Digital Commons Network^™

Targeting Alk Averts Ribonuclease 1-Induced Immunosuppression And Enhances Antitumor Immunity In Hepatocellular Carcinoma, Chunxiao Liu, Chenhao Zhou, Weiya Xia, Yifan Zhou, Yufan Qiu, Jialei Weng, Qiang Zhou, Wanyong Chen, Ying-Nai Wang, Heng-Huan Lee, Shao-Chun Wang, Ming Kuang, Dihua Yu, Ning Ren, Mien-Chie Hung

Faculty, Staff and Student Publications

Tumor-secreted factors contribute to the development of a microenvironment that facilitates the escape of cancer cells from immunotherapy. In this study, we conduct a retrospective comparison of the proteins secreted by hepatocellular carcinoma (HCC) cells in responders and non-responders among a cohort of ten patients who received Nivolumab (anti-PD-1 antibody). Our findings indicate that non-responders have a high abundance of secreted RNase1, which is associated with a poor prognosis in various cancer types. Furthermore, mice implanted with HCC cells that overexpress RNase1 exhibit immunosuppressive tumor microenvironments and diminished response to anti-PD-1 therapy. RNase1 induces the polarization of macrophages towards a …

Tumor-Specific Polycistronic Mirna Delivered By Engineered Exosomes For The Treatment Of Glioblastoma, Malcolm F Mcdonald, Anwar Hossain, Eric N Momin, Irtiza Hasan, Sanjay Singh, Satoshi Adachi, Joy Gumin, Daniel Ledbetter, Jing Yang, Lihong Long, Marc Daou, Sricharan Gopakumar, Lynette M Phillips, Brittany Parker Kerrigan, Frederick F Lang

Faculty, Staff and Student Publications

Background: Glioblastoma (GBM) has poor prognosis due to ineffective agents and poor delivery methods. MicroRNAs (miRs) have been explored as novel therapeutics for GBM, but the optimal miRs and the ideal delivery strategy remain unresolved. In this study, we sought to identify the most effective pan-subtype anti-GBM miRs and to develop an improved delivery system for these miRs.

Methods: We conducted an unbiased screen of over 600 miRs against 7 glioma stem cell (GSC) lines representing all GBM subtypes to identify a set of pan-subtype-specific anti-GBM miRs and then used available TCGA GBM patient outcomes and miR expression data to …

Targeting Prostate Tumor Low-Molecular Weight Tyrosine Phosphatase For Oxidation-Sensitizing Therapy, Stephanie M Stanford, Tiffany P Nguyen, Joseph Chang, Zixuan Zhao, G Lavender Hackman, Eugenio Santelli, Colton M Sanders, Madhusudhanarao Katiki, Eleonora Dondossola, Brooke L Brauer, Michael A Diaz, Yuan Zhan, Sterling H Ramsey, Philip A Watson, Banumathi Sankaran, Claudia Paindelli, Vanessa Parietti, Antonios G Mikos, Alessia Lodi, Aditya Bagrodia, Andrew Elliott, Rana R Mckay, Ramachandran Murali, Stefano Tiziani, Arminja N Kettenbach, Nunzio Bottini

Faculty, Staff and Student Publications

Protein tyrosine phosphatases (PTPs) play major roles in cancer and are emerging as therapeutic targets. Recent reports suggest low-molecular weight PTP (LMPTP)-encoded by the ACP1 gene-is overexpressed in prostate tumors. We found ACP1 up-regulated in human prostate tumors and ACP1 expression inversely correlated with overall survival. Using CRISPR-Cas9-generated LMPTP knockout C4-2B and MyC-CaP cells, we identified LMPTP as a critical promoter of prostate cancer (PCa) growth and bone metastasis. Through metabolomics, we found that LMPTP promotes PCa cell glutathione synthesis by dephosphorylating glutathione synthetase on inhibitory Tyr270. PCa cells lacking LMPTP showed reduced glutathione, enhanced activation of eukaryotic initiation factor …

