Digital Commons Network^™

The Impact Of Covid-19 On Pediatric Cardiac Arrest Outcomes: A Systematic Review And Meta-Analysis, Alla Navolokina, Jacek Smereka, Bernd W Böttiger, Michal Pruc, Raúl Juárez-Vela, Mansur Rahnama-Hezavah, Zubaid Rafique, Frank W Peacock, Kamil Safiejko, Lukasz Szarpak

Faculty, Staff and Students Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic, required the donning of personal protective equipment during clinical contact, and continues to be a significant worldwide public health concern. Pediatric cardiac arrest is a rare but critical condition with a high mortality rate, the outcomes of which may be negatively affected by donning personal protective equipment. The aim of this study is to perform a systematic review and meta-analysis of the impact of the COVID-19 pandemic on pediatric cardiac arrest outcomes. We conducted a systematic review with meta-analysis in the following databases: PubMed, EMBASE, Scopus, Web of Science, …

Book Review: Animal, Vegetable, Junk: A History Of Food, From Sustainable To Suicidal, Miguel A. Quintana

Natural Resources Journal

No abstract provided.

Graph Theoretical Measures Of Fast Ripple Networks Improve The Accuracy Of Post-Operative Seizure Outcome Prediction, Shennan A Weiss, Itzhak Fried, Chengyuan Wu, Ashwini Sharan, Daniel Y. Rubinstein, Jerome Engel, Michael R Sperling, Richard J Staba

Department of Neurosurgery Faculty Papers

Fast ripples (FR) are a biomarker of epileptogenic brain, but when larger portions of FR generating regions are resected seizure freedom is not always achieved. To evaluate and improve the diagnostic accuracy of FR resection for predicting seizure freedom we compared the FR resection ratio (RR) with FR network graph theoretical measures. In 23 patients FR were semi-automatically detected and quantified in stereo EEG recordings during sleep. MRI normalization and co-registration localized contacts and relation to resection margins. The number of FR, and graph theoretical measures, which were spatial (i.e., FR rate-distance radius) or temporal correlational (i.e., FR mutual information), …

Silencing Mir-146a-5p Protects Against Injury-Induced Osteoarthritis In Mice, Haocheng Qin, Cuicui Wang, Yonghua He, Aiwu Lu, Tiandao Li, Bo Zhang, Jie Shen

2020-Current year OA Pubs

Osteoarthritis (OA), the most prevalent joint disease and the leading cause of disability, remains an incurable disease largely because the etiology and pathogenesis underlying this degenerative process are poorly understood. Low-grade inflammation within joints is a well-established factor that disturbs joint homeostasis and leads to an imbalance between anabolic and catabolic processes in articular cartilage; however, the complexity of the network between inflammatory factors that often involves positive and negative feedback loops makes current anti-cytokine therapy ineffective. MicroRNAs (miRNAs) have emerged as key regulators to control inflammation, and aberrant miRNAs expression has recently been linked to OA pathophysiology. In the …

Protocol For The Phase 2 Edelife Trial Investigating The Efficacy And Safety Of Intra-Amniotic Er004 Administration To Male Subjects With X-Linked Hypohidrotic Ectodermal Dysplasia, Holm Schneider, Smail Hadj-Rabia, Florian Faschingbauer, Christine Bodemer, Dorothy K Grange, Mary E Norton, Riccardo Cavalli, Gianluca Tadini, Holger Stepan, Angus Clarke, Encarna Guillén-Navarro, Sigrun Maier-Wohlfart, Athmane Bouroubi, Florence Porte

2020-Current year OA Pubs

X-linked hypohidrotic ectodermal dysplasia (XLHED) is a rare genetic disorder characte-rised by abnormal development of the skin and its appendages, such as hair and sweat glands, the teeth, and mucous glands of the airways, resulting in serious, sometimes life-threatening complications like hyperthermia or recurrent respiratory infections. It is caused by pathogenic variants of the ectodysplasin A gene (

Multimodal Brain Age Estimates Relate To Alzheimer Disease Biomarkers And Cognition In Early Stages: A Cross-Sectional Observational Study, Peter R Millar, Brian A Gordon, Patrick H Luckett, Tammie L S Benzinger, Carlos Cruchaga, Anne M Fagan, Jason J Hassenstab, Richard J Perrin, Suzanne E Schindler, Randall J Bateman, John C Morris, Beau M Ances, Et Al.

