Digital Commons Network^™

The Utilization Of Microbial Cell-Free Dna Next-Generation Sequencing For The Detection Of Human Herpesvirus-8 In A Quaternary Care Center, Rebecca Berger, Jennifer Jacobe, Fernando H Centeno, Todd Lasco, Mayar Al Mohajer

Faculty, Staff and Students Publications

Background: Human herpesvirus-8 (HHV8) can present with cutaneous or extracutaneous manifestations. While violaceous skin lesions characterize cutaneous Kaposi sarcoma, extracutaneous HHV8 is challenging to diagnose due to nonspecific symptoms.

Objectives: We evaluated the role of microbial cell-free DNA next-generation sequencing (mcfDNA NGS) in diagnosing HHV8-related illness.

Design: Retrospective analysis.

Methods: Between 2017 and 2024, we reviewed the medical charts of 10 immunosuppressed patients at a quaternary care center who had positive HHV8 mcfDNA NGS results.

Results: The clinical and laboratory turnaround times of mcfDNA NGS were 3 and 1 days, respectively (8.5 and 7 days for immunohistochemistry vs 5.5 and …

Advancing Narcolepsy Advocacy: Bridging Patient Narratives And Systemic Change, Ahmed Salem Bahammam, Lindsay Jesteadt, Hamza Dhafar, Amir Sharafkhaneh

Faculty, Staff and Students Publications

We introduce the Stigma-to-Structure Advocacy Framework, a novel, evidence-based model designed to transform narcolepsy advocacy by systematically bridging patient narratives with structural change. Narcolepsy remains a profoundly underdiagnosed and misunderstood neurological disorder, with persistent diagnostic delays and pervasive cultural stigma undermining patient well-being and access to care. Despite recent progress in awareness and support, advocacy efforts remain fragmented and insufficiently integrated with health policy, particularly in low- and middle-income countries. This perspective advances a strategic evolution of narcolepsy advocacy through the Stigma-to-Structure Advocacy Framework, which is anchored in three pillars: narrative-driven awareness, clinical system integration, and policy activation. Drawing on …

Gut Microbial Community Structure Of The Adult Citrus Root Weevil Diaprepes Abbreviatus, Imilce A Rodriguez-Fernandez, Tasha M Santiago-Rodriguez, Paola G Figueroa-Pratts, Keislamarí Cintrón-Berríos, Nichole D Rodriguez-Cornier, Gary A Toranzos

Faculty, Staff and Students Publications

Diaprepes abbreviatus is an agricultural pest known to affect around 270 plant species across the Caribbean and the United States, posing significant challenges to pest management. Chemical control dominates management, but environmental and health concerns motivate microbiome-informed alternatives. However, limited information exists on the gut anatomy, physicochemical environment, and microbial composition of D. abbreviatus. In this study, we provide the first comprehensive characterization of the gut morphology, pH, and microbiota of adult D. abbreviatus in both females and males collected in Puerto Rico. Using dye-based gut tracing, we identified foregut, midgut, and hindgut or posterior gut compartments, and confirmed the …

The Department Of Cardiovascular Anesthesia Of The Texas Heart Institute: An Informal History, John R Cooper, N Martin Giesecke

Faculty, Staff and Students Publications

No abstract provided.

Influence Of Preoperative Blood Pressure On Postoperative Bleeding Complications Following Mohs Micrographic Surgery, Riyad N H Seervai, Sarah K Friske, Emily Powell, Ida F Orengo, Ikue Shimizu, Suzanne Alkul

Faculty, Staff and Students Publications

Background: Hypertension is a common comorbidity in patients undergoing Mohs micrographic surgery (MMS). Evidence in other surgical fields has suggested that high blood pressure increases the risk of perioperative bleeding, predisposing patients to complications such as hematomas, dehiscence, wound infection, and necrosis.

Methods: We reviewed medical charts of all 530 patients who underwent MMS at our institution in one calendar year to identify whether an association exists between preoperative blood pressure and bleeding outcomes in patients undergoing MMS.

Results: Perioperative variables, including history of diagnosed hypertension, preoperative systolic blood pressure >160 mm Hg, systolic blood pressure >180 mm Hg, anticoagulation/antiplatelet …

Influence Of Preoperative Blood Pressure On Postoperative Bleeding Complications Following Mohs Micrographic Surgery, Riyad N H Seervai, Sarah K Friske, Emily Powell, Ida F Orengo, Ikue Shimizu, Suzanne Alkul

Faculty, Staff and Students Publications

Background: Hypertension is a common comorbidity in patients undergoing Mohs micrographic surgery (MMS). Evidence in other surgical fields has suggested that high blood pressure increases the risk of perioperative bleeding, predisposing patients to complications such as hematomas, dehiscence, wound infection, and necrosis.

Methods: We reviewed medical charts of all 530 patients who underwent MMS at our institution in one calendar year to identify whether an association exists between preoperative blood pressure and bleeding outcomes in patients undergoing MMS.

Results: Perioperative variables, including history of diagnosed hypertension, preoperative systolic blood pressure >160 mm Hg, systolic blood pressure >180 mm Hg, anticoagulation/antiplatelet …

The Utility Of Brain Biomarkers In Predicting Survival And Neurological Outcomes In Pediatric Patients After Cardiac Arrest: A Systematic Review And Meta-Analysis, Halla Kamińska, Krzysztof Kurek, Michał Zembala, Sagar Galwankar, Monika Tomaszewska, Shraddha Singh, Nicola Luigi Bragazzi, Michał Pruc, Basar Cander, Francesco Chirico, Amelia Rizzo, Jacek Kubica, Ayman El-Menyar, Anne Lepetit, Pawel Patrzylas, Zubaid Rafique, W Frank Peacock, Łukasz Szarpak

Faculty, Staff and Students Publications

Background: Cardiac arrest in children is associated with high morbidity and mortality, primarily due to neurological injury. Biomarkers linked to brain injury, released into circulation from compromised elements of the neurovascular unit, act as significant prognostic indicators in patients suffering from hypoxic-ischemic brain injury (HIBI) subsequent to the restoration of spontaneous circulation (ROSC) after pediatric cardiac arrest. The aim of this systematic review and meta-analysis is to evaluate the prognostic utility of brain injury biomarkers in predicting neurological outcomes and survival in patients following cardiac arrest in the pediatric population.

Methods: Bibliographic databases (PubMed, the Cochrane Library, and Embase) were …

Zero-Inflated Models For The Evaluation Of Colorectal Polyps In Colon Cancer Screening Studies-A Value-Based Biostatistics Practice, Alok K Dwivedi, Sherif E Elhanafi, Mohamed O Othman, Marc J Zuckerman

Faculty, Staff and Students Publications

Background: Colon cancer screening studies are needed for the early detection of colorectal polyps to reduce the risk of colorectal cancer. Unfortunately, the data generated on colon polyps are typically analyzed in their dichotomized form and sometimes with standard count models, which leads to potentially inaccurate findings in research studies. A more appropriate approach for evaluating colon polyps is zero-inflated models, considering undetected existing polyps at colonoscopy screening.

Method: We demonstrated the application of the zero-inflated and hurdle models including zero-inflated Poisson (ZIP), zero-inflated robust Poisson (ZIRP), zero-inflated negative binomial (ZINB), zero-inflated generalized Poisson (ZIGP), zero hurdle Poisson (ZHP), and …

Prevalence Of Exocrine Pancreatic Insufficiency In Patients With Chronic Diarrhea, Tara Keihanian, Suneal Agarwal, Nabil Mansour, Michael Mercado, Hashem B El-Serag, Mohamed O Othman

Faculty, Staff and Students Publications

Background: Exocrine pancreatic insufficiency (EPI) is an underdiagnosed entity among patients with new-onset chronic diarrhea (CD). The aim of this study is to investigate the prevalence of EPI in patients with CD.

Materials and methods: Patients with new-onset CD (≥4 weeks) from 2018 to 2021 were enrolled in this single-center prospective study. If stool fecal elastase (FE) was < 200 μg/g, patients were offered a confirmatory 72-hour fecal fat test.

Results: FE testing was completed by 97 patients, of which 9 had low FE (9.3%). Average weight was significantly higher in patients with low FE (98.5 ± 29.3 kg vs 82.2 ± 22.2 kg; P = 0.045). There was no significant difference …

Increasing Premedication For Neonatal Intubation: A Quality Improvement Initiative, Michelle H Lucena, Toshiba Morgan-Joseph, Alecia Thompson-Branch

Faculty, Staff and Students Publications

INTRODUCTION: Endotracheal intubation is frequent in the neonatal intensive care unit (NICU) but may result in neonatal distress and instability. Premedication reduces adverse effects, such as hypoxia, bradycardia, and pain. The Specific, Measurable, Achievable, Relevant and Time-Bound aim for this project was to increase premedication use for nonemergent neonatal intubation in a specific NICU from 22% to 80% from March 2021 to May 2023.

METHODS: We use quality improvement methodology to explain our theory for improvement. Our key driver diagram depicts this initiative's aims, key drivers, and interventions to increase premedication use for neonatal intubation. We defined exclusion criteria and …

Comparative Analysis Of Aav Serotypes For Transduction Of Olfactory Sensory Neurons, Benjamin D W Belfort, Johnathan D Jia, Alexandra R Garza, Anthony M Insalaco, J P Mcginnis, Brandon T Pekarek, Joshua Ortiz-Guzman, Burak Tepe, Hu Chen, Ascent-Pd Investigators, Zhandong Liu, Benjamin R Arenkiel

Faculty, Staff and Students Publications

Olfactory sensory neurons within the nasal epithelium detect volatile odorants and relay odor information to the central nervous system. Unlike other sensory inputs, olfactory sensory neurons interface with the external environment and project their axons directly into the central nervous system. The use of adeno-associated viruses to target these neurons has garnered interest for applications in gene therapy, probing olfactory sensory neuron biology, and modeling disease. To date, there is no consensus on the optimal AAV serotype for efficient and selective transduction of olfactory sensory neurons

Altering The Intracellular Trafficking Of Necator Americanus Gst-1 Antigen Yields Novel Hookworm Mrna Vaccine Candidates, Athos Silva De Oliveira, Leroy Versteeg, Neima Briggs, Rakesh Adhikari, Maria Jose Villar, Jeanna R Redd, Peter Hotez, Maria Elena Bottazzi, Jeroen Pollet

Faculty, Staff and Students Publications

BACKGROUND: The antigen Na-GST-1, expressed by the hookworm Necator americanus, plays crucial biochemical roles in parasite survival. This study explores the development of mRNA vaccine candidates based on Na-GST-1, building on the success of recombinant Na-GST-1 (rNa-GST-1) protein, currently assessed as a subunit vaccine candidate, which has shown promise in preclinical and clinical studies.

METHODOLOGY/FINDINGS: By leveraging the flexible design of RNA vaccines and protein intracellular trafficking signal sequences, we developed three variants of Na-GST-1 as native (cytosolic), secretory, and plasma membrane-anchored (PM) antigens. After one immunization in mice, mRNA vaccines induced an earlier onset of antigen-specific antibodies compared to …

Technical Considerations In The Tcd Evaluation Of Cerebral Circulatory Arrest In Death By Neurological Criteria, Alexandra S Reynolds, Jimmy Suh, Ahmedyar Hasan, Parth Upadhyaya, Venkatakrishna Rajajee, Mohammad I Hirzallah, David M Greer, Aarti Sarwal

Faculty, Staff and Students Publications

Background and purpose: Ancillary testing is essential for diagnosing brain death/death by neurologic criteria (BD/DNC) when clinical determination (neurologic exam and apnea testing) cannot be fully or safely performed. Transcranial Doppler ultrasound (TCD) has been recommended as an ancillary test; however, the technical descriptions have been heterogeneous. We aimed to consolidate the technical considerations related to the use of TCD as an ancillary test in the evaluation of BD/DNC.

Methods: We performed a scoping review of the available literature from inception to December 2024. Articles describing TCD as an ancillary test for BD/DNC were included using appropriate Medical Subject Headings …

Optic Nerve Sheath Diameter: Which Axis Should Be Measured?, Jakob Pansell, Tina Thomsson, Emelie Eng, Andreas Wallin, Mohammad Hirzallah

Faculty, Staff and Students Publications

Background and purpose: Optic nerve sheath diameter (ONSD) measured by point-of-care ultrasound (POCUS) is a commonly used non-invasive estimate of intracranial pressure (ICP). However, methodological variations limit standardization of this promising technique. Different imaging axes are identified as one such source of ONSD POCUS methodological variation. This study aimed to evaluate the agreement and diagnostic accuracy for elevated ICP between transverse and sagittal ONSD measurements.

Methods: We conducted a post-hoc analysis of 213 intensive care patients from three prior studies. ONSD was measured in both transverse and sagittal planes, externally (ONSDext) and internally (ONSDint) of the dura mater. Agreement was …

Early Cerebrospinal Fluid Elevations Of Ptau-217 In Severe Traumatic Brain Injury Subjects, Hamad Yadikar, Firas H Kobeissy, Claudia Robertson, Spyridoula Tsetsou, John B Williamson, Damon G Lamb, Amy K Wagner, Todd Kibaugh, Shih-Han Kao, Zhifeng Kou, Robert D Welch, Jose-Miguel Yamal, Luis Leon-Novelo, Richard Rubenstein, Kevin K W Wang

Faculty, Staff and Students Publications

Introduction: Tauopathies, including Alzheimer's disease (AD), feature abnormal accumulations of hyperphosphorylated Tau protein; however, their biomarker potential in traumatic brain injury (TBI) is not well-defined. This study investigated whether cerebrospinal fluid (CSF) phosphorylated Tau at threonine-217 (pTau-217) could serve as an early biomarker for severe TBI (sTBI).

Methods: CSF samples from 26 sTBI patients, collected between 6 and 240 h post-injury, and 19 healthy controls were analyzed using an optimized direct enzyme-linked immunosorbent assay (ELISA; sensitivity < 4.7 pg/mL) for pTau-217 detection, complemented by Western blot validation. Temporal analysis, ROC curves, and trajectory clustering were used for interpretation.

Results: CSF pTau-217 levels were significantly elevated in sTBI patients at 6, 12, 18, 24, and 48 h post-injury compared to controls (p …

Htr1b Is Necessary For Normal Retinal Function In Mice, Solomon E Gibson, Xiaofeng Tao, Guofu Shen, Justin Ma, Yong H Park, Maria Polo-Prieto, Benjamin J Frankfort

Faculty, Staff and Students Publications

Introduction: Serotonin (5-HT) is a neurotransmitter that is involved in retinal development, physiology, and vision, yet the specific contribution of individual 5-HT receptors to retinal function is poorly characterized. We identified 5-HT receptor 1B (Htr1b) as a potential key regulator of serotonergic signaling in the retina.

Methods: Htr1b localization was examined using RNAseq and in situ labeling. Retinal structure was assessed using histology and SD-OCT. Visual function was evaluated using optomotor behavioral experiments. Retinal function was characterized in vivo using electroretinography (ERG) and ex vivo using multielectrode array (MEA) recordings.

Results: Htr1b transcript and HTR1B protein localized primarily …

Emerging Pharmacological Strategies In Lipoprotein(A) Reduction, Taha Mansoor, Mahmoud Ismayl, Sachin Parikh, Vijay Nambi, Salim S Virani, Anurag Mehta, Xiaoming Jia, Abdul Mannan Khan Minhas

Faculty, Staff and Students Publications

Background: Lipoprotein(a) (Lp(a)) is an low-density lipoprotein (LDL)-like particle whose elevation is considered a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve stenosis. Currently, there are no published clinical trials showing whether Lp(a) lowering in conjunction with optimal LDL cholesterol control reduces ASCVD risk.

Methods: Clinicaltrials.gov, an online database for clinical research studies, was used to identify ongoing clinical trials studying targeted Lp(a) lowering pharmacotherapy as of May 2025. Twelve clinical studies met the criteria and were included in this summary.

Results: The three large, multicenter phase 3 outcome trials evaluating clinical cardiovascular disease endpoints of …

Strategies For The Secondary Prevention Of Atherosclerotic Cardiovascular Disease, Madelyn Hurwitz, Olayinka J Agboola, Abhishek Gami, Marlene S Williams, Salim S Virani, Garima V Sharma, Jaideep Patel

Faculty, Staff and Students Publications

Patients with atherosclerotic cardiovascular disease (ASCVD), such as those with a history of MI or stroke, are at high risk for morbidity and mortality associated with future cardiovascular events. Ideal management of these patients requires a multifactorial strategy for risk factor mitigation and prevention of additional cardiovascular events. Traditional management of secondary prevention patients involves lipid-lowering with statins, blood pressure control, and anti-platelet treatment. Several additional targets have been identified to optimize the secondary prevention of ASCVD, such as further lipid control, inflammation management, lifestyle and weight optimization, strict diabetes control, use of β-blockers, use of renin-angiotensin-aldosterone system inhibitors, vaccinations, …

Examining Parents’ Perceptions Of Their Children’S Autism And Completion Of Genetic Testing, Georgina J Sakyi, Sarah S Mire, Robin P Goin-Kochel, Chaya N Murali, Susan X Day

Faculty, Staff and Students Publications

Though genetic testing is recommended for children diagnosed with autism spectrum disorder (ASD), both internal (e.g. parents’ and providers’ valuation of genetic testing) and external (e.g. insurance coverage) barriers exist, and exploration of these factors is required to close the gap between provider recommendations and parent follow-through. In a sample of 290 parents, we explored (a) how parents’ ASD-related etiological beliefs and symptom attributions, as well as income, affected genetic testing completion; and (b) whether these factors influence parents’ hopes or concerns about genetic testing. Principal component analysis (PCA) was used to investigate the factor structure of the ASD attribution …

Promotion Of Hiv Clearance By Sensitization Of Hiv Reservoirs To Cell Death, Min Li, Baichao Sun, Jing Dong, Jian-Rong Li, Laurie J Minze, Min Chen, Chao Cheng, Jin Wang

Faculty, Staff and Students Publications

Introduction: HIV integrates its proviral DNA into the host genome to establish persistent infection. To promote HIV clearance, we have designed an approach for selective elimination of host cells harboring replication-competent HIV (SECH), through inhibition of autophagy and anti-apoptotic molecules during viral reactivation. SECH approach can clear HIV-infected cells in approximately 50% humanized mice. However, the mechanisms for the resistance of reservoirs to depletion in mice with failure in HIV clearance are unclear.

Methods: We have performed single cell transcriptome analyses of HIV-infected T cells that escaped the treatments, in order to identify cellular pathways that could be targeted to …

Relationships Of Personality Traits With The Taxonomic Composition Of The Gut Microbiome Among Psychiatric Inpatients, William Orme, Sandra L Grimm, Divya S N Vella, J Christopher Fowler, B Christopher Frueh, Benjamin L Weinstein, Joseph Petrosino, Cristian Coarfa, Alok Madan

Faculty, Staff and Students Publications

Objective: Through the brain-gut-microbiome axis, myriad psychological functions that affect behavior share a dynamic, bidirectional relationship with the intestinal microbiome. Little is known about the relationship between personality-a stable construct that influences social- and health-related behaviors-and the bacterial ecosystem. The authors of this exploratory study examined the relationship between general and maladaptive personality traits and the composition of the gut microbiome.

Methods: In total, 105 psychiatric inpatients provided clinical data and fecal samples. Personality traits were measured with the five-factor model of personality, the Structured Clinical Interview for DSM-IV Axis II Personality Disorders, and the Personality Inventory for DSM-5; 16S …

Cervical Cancer Prevention Behaviors In Young Black Women, Angela J Johnson, Monica J Johnson, Juinell B Williams, Emma Muscari, Laura Palmo, Michelle Ruiz, Brianna Bush, Lisa C Campbell

Faculty, Staff and Students Publications

Background: In the United States, Black women have the second highest incidence of cervical cancer (CC) due to high incidence of human papillomavirus (HPV), slow HPV clearance rates, and low receipt of preventive pap smears and vaccines.

Objective: A Black Feminist Thought framework was used to examine how the media portrayal of Black women, racial identity, and familial factors impact CC prevention behaviors among young Black women.

Design: Black women enrolled at a large southeastern university consented and participated in an online mixed-methods survey examining facilitators and barriers to CC prevention behaviors. Quantitative items were analyzed via descriptive statistics, and …

Modeling Functional Connectivity With Learning And Memory In A Mouse Model Of Alzheimer’S Disease, Lindsay Fadel, Elizabeth Hipskind, Steen E Pedersen, Jonathan Romero, Caitlyn Ortiz, Eric Shin, Md Abul Hassan Samee, Robia G Pautler

Faculty, Staff and Students Publications

Introduction: Functional connectivity (FC) is a metric of how different brain regions interact with each other. Although there have been some studies correlating learning and memory with FC, there have not yet been, to date, studies that use machine learning (ML) to explain how FC changes can be used to explain behavior not only in healthy mice, but also in mouse models of Alzheimer's Disease (AD). Here, we investigated changes in FC and their relationship to learning and memory in a mouse model of AD across disease progression.

Methods: We assessed the APP/PS1 mouse model of AD and wild-type controls …

Bcg-Induced Dna Methylation Changes Improve Coronavirus Disease 2019 Vaccine Immunity Without Decreasing The Risk For Severe Acute Respiratory Syndrome Coronavirus 2 Infection, Santiago Carrero Longlax, Kent J Koster, Ashish M Kamat, Marisa Lozano, Seth P Lerner, Rebecca Hannigan, Tomoki Nishiguchi, Abhimanyu, Daanish Sheikh, Malik Ladki, Alexandra Portillo, Amrit Koirala, Tajhal D Patel, Zoe Spieler, Aaron B Benjamin, Maxim Lebedev, Theresa U Ofili, Robert W Hutchison, George Udeani, Lynne A Opperman, Gabriel Neal, Anna M Mandalakas, Mihai G Netea, Moshe Arditi, Pablo Avalos, Sandra L Grimm, Cristian Coarfa, Jeffrey D Cirillo, Andrew R Dinardo

Faculty, Staff and Students Publications

BACKGROUND: The BCG vaccine induces trained immunity, an epigenetic-mediated increase in innate immune responsiveness. Therefore, this clinical trial evaluated if BCG-induced trained immunity could decrease coronavirus disease 2019 (COVID-19)-related frequency or severity.

METHODS: A double-blind, placebo-controlled clinical trial of healthcare workers randomized participants to vaccination with BCG TICE or placebo (saline). Enrollment included 529 healthcare workers randomized to receive BCG or placebo. Primary analysis evaluated COVID-19 disease frequency, while secondary analysis evaluated coronavirus immunity in a subset of participants. Study enrollment ceased early in December 2020 following introduction of COVID-19-specific vaccines.

RESULTS: Study enrollment was halted early, prior to reaching …

Vascularized Iliac Crest Bone Graft For The Reconstruction Of Anterior Vertebral Corpus Defects: A Literature Review And Cadaveric Feasibility Study, Jonathan L Jeger, Casey J Martinez, Maria Shvedova, Alec Simoni, Alanna Rebecca, Sebastian Winocour, Alexander E Ropper, Michael Bohl, William J Casey, Maziyar Kalani, Edward M Reece

Faculty, Staff and Students Publications

BACKGROUND: Vertebral body defects pose a significant challenge in spinal reconstructive surgery. Compression fractures of the vertebral corpus are typically treated with vertebral augmentation procedures. There are significant risks associated with the introduction of foreign material in the spine, including infection and pseudarthrosis. Vascularized bone grafts (VBGs) have become a popular alternative for spinal reconstruction in the last decade thanks to their robust blood supply and autologous nature. VBGs have been described predominantly for the reconstruction of posterior vertebral defects. The objective of this study is to describe a novel procedure for the reconstruction of vertebral corpus defects in the …

Zic1 Is A Context-Dependent Medulloblastoma Driver In The Rhombic Lip, John J Y Lee, Ran Tao, Zhen You, Parthiv Haldipur, Anders W Erickson, Hamza Farooq, Liam D Hendriske, Namal Abeysundara, Cory M Richman, Evan Y Wang, Neha Das Gupta, Jennifer Hadley, Melissa Batts, Christopher W Mount, Xiaochong Wu, Alex Rasnitsyn, Swneke Bailey, Florence M G Cavalli, Sorana Morrissy, Livia Garzia, Kulandaimanuvel Antony Michealraj, Abhi Visvanathan, Vernon Fong, Jonelle Palotta, Raul Suarez, Bryn G Livingston, Miao Liu, Betty Luu, Craig Daniels, James Loukides, Anne Bendel, Pim J French, Johan M Kros, Andrey Korshunov, Marcel Kool, Fernando Chico Ponce De León, Mario Perezpeña-Diazconti, Boleslaw Lach, Sheila K Singh, Sarah E S Leary, Byung-Kyu Cho, Seung-Ki Kim, Kyu-Chang Wang, Ji-Yeoun Lee, Teiji Tominaga, William A Weiss, Joanna J Phillips, Shizhong Dai, Gelareh Zadeh, Ali G Saad, László Bognár, Almos Klekner, Ian F Pollack, Ronald L Hamilton, Young-Shin Ra, Wieslawa A Grajkowska, Marta Perek-Polnik, Reid C Thompson, Anna M Kenney, Michael K Cooper, Stephen C Mack, Nada Jabado, Mathieu Lupien, Marco Gallo, Vijay Ramaswamy, Mario L Suva, Hiromichi Suzuki, Kathleen J Millen, L Frank Huang, Paul A Northcott, Michael D Taylor

Faculty, Staff and Students Publications

Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma). Overexpression of ZIC1 suppresses the growth of group 3 medulloblastoma models, whereas it promotes the proliferation of SHH medulloblastoma precursor cells. SHH medulloblastoma ZIC1 mutants show increased activity versus wild-type ZIC1, whereas G4 medulloblastoma …

Visual Acuity, Full-Field Stimulus Thresholds, And Electroretinography For 4 Years In The Rate Of Progression Of Ush2a-Related Retinal Degeneration (Rush2a) Study, David G Birch, Peiyao Cheng, Maureen G Maguire, Jacque L Duncan, Allison R Ayala, Janet K Cheetham, Nicole R Doucet, Todd A Durham, Abigail T Fahim, Frederick L Ferris, Rachel M Huckfeldt, Michele Melia, Michel Michaelides, Mark E Pennesi, José-Alain Sahel, Katarina Stingl, Ajoy Vincent, Christina Y Weng

Faculty, Staff and Students Publications

PURPOSE: To describe progression of best-corrected visual acuity (BCVA), full-field stimulus thresholds (FST), and electroretinography (ERG) over 4 years in the

DESIGN: Prospective natural history study.

PARTICIPANTS: Participants (n = 105) with biallelic disease-causing sequence variants in USH2A and BCVA letter scores of ≥54 were included.

METHODS: BCVA, FST, fundus-guided microperimetry, static perimetry, and spectral domain OCT were performed annually and ERG at baseline and 4 years only. Mixed effects models were used to estimate annual