Rapid And Accurate Remethylation Of Dna In Dnmt3a- Deficient Hematopoietic Cells With Restoration Of Dnmt3a Activity, Yang Li, Haley J Abel, Michelle Cai, Taylor A Lavalle, Tiankai Yin, Nichole M Helton, Amanda M Smith, Christopher A Miller, Timothy J Ley

2020-Current year OA Pubs

Here, we characterize the DNA methylation phenotypes of bone marrow cells from mice with hematopoietic deficiency of

A Comparative Biochemical And Pathological Evaluation Of Brain Samples From Knock-In Murine Models Of Gaucher Disease, Makaila L Furderer, Bahafta Berhe, Tiffany C Chen, Stephen Wincovitch, Xuntian Jiang, Nahid Tayebi, Ellen Sidransky, Tae-Un Han

2020-Current year OA Pubs

Gaucher disease (GD) is a lysosomal storage disorder stemming from biallelic mutations in

Prenatal Exposure To Maternal Disadvantage-Related Inflammatory Biomarkers: Associations With Neonatal White Matter Microstructure, Ashley F P Sanders, Brian Tirado, Nicole A Seider, Regina L Triplett, Rachel E Lean, Jeffrey J Neil, J Philip Miller, Rebecca Tillman, Tara A Smyser, Deanna M Barch, Joan L Luby, Cynthia E Rogers, Christopher D Smyser, Barbara B Warner, Et Al.

2020-Current year OA Pubs

Prenatal exposure to heightened maternal inflammation has been associated with adverse neurodevelopmental outcomes, including atypical brain maturation and psychiatric illness. In mothers experiencing socioeconomic disadvantage, immune activation can be a product of the chronic stress inherent to such environmental hardship. While growing preclinical and clinical evidence has shown links between altered neonatal brain development and increased inflammatory states in utero, the potential mechanism by which socioeconomic disadvantage differentially impacts neural-immune crosstalk remains unclear. In the current study, we investigated associations between socioeconomic disadvantage, gestational inflammation, and neonatal white matter microstructure in 320 mother-infant dyads over-sampled for poverty. We analyzed maternal …

Phenotypic Features Determining Visual Acuity In Albinism And The Role Of Amblyogenic Factors., Frank A Proudlock, Rebecca J Mclean, Viral Sheth, Sarim Ather, Irene Gottlob

Cooper Medical School of Rowan University Departmental Research

Albinism is a spectrum disorder causing foveal hypoplasia, nystagmus, and hypopigmentation of the iris and fundus along with other visual deficits, which can all impact vision. Albinism is also associated with amblyogenic factors which could affect monocular visual acuity. The foveal appearance in albinism can range from mild foveal hypoplasia to that which is indistinguishable from the peripheral retina. The appearance can be quickly and easily graded using the Leicester Grading System in the clinic. However, interquartile ranges of 0.3 logMAR for the grades associated with albinism limit the accuracy of the grading system in predicting vision. Here, we discuss …

Visual Field Deficits In Albinism In Comparison To Idiopathic Infantile Nystagmus., Viral Sheth, Rebecca J Mclean, Zhanhan Tu, Sarim Ather, Irene Gottlob, Frank A Proudlock

Cooper Medical School of Rowan University Departmental Research

PURPOSE: This is the first systematic comparison of visual field (VF) deficits in people with albinism (PwA) and idiopathic infantile nystagmus (PwIIN) using static perimetry. We also compare best-corrected visual acuity (BCVA) and optical coherence tomography measures of the fovea, parafovea, and circumpapillary retinal nerve fiber layer in PwA.

METHODS: VF testing was performed on 62 PwA and 36 PwIIN using a Humphrey Field Analyzer (SITA FAST 24-2). Mean detection thresholds for each eye were calculated, along with quadrants and central measures. Retinal layers were manually segmented in the macular region.