2020-Current year OA Pubs

BACKGROUND: Estimates of 'brain-predicted age' quantify apparent brain age compared to normative trajectories of neuroimaging features. The brain age gap (BAG) between predicted and chronological age is elevated in symptomatic Alzheimer disease (AD) but has not been well explored in presymptomatic AD. Prior studies have typically modeled BAG with structural MRI, but more recently other modalities, including functional connectivity (FC) and multimodal MRI, have been explored.

METHODS: We trained three models to predict age from FC, structural (S), or multimodal MRI (S+FC) in 390 amyloid-negative cognitively normal (CN/A-) participants (18-89 years old). In independent samples of 144 CN/A-, 154 CN/A+, …

An Entosis-Like Process Induces Mitotic Disruption In Pals1 Microcephaly Pathogenesis, Noelle A Sterling, Jun Young Park, Raehee Park, Seo-Hee Cho, Seonhee Kim

Center for Translational Medicine Faculty Papers

Entosis is cell cannibalism utilized by tumor cells to engulf live neighboring cells for pro- or anti-tumorigenic purposes. It is unknown whether this extraordinary cellular event can be pathogenic in other diseases such as microcephaly, a condition characterized by a smaller than normal brain at birth. We find that mice mutant for the human microcephaly-causing gene Pals1, which exhibit diminished cortices due to massive cell death, also exhibit nuclei enveloped by plasma membranes inside of dividing cells. These cell-in-cell (CIC) structures represent a dynamic process accompanied by lengthened mitosis and cytokinesis abnormalities. As shown in tumor cells, ROCK inhibition completely …

Therapeutic Targeting Of Prenatal Pontine Id1 Signaling In Diffuse Midline Glioma., Dana Messinger, Micah K. Harris, Jessica R. Cummings, Chase Thomas, Tao Yang, Stefan R. Sweha, Rinette Woo, Robert Siddaway, Martin Burkert, Stefanie Stallard, Tingting Qin, Brendan Mullan, Ruby Siada, Ramya Ravindran, Michael Niculcea, Abigail R. Dowling, Joshua Bradin, Kevin Ginn, Melissa Gener, Kathleen Dorris, Nicholas A. Vitanza, Susanne V. Schmidt, Jasper Spitzer, Jiang Li, Mariella G. Filbin, Xuhong Cao, Maria G. Castro, Pedro R. Lowenstein, Rajen Mody, Arul Chinnaiyan, Pierre-Yves Desprez, Sean Mcallister, Matthew D. Dun, Cynthia Hawkins, Sebastian M. Waszak, Sriram Venneti, Carl Koschmann, Viveka Nand Yadav

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Diffuse midline gliomas (DMG) are highly invasive brain tumors with rare survival beyond two years past diagnosis and limited understanding of the mechanism behind tumor invasion. Previous reports demonstrate upregulation of the protein ID1 with H3K27M and ACVR1 mutations in DMG, but this has not been confirmed in human tumors or therapeutically targeted.

METHODS: Whole exome, RNA, and ChIP-sequencing was performed on the ID1 locus in DMG tissue. Scratch-assay migration and transwell invasion assays of cultured cells were performed following shRNA-mediated ID1-knockdown. In vitro and in vivo genetic and pharmacologic [cannabidiol (CBD)] inhibition of ID1 on DMG tumor growth …

Rare Eif4a2 Variants Are Associated With A Neurodevelopmental Disorder Characterized By Intellectual Disability, Hypotonia, And Epilepsy, Maimuna S Paul, Anna R Duncan, Casie A Genetti, Hongling Pan, Adam Jackson, Patricia E Grant, Jiahai Shi, Michele Pinelli, Nicola Brunetti-Pierri, Alexandra Garza-Flores, Dave Shahani, Russell P Saneto, Giuseppe Zampino, Chiara Leoni, Emanuele Agolini, Antonio Novelli, Ulrike Blümlein, Tobias B Haack, Wolfram Heinritz, Eva Matzker, Bader Alhaddad, Rami Abou Jamra, Tobias Bartolomaeus, Saber Alhamdan, Raphael Carapito, Bertrand Isidor, Seiamak Bahram, Alyssa Ritter, Kosuke Izumi, Ben Pode Shakked, Ortal Barel, Bruria Ben Zeev, Amber Begtrup, Deanna Alexis Carere, Sureni V Mullegama, Timothy Blake Palculict, Daniel G Calame, Katharina Schwan, Alicia R P Aycinena, Rasa Traberg, Genomics England Research Consortium, Sofia Douzgou, Harrison Pirt, Naila Ismayilova, Siddharth Banka, Hsiao-Tuan Chao, Pankaj B Agrawal

Faculty, Staff and Students Publications

Eukaryotic initiation factor-4A2 (EIF4A2) is an ATP-dependent RNA helicase and a member of the DEAD-box protein family that recognizes the 5' cap structure of mRNAs, allows mRNA to bind to the ribosome, and plays an important role in microRNA-regulated gene repression. Here, we report on 15 individuals from 14 families presenting with global developmental delay, intellectual disability, hypotonia, epilepsy, and structural brain anomalies, all of whom have extremely rare de novo mono-allelic or inherited bi-allelic variants in EIF4A2. Neurodegeneration was predominantly reported in individuals with bi-allelic variants. Molecular modeling predicts these variants would perturb structural interactions in key protein domains. …

Phase I Dose Escalation Study Of Topical Bexarotene In Women At High Risk For Breast Cancer, Parijatham S Thomas, Anisha B Patel, J Jack Lee, Diane D Liu, Mike Hernandez, Miguel Muzzio, Alejandro Contreras, Valerie Sepeda, Carrie Mays, Diane Weber, Lana A Vornik, Seema A Khan, Eileen Dimond, Brandy M Heckman-Stoddard, Marjorie Perloff, Powel H Brown

Faculty, Staff and Student Publications

Bexarotene is a rexinoid that has been shown to prevent mammary tumors in mouse models but oral dosing has toxicities. This phase I study evaluates topical bexarotene, as a potential chemoprevention agent, for safety and toxicity in high-risk women for breast cancer.

Molecular Mechanisms And Future Implications Of Vegf/Vegfr In Cancer Therapy, Sonia A Patel, Monique B Nilsson, Xiuning Le, Tina Cascone, Rakesh K Jain, John V Heymach

Faculty, Staff and Student Publications

Angiogenesis, the sprouting of new blood vessels from existing vessels, is one of six known mechanisms employed by solid tumors to recruit blood vessels necessary for their initiation, growth, and metastatic spread. The vascular network within the tumor facilitates the transport of nutrients, oxygen, and immune cells and is regulated by pro- and anti-angiogenic factors. Nearly four decades ago, VEGF was identified as a critical factor promoting vascular permeability and angiogenesis, followed by identification of VEGF family ligands and their receptors (VEGFR). Since then, over a dozen drugs targeting the VEGF/VEGFR pathway have been approved for approximately 20 solid tumor …

The Lysosomal Ragulator Complex Activates Nlrp3 Inflammasome In Vivo Via Hdac6, Kohei Tsujimoto, Tatsunori Jo, Daiki Nagira, Hachiro Konaka, Jeong Hoon Park, Shin-Ichiro Yoshimura, Akinori Ninomiya, Fuminori Sugihara, Takehiro Hirayama, Eri Itotagawa, Yusei Matsuzaki, Yuki Takaichi, Wataru Aoki, Shotaro Saita, Shuhei Nakamura, Andrea Ballabio, Shigeyuki Nada, Masato Okada, Hyota Takamatsu, Atsushi Kumanogoh

Duncan NRI Faculty and Staff Publications

The cellular activation of the NLRP3 inflammasome is spatiotemporally orchestrated by various organelles, but whether lysosomes contribute to this process remains unclear. Here, we show the vital role of the lysosomal membrane-tethered Ragulator complex in NLRP3 inflammasome activation. Deficiency of Lamtor1, an essential component of the Ragulator complex, abrogated NLRP3 inflammasome activation in murine macrophages and human monocytic cells. Myeloid-specific Lamtor1-deficient mice showed marked attenuation of NLRP3-associated inflammatory disease severity, including LPS-induced sepsis, alum-induced peritonitis, and monosodium urate (MSU)-induced arthritis. Mechanistically, Lamtor1 interacted with both NLRP3 and histone deacetylase 6 (HDAC6). HDAC6 enhances the interaction between Lamtor1 and NLRP3, resulting …

Feasibility And Preclinical Efficacy Of Cd7-Unedited Cd7 Car T Cells For T Cell Malignancies, Norihiro Watanabe, Feiyan Mo, Rong Zheng, Royce Ma, Vanesa C Bray, Dayenne G Van Leeuwen, Juntima Sritabal-Ramirez, Hongxiang Hu, Sha Wang, Birju Mehta, Madhuwanti Srinivasan, Lauren D Scherer, Huimin Zhang, Sachin G Thakkar, Laquisa C Hill, Helen E Heslop, Chonghui Cheng, Malcolm K Brenner, Maksim Mamonkin

Faculty, Staff and Students Publications

Chimeric antigen receptor (CAR)-mediated targeting of T lineage antigens for the therapy of blood malignancies is frequently complicated by self-targeting of CAR T cells or their excessive differentiation driven by constant CAR signaling. Expression of CARs targeting CD7, a pan-T cell antigen highly expressed in T cell malignancies and some myeloid leukemias, produces robust fratricide and often requires additional mitigation strategies, such as CD7 gene editing. In this study, we show fratricide of CD7 CAR T cells can be fully prevented using ibrutinib and dasatinib, the pharmacologic inhibitors of key CAR/CD3ζ signaling kinases. Supplementation with ibrutinib and dasatinib rescued the …

Inhibiting Androgen Receptor Splice Variants With Cysteine-Selective Irreversible Covalent Inhibitors To Treat Prostate Cancer, Thirumagal Thiyagarajan, Suriyan Ponnusamy, Dong-Jin Hwang, Yali He, Sarah Asemota, Kirsten L Young, Daniel L Johnson, Vera Bocharova, Weidong Zhou, Abhinav K Jain, Emanuel F Petricoin, Zheng Yin, Lawrence M Pfeffer, Duane D Miller, Ramesh Narayanan

Faculty, Staff and Student Publications

Androgen receptor (AR) and its splice variants (AR-SVs) promote prostate cancer (PCa) growth by orchestrating transcriptional reprogramming. Mechanisms by which the low complexity and intrinsically disordered primary transactivation domain (AF-1) of AR and AR-SVs regulate transcriptional programming in PCa remains poorly defined. Using omics, live and fixed fluorescent microscopy of cells, and purified AF-1 and AR-V7 recombinant proteins we show here that AF-1 and the AR-V7 splice variant form molecular condensates by liquid-liquid phase separation (LLPS) that exhibit disorder characteristics such as rapid intracellular mobility, coactivator interaction, and euchromatin induction. The LLPS and other disorder characteristics were reversed by a …

Subtype And Site Specific-Induced Metabolic Vulnerabilities In Prostate Cancer, Federica Mossa, Daniele Robesti, Ramachandran Sumankalai, Eva Corey, Mark Titus, Yuqi Kang, Jianhua Zhang, Alberto Briganti, Francesco Montorsi, Christopher P Vellano, Joseph R Marszalek, Daniel E Frigo, Christopher J Logothetis, Taranjit S Gujral, Eleonora Dondossola

Faculty, Staff and Student Publications

Aberrant metabolic functions play a crucial role in prostate cancer progression and lethality. Currently, limited knowledge is available on subtype-specific metabolic features and their implications for treatment. We therefore investigated the metabolic determinants of the two major subtypes of castration-resistant prostate cancer [androgen receptor-expressing prostate cancer (ARPC) and aggressive variant prostate cancer (AVPC)]. Transcriptomic analyses revealed enrichment of gene sets involved in oxidative phosphorylation (OXPHOS) in ARPC tumor samples compared with AVPC. Unbiased screening of metabolic signaling pathways in patient-derived xenograft models by proteomic analyses further supported an enrichment of OXPHOS in ARPC compared with AVPC, and a skewing toward …

Radiofrequency Ablation Remodels The Tumor Microenvironment And Promotes Neutrophil-Mediated Abscopal Immunomodulation In Pancreatic Cancer, Erika Y Faraoni, Baylee J O'Brien, Lincoln N Strickland, Baron K Osborn, Victoria Mota, Jarod Chaney, Constance Lynn Atkins, Putao Cen, Julie Rowe, Jessica Cardenas, Kyle L Poulsen, Curtis J Wray, Nirav C Thosani, Jennifer M Bailey-Lundberg

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) presents a 5-year overall survival rate of 11%, despite efforts to improve clinical outcomes in the past two decades. Therapeutic resistance is a hallmark of this disease, due to its dense and suppressive tumor microenvironment (TME). Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is a promising local ablative and potential immunomodulatory therapy for PDAC. In this study, we performed RFA in a preclinical tumor-bearing KrasG12D; Trp53R172H/+; Pdx1:Cre (KPC) syngeneic model, analyzed local and abscopal affects after RFA and compared our findings with resected PDAC specimens. We found that RFA reduced PDAC tumor progression in vivo and promoted strong …

Increased Camkk2 Expression Is An Adaptive Response That Maintains The Fitness Of Tumor-Infiltrating Natural Killer Cells, Patrick K Juras, Luigi Racioppi, Debarati Mukherjee, Sandeep Artham, Xia Gao, Laura Akullian D'Agostino, Ching-Yi Chang, Donald P Mcdonnell

Faculty, Staff and Students Publications

Calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a key regulator of energy homeostasis in several cell types. Expression of this enzyme in tumor cells promotes proliferation and migration, and expression in tumor-associated immune cells facilitates M2 macrophage polarization and the development of myeloid-derived suppressor cells. Thus, there has been interest in developing CaMKK2 inhibitors as potential anticancer therapeutics. One impediment to clinical development of these agents is that the roles of CaMKK2 in other cellular compartments within the tumor immune microenvironment remain to be established. We report herein that CaMKK2 is expressed at low basal levels in natural killer (NK) …

Vista Targeting Of T-Cell Quiescence And Myeloid Suppression Overcomes Adaptive Resistance, Evelien Schaafsma, Walburga Croteau, Mohamed Eltanbouly, Elizabeth C Nowak, Nicole C Smits, Jie Deng, Aurelien Sarde, Cecilia A Webber, Dina Rabadi, Chao Cheng, Randolph Noelle, J Louise Lines

Faculty, Staff and Students Publications

VISTA is a premier target for cancer treatment due to its broad expression in many cancer types and enhanced expression upon development of adaptive immune checkpoint resistance. In the CT26 colorectal cancer model, monotherapy of small tumors with anti-VISTA resulted in slowed tumor growth. In a combination therapy setting, large CT26 tumors showed complete adaptive resistance to anti-PD-1/CTLA-4, but inclusion of anti-VISTA led to rejection of half the tumors. Mechanisms of enhanced anti-tumor immunity were investigated using scRNA-seq, multiplex image analysis and flow cytometry of the tumor immune infiltrate. In both treatment models, anti-VISTA upregulated stimulated antigen-presentation pathways and reduced …

Fn14-Directed Dart Nanoparticles Selectively Target Neoplastic Cells In Preclinical Models Of Triple-Negative Breast Cancer Brain Metastasis, Christine P Carney, Anshika Kapur, Pavlos Anastasiadis, Rodney M Ritzel, Chixiang Chen, Graeme F Woodworth, Jeffrey A Winkles, Anthony J Kim

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC) patients with brain metastasis (BM) face dismal prognosis due to the limited therapeutic efficacy of the currently available treatment options. We previously demonstrated that paclitaxel-loaded PLGA−PEG nanoparticles (NPs) directed to the Fn14 receptor, termed “DARTs”, are more efficacious than Abraxane—an FDA-approved paclitaxel nanoformulation—following intravenous delivery in a mouse model of TNBC BM. However, the precise basis for this difference was not investigated. Here, we further examine the utility of the DART drug delivery platform in complementary xenograft and syngeneic TNBC BM models. First, we demonstrated that, in comparison to nontargeted NPs, DART NPs exhibit preferential association …

Inherited Human Itk Deficiency Impairs Ifn-Γ Immunity And Underlies Tuberculosis, Masato Ogishi, Rui Yang, Rémy Rodriguez, Dominic P Golec, Emmanuel Martin, Quentin Philippot, Jonathan Bohlen, Simon J Pelham, Andrés Augusto Arias, Taushif Khan, Manar Ata, Fatima Al Ali, Flore Rozenberg, Xiao-Fei Kong, Maya Chrabieh, Candice Laine, Wei-Te Lei, Ji Eun Han, Yoann Seeleuthner, Zenia Kaul, Emmanuelle Jouanguy, Vivien Béziat, Leila Youssefian, Hassan Vahidnezhad, V Koneti Rao, Bénédicte Neven, Claire Fieschi, Davood Mansouri, Mohammad Shahrooei, Sevgi Pekcan, Gulsum Alkan, Melike Emiroğlu, Hüseyin Tokgöz, Jouni Uitto, Fabian Hauck, Jacinta Bustamante, Laurent Abel, Sevgi Keles, Nima Parvaneh, Nico Marr, Pamela L Schwartzberg, Sylvain Latour, Jean-Laurent Casanova, Stéphanie Boisson-Dupuis

Department of Dermatology and Cutaneous Biology Faculty Papers

Inborn errors of IFN-γ immunity can underlie tuberculosis (TB). We report three patients from two kindreds without EBV viremia or disease but with severe TB and inherited complete ITK deficiency, a condition associated with severe EBV disease that renders immunological studies challenging. They have CD4+ αβ T lymphocytopenia with a concomitant expansion of CD4-CD8- double-negative (DN) αβ and Vδ2- γδ T lymphocytes, both displaying a unique CD38+CD45RA+T-bet+EOMES- phenotype. Itk-deficient mice recapitulated an expansion of the γδ T and DN αβ T lymphocyte populations in the thymus and spleen, respectively. Moreover, the patients' T lymphocytes secrete small amounts of IFN-γ in …

Magnify Is A Universal Molecular Anchoring Strategy For Expansion Microscopy, Aleksandra Klimas, Brendan R Gallagher, Piyumi Wijesekara, Sinda Fekir, Emma F Dibernardo, Zhangyu Cheng, Donna B Stolz, Franca Cambi, Simon C Watkins, Steven L Brody, Amjad Horani, Alison L Barth, Christopher I Moore, Xi Ren, Yongxin Zhao

2020-Current year OA Pubs

Expansion microscopy enables nanoimaging with conventional microscopes by physically and isotropically magnifying preserved biological specimens embedded in a crosslinked water-swellable hydrogel. Current expansion microscopy protocols require prior treatment with reactive anchoring chemicals to link specific labels and biomolecule classes to the gel. We describe a strategy called Magnify, which uses a mechanically sturdy gel that retains nucleic acids, proteins and lipids without the need for a separate anchoring step. Magnify expands biological specimens up to 11 times and facilitates imaging of cells and tissues with effectively around 25-nm resolution using a diffraction-limited objective lens of about 280 nm on conventional …

Human Alcohol-Microbiota Mice Have Increased Susceptibility To Bacterial Pneumonia, Kelly C. Cunningham, Deandra R. Smith, Daniel Villageliu, Christi M. Ellis, Amanda E. Ramer-Tait, Jeffrey D. Price, Todd A. Wyatt, Daren L. Knoell, Mystera M. Samuelson, Patricia E Molina, David A. Welsh, Derrick R. Samuelson

Journal Articles: Environmental, Agricultural & Occupational Health

Preclinical studies have shown that chronic alcohol abuse leads to alterations in the gastrointestinal microbiota that are associated with behavior changes, physiological alterations, and immunological effects. However, such studies have been limited in their ability to evaluate the direct effects of alcohol-associated dysbiosis. To address this, we developed a humanized alcohol-microbiota mouse model to systematically evaluate the immunological effects of chronic alcohol abuse mediated by intestinal dysbiosis. Germ-free mice were colonized with human fecal microbiota from individuals with high and low Alcohol Use Disorders Identification Test (AUDIT) scores and bred to produce human alcohol-associated microbiota or human control-microbiota F1 progenies. …

An Intravenous Pancreatic Cancer Therapeutic: Characterization Of Crispr/Cas9n-Modified Clostridium Novyi-Non Toxic, Kaitlin M. Dailey, James M. Small, Jessica E. Pullan, Seth Winfree, Krysten E. Vance, Megan Orr, Sanku Mallik, Kenneth W. Bayles, Michael A. Hollingsworth, Amanda E Brooks

Journal Articles: Pathology and Microbiology

Clostridium novyi has demonstrated selective efficacy against solid tumors largely due to the microenvironment contained within dense tumor cores. The core of a solid tumor is typically hypoxic, acidic, and necrotic-impeding the penetration of current therapeutics. C. novyi is attracted to the tumor microenvironment and once there, can both lyse and proliferate while simultaneously re-activating the suppressed immune system. C. novyi systemic toxicity is easily mitigated by knocking out the phage DNA plasmid encoded alpha toxin resulting in C. novyi-NT; but, after intravenous injection spores are quickly cleared by phagocytosis before accomplishing significant tumor localization. C. novyi-NT could be designed …

Agricultural Dust Derived Bacterial Extracellular Vesicle Mediated Inflammation Is Attenuated By Dha, Art J. Heires, Derrick R. Samuelson, Daniel Villageliu, Tara M. Nordgren, Debra J. Romberger

Journal Articles: Pulmonary & Critical Care Med

Dietary long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) and their pro-resolving metabolites are protective against atherosclerotic disease, and ameliorate systemic inflammatory conditions including lupus erythematosus, psoriasis, and bronchial asthma. Organic bioaerosol inhalation is a common and injurious hazard associated with agricultural occupations such as work in swine concentrated animal feeding operations (CAFOs) and is known to increase the risk for developing respiratory conditions such as asthma and COPD. Nearly all cells secrete membrane-bound vesicles (extracellular vesicles, EVs) that have the capacity to transmit protein, nucleic acid, and lipid signaling mediators between cells. Using a polymer-based isolation technique (ExoQuick, PEG) followed …

Planned Adaptation And Implementation Of The Community Guide Recommendations For Increasing Physical Activity In Rural Community Settings: A Qualitative Study, Julia Meredith Hess, Sally M. Davis

Pediatrics Research and Scholarship

BACKGROUND: The purpose of this paper is to report on the implementation of an evidence-based model, VIVA, which was developed to translate physical activity (PA) recommendations to rural environments and was scaled-up to 12 rural communities across New Mexico. Our longitudinal qualitative research describes processes of planned adaptation in the rural context with an exploration of inner and outer context adaptations that consider important implementation constructs including leadership, partnership and collaboration.

MATERIALS & METHODS: An enhanced version of the RE-AIM framework was used to formulate community-level engagement and process questions essential to implementation science. Qualitative methods, using a thematic approach …

Exploring Barriers And Promoters Of Crc Screening Use Among Agricultural Operators: A Pilot Study Of An Application Of Concept Mapping, Cheryl Beseler, Jungyoon Kim, Roma Subramanian, Susan Harris, Karen Funkenbusch, Aaron Yoder, Tamara Robinson, Jason M. Foster, Shinobu Watanabe-Galloway

Journal Articles: Epidemiology

INTRODUCTION: The purpose of the study was to identify barriers and facilitators of colorectal cancer (CRC) screening use among agricultural operators in Nebraska, US.

METHODS: The concept mapping approach was used to engage participants and enhance the generation of ideas and opinions regarding CRC screening. Two focus groups (seven women and seven men) were conducted.

RESULTS: Among women, the cost domain was most agreed upon as important, followed by experiencing symptoms, awareness, and family. Among men, the important concepts related to CRC screening were family and friend support, feeling too young to get CRC, family or personal history of CRC, …

How The Commonwealth Of The Northern Mariana Islands Stalled Covid-19 For 22 Months And Managed Its First Significant Community Transmission, Dwayne Davis, Stephanie Kern-Allely, Lily Muldoon, John M. Tudela, Jesse Tudela, Renea Raho, Heather S. Pangelinan, Halina Palacios, John Tabaguel, Alan Hinson, Guillermo Lifoifoi, Warren Villagomez, Joseph R. Fauver, Haley L. Cash, Esther Muña, Sean T. Casey, Ali S. Khan

Journal Articles: Epidemiology

OBJECTIVE: The Commonwealth of the Northern Mariana Islands (CNMI) is a remote Pacific island territory with a population of 47 329 that successfully prevented the significant introduction of coronavirus disease (COVID-19) until late 2021. This study documents how the response to the introduction of COVID-19 in CNMI in 2021 was conducted with limited resources without overwhelming local clinical capacity or compromising health service delivery for the population.

METHODS: Data from COVID-19 case investigations, contact tracing, the Commonwealth's immunization registry and whole genome sequencing were collated and analysed as part of this study.

RESULTS: Between 26 March 2020 and 31 December …

Exposure To Pcb126 During The Nursing Period Reversibly Impacts Early-Life Glucose Tolerance, Brittany B. Rice, Keegan W. Sammons, Sara Y. Ngo Tenlep, Madeline T. Weltzer, Leryn J. Reynolds, Cetewayo S. Rashid, Hollie I. Swanson, Kevin J. Pearson

Human Movement Studies & Special Education Faculty Publications

Polychlorinated biphenyls (PCBs) are persistent environmental organic pollutants known to have detrimental health effects. Using a mouse model, we previously demonstrated that PCB126 exposure before and during pregnancy and throughout the perinatal period adversely affected offspring glucose tolerance and/or body composition profiles. The purpose of this study was to investigate the glucose tolerance and body composition of offspring born to dams exposed to PCB126 during the nursing period only. Female ICR mice were bred, and half of the dams were exposed to either vehicle (safflower oil) or 1 µmole PCB126 per kg of body weight via oral gavage on postnatal …

Prodromal Glutamatergic Modulation With Riluzole Impacts Glucose Homeostasis And Spatial Cognition In Alzheimer's Disease Mice., Caleigh A Findley, Samuel A Mcfadden, Makayla F Cox, Lindsey N Sime, Mackenzie R Peck, Kathleen Quinn, Andrzej Bartke, Kevin N Hascup, Erin R Hascup

Articles

BACKGROUND: Prior research supports a strong link between Alzheimer's disease (AD) and metabolic dysfunction that involves a multi-directional interaction between glucose, glutamatergic homeostasis, and amyloid pathology. Elevated soluble amyloid-β (Aβ) is an early biomarker for AD-associated cognitive decline that contributes to concurrent glutamatergic and metabolic dyshomeostasis in humans and male transgenic AD mice. Yet, it remains unclear how primary time-sensitive targeting of hippocampal glutamatergic activity may impact glucose regulation in an amyloidogenic mouse model. Previous studies have illustrated increased glucose uptake and metabolism using a neuroprotective glutamate modulator (riluzole), supporting the link between glucose and glutamatergic homeostasis.

OBJECTIVE: We hypothesized …

A Single-Cell Atlas Of Bovine Skeletal Muscle Reveals Mechanisms Regulating Intramuscular Adipogenesis And Fibrogenesis, Leshan Wang, Peidong Gao, Chaoyag Li, Qianglin Liu, Zeyang Yao, Yuxia Li, Xujia Zhang, Jiangwen Sun, Constantine Simintiras, Matthew Welborn, Kenneth Mcmillin, Stephanie Oprescu, Shihuan Kuang, Xing Fu

Computer Science Faculty Publications

Background: Intramuscular fat (IMF) and intramuscular connective tissue (IMC) are often seen in human myopathies and are central to beef quality. The mechanisms regulating their accumulation remain poorly understood. Here, we explored the possibility of using beef cattle as a novel model for mechanistic studies of intramuscular adipogenesis and fibrogenesis.

Methods: Skeletal muscle single-cell RNAseq was performed on three cattle breeds, including Wagyu (high IMF), Brahman (abundant IMC but scarce IMF), and Wagyu/Brahman cross. Sophisticated bioinformatics analyses, including clustering analysis, gene set enrichment analyses, gene regulatory network construction, RNA velocity, pseudotime analysis, and cell-cell communication analysis, were performed to elucidate …