyd H Gilles, Roberta H Adams, Jasmine Pauly, Katrina O'Halloran, Ashley S Margol, Girish Dhall, Jonathan L Finlay

Faculty, Staff and Student Publications

Background: Patients with relapsed intracranial germinoma can achieve durable remission with standard chemotherapy regimens and/or reirradiation; however, innovative therapies are required for patients with relapsed and/or refractory intracranial nongerminomatous germ cell tumors (NGGCTs) due to their poor prognosis. Improved outcomes have been reported using reinduction chemotherapy to achieve minimal residual disease, followed by marrow-ablative chemotherapy (HDCx) with autologous hematopoietic progenitor cell rescue (AuHPCR). We conducted a phase II trial evaluating the response and toxicity of a 3-drug combination developed for recurrent intracranial germ cell tumors consisting of gemcitabine, paclitaxel, and oxaliplatin (GemPOx).

Methods: A total of 9 patients with confirmed …

Fear Antiviral Response Pathway Is Independent Of Interferons And Countered By Poxvirus Proteins, Emily A Rex, Dahee Seo, Sruthi Chappidi, Chelsea Pinkham, Sabrynna Brito Oliveira, Aaron Embry, David Heisler, Yang Liu, Moiz Munir, Karolin Luger, Neal M Alto, Flávio Guimarães Da Fonseca, Robert Orchard, Dustin C Hancks, Don B Gammon

Faculty, Staff and Student Publications

The human facilitates chromatin transcription (FACT) complex is a chromatin remodeller composed of human suppressor of Ty 16 homologue (hSpt16) and structure-specific recognition protein-1 subunits that regulates cellular gene expression. Whether FACT regulates host responses to infection remained unclear. We identify a FACT-mediated, interferon-independent, antiviral pathway that restricts poxvirus replication. Cell culture and bioinformatics approaches suggest that early viral gene expression triggers nuclear accumulation of SUMOylated hSpt16 subunits required for the expression of E26 transformation-specific sequence-1 (ETS-1)-a transcription factor that activates virus restriction programs. However, biochemical studies show that poxvirus-encoded A51R proteins block ETS-1 expression by outcompeting structure-specific recognition protein-1 …

Loss-Of-Function Mutation In Prmt9 Causes Abnormal Synapse Development By Dysregulation Of Rna Alternative Splicing, Lei Shen, Xiaokuang Ma, Yuanyuan Wang, Zhihao Wang, Yi Zhang, Hoang Quoc Hai Pham, Xiaoqun Tao, Yuehua Cui, Jing Wei, Dimitri Lin, Tharindumala Abeywanada, Swanand Hardikar, Levon Halabelian, Noah Smith, Taiping Chen, Dalia Barsyte-Lovejoy, Shenfeng Qiu, Yi Xing, Yanzhong Yang

Faculty, Staff and Student Publications

Protein arginine methyltransferase 9 (PRMT9) is a recently identified member of the PRMT family, yet its biological function remains largely unknown. Here, by characterizing an intellectual disability associated PRMT9 mutation (G189R) and establishing a Prmt9 conditional knockout (cKO) mouse model, we uncover an important function of PRMT9 in neuronal development. The G189R mutation abolishes PRMT9 methyltransferase activity and reduces its protein stability. Knockout of Prmt9 in hippocampal neurons causes alternative splicing of ~1900 genes, which likely accounts for the aberrant synapse development and impaired learning and memory in the Prmt9 cKO mice. Mechanistically, we discover a methylation-sensitive protein-RNA interaction between …

Intraprocedural Versus Initial Follow-Up Minimal Ablative Margin Assessment After Colorectal Liver Metastasis Thermal Ablation: Which One Better Predicts Local Outcomes?, Yuan-Mao Lin, Iwan Paolucci, Jessica Albuquerque Marques Silva, Caleb S O'Connor, Bryan M Fellman, Aaron K Jones, Joshua D Kuban, Steven Y Huang, Zeyad A Metwalli, Kristy K Brock, Bruno C Odisio

Faculty, Staff and Student Publications

Objectives: The aim of this study was to investigate the prognostic value of 3-dimensional minimal ablative margin (MAM) quantified by intraprocedural versus initial follow-up computed tomography (CT) in predicting local tumor progression (LTP) after colorectal liver metastasis (CLM) thermal ablation.

Materials and methods: This single-institution, patient-clustered, tumor-based retrospective study included patients undergoing microwave and radiofrequency ablation between 2016 and 2021. Patients without intraprocedural and initial follow-up contrast-enhanced CT, residual tumors, or with follow-up less than 1 year without LTP were excluded. Minimal ablative margin was quantified by a biomechanical deformable image registration method with segmentations of CLMs on intraprocedural preablation …

Sting-Activating Cyclic Dinucleotide-Manganese Nanoparticles Evoke Robust Immunity Against Acute Myeloid Leukemia, Marisa E Aikins, Xiaoqi Sun, Hannah Dobson, Xingwu Zhou, Yao Xu, Yu Leo Lei, James J Moon

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) is one of the most common types of leukemia in adults with a 5-year survival rate of 30.5%. These poor patient outcomes are attributed to tumor relapse, stemming from ineffective innate immune activation, T cell tolerance, and a lack of immunological memory. Thus, new strategies are needed to activate innate and effector immune cells and evoke long-term immunity against AML. One approach to address these issues is through Stimulator of Interferon Genes (STING) pathway activation, which produces Type I Interferons (Type I IFN) critical for innate and adaptive immune activation. Here, we report that systemic immunotherapy …

Exploring Ferroptosis-Inducing Therapies For Cancer Treatment: Challenges And Opportunities, Guang Lei, Boyi Gan

Faculty, Staff and Student Publications

Conventional cancer therapies typically aim to eliminate tumor cells by inducing cell death. The emergence of resistance to these standard treatments has spurred a shift in focus toward exploring alternative cell death pathways beyond apoptosis. Ferroptosis-an iron-dependent regulated cell death triggered by lipid peroxide accumulation-has gained prominence in cancer research in recent years. Ferroptosis-inducing therapies hold promise for overcoming resistance encountered with conventional treatments. However, challenges, including the lack of distinctive ferroptosis markers and the intricate role of ferroptosis within the tumor microenvironment, currently hinder the clinical translation of these therapies. This perspective article critically outlines these hurdles and highlights …

Early Elevations Of Ras Protein Level And Activity Are Critical For The Development Of Pdac In The Context Of Inflammation, Jianjia Ma, Fanghua Gong, Eunice Kim, James Xianxing Du, Cindy Leung, Qingchun Song, Craig D Logsdon, Yongde Luo, Xiaokun Li, Weiqin Lu

Faculty, Staff and Student Publications

The KRASG12D mutation was believed to be locked in a GTP-bound form, rendering it fully active. However, recent studies have indicated that the presence of mutant KRAS alone is insufficient; it requires additional activation through inflammatory stimuli to effectively drive the development of pancreatic ductal adenocarcinoma (PDAC). It remains unclear to what extent RAS activation occurs during the development of PDAC in the context of inflammation. Here, in a mouse model with the concurrent expression of KrasG12D/+ and inflammation mediator IKK2 in pancreatic acinar cells, we showed that, compared to KRASG12D alone, the cooperative interaction between KRASG12D and IKK2 rapidly …

Intraprocedural Versus Initial Follow-Up Minimal Ablative Margin Assessment After Colorectal Liver Metastasis Thermal Ablation: Which One Better Predicts Local Outcomes?, Yuan-Mao Lin, Iwan Paolucci, Jessica Albuquerque Marques Silva, Caleb S O'Connor, Bryan M Fellman, Aaron K Jones, Joshua D Kuban, Steven Y Huang, Zeyad A Metwalli, Kristy K Brock, Bruno C Odisio

Faculty, Staff and Student Publications

Objectives: The aim of this study was to investigate the prognostic value of 3-dimensional minimal ablative margin (MAM) quantified by intraprocedural versus initial follow-up computed tomography (CT) in predicting local tumor progression (LTP) after colorectal liver metastasis (CLM) thermal ablation.

Materials and methods: This single-institution, patient-clustered, tumor-based retrospective study included patients undergoing microwave and radiofrequency ablation between 2016 and 2021. Patients without intraprocedural and initial follow-up contrast-enhanced CT, residual tumors, or with follow-up less than 1 year without LTP were excluded. Minimal ablative margin was quantified by a biomechanical deformable image registration method with segmentations of CLMs on intraprocedural preablation …

Bone Mimetic Environments Support Engineering, Propagation, And Analysis Of Therapeutic Response Of Patient-Derived Cells, Ex Vivo And In Vivo, Claudia Paindelli, Vanessa Parietti, Sergio Barrios, Peter Shepherd, Tianhong Pan, Wei-Lien Wang, Robert L Satcher, Christopher J Logothetis, Nora Navone, Matthew T Campbell, Antonios G Mikos, Eleonora Dondossola

Faculty, Staff and Student Publications

Bone metastases are the most common milestone in the lethal progression of prostate cancer and prominent in a substantial portion of renal malignancies. Interactions between cancer and bone host cells have emerged as drivers of both disease progression and therapeutic resistance. To best understand these central host-epithelial cell interactions, biologically relevant preclinical models are required. To achieve this goal, we here established and characterized tissue-engineered bone mimetic environments (BME) capable of supporting the growth of patient-derived xenograft (PDX) cells, ex vivo and in vivo. The BME consisted of a polycaprolactone (PCL) scaffold colonized by human mesenchymal stem cells (hMSCs) differentiated …

Genome-Wide Crispr Screen Reveals The Synthetic Lethality Between Bcl2l1 Inhibition And Radiotherapy, Ling Yin, Xiaoding Hu, Guangsheng Pei, Mengfan Tang, You Zhou, Huimin Zhang, Min Huang, Siting Li, Jie Zhang, Citu Citu, Zhongming Zhao, Bisrat G Debeb, Xu Feng, Junjie Chen

Faculty, Staff and Student Publications

Radiation therapy (RT) is one of the most commonly used anticancer therapies. However, the landscape of cellular response to irradiation, especially to a single high-dose irradiation, remains largely unknown. In this study, we performed a whole-genome CRISPR loss-of-function screen and revealed temporal inherent and acquired responses to RT. Specifically, we found that loss of the IL1R1 pathway led to cellular resistance to RT. This is in part because of the involvement of radiation-induced IL1R1-dependent transcriptional regulation, which relies on the NF-κB pathway. Moreover, the mitochondrial anti-apoptotic pathway, particularly the BCL2L1 gene, is crucially important for cell survival after radiation. BCL2L1 …

Lymphocyte-Activation Gene 3 Facilitates Pathological Tau Neuron-To-Neuron Transmission, Chan Chen, Ramhari Kumbhar, Hu Wang, Xiuli Yang, Kundlik Gadhave, Cyrus Rastegar, Yasuyoshi Kimura, Adam Behensky, Sumasri Kotha, Grace Kuo, Sruthi Katakam, Deok Jeong, Liang Wang, Anthony Wang, Rong Chen, Shu Zhang, Lingtao Jin, Creg J Workman, Dario A A Vignali, Olga Pletinkova, Hongpeng Jia, Weiyi Peng, David W Nauen, Philip C Wong, Javier Redding-Ochoa, Juan C Troncoso, Mingyao Ying, Valina L Dawson, Ted M Dawson, Xiaobo Mao

Faculty, Staff and Student Publications

The spread of prion-like protein aggregates is a common driver of pathogenesis in various neurodegenerative diseases, including Alzheimer's disease (AD) and related Tauopathies. Tau pathologies exhibit a clear progressive spreading pattern that correlates with disease severity. Clinical observation combined with complementary experimental studies has shown that Tau preformed fibrils (PFF) are prion-like seeds that propagate pathology by entering cells and templating misfolding and aggregation of endogenous Tau. While several cell surface receptors of Tau are known, they are not specific to the fibrillar form of Tau. Moreover, the underlying cellular mechanisms of Tau PFF spreading remain poorly understood. Here, it …

Case Of Human Orthohantavirus Infection, Michigan, Usa, 2021, Samuel M Goodfellow, Robert A Nofchissey, Dustin Arsnoe, Chunyan Ye, Seonghyeon Lee, Jieun Park, Won-Keun Kim, Kartik Chandran, Shannon L M Whitmer, John D Klena, Jonathan W Dyal, Trevor Shoemaker, Diana Riner, Mary Grace Stobierski, Kimberly Signs, Steven B Bradfute

Faculty, Staff and Student Publications

Orthohantaviruses cause hantavirus cardiopulmonary syndrome; most cases occur in the southwest region of the United States. We discuss a clinical case of orthohantavirus infection in a 65-year-old woman in Michigan and the phylogeographic link of partial viral fragments from the patient and rodents captured near the presumed site of infection.

Intraprocedural Versus Initial Follow-Up Minimal Ablative Margin Assessment After Colorectal Liver Metastasis Thermal Ablation: Which One Better Predicts Local Outcomes?, Yuan-Mao Lin, Iwan Paolucci, Jessica Albuquerque Marques Silva, Caleb S O'Connor, Bryan M Fellman, Aaron K Jones, Joshua D Kuban, Steven Y Huang, Zeyad A Metwalli, Kristy K Brock, Bruno C Odisio

Faculty, Staff and Student Publications

Objectives: The aim of this study was to investigate the prognostic value of 3-dimensional minimal ablative margin (MAM) quantified by intraprocedural versus initial follow-up computed tomography (CT) in predicting local tumor progression (LTP) after colorectal liver metastasis (CLM) thermal ablation.

Materials and methods: This single-institution, patient-clustered, tumor-based retrospective study included patients undergoing microwave and radiofrequency ablation between 2016 and 2021. Patients without intraprocedural and initial follow-up contrast-enhanced CT, residual tumors, or with follow-up less than 1 year without LTP were excluded. Minimal ablative margin was quantified by a biomechanical deformable image registration method with segmentations of CLMs on intraprocedural preablation …

Chromatin Remodeling In Patient-Derived Colorectal Cancer Models, Kun Xiang, Ergang Wang, John Mantyh, Gabrielle Rupprecht, Marcos Negrete, Golshid Sanati, Carolyn Hsu, Peggy Randon, Anders Dohlman, Kai Kretzschmar, Shree Bose, Nicholas Giroux, Shengli Ding, Lihua Wang, Jorge Prado Balcazar, Qiang Huang, Pasupathi Sundaramoorthy, Rui Xi, Shannon Jones Mccall, Zhaohui Wang, Chongming Jiang, Yubin Kang, Scott Kopetz, Gregory E Crawford, Steven M Lipkin, Xiao-Fan Wang, Hans Clevers, David Hsu, Xiling Shen

Faculty, Staff and Student Publications

Patient-Derived Organoids (PDO) and Xenografts (PDX) are the current gold standards for patient-derived models of cancer (PDMC). Nevertheless, how patient tumor cells evolve in these models and the impact on drug response remains unclear. Herein, the transcriptomic and chromatin accessibility landscapes of matched colorectal cancer (CRC) PDO, PDX, PDO-derived PDX (PDOX), and original patient tumors (PT) are compared. Two major remodeling axes are discovered. The first axis delineates PDMC from PT, and the second axis distinguishes PDX and PDO. PDOX are more similar to PDX than PDO, indicating the growth environment is a driving force for chromatin adaptation. Transcription factors …

Clinical Epidemiological Characteristics And Risk Factors For Severity Of Sars-Cov-2 Pneumonia In Pediatric Patients: A Hospital-Based Study In Vietnam, Sang N Nguyen, Lam T Vu, Ha T Nguyen, Giang H Dao, Anh Ngoc T Nguyen

Faculty, Staff and Student Publications

Introduction Coronavirus disease (COVID-19) is an infectious disease caused by SARS-CoV-2, which can cause organ failure in several organs, cardiac problems, or acute respiratory distress syndrome (ARDS). Identifying clinical epidemiological characteristics and risk factors for complications of COVID-19 allows clinicians to diagnose and treat promptly. Objectives This study aims to describe the clinical epidemiological characteristics of COVID-19 and assess risk factors for the severity of SARS-CoV-2 pneumonia in children treated at Haiphong Children's Hospital. Methods A descriptive cross-sectional study was conducted in Haiphong Children's Hospital, Haiphong, Vietnam, for one year, from January 1, 2022, to December 31, 2022. Results In …

Dietary Magnesium Replacement For Prevention Of Hypomagnesemia In Patients With Ovarian Cancer Receiving Carboplatin-Based Chemotherapy, Wenli Liu, Larissa Meyer, Meroë Morse, Yisheng Li, Juhee Song, Rosalinda Engle, Gabriel Lopez, Santhosshi Narayanan, Pamela T Soliman, Lois Ramondetta, Eduardo Bruera, Lorenzo Cohen

Faculty, Staff and Student Publications

Purpose: Hypomagnesemia is a common side effect of platinum-based chemotherapy and predicts poor overall survival in some cancers. Standard magnesium replacement strategies are often inadequate for maintaining magnesium levels. We hypothesized that a daily dietary magnesium replacement approach through magnesium-rich foods would help maintain adequate magnesium levels during platinum-based treatment.

Materials and methods: We conducted a prospective feasibility study of magnesium-rich diets in patients 18 years and older with previously untreated ovarian cancer scheduled to receive carboplatin-containing chemotherapy of at least six consecutive cycles. Education about magnesium-rich diets was provided at enrollment and then weekly during chemotherapy. Feasibility was defined …

Reciprocal Relationships Between Stress And Depressive Symptoms: The Essential Role Of The Nucleus Accumbens, Yizhou Ma, Peter Kochunov, Mark D Kvarta, Tara Legates, Bhim M Adhikari, Joshua Chiappelli, Andrew Van Der Vaart, Eric L Goldwaser, Heather Bruce, Kathryn S Hatch, Si Gao, Shuo Chen, Ann Summerfelt, Thomas E Nichols, L Elliot Hong

Faculty, Staff and Student Publications

BACKGROUND: Stress and depression have a reciprocal relationship, but the neural underpinnings of this reciprocity are unclear. We investigated neuroimaging phenotypes that facilitate the reciprocity between stress and depressive symptoms.

METHODS: In total, 22 195 participants (52.0% females) from the population-based UK Biobank study completed two visits (initial visit: 2006-2010, age = 55.0 ± 7.5 [40-70] years; second visit: 2014-2019; age = 62.7 ± 7.5 [44-80] years). Structural equation modeling was used to examine the longitudinal relationship between self-report stressful life events (SLEs) and depressive symptoms. Cross-sectional data were used to examine the overlap between neuroimaging correlates of SLEs and …

Cytokine Release By Microglia Exposed To Neurologic Injury Is Amplified By Lipopolysaccharide, Michael C Scott, Olivia Leblanc, Harper Day, Candice Haase, Scott D Olson, Charles S Cox

Faculty, Staff and Student Publications

Introduction: Traumatic brain injury (TBI) is a leading cause of death and morbidity in the trauma population. Microglia drive the secondary neuroinflammatory response after TBI. We sought to determine if the microglial response to neurologic injury was exacerbated by a second stimulus after exposure to neurologic injury.

Methods: Sprague-Dawley rats (age 2-3 wk) were divided into injured and noninjured groups. Injured rats underwent a controlled cortical impact injury; noninjured rats remained naïve to any injury and served as the control group. Primary rat microglia were isolated and applied to in vitro cultures. After incubation for 24 h, the microglia were …

Combined Ion Beam Irradiation Platform And 3d Fluorescence Microscope For Cellular Cancer Research, Andrew D Harken, Naresh T Deoli, Citlali Perez Campos, Brian Ponnaiya, Guy Garty, Grace S Lee, Malte J Casper, Shikhar Dhingra, Wenze Li, Gary W Johnson, Sally A Amundson, Peter W Grabham, Elizabeth M C Hillman, David J Brenner

Faculty, Staff and Student Publications

To improve particle radiotherapy, we need a better understanding of the biology of radiation effects, particularly in heavy ion radiation therapy, where global responses are observed despite energy deposition in only a subset of cells. Here, we integrated a high-speed swept confocally-aligned planar excitation (SCAPE) microscope into a focused ion beam irradiation platform to allow real-time 3D structural and functional imaging of living biological samples during and after irradiation. We demonstrate dynamic imaging of the acute effects of irradiation on 3D cultures of U87 human glioblastoma cells, revealing characteristic changes in cellular movement and intracellular calcium signaling following ionizing irradiation.

Blockade Of Rho-Associated Kinase Prevents Inhibition Of Axon Regeneration Of Peripheral Nerves Induced By Anti-Ganglioside Antibodies, Andrés Berardo, Cristian R Bacaglio, Bárbara B Báez, Rubén Sambuelli, Kazim A Sheikh, Pablo H H Lopez

Faculty, Staff and Student Publications

Anti-ganglioside antibodies are associated with delayed/poor clinical recovery in Guillain-Barrè syndrome, mostly related to halted axon regeneration. Cross-linking of cell surface gangliosides by anti-ganglioside antibodies triggers inhibition of nerve repair in in vitro and in vivo paradigms of axon regeneration. These effects involve the activation of the small GTPase RhoA/ROCK signaling pathways, which negatively modulate growth cone cytoskeleton, similarly to well stablished inhibitors of axon regeneration described so far. The aim of this work was to perform a proof of concept study to demonstrate the effectiveness of Y-27632, a selective pharmacological inhibitor of ROCK, in a mouse model of axon …

Activation Of Cerebral Ras-Related C3 Botulinum Toxin Substrate (Rac) 1 Promotes Post-Ischemic Stroke Functional Recovery In Aged Mice, Fan Bu, Jia-Wei Min, Md Abdur Razzaque, Ahmad El Hamamy, Anthony Patrizz, Li Qi, Akihiko Urayama, Jun Li

Faculty, Staff and Student Publications

Brain functional impairment after stroke is common; however, the molecular mechanisms of post-stroke recovery remain unclear. It is well-recognized that age is the most important independent predictor of poor outcomes after stroke as older patients show poorer functional outcomes following stroke. Mounting evidence suggests that axonal regeneration and angiogenesis, the major forms of brain plasticity responsible for post-stroke recovery, diminished with advanced age. Previous studies suggest that Ras-related C3 botulinum toxin substrate (Rac) 1 enhances stroke recovery as activation of Rac1 improved behavior recovery in a young mice stroke model. Here, we investigated the role of Rac1 signaling in long-term …

How Territoriality And Sociality Influence The Habitat Selection And Movements Of A Large Carnivore, K Whitney Hansen, Nathan Ranc, John Morgan, Neil R Jordan, J Weldon Mcnutt, Alan Wilson, Christopher C Wilmers

Faculty, Staff and Student Publications

While territoriality is one of the key mechanisms influencing carnivore space use, most studies quantify resource selection and movement in the absence of conspecific influence or territorial structure. Our analysis incorporated social information in a resource selection framework to investigate mechanisms of territoriality and intra‐specific competition on the habitat selection of a large, social carnivore. We fit integrated step selection functions to 3‐h GPS data from 12 collared African wild dog packs in the Okavango Delta and estimated selection coefficients using a conditional Poisson likelihood with random effects. Packs selected for their neighbors' 30‐day boundary (defined as their 95% kernel …

Readiness Of Nociceptor Cell Bodies To Generate Spontaneous Activity Results From Background Activity Of Diverse Ion Channels And High Input Resistance, Jinbin Tian, Alexis G Bavencoffe, Michael X Zhu, Edgar T Walters

Faculty, Staff and Student Publications

Nociceptor cell bodies generate "spontaneous" discharge that can promote ongoing pain in persistent pain conditions. Little is known about the underlying mechanisms. Recordings from nociceptor cell bodies (somata) dissociated from rodent and human dorsal root ganglia have shown that previous pain in vivo is associated with low-frequency discharge controlled by irregular depolarizing spontaneous fluctuations of membrane potential (DSFs), likely produced by transient inward currents across the somal input resistance. Using mouse nociceptors, we show that DSFs are associated with high somal input resistance over a wide range of membrane potentials, including depolarized levels where DSFs approach action potential (AP) threshold. …