RESULTS: Mean detection thresholds were significantly lower than normative …

Utilizing Primary Human Airway Mucociliary Tissue Cultures To Model Ramifications Of Chronic E-Cigarette Usage., Vincent J Manna, Shannon Dwyer, Vanessa Pizutelli, Salvatore J Caradonna

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Electronic cigarettes are battery powered devices that use a vape-liquid to produce a vapor that is inhaled. A consequence of the rise in e-cigarette usage was the 2019 emergence of a vaping-induced respiratory disease denoted as 'e-cigarette or vaping use-associated lung injury' (EVALI). One of the suspected causes of EVALI is Vitamin E Acetate (VEA), which was found to be a diluent in certain illicit vape-pens, whereas nicotine is commonly diluted in equal parts propylene glycol and vegetable glycerin (PG:VG). The prevalent use of e-cigarettes and the emergence of a novel illness has made understanding how e-cigarette vapors affect our …

Phenotypic Similarity-Based Approach For Variant Prioritization For Unsolved Rare Disease: A Preliminary Methodological Report., David Lagorce, Emeline Lebreton, Leslie Matalonga, Oscar Hongnat, Maroua Chahdil, Davide Piscia, Ida Paramonov, Kornelia Ellwanger, Sebastian Köhler, Peter N Robinson, Holm Graessner, Sergi Beltran, Caterina Lucano, Marc Hanauer, Ana Rath

Faculty Research 2024

Rare diseases (RD) have a prevalence of not more than 1/2000 persons in the European population, and are characterised by the difficulty experienced in obtaining a correct and timely diagnosis. According to Orphanet, 72.5% of RD have a genetic origin although 35% of them do not yet have an identified causative gene. A significant proportion of patients suspected to have a genetic RD receive an inconclusive exome/genome sequencing. Working towards the International Rare Diseases Research Consortium (IRDiRC)'s goal for 2027 to ensure that all people living with a RD receive a diagnosis within one year of coming to medical attention, …

Genetic Context Drives Age-Related Disparities In Synaptic Maintenance And Structure Across Cortical And Hippocampal Neuronal Circuits., Sarah E Heuer, Emily W Nickerson, Gareth R Howell, Erik B Bloss

Faculty Research 2024

The disconnection of neuronal circuitry through synaptic loss is presumed to be a major driver of age-related cognitive decline. Age-related cognitive decline is heterogeneous, yet whether genetic mechanisms differentiate successful from unsuccessful cognitive decline through maintenance or vulnerability of synaptic connections remains unknown. Previous work using rodent and primate models leveraged various techniques to imply that age-related synaptic loss is widespread on pyramidal cells in prefrontal cortex (PFC) circuits but absent on those in area CA1 of the hippocampus. Here, we examined the effect of aging on synapses on projection neurons forming a hippocampal-cortico-thalamic circuit important for spatial working memory …

Immune Evasion, Infectivity, And Fusogenicity Of Sars-Cov-2 Ba286 And Flip Variants, Panke Qu, Kai Xu, Julia N Faraone, Negin Goodarzi, Yi-Min Zheng, Claire Carlin, Joseph S Bednash, Jeffrey C Horowitz, Rama K Mallampalli, Linda J Saif, Eugene M Oltz, Daniel Jones, Richard J Gumina, Shan-Lu Liu

Faculty, Staff and Student Publications

Evolution of SARS-CoV-2 requires the reassessment of current vaccine measures. Here, we characterized BA.2.86 and XBB-derived variant FLip by investigating their neutralization alongside D614G, BA.1, BA.2, BA.4/5, XBB.1.5, and EG.5.1 by sera from 3-dose-vaccinated and bivalent-vaccinated healthcare workers, XBB.1.5-wave-infected first responders, and monoclonal antibody (mAb) S309. We assessed the biology of the variant spikes by measuring viral infectivity and membrane fusogenicity. BA.2.86 is less immune evasive compared to FLip and other XBB variants, consistent with antigenic distances. Importantly, distinct from XBB variants, mAb S309 was unable to neutralize BA.2.86, likely due to a D339H mutation based on modeling. BA.2.86 had …

Firearm-Related Traumatic Brain Injuries In Adults: A Scoping Review, Gabriel Reyes, Ron Gadot, Lara Ouellette, Shervin H Nouri, Shankar P Gopinath, Akash J Patel

Library Staff Publications

BACKGROUND AND OBJECTIVES: Firearm-related traumatic brain injury (TBI) has emerged as a significant public health issue in the United States, coinciding with a rapid increase in gun-related deaths. This scoping review aims to update our understanding of firearm-related TBI in adult populations.

METHODS: A comprehensive search of 6 online databases yielded 22 studies that met the inclusion criteria. The reviewed studies predominantly focused on young adult men who were victims of assault, although other vulnerable populations were also affected.

RESULTS: Key factors in evaluating patients with firearm-related TBI included low Glasgow Coma Scale scores, central nervous system involvement, hypotension, and …

Endothelial Cells Adopt A Pro-Reparative Immune Responsive Signature During Cardiac Injury, Hali Long, Jeffrey D Steimle, Francisco Jose Grisanti Canozo, Jong Hwan Kim, Xiao Li, Yuka Morikawa, Minjun Park, Diwakar Turaga, Iki Adachi, Joshua D Wythe, Md Abul Hassan Samee, James F Martin

Faculty, Staff and Students Publications

Modulation of the heart’s immune microenvironment is crucial for recovery after ischemic events such as myocardial infarction (MI). Endothelial cells (ECs) can have immune regulatory functions; however, interactions between ECs and the immune environment in the heart after MI remain poorly understood. We identified an EC-specific IFN responsive and immune regulatory gene signature in adult and pediatric heart failure (HF) tissues. Single-cell transcriptomic analysis of murine hearts subjected to MI uncovered an EC population (IFN-ECs) with immunologic gene signatures similar to those in human HF. IFN-ECs were enriched in regenerative-stage mouse hearts and expressed genes encoding immune responsive transcription factors …

Host Gastric Corpus Microenvironment Facilitates Ascaris Suum Larval Hatching And Infection In A Murine Model, Yifan Wu, Grace Adeniyi-Ipadeola, Mahliyah Adkins-Threats, Matthew Seasock, Charlie Suarez-Reyes, Ricardo Fujiwara, Maria Elena Bottazzi, Lizhen Song, Jason C Mills, Jill E Weatherhead

Faculty, Staff and Students Publications

Ascariasis (roundworm) is the most common parasitic helminth infection globally and can lead to significant morbidity in children including chronic lung disease. Children become infected with Ascaris spp. via oral ingestion of eggs. It has long been assumed that Ascaris egg hatching and larval translocation across the gastrointestinal mucosa to initiate infection occurs in the small intestine. Here, we show that A. suum larvae hatched in the host stomach in a murine model. Larvae utilize acidic mammalian chitinase (AMCase; acid chitinase; Chia) from chief cells and acid pumped by parietal cells to emerge from eggs on the surface of gastric …

Antiretroviral Therapy In Pregnancy: A 2023 Review Of The Literature, Alison N Goulding, Kasey Meeks, Lena Shay, Sarah Casey, Colton Applegarth, Jennifer Mckinney

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: Selection of antiretroviral therapy during pregnancy must consider maternal physiology and resulting pharmacokinetic changes in pregnancy, resistance and efficacy profiles, tolerability and frequency of adverse effects, teratogenicity, and maternal, neonatal, and pregnancy outcomes. The objective of this review is to summarize the underlying data that informs the current clinical perinatal guidelines in the USA.

RECENT FINDINGS: Data now supports the use of dolutegravir at all stages of pregnancy with no significant increase in neural tube defects. Safety and pharmacokinetic data on newer antiretroviral medications in pregnancy continue to lag behind the general population. While there are multiple …

A Practical Guide To Evaluating And Using Big Data In Digestive Disease Research, Madeline Alizadeh, Natalia Sampaio Moura, Alyssa Schledwitz, Seema A Patil, Hashem El-Serag, Jacques Ravel, Jean-Pierre Raufman

Faculty, Staff and Students Publications

No abstract provided.

Low Molecular Weight Heparin Decreases Pro-Coagulant Activity In Clinical Msc Products, Jacob B Schriner, Fabio Triolo, Brijesh S Gill, Jessica C Cardenas, Scott D Olson, Charles S Cox

Faculty, Staff and Student Publications

Background aims: Mesenchymal stromal cells (MSCs) are multipotent adult cells that can be isolated from tissues including bone marrow [MSC(BM)], adipose [MSC(AT)] and umbilical cord [MSC(CT)]. Previous studies have linked expression of tissue factor (TF) on MSC surfaces to a procoagulant effect. Venous thromboembolism (VTE), immediate blood-mediated inflammatory reaction (IBMIR) and microvascular thrombosis remain a risk with intravascular MSC therapy. We examined the effect of low molecular weight heparin (LMWH) on clinical-grade MSCs using calibrated automated thrombography (CAT).

Methods: Clinical grade MSC(BM)s, MSC(AT)s and MSC(CT)s harvested at passage 4 were added to normal pooled plasma (NPP) to a final concentration …

Convergent Mapk Pathway Alterations Mediate Acquired Resistance To Fgfr Inhibitors In Fgfr2 Fusion-Positive Cholangiocarcinoma, Timothy P Diperi, Ming Zhao, Kurt W Evans, Kaushik Varadarajan, Tyler Moss, Stephen Scott, Michael P Kahle, Charnel C Byrnes, Huiqin Chen, Sunyoung S Lee, Abdel-Baset Halim, Hiroshi Hirai, Volker Wacheck, Lawrence N Kwong, Jordi Rodon, Milind Javle, Funda Meric-Bernstam

Faculty, Staff and Student Publications

Background & aims: There is a knowledge gap in understanding mechanisms of resistance to fibroblast growth factor receptor (FGFR) inhibitors (FGFRi) and a need for novel therapeutic strategies to overcome it. We investigated mechanisms of acquired resistance to FGFRi in patients with FGFR2-fusion-positive cholangiocarcinoma (CCA).

Methods: A retrospective analysis of patients who received FGFRi therapy and underwent tumor and/or cell-free DNA analysis, before and after treatment, was performed. Longitudinal circulating tumor DNA samples from a cohort of patients in the phase I trial of futibatinib (NCT02052778) were assessed. FGFR2-BICC1 fusion cell lines were developed and secondary acquired resistance …

Enhancing Anti-Aml Activity Of Venetoclax By Isoflavone Me-344 Through Suppression Of Oxphos And/Or Purine Biosynthesis In Vitro, Katie H Hurrish, Yongwei Su, Shraddha Patel, Cassandra L Ramage, Jianlei Zhao, Brianna R Temby, Jenna L Carter, Holly Edwards, Steven A Buck, Sandra E Wiley, Maik Hüttemann, Lisa Polin, Juiwanna Kushner, Sijana H Dzinic, Kathryn White, Xun Bao, Jing Li, Jay Yang, Julie Boerner, Zhanjun Hou, Gheath Al-Atrash, Sergej N Konoplev, Jonathan Busquets, Stefano Tiziani, Larry H Matherly, Jeffrey W Taub, Marina Konopleva, Yubin Ge, Natalia Baran

Faculty, Staff and Student Publications

Venetoclax (VEN), in combination with low dose cytarabine (AraC) or a hypomethylating agent, is FDA approved to treat acute myeloid leukemia (AML) in patients who are over the age of 75 or cannot tolerate standard chemotherapy. Despite high response rates to these therapies, most patients succumb to the disease due to relapse and/or drug resistance, providing an unmet clinical need for novel therapies to improve AML patient survival. ME-344 is a potent isoflavone with demonstrated inhibitory activity toward oxidative phosphorylation (OXPHOS) and clinical activity in solid tumors. Given that OXPHOS inhibition enhances VEN antileukemic activity against AML, we hypothesized that …

Age-Associated Disparity In Phagocytic Clearance Affects The Efficacy Of Cancer Nanotherapeutics, Yifan Wang, Weiye Deng, Daeyong Lee, Long Yan, Yifei Lu, Shiyan Dong, Kristin Huntoon, Abin Antony, Xuefeng Li, Rui Ye, Yan Zhao, Feiyan Zhao, Benjamin R Schrank, Jonghoon Ha, Minjeong Kang, Mingming Yang, Ping Gong, Philip L Lorenzi, Lin Tan, Thomas D Gallup, Sarah K Tang, Zhaogang Yang, Jing Li, Nina N Sanford, Hongmei Wang, Betty Y S Kim, Wen Jiang

Faculty, Staff and Student Publications

Nanomedicines have been approved to treat multiple human diseases. However, clinical adoption of nanoformulated agents is often hindered by concerns about hepatic uptake and clearance, a process that is not fully understood. Here we show that the antitumour efficacy of cancer nanomedicine exhibits an age-associated disparity. Tumour delivery and treatment outcomes are superior in old versus young mice, probably due to an age-related decline in the ability of hepatic phagocytes to take up and remove nanoparticles. Transcriptomic- and protein-level analysis at the single-cell and bulk levels reveals an age-associated decrease in the numbers of hepatic macrophages that express the scavenger …

Activation Of Testosterone-Androgen Receptor Mediates Cerebrovascular Protection By Photobiomodulation Treatment In Photothrombosis-Induced Stroke Rats, Yu Feng, Zhihai Huang, Xiaohui Ma, Xuemei Zong, Celeste Yin-Chieh Wu, Reggie Hui-Chao Lee, Hung Wen Lin, Michael R Hamblin, Quanguang Zhang

Faculty, Staff and Student Publications

RATIONALE: Numerous epidemiological studies have reported a link between low testosterone levels and an increased risk of cerebrovascular disease in men. However, there is ongoing controversy surrounding testosterone replacement therapy due to potential side effects. PBMT has been demonstrated to improve cerebrovascular function and promote testosterone synthesis in peripheral tissues. Despite this, the molecular mechanisms that could connect PBMT with testosterone and vascular function in the brain of photothrombosis (PT)-induced stroke rats remain largely unknown.

METHODS: We measured behavioral performance, cerebral blood flow (CBF), vascular permeability, and the expression of vascular-associated and apoptotic proteins in PT-induced stroke rats treated with …

Successful Reuse Of A Donor Heart, Isaac S Alderete, Qimeng Gao, Abigail Benkert, Katherine Sun, Riley Kahan, Kannan Samy, Vincenzo Villani, Joseph W Turek, Deepak Vikraman, Carmelo A Milano, Michael W Manning, Andrew S Barbas

Faculty, Staff and Student Publications

Advances in surgical technique and multidisciplinary management have improved long-term survival for patients born with single ventricle physiology. However, patients who have undergone Fontan completion remain at risk for long-term comorbidities associated with the complex hemodynamic changes following the procedure, including Fontan failure and Fontan-associated liver disease.1 Combined heart-liver transplantation (CHLT) is a rare but lifesaving procedure that has been described in the setting of heart and liver failure secondary to Fontan failure.2 As long-term survival continues to improve for Fontan patients, the incidence of Fontan-associated liver disease will increase. Thus, improving CHLT outcomes and access to both …

Drosophila Tweety Facilitates Autophagy To Regulate Mitochondrial Homeostasis And Bioenergetics In Glia, Ho Hang Leung, Christina Mansour, Morgan Rousseau, Anwar Nakhla, Kirill Kiselyov, Kartik Venkatachalam, Ching-On Wong

Faculty, Staff and Student Publications

Mitochondria support the energetic demands of the cells. Autophagic turnover of mitochondria serves as a critical pathway for mitochondrial homeostasis. It is unclear how bioenergetics and autophagy are functionally connected. Here, we identify an endolysosomal membrane protein that facilitates autophagy to regulate ATP production in glia. We determined that Drosophila tweety (tty) is highly expressed in glia and localized to endolysosomes. Diminished fusion between autophagosomes and endolysosomes in tty-deficient glia was rescued by expressing the human Tweety Homolog 1 (TTYH1). Loss of tty in glia attenuated mitochondrial turnover, elevated mitochondrial oxidative stress, and impaired locomotor functions. The cellular and organismal …

Mediators Of Necroptosis: From Cell Death To Metabolic Regulation, Xiaoqin Wu, Laura E Nagy, Jérémie Gautheron

Faculty, Staff and Student Publications

Necroptosis, a programmed cell death mechanism distinct from apoptosis, has garnered attention for its role in various pathological conditions. While initially recognized for its involvement in cell death, recent research has revealed that key necroptotic mediators, including receptor-interacting protein kinases (RIPKs) and mixed lineage kinase domain-like protein (MLKL), possess additional functions that go beyond inducing cell demise. These functions encompass influencing critical aspects of metabolic regulation, such as energy metabolism, glucose homeostasis, and lipid metabolism. Dysregulated necroptosis has been implicated in metabolic diseases, including obesity, diabetes, metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease (ALD), contributing to chronic …

Allogeneic Stem Cell Therapy For Acute Ischemic Stroke: The Phase 2/3 Treasure Randomized Clinical Trial, Kiyohiro Houkin, Toshiya Osanai, Shinichiro Uchiyama, Kazuo Minematsu, Akihiko Taguchi, Katsuhiko Maruichi, Yoshimasa Niiya, Katsuyuki Asaoka, Yoshihiro Kuga, Katsumi Takizawa, Koichi Haraguchi, Shinichi Yoshimura, Kazumi Kimura, Koji Tokunaga, Atsuo Aoyama, Fusao Ikawa, Chikanori Inenaga, Tatsuya Abe, Atsushi Tominaga, Shinichi Takahashi, Kohsuke Kudo, Miki Fujimura, Taku Sugiyama, Masaki Ito, Masahito Kawabori, David C Hess, Sean I Savitz, Teruyuki Hirano

Faculty, Staff and Student Publications

IMPORTANCE: Cell therapy is a promising treatment approach for stroke and other diseases. However, it is unknown whether MultiStem (HLCM051), a bone marrow-derived, allogeneic, multipotent adult progenitor cell product, has the potential to treat ischemic stroke.

OBJECTIVE: To assess the efficacy and safety of MultiStem when administered within 18 to 36 hours of ischemic stroke onset.

DESIGN, SETTING, AND PARTICIPANTS: The Treatment Evaluation of Acute Stroke Using Regenerative Cells (TREASURE) multicenter, double-blind, parallel-group, placebo-controlled phase 2/3 randomized clinical trial was conducted at 44 academic and clinical centers in Japan between November 15, 2017, and March 29, 2022. Inclusion criteria were …

Tumor Treating Fields Increases Blood-Brain Barrier Permeability And Relative Cerebral Blood Volume In Patients With Glioblastoma, Michael Iv, Lewis Naya, Sajal Sanan, Samuel L Van Buskirk, Seema Nagpal, Reena P Thomas, Lawrence D Recht, Chirag B Patel

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVE: 200 kHz tumor treating fields (TTFields) is clinically approved for newly-diagnosed glioblastoma (nGBM). Because its effects on conventional surveillance MRI brain scans are equivocal, we investigated its effects on perfusion MRI (pMRI) brain scans.

METHODS: Each patient underwent institutional standard pMRI: dynamic contrast-enhanced (DCE) and dynamic susceptibility contrast (DSC) pMRI at three time points: baseline, 2-, and 6-months on-adjuvant therapy. At each timepoint, the difference between T1 pre- versus post-contrast tumor volume (ΔT1) and these pMRI metrics were evaluated: normalized and standardized relative cerebral blood volume (nRCBV, sRCBV); fractional plasma volume (V

RESULTS: Among 13 pMRI datasets …

Control Intervention Design For Preclinical And Clinical Trials: Consensus-Based Core Recommendations From The Third Stroke Recovery And Rehabilitation Roundtable, Kathryn S Hayward, Emily J Dalton, Jessica Barth, Marian Brady, Leora R Cherney, Leonid Churilov, Andrew N Clarkson, Jesse Dawson, Sean P Dukelow, Peter Feys, Maree Hackett, Steve R Zeiler, Catherine E Lang

2020-Current year OA Pubs

Control comparator selection is a critical trial design issue. Preclinical and clinical investigators who are doing trials of stroke recovery and rehabilitation interventions must carefully consider the appropriateness and relevance of their chosen control comparator as the benefit of an experimental intervention is established relative to a comparator. Establishing a strong rationale for a selected comparator improves the integrity of the trial and validity of its findings. This Stroke Recovery and Rehabilitation Roundtable (SRRR) taskforce used a graph theory voting system to rank the importance and ease of addressing challenges during control comparator design. "Identifying appropriate type of control" was …

Zika Virus Co-Opts Microrna Networks To Persist In Placental Niches Detected By Spatial Transcriptomics, Enrico R Barrozo, Maxim D Seferovic, Mark P Hamilton, David N Moorshead, Michael D Jochum, Trang Do, Derek S O'Neil, Melissa A Suter, Kjersti M Aagaard

Faculty, Staff and Students Publications

BACKGROUND: Zika virus congenital infection evades double-stranded RNA detection and may persist in the placenta for the duration of pregnancy without accompanying overt histopathologic inflammation. Understanding how viruses can persist and replicate in the placenta without causing overt cellular or tissue damage is fundamental to deciphering mechanisms of maternal-fetal vertical transmission.

OBJECTIVE: Placenta-specific microRNAs are believed to be a tenet of viral resistance at the maternal-fetal interface. We aimed to test the hypothesis that the Zika virus functionally disrupts placental microRNAs, enabling viral persistence and fetal pathogenesis.

STUDY DESIGN: To test this hypothesis, we used orthogonal approaches in human and …

The History Of Extracorporeal Membrane Oxygenation And The Development Of Extracorporeal Membrane Oxygenation Anticoagulation, Robert Bartlett, Deepa J Arachichilage, Meera Chitlur, Shiu-Ki Rocky Hui, Cindy Neunert, Andrew Doyle, Andrew Retter, Beverley J Hunt, Hoong Sern Lim, Arun Saini, Thomas Renné, Vadim Kostousov, Jun Teruya

Faculty, Staff and Students Publications

Extracorporeal membrane oxygenation (ECMO) was first started for humans in early 1970s by Robert Bartlett. Since its inception, there have been numerous challenges with extracorporeal circulation, such as coagulation and platelet activation, followed by consumption of coagulation factors and platelets, and biocompatibility of tubing, pump, and oxygenator. Unfractionated heparin (heparin hereafter) has historically been the defacto anticoagulant until recently. Also, coagulation monitoring was mainly based on bedside activated clotting time and activated partial thromboplastin time. In the past 50 years, the technology of ECMO has advanced tremendously, and thus, the survival rate has improved significantly. The indication for ECMO has …