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Bi-Allelic Variants In The Esam Tight-Junction Gene Cause A Neurodevelopmental Disorder Associated With Fetal Intracranial Hemorrhage, Mauro Lecca, Davut Pehlivan, Damià Heine Suñer, Karin Weiss, Thibault Coste, Markus Zweier, Yavuz Oktay, Nada Danial-Farran, Vittorio Rosti, Maria Paola Bonasoni, Alessandro Malara, Gianluca Contrò, Roberta Zuntini, Marzia Pollazzon, Rosario Pascarella, Alberto Neri, Carlo Fusco, Dana Marafi, Tadahiro Mitani, Jennifer Ellen Posey, Sadik Etka Bayramoglu, Alper Gezdirici, Jessica Hernandez-Rodriguez, Emilia Amengual Cladera, Elena Miravet, Jorge Roldan-Busto, María Angeles Ruiz, Cristofol Vives Bauzá, Liat Ben-Sira, Sabine Sigaudy, Anaïs Begemann, Sheila Unger, Serdal Güngör, Semra Hiz, Ece Sonmezler, Yoav Zehavi, Michael Jerdev, Alessandra Balduini, Orsetta Zuffardi, Rita Horvath, Hanns Lochmüller, Anita Rauch, Livia Garavelli, Elisabeth Tournier-Lasserve, Ronen Spiegel, James R Lupski, Edoardo Errichiello Apr 2023

Bi-Allelic Variants In The Esam Tight-Junction Gene Cause A Neurodevelopmental Disorder Associated With Fetal Intracranial Hemorrhage, Mauro Lecca, Davut Pehlivan, Damià Heine Suñer, Karin Weiss, Thibault Coste, Markus Zweier, Yavuz Oktay, Nada Danial-Farran, Vittorio Rosti, Maria Paola Bonasoni, Alessandro Malara, Gianluca Contrò, Roberta Zuntini, Marzia Pollazzon, Rosario Pascarella, Alberto Neri, Carlo Fusco, Dana Marafi, Tadahiro Mitani, Jennifer Ellen Posey, Sadik Etka Bayramoglu, Alper Gezdirici, Jessica Hernandez-Rodriguez, Emilia Amengual Cladera, Elena Miravet, Jorge Roldan-Busto, María Angeles Ruiz, Cristofol Vives Bauzá, Liat Ben-Sira, Sabine Sigaudy, Anaïs Begemann, Sheila Unger, Serdal Güngör, Semra Hiz, Ece Sonmezler, Yoav Zehavi, Michael Jerdev, Alessandra Balduini, Orsetta Zuffardi, Rita Horvath, Hanns Lochmüller, Anita Rauch, Livia Garavelli, Elisabeth Tournier-Lasserve, Ronen Spiegel, James R Lupski, Edoardo Errichiello

Faculty, Staff and Students Publications

The blood-brain barrier (BBB) is an essential gatekeeper for the central nervous system and incidence of neurodevelopmental disorders (NDDs) is higher in infants with a history of intracerebral hemorrhage (ICH). We discovered a rare disease trait in thirteen individuals, including four fetuses, from eight unrelated families associated with homozygous loss-of-function variant alleles of ESAM which encodes an endothelial cell adhesion molecule. The c.115del (p.Arg39Glyfs∗33) variant, identified in six individuals from four independent families of Southeastern Anatolia, severely impaired the in vitro tubulogenic process of endothelial colony-forming cells, recapitulating previous evidence in null mice, and caused lack of ESAM expression in …


Application Of A Novel Lytic Jerseyvirus Phage Lpsent1 For The Biological Control Of The Multidrug-Resistant Salmonella Enteritidis In Foods, Rashad R. Al-Hindi, Mona G. Alharbi, Ibrahim Alotibi, Sheren A. Azhari, Khloud M. Algothmi, Ahmed Esmael Apr 2023

Application Of A Novel Lytic Jerseyvirus Phage Lpsent1 For The Biological Control Of The Multidrug-Resistant Salmonella Enteritidis In Foods, Rashad R. Al-Hindi, Mona G. Alharbi, Ibrahim Alotibi, Sheren A. Azhari, Khloud M. Algothmi, Ahmed Esmael

Nebraska Center for Virology: Faculty Publications

Non-typhoidal Salmonella is the tremendously predominant source of acquired foodborne infection in humans, causing salmonellosis which is a global threat to the healthcare system. This threat is even worse when it is combined with the incidence of multidrug-resistant Salmonella strains. Bacteriophage therapy has been proposed as a promising potential candidate to control a diversity of foodborne infective bacteria. The objective of this study designed to isolate and characterize lytic phages infecting zoonotic multi-drug resistant and strong biofilm producer Salmonella enterica serovar Enteritidis EG.SmE1 and then apply the isolated phage/s as a biocontrol agent against infections in ready-to-eat food articles including …


Impact Of Intravesical Bacillus Calmette-GuéRin And Chemotherapy On The Bladder Microbiome In Patients With Non-Muscle Invasive Bladder Cancer, Kayeromi Gomez, Christopher James, Shalin Desai, Hiten Patel, Goran Rac, Chirag Doshi, Ryan Dornbier, Petar Bajic, Thomas Halverson, Gopal Gupta, Marcus Quek, Alex Gorbonos, Robert Flanigan, Alan J. Wolfe Apr 2023

Impact Of Intravesical Bacillus Calmette-GuéRin And Chemotherapy On The Bladder Microbiome In Patients With Non-Muscle Invasive Bladder Cancer, Kayeromi Gomez, Christopher James, Shalin Desai, Hiten Patel, Goran Rac, Chirag Doshi, Ryan Dornbier, Petar Bajic, Thomas Halverson, Gopal Gupta, Marcus Quek, Alex Gorbonos, Robert Flanigan, Alan J. Wolfe

Biostatistics Collaborative Core: Faculty Publications and Other Works

Introduction: Intravesical therapy (IVT), including Bacillus Calmette-Guérin (BCG), is the standard of care for high grade (HG) non-muscle invasive bladder cancer (NMIBC). Despite the use of IVT, many patients recur after treatment. The bladder microbiome and its role in disease processes has recently risen to prominence. We aim to characterize changes that occur in the bladder microbiome over the course of intravesical therapy and assess whether these changes correlate with outcomes in patients with NMIBC.

Methods: Patients with NMIBC undergoing induction BCG or intravesical therapy were prospectively enrolled from January 2019 to March 2020. Patients with clinical T2 or greater …


The Impact Of Gamma Transcranial Alternating Current Stimulation (Tacs) On Cognitive And Memory Processes In Patients With Mild Cognitive Impairment Or Alzheimer’S Disease: A Literature Review, N.R. Nissim, D.V.H. Pham, T. Poddar, E. Blutt, R.H. Hamilton Apr 2023

The Impact Of Gamma Transcranial Alternating Current Stimulation (Tacs) On Cognitive And Memory Processes In Patients With Mild Cognitive Impairment Or Alzheimer’S Disease: A Literature Review, N.R. Nissim, D.V.H. Pham, T. Poddar, E. Blutt, R.H. Hamilton

Moss-Magee Rehabilitation Papers

BACKGROUND: Transcranial alternating current stimulation (tACS)-a noninvasive brain stimulation technique that modulates cortical oscillations through entrainment-has been demonstrated to alter oscillatory activity and enhance cognition in healthy adults. TACS is being explored as a tool to improve cognition and memory in patient populations with mild cognitive impairment (MCI) and Alzheimer's disease (AD).

OBJECTIVE: To review the growing body of literature and current findings obtained from the application of tACS in patients with MCI or AD, highlighting the effects of gamma tACS on brain function, memory, and cognition. Evidence on the use of brain stimulation in animal models of AD is …


Dpp8 Selective Inhibitor Tominostat As A Novel And Broad-Spectrum Anticancer Agent Against Hematological Malignancies, Shohei Kikuchi, Akinori Wada, Yusuke Kamihara, Kosuke Okazaki, Paras Jawaid, Mati Ur Rehman, Eiji Kobayashi, Takeshi Susukida, Tomoki Minemura, Yoshimi Nabe Apr 2023

Dpp8 Selective Inhibitor Tominostat As A Novel And Broad-Spectrum Anticancer Agent Against Hematological Malignancies, Shohei Kikuchi, Akinori Wada, Yusuke Kamihara, Kosuke Okazaki, Paras Jawaid, Mati Ur Rehman, Eiji Kobayashi, Takeshi Susukida, Tomoki Minemura, Yoshimi Nabe

Department of Biological & Biomedical Sciences

DPP8/9 inhibition induces either pyroptotic or apoptotic cell death in hematological malignancies. We previously reported that treatment with the DPP8/9 inhibitor 1G244 resulted in apoptotic cell death in myeloma, and our current study further evaluates the mechanism of action of 1G244 in different blood cancer cell lines. Specifically, 1G244 inhibited DPP9 to induce GSDMD-mediated-pyroptosis at low concentrations and inhibited DPP8 to cause caspase-3-mediated-apoptosis at high concentrations. HCK expression is necessary to induce susceptibility to pyroptosis but does not participate in the induction of apoptosis. To further characterize this DPP8-dependent broad-spectrum apoptosis induction effect, we evaluated the potential antineoplastic role for …


Cd73-Dependent Adenosine Signaling Through Adora2b Drives Immunosuppression In Ductal Pancreatic Cancer, Erika Y Faraoni, Kanchan Singh, Vidhi Chandra, Olivereen Le Roux, Yulin Dai, Ismet Sahin, Baylee J O'Brien, Lincoln N Strickland, Le Li, Emily Vucic, Amanda N Warner, Melissa Pruski, Trent Clark, George Van Buren, Nirav C Thosani, John S Bynon, Curtis J Wray, Dafna Bar-Sagi, Kyle L Poulsen, Lana A Vornik, Michelle I Savage, Shizuko Sei, Altaf Mohammed, Zhongming Zhao, Powel H Brown, Tingting Mills, Holger K Eltzschig, Florencia Mcallister, Jennifer M Bailey-Lundberg Apr 2023

Cd73-Dependent Adenosine Signaling Through Adora2b Drives Immunosuppression In Ductal Pancreatic Cancer, Erika Y Faraoni, Kanchan Singh, Vidhi Chandra, Olivereen Le Roux, Yulin Dai, Ismet Sahin, Baylee J O'Brien, Lincoln N Strickland, Le Li, Emily Vucic, Amanda N Warner, Melissa Pruski, Trent Clark, George Van Buren, Nirav C Thosani, John S Bynon, Curtis J Wray, Dafna Bar-Sagi, Kyle L Poulsen, Lana A Vornik, Michelle I Savage, Shizuko Sei, Altaf Mohammed, Zhongming Zhao, Powel H Brown, Tingting Mills, Holger K Eltzschig, Florencia Mcallister, Jennifer M Bailey-Lundberg

Faculty, Staff and Student Publications

The microenvironment that surrounds pancreatic ductal adenocarcinoma (PDAC) is profoundly desmoplastic and immunosuppressive. Understanding triggers of immunosuppression during the process of pancreatic tumorigenesis would aid in establishing targets for effective prevention and therapy. Here, we interrogated differential molecular mechanisms dependent on cell of origin and subtype that promote immunosuppression during PDAC initiation and in established tumors. Transcriptomic analysis of cell-of-origin-dependent epithelial gene signatures revealed that Nt5e/CD73, a cell-surface enzyme required for extracellular adenosine generation, is one of the top 10% of genes overexpressed in murine tumors arising from the ductal pancreatic epithelium as opposed to those rising from acinar cells. …


Swi/Snf Blockade Disrupts Pu1-Directed Enhancer Programs In Normal Hematopoietic Cells And Acute Myeloid Leukemia, Courtney Chambers, Katerina Cermakova, Yuen San Chan, Kristen Kurtz, Katharina Wohlan, Andrew Henry Lewis, Christiana Wang, Anh Pham, Milan Dejmek, Michal Sala, Mario Loeza Cabrera, Rogelio Aguilar, Radim Nencka, H Daniel Lacorazza, Rachel E Rau, H Courtney Hodges Apr 2023

Swi/Snf Blockade Disrupts Pu1-Directed Enhancer Programs In Normal Hematopoietic Cells And Acute Myeloid Leukemia, Courtney Chambers, Katerina Cermakova, Yuen San Chan, Kristen Kurtz, Katharina Wohlan, Andrew Henry Lewis, Christiana Wang, Anh Pham, Milan Dejmek, Michal Sala, Mario Loeza Cabrera, Rogelio Aguilar, Radim Nencka, H Daniel Lacorazza, Rachel E Rau, H Courtney Hodges

Faculty, Staff and Students Publications

UNLABELLED: In acute myeloid leukemia (AML), SWI/SNF chromatin remodeling complexes sustain leukemic identity by driving high levels of MYC. Previous studies have implicated the hematopoietic transcription factor PU.1 (SPI1) as an important target of SWI/SNF inhibition, but PU.1 is widely regarded to have pioneer-like activity. As a result, many questions have remained regarding the interplay between PU.1 and SWI/SNF in AML as well as normal hematopoiesis. Here we found that PU.1 binds to most of its targets in a SWI/SNF-independent manner and recruits SWI/SNF to promote accessibility for other AML core regulatory factors, including RUNX1, LMO2, and MEIS1. SWI/SNF inhibition …


Pattern Dynamics And Stochasticity Of The Brain Rhythms, Clarissa Hoffman, Jingheng Cheng, Daoyun Ji, Yuri Dabaghian Apr 2023

Pattern Dynamics And Stochasticity Of The Brain Rhythms, Clarissa Hoffman, Jingheng Cheng, Daoyun Ji, Yuri Dabaghian

Faculty, Staff and Student Publications

Our current understanding of brain rhythms is based on quantifying their instantaneous or time-averaged characteristics. What remains unexplored is the actual structure of the waves-their shapes and patterns over finite timescales. Here, we study brain wave patterning in different physiological contexts using two independent approaches: The first is based on quantifying stochasticity relative to the underlying mean behavior, and the second assesses "orderliness" of the waves' features. The corresponding measures capture the waves' characteristics and abnormal behaviors, such as atypical periodicity or excessive clustering, and demonstrate coupling between the patterns' dynamics and the animal's location, speed, and acceleration. Specifically, we …


Pattern Dynamics And Stochasticity Of The Brain Rhythms, Clarissa Hoffman, Jingheng Cheng, Daoyun Ji, Yuri Dabaghian Apr 2023

Pattern Dynamics And Stochasticity Of The Brain Rhythms, Clarissa Hoffman, Jingheng Cheng, Daoyun Ji, Yuri Dabaghian

Faculty, Staff and Students Publications

Our current understanding of brain rhythms is based on quantifying their instantaneous or time-averaged characteristics. What remains unexplored is the actual structure of the waves—their shapes and patterns over finite timescales. Here, we study brain wave patterning in different physiological contexts using two independent approaches: The first is based on quantifying stochasticity relative to the underlying mean behavior, and the second assesses “orderliness” of the waves’ features. The corresponding measures capture the waves’ characteristics and abnormal behaviors, such as atypical periodicity or excessive clustering, and demonstrate coupling between the patterns’ dynamics and the animal’s location, speed, and acceleration. Specifically, we …


Alopecia In Patients With Collagen Vi-Related Myopathies: A Novel/Unrecognized Scalp Phenotype, Michela Starace, Francesca Pampaloni, Francesca Bruni, Federico Quadrelli, Stephano Cedirian, Carlotta Baraldi, Cosimo Misciali, Alberto Di Martino, Patrizia Sabatelli, Luciano Merlini, Bianca Maria Piraccini Apr 2023

Alopecia In Patients With Collagen Vi-Related Myopathies: A Novel/Unrecognized Scalp Phenotype, Michela Starace, Francesca Pampaloni, Francesca Bruni, Federico Quadrelli, Stephano Cedirian, Carlotta Baraldi, Cosimo Misciali, Alberto Di Martino, Patrizia Sabatelli, Luciano Merlini, Bianca Maria Piraccini

Department of Dermatology and Cutaneous Biology Faculty Papers

Collagen VI-related myopathies are characterized by severe muscle involvement and skin involvement (keratosis pilaris and impaired healing with the development of abnormal scars, especially keloids). Scalp involvement and hair loss have not been reported among cutaneous changes associated with collagen VI mutations. The aim of this study is to describe the clinical, trichoscopic, and histological findings of the scalp changes in patients affected by COL VI mutations and to estimate their prevalence. Patients with Ullrich congenital muscular dystrophy were enrolled and underwent clinical and trichoscopic examinations and a scalp biopsy for histopathology. Five patients were enrolled, and all complained of …


Inhibition Of Stat6 With Antisense Oligonucleotides Enhances The Systemic Antitumor Effects Of Radiotherapy And Anti-Pd-1 In Metastatic Non-Small Cell Lung Cancer, Kewen He, Hampartsoum B Barsoumian, Nahum Puebla-Osorio, Yun Hu, Duygu Sezen, Mark D Wasley, Genevieve Bertolet, Jie Zhang, Carola Leuschner, Liangpeng Yang, Claudia S Kettlun Leyton, Natalie Wall Fowlkes, Morgan Maureen Green, Lisa Hettrick, Dawei Chen, Fatemeh Masrorpour, Meidi Gu, Hadi Maazi, Alexey S Revenko, Maria Angelica Cortez, James W Welsh Apr 2023

Inhibition Of Stat6 With Antisense Oligonucleotides Enhances The Systemic Antitumor Effects Of Radiotherapy And Anti-Pd-1 In Metastatic Non-Small Cell Lung Cancer, Kewen He, Hampartsoum B Barsoumian, Nahum Puebla-Osorio, Yun Hu, Duygu Sezen, Mark D Wasley, Genevieve Bertolet, Jie Zhang, Carola Leuschner, Liangpeng Yang, Claudia S Kettlun Leyton, Natalie Wall Fowlkes, Morgan Maureen Green, Lisa Hettrick, Dawei Chen, Fatemeh Masrorpour, Meidi Gu, Hadi Maazi, Alexey S Revenko, Maria Angelica Cortez, James W Welsh

Faculty, Staff and Student Publications

Diverse factors contribute to the limited clinical response to radiotherapy (RT) and immunotherapy in metastatic non-small cell lung cancer (NSCLC), among which is the ability of these tumors to recruit a retinue of suppressive immune cells-such as M2 tumor-associated macrophages (TAM)-thereby establishing an immunosuppressive tumor microenvironment that contributes to tumor progression and radio resistance. M2 TAMs are activated by the STAT6 signaling pathway. Therefore, we targeted STAT6 using an antisense oligonucleotide (ASO) along with hypofractionated RT (hRT; 3 fractions of 12 Gy each) to primary tumors in three bilateral murine NSCLC models (Lewis lung carcinoma, 344SQ-parental, and anti-PD-1-resistant 344SQ lung …


Dna Damage Repair Kinase Dna-Pk And Cgas Synergize To Induce Cancer-Related Inflammation In Glioblastoma, Clara Taffoni, Johanna Marines, Hanane Chamma, Soumyabrata Guha, Mathilde Saccas, Amel Bouzid, Ana-Luiza Chaves Valadao, Clément Maghe, Jane Jardine, Mi Kyung Park, Katarzyna Polak, Mara De Martino, Claire Vanpouille-Box, Maguy Del Rio, Celine Gongora, Julie Gavard, Nicolas Bidère, Min Sup Song, Donovan Pineau, Jean-Philippe Hugnot, Karima Kissa, Laura Fontenille, Fabien P Blanchet, Isabelle K Vila, Nadine Laguette Apr 2023

Dna Damage Repair Kinase Dna-Pk And Cgas Synergize To Induce Cancer-Related Inflammation In Glioblastoma, Clara Taffoni, Johanna Marines, Hanane Chamma, Soumyabrata Guha, Mathilde Saccas, Amel Bouzid, Ana-Luiza Chaves Valadao, Clément Maghe, Jane Jardine, Mi Kyung Park, Katarzyna Polak, Mara De Martino, Claire Vanpouille-Box, Maguy Del Rio, Celine Gongora, Julie Gavard, Nicolas Bidère, Min Sup Song, Donovan Pineau, Jean-Philippe Hugnot, Karima Kissa, Laura Fontenille, Fabien P Blanchet, Isabelle K Vila, Nadine Laguette

Faculty, Staff and Student Publications

Cytosolic DNA promotes inflammatory responses upon detection by the cyclic GMP-AMP (cGAMP) synthase (cGAS). It has been suggested that cGAS downregulation is an immune escape strategy harnessed by tumor cells. Here, we used glioblastoma cells that show undetectable cGAS levels to address if alternative DNA detection pathways can promote pro-inflammatory signaling. We show that the DNA-PK DNA repair complex (i) drives cGAS-independent IRF3-mediated type I Interferon responses and (ii) that its catalytic activity is required for cGAS-dependent cGAMP production and optimal downstream signaling. We further show that the cooperation between DNA-PK and cGAS favors the expression of chemokines that promote …


Il6 Mediates Suppression Of T- And Nk-Cell Function In Emt-Associated Tki-Resistant Egfr-Mutant Nsclc, Sonia A Patel, Monique B Nilsson, Yan Yang, Xiuning Le, Hai T Tran, Yasir Y Elamin, Xiaoxing Yu, Fahao Zhang, Alissa Poteete, Xiaoyang Ren, Li Shen, Jing Wang, Seyed Javad Moghaddam, Tina Cascone, Michael Curran, Don L Gibbons, John V Heymach Apr 2023

Il6 Mediates Suppression Of T- And Nk-Cell Function In Emt-Associated Tki-Resistant Egfr-Mutant Nsclc, Sonia A Patel, Monique B Nilsson, Yan Yang, Xiuning Le, Hai T Tran, Yasir Y Elamin, Xiaoxing Yu, Fahao Zhang, Alissa Poteete, Xiaoyang Ren, Li Shen, Jing Wang, Seyed Javad Moghaddam, Tina Cascone, Michael Curran, Don L Gibbons, John V Heymach

Faculty, Staff and Student Publications

Purpose: Patients with advanced non-small cell lung cancer (NSCLC) harboring activating EGFR mutations are initially responsive to tyrosine kinase inhibitors (TKI). However, therapeutic resistance eventually emerges, often via secondary EGFR mutations or EGFR-independent mechanisms such as epithelial-to-mesenchymal transition. Treatment options after EGFR-TKI resistance are limited as anti-PD-1/PD-L1 inhibitors typically display minimal benefit. Given that IL6 is associated with worse outcomes in patients with NSCLC, we investigate whether IL6 in part contributes to this immunosuppressed phenotype.

Experimental design: We utilized a syngeneic genetically engineered mouse model (GEMM) of EGFR-mutant NSCLC to investigate the effects of IL6 on the tumor microenvironment and …


Emt-Activated Secretory And Endocytic Vesicular Trafficking Programs Underlie A Vulnerability To Pi4k2a Antagonism In Lung Cancer, Xiaochao Tan, Guan-Yu Xiao, Shike Wang, Lei Shi, Yanbin Zhao, Xin Liu, Jiang Yu, William K Russell, Chad J Creighton, Jonathan M Kurie Apr 2023

Emt-Activated Secretory And Endocytic Vesicular Trafficking Programs Underlie A Vulnerability To Pi4k2a Antagonism In Lung Cancer, Xiaochao Tan, Guan-Yu Xiao, Shike Wang, Lei Shi, Yanbin Zhao, Xin Liu, Jiang Yu, William K Russell, Chad J Creighton, Jonathan M Kurie

Faculty, Staff and Students Publications

Hypersecretory malignant cells underlie therapeutic resistance, metastasis, and poor clinical outcomes. However, the molecular basis for malignant hypersecretion remains obscure. Here, we showed that epithelial-mesenchymal transition (EMT) initiates exocytic and endocytic vesicular trafficking programs in lung cancer. The EMT-activating transcription factor zinc finger E-box-binding homeobox 1 (ZEB1) executed a PI4KIIIβ-to-PI4KIIα (PI4K2A) dependency switch that drove PI4P synthesis in the Golgi and endosomes. EMT enhanced the vulnerability of lung cancer cells to PI4K2A small-molecule antagonists. PI4K2A formed a MYOIIA-containing protein complex that facilitated secretory vesicle biogenesis in the Golgi, thereby establishing a hypersecretory state involving osteopontin (SPP1) and other prometastatic ligands. …


Induction Of Innate Inflammatory Pathways In The Corneal Epithelium In The Desiccating Stress Dry Eye Model, Zhiyuan Yu, Ghasem Yazdanpanah, Jehan Alam, Cintia S De Paiva, Stephen Pflugfelder Apr 2023

Induction Of Innate Inflammatory Pathways In The Corneal Epithelium In The Desiccating Stress Dry Eye Model, Zhiyuan Yu, Ghasem Yazdanpanah, Jehan Alam, Cintia S De Paiva, Stephen Pflugfelder

Faculty, Staff and Students Publications

PURPOSE: To determine whether 24-hour exposure to the desiccating stress (DS) dry eye model induces NF-kB and NLRP3 inflammasome pathways in the mouse cornea epithelium.

METHODS: Six- to 8-week-old C57BL/6J mice were housed under normal humidity (nonstressed) or subjected to DS from a drafty, low-humidity environment combined with subcutaneous scopolamine four times/day for one day to suppress tear production (DS1). Cornea whole mounts were prepared for immunofluorescent staining, or the corneal epithelium was scraped for NF-kB p-p65 ELISA, Western blot, or real-time PCR to detect NF-kB and inflammasome pathway proteins and gene transcripts, respectively.

RESULTS: NF-kB phospho-p65 protein, nuclear NF-kB …


Dysregulation And Epigenetic Reprogramming Of Nrf2 Signaling Axis Promote Acquisition Of Cisplatin Resistance And Metastasis In Head And Neck Squamous Cell Carcinoma, Abdullah A Osman, Emre Arslan, Mason Bartels, Chieko Michikawa, Antje Lindemann, Katarzyna Tomczak, Wangjie Yu, Vlad Sandulache, Wencai Ma, Li Shen, Jing Wang, Anand K Singh, Mitchell J Frederick, Nakia D Spencer, Jeffery Kovacs, Timothy Heffernan, William F Symmans, Kunal Rai, Jeffrey N Myers Apr 2023

Dysregulation And Epigenetic Reprogramming Of Nrf2 Signaling Axis Promote Acquisition Of Cisplatin Resistance And Metastasis In Head And Neck Squamous Cell Carcinoma, Abdullah A Osman, Emre Arslan, Mason Bartels, Chieko Michikawa, Antje Lindemann, Katarzyna Tomczak, Wangjie Yu, Vlad Sandulache, Wencai Ma, Li Shen, Jing Wang, Anand K Singh, Mitchell J Frederick, Nakia D Spencer, Jeffery Kovacs, Timothy Heffernan, William F Symmans, Kunal Rai, Jeffrey N Myers

Faculty, Staff and Student Publications

PURPOSE: Cisplatin (CDDP)-based chemotherapy is a first-line treatment for patients with advanced head and neck squamous cell carcinomas (HNSCC), despite a high rate of treatment failures, acquired resistance, and subsequent aggressive behavior. The purpose of this study was to study the mechanism of CDDP resistance and metastasis in HNSCC. We investigated the role of NRF2 pathway activation as a driven event for tumor progression and metastasis of HNSCC.

EXPERIMENTAL DESIGN: Human HNSCC cell lines that are highly resistant to CDDP were generated. Clonogenic survival assays and a mouse model of oral cancer were used to examine the impact of NRF2 …


The Association Between Caffeine Intake And The Colonic Mucosa-Associated Gut Microbiota In Humans-A Preliminary Investigation, Annie Dai, Kristi Hoffman, Anthony A Xu, Shawn Gurwara, Donna L White, Fasiha Kanwal, Albert Jang, Hashem B El-Serag, Joseph F Petrosino, Li Jiao Apr 2023

The Association Between Caffeine Intake And The Colonic Mucosa-Associated Gut Microbiota In Humans-A Preliminary Investigation, Annie Dai, Kristi Hoffman, Anthony A Xu, Shawn Gurwara, Donna L White, Fasiha Kanwal, Albert Jang, Hashem B El-Serag, Joseph F Petrosino, Li Jiao

Faculty, Staff and Students Publications

We examined the association between caffeine and coffee intake and the community composition and structure of colonic microbiota. A total of 34 polyp-free adults donated 97 colonic biopsies. Microbial DNA was sequenced for the 16S rRNA gene V4 region. The amplicon sequence variant was assigned using DADA2 and SILVA. Food consumption was ascertained using a food frequency questionnaire. We compared the relative abundance of taxonomies by low (<82.9 mg) vs. high (≥82.9 mg) caffeine intake and by never or <2 cups vs. 2 cups vs. ≥3 cups coffee intake. False discovery rate-adjusted p values (q values) <0.05 indicated statistical significance. Multivariable negative binomial regression models were used to estimate the incidence rate ratio and its 95% confidence interval of having a non-zero count of certain bacteria by intake level. Higher caffeine and coffee intake was related to higher alpha diversity (Shannon index p < 0.001), higher relative abundance of Faecalibacterium and Alistipes, and lower relative abundance of Erysipelatoclostridium (q values < 0.05). After adjustment of vitamin B2 in multivariate analysis, the significant inverse association between Erysipelatoclostridium count and caffeine intake remained statistically significant. Our preliminary study could not …


Independent Reproduction Of The Flash Effect On The Gastrointestinal Tract: A Multi-Institutional Comparative Study, Anet Valdés Zayas, Neeraj Kumari, Kevin Liu, Denae Neill, Abagail Delahoussaye, Patrik Gonçalves Jorge, Reiner Geyer, Steven H Lin, Claude Bailat, François Bochud, Raphael Moeckli, Albert C Koong, Jean Bourhis, Cullen M Taniguchi, Fernanda G Herrera, Emil Schüler Apr 2023

Independent Reproduction Of The Flash Effect On The Gastrointestinal Tract: A Multi-Institutional Comparative Study, Anet Valdés Zayas, Neeraj Kumari, Kevin Liu, Denae Neill, Abagail Delahoussaye, Patrik Gonçalves Jorge, Reiner Geyer, Steven H Lin, Claude Bailat, François Bochud, Raphael Moeckli, Albert C Koong, Jean Bourhis, Cullen M Taniguchi, Fernanda G Herrera, Emil Schüler

Faculty, Staff and Student Publications

FLASH radiation therapy (RT) is a promising new paradigm in radiation oncology. However, a major question that remains is the robustness and reproducibility of the FLASH effect when different irradiators are used on animals or patients with different genetic backgrounds, diets, and microbiomes, all of which can influence the effects of radiation on normal tissues. To address questions of rigor and reproducibility across different centers, we analyzed independent data sets from The University of Texas MD Anderson Cancer Center and from Lausanne University (CHUV). Both centers investigated acute effects after total abdominal irradiation to C57BL/6 animals delivered by the FLASH …


Ua12/2/2 Talisman: Surreal Issue No. 14, Wku Student Affairs Apr 2023

Ua12/2/2 Talisman: Surreal Issue No. 14, Wku Student Affairs

WKU Administration Documents

Spring 2023 Talisman:

  • Broekema, Gabi. Surrealism
  • Hunter, Leah. Surreal
  • Cox, Samantha. Surrealism
  • Plescia, Audrey. Horoscopes
  • Booth, Pandora. Dreamscapes
  • Ousley, Rachael. Body & Soul – Yoga, Susan Tutino
  • Coles, Jack. Tool for the Future – Artificial Intelligence
  • Sandlin, Ellie. Altered Minds – Drug Experimentation
  • Neidlinger, Heather. Little Dipper
  • White, Peyton. Pure Adrenaline – Rodeo, Skateboarding, Boxing, Rock Climbing
  • Plescia, Audrey. The Hill is Haunted
  • Richer, Cailyn. Threads of Expression – Fashion
  • Jefferson, Reginald. Momentum
  • Bruck, Lasikka. At Death’s Door – Yenni Gonzalez, Zoe Avery, Hannah Smith
  • Meyers, Jeffrey. Voice in Movement – Theatre & Dance, National Dance Education Association
  • Surreal Playlist


Maternal Healthcare Access And Obstetric Complications: A Cause And Effect Relationship?, Lena Sharara Apr 2023

Maternal Healthcare Access And Obstetric Complications: A Cause And Effect Relationship?, Lena Sharara

Independent Study Project (ISP) Collection

Poverty-stricken migrant women, named ‘Kayayei or Kayayo’ because of the nature of their job in the informal sector, have high birth rates and are said to have many barriers affecting their access to maternal health resources. In this study, Kayayei in Madina Market were interviewed and both quantitative and qualitative data were gathered to determine whether a relationship exists between access to maternal health and the obstetric complications and outcomes experienced by Kayayei. A Chi-Squared Test of Independence and a Qualitative Content Analysis were both used to analyze the data. Due to a non-significant p-value, it was found that the …


Efficacy Of Kidney Reperfusion Treatments Relative To Function And Survival Rates After Transplantation, Mitchell Rohr Apr 2023

Efficacy Of Kidney Reperfusion Treatments Relative To Function And Survival Rates After Transplantation, Mitchell Rohr

Senior Honors Theses

Donor kidneys are damaged upon circulatory death before being preserved with machine perfusion until transplantation. During machine perfusion, blood is pumped back into the vasculature of the kidney, causing damage called ischemic reperfusion injury. The two forms of machine perfusion are hypothermic machine perfusion and normothermic machine perfusion. Different methods of treatment can be used during either hypothermic machine perfusion or normothermic machine perfusion to prevent ischemic reperfusion injury. Each of the treatment methods that were reviewed showed potential for preventing ischemic reperfusion injury, with hypothermic treatments having higher average levels of feasibility than normothermic treatments. The effect of the …


Validation Of A Brief Measure For Complicated Grief Specific To Reproductive Loss, Cara Buskmiller, Kathryn R Grauerholz, Jennifer Bute, Maria Brann, Michaelene Fredenburg, Jerrie S Refuerzo Apr 2023

Validation Of A Brief Measure For Complicated Grief Specific To Reproductive Loss, Cara Buskmiller, Kathryn R Grauerholz, Jennifer Bute, Maria Brann, Michaelene Fredenburg, Jerrie S Refuerzo

Faculty, Staff and Student Publications

Objective

Complicated grief reactions follow some pregnancy outcomes, like miscarriage, stillbirth, neonatal death, infant death, selective reduction, or termination of pregnancy. Stigma can delay treatment and worsen outcomes. Screening tools such as the Edinburgh Postnatal Depression Scale detect complicated grief poorly, and specific tools for prolonged or complicated grief after a reproductive loss are cumbersome. In this study, a five-item questionnaire to detect complicated grief after reproductive loss of any type was designed and preliminary validated.

Methods

A questionnaire patterned after the extensively validated Brief Grief Questionnaire (BGQ) was created by a group of physicians and lay advocates to employ …


Neurotoxic Effects Of General Anesthesia On The Developing Brain And The Use Of Spinal Anesthesia As An Alternative Approach For The Neonate And Infant Undergoing Genitourinary Surgery, Makaela E. Delucca Apr 2023

Neurotoxic Effects Of General Anesthesia On The Developing Brain And The Use Of Spinal Anesthesia As An Alternative Approach For The Neonate And Infant Undergoing Genitourinary Surgery, Makaela E. Delucca

Nurse Anesthesia MSNA Student Capstones

Spinal anesthesia (SA) in the child under two years old is an excellent option when undergoing short genitourinary procedures. The use of SA in this patient population can avoid the potential deleterious neurocognitive effects on the developing brain that general anesthesia (GA) poses. A comprehensive literature review was conducted via retrospective case study, case control study, integrated review, and prospective study. The objective of this literature review is to examine the potential long-term neurotoxic effects of GA in the infant, as well as the benefits of SA. GA in the younger population has been shown to produce lower gray matter …


Effect Of Exercise Training Intensity On Cognition, Jaclyn Voyt Apr 2023

Effect Of Exercise Training Intensity On Cognition, Jaclyn Voyt

Honors Projects

A literature review examining the effects of exercise intensity and modality on cognitive performance.


Regeneration Of Neurons In Human Brain Tissue; A Revolutionary Concept With Therapeutic Potential, Mackenzie R. Dunn Apr 2023

Regeneration Of Neurons In Human Brain Tissue; A Revolutionary Concept With Therapeutic Potential, Mackenzie R. Dunn

Biomedical Sciences Undergraduate Research

There is current research to suggest that endogenous neuronal regeneration, exogenous neuronal stem cell transplantation and glial cell reprogramming could be prospective therapeutic treatments for neurodegeneration and traumatic injury. With these conditions, there is significant brain atrophy, loss of neurons and loss of synaptic connections which can have devastating effects on executive functioning, cognition, learning and memory. This review will examine these modern approaches to adult neurogenesis, and assess the viable mechanisms and future outlook of these three therapies for neurological regenerative medicine.


Serotonin Reuptake Inhibitor Increases Pseudarthrosis Rates In Anterior Cervical Discectomy And Fusions, Mark J. Lambrechts, Nicholas D. D'Antonio, Gregory R R. Toci, Brian A. Karamian, Josuhu Pezzulo, Dominic Farronato, Jose Canseco, Ian David Kaye, Barrett Woods, Jeffrey A. Rihn, Mark Kurd, Joseph K. Lee, Md, Alan S. Hilibrand, Christopher K. Kepler, Alexander R. Vaccaro, Gregory D. Schroeder Apr 2023

Serotonin Reuptake Inhibitor Increases Pseudarthrosis Rates In Anterior Cervical Discectomy And Fusions, Mark J. Lambrechts, Nicholas D. D'Antonio, Gregory R R. Toci, Brian A. Karamian, Josuhu Pezzulo, Dominic Farronato, Jose Canseco, Ian David Kaye, Barrett Woods, Jeffrey A. Rihn, Mark Kurd, Joseph K. Lee, Md, Alan S. Hilibrand, Christopher K. Kepler, Alexander R. Vaccaro, Gregory D. Schroeder

Rothman Institute Papers

STUDY DESIGN: Retrospective cohort.

PURPOSE: To determine (1) the effects of serotonin reuptake inhibitors in pseudarthrosis rates after anterior cervical decompression and fusion (ACDF) and (2) to identify patient-reported outcome measures in patients taking serotonin reuptake inhibitors.

OVERVIEW OF LITERATURE: Recent literature suggests that selective serotonin reuptake inhibitors (SSRIs) may inhibit fracture healing via downregulation of osteoblast differentiation. Spinal fusion supplementation with osteoblast-rich substances enhances spinal fusion, thus SSRIs may be detrimental.

METHODS: Patients with 1-year postoperative dynamic cervical spine radiographs following ACDF were grouped into serotonin reuptake inhibitor prescriptions (SSRI, serotonin-norepinephrine reuptake inhibitor [SNRI], or tricyclic antidepressant [TCA]) and …


2023 Research Day Program, Lincoln Memorial University Apr 2023

2023 Research Day Program, Lincoln Memorial University

Research Day

This program contains abstracts and presentation summaries from LMU's 2023 Annual Research Day conference.


Conflicting Socio-Cultural Attitudes And Community Factors Resulting In Backstreet Abortion In Cato Manor, Kwazulu Natal, Chloe Sachs Apr 2023

Conflicting Socio-Cultural Attitudes And Community Factors Resulting In Backstreet Abortion In Cato Manor, Kwazulu Natal, Chloe Sachs

Independent Study Project (ISP) Collection

Abortion in South Africa is a complex topic, rife with augmenting and limiting political, social, religious, and cultural factors. In South Africa, abortion has been legal since 1996; however, abortions have been performed for centuries in the region. Although abortion is legal, many factors influence a woman’s choice and ability to terminate a pregnancy. Religious and cultural norms within morally conservative societies contribute to negative abortion sentiments and hesitation to seek formal medical abortions. This study explored multiple age groups within Cato Manor and whether the attitudes towards abortion and factors impacting the choice of where and whether to receive …


The Effects Of Stigma Against Hiv And Tuberculosis On Patient Mental Health And Healthcare-Seeking Behavior In Dharamshala, Isabel Powell Apr 2023

The Effects Of Stigma Against Hiv And Tuberculosis On Patient Mental Health And Healthcare-Seeking Behavior In Dharamshala, Isabel Powell

Independent Study Project (ISP) Collection

HIV and tuberculosis are highly impactful diseases in India, causing severe morbidity, mortality, and suffering for millions. The stigmatization of these diseases unnecessarily exacerbates suffering for those afflicted and their families, compounding to the existing physical and emotional burden of diagnosis. Individual interviews with healthcare workers were conducted at Delek Hospital and the Tibetan Children’s Village in order to identify the existence and effects of stigma in the Tibetan refugee population in Dharamshala. Respondents reported an extremely high burden of tuberculosis in the community, complicated by the refugee status and unique infrastructural challenges of the population. The burden of HIV …


Genomic Analysis Of Two Phlebotomine Sand Fly Vectors Of Leishmania From The New And Old World, Frédéric Labbé, Maha Abdeladhim, Jenica Abrudan, Alejandra Saori Araki, Ricardo N Araujo, Peter Arensburger, Joshua B Benoit, Reginaldo Pecanha Brazil, Rafaela V Bruno, Gustavo Bueno Da Silva Rivas, Vinicius Carvalho De Abreu, Jason Charamis, Iliano V Coutinho-Abreu, Samara G Da Costa-Latgé, Alistair Darby, Viv M Dillon, Scott J Emrich, Daniela Fernandez-Medina, Nelder Figueiredo Gontijo, Catherine M Flanley, Derek Gatherer, Fernando A Genta, Sandra Gesing, Gloria I Giraldo-Calderón, Bruno Gomes, Eric Roberto Guimaraes Rocha Aguiar, James G C Hamilton, Omar Hamarsheh, Mallory Hawksworth, Jacob M Hendershot, Paul V Hickner, Jean-Luc Imler, Panagiotis Ioannidis, Emily C Jennings, Shaden Kamhawi, Charikleia Karageorgiou, Ryan C Kennedy, Andreas Krueger, José M Latorre-Estivalis, Petros Ligoxygakis, Antonio Carlos A Meireles-Filho, Patrick Minx, Jose Carlos Miranda, Michael J Montague, Ronald J Nowling, Fabiano Oliveira, João Ortigão-Farias, Marcio G Pavan, Marcos Horacio Pereira, Andre Nobrega Pitaluga, Roenick Proveti Olmo, Marcelo Ramalho-Ortigao, José M C Ribeiro, Andrew J Rosendale, Mauricio R V Sant'anna, Steven E Scherer, Nágila F C Secundino, Douglas A Shoue, Caroline Da Silva Moraes, João Silveira Moledo Gesto, Nataly Araujo Souza, Zainulabueddin Syed, Samuel Tadros, Rayane Teles-De-Freitas, Erich L Telleria, Chad Tomlinson, Yara M Traub-Csekö, João Trindade Marques, Zhijian Tu, Maria F Unger, Jesus Valenzuela, Flávia V Ferreira, Karla P V De Oliveira, Felipe M Vigoder, John Vontas, Lihui Wang, Gareth D Weedall, Elyes Zhioua, Stephen Richards, Wesley C Warren, Robert M Waterhouse, Rod J Dillon, Mary Ann Mcdowell Apr 2023

Genomic Analysis Of Two Phlebotomine Sand Fly Vectors Of Leishmania From The New And Old World, Frédéric Labbé, Maha Abdeladhim, Jenica Abrudan, Alejandra Saori Araki, Ricardo N Araujo, Peter Arensburger, Joshua B Benoit, Reginaldo Pecanha Brazil, Rafaela V Bruno, Gustavo Bueno Da Silva Rivas, Vinicius Carvalho De Abreu, Jason Charamis, Iliano V Coutinho-Abreu, Samara G Da Costa-Latgé, Alistair Darby, Viv M Dillon, Scott J Emrich, Daniela Fernandez-Medina, Nelder Figueiredo Gontijo, Catherine M Flanley, Derek Gatherer, Fernando A Genta, Sandra Gesing, Gloria I Giraldo-Calderón, Bruno Gomes, Eric Roberto Guimaraes Rocha Aguiar, James G C Hamilton, Omar Hamarsheh, Mallory Hawksworth, Jacob M Hendershot, Paul V Hickner, Jean-Luc Imler, Panagiotis Ioannidis, Emily C Jennings, Shaden Kamhawi, Charikleia Karageorgiou, Ryan C Kennedy, Andreas Krueger, José M Latorre-Estivalis, Petros Ligoxygakis, Antonio Carlos A Meireles-Filho, Patrick Minx, Jose Carlos Miranda, Michael J Montague, Ronald J Nowling, Fabiano Oliveira, João Ortigão-Farias, Marcio G Pavan, Marcos Horacio Pereira, Andre Nobrega Pitaluga, Roenick Proveti Olmo, Marcelo Ramalho-Ortigao, José M C Ribeiro, Andrew J Rosendale, Mauricio R V Sant'anna, Steven E Scherer, Nágila F C Secundino, Douglas A Shoue, Caroline Da Silva Moraes, João Silveira Moledo Gesto, Nataly Araujo Souza, Zainulabueddin Syed, Samuel Tadros, Rayane Teles-De-Freitas, Erich L Telleria, Chad Tomlinson, Yara M Traub-Csekö, João Trindade Marques, Zhijian Tu, Maria F Unger, Jesus Valenzuela, Flávia V Ferreira, Karla P V De Oliveira, Felipe M Vigoder, John Vontas, Lihui Wang, Gareth D Weedall, Elyes Zhioua, Stephen Richards, Wesley C Warren, Robert M Waterhouse, Rod J Dillon, Mary Ann Mcdowell

Faculty, Staff and Students Publications

Phlebotomine sand flies are of global significance as important vectors of human disease, transmitting bacterial, viral, and protozoan pathogens, including the kinetoplastid parasites of the genus Leishmania, the causative agents of devastating diseases collectively termed leishmaniasis. More than 40 pathogenic Leishmania species are transmitted to humans by approximately 35 sand fly species in 98 countries with hundreds of millions of people at risk around the world. No approved efficacious vaccine exists for leishmaniasis and available therapeutic drugs are either toxic and/or expensive, or the parasites are becoming resistant to the more recently developed drugs. Therefore, sand fly and/or reservoir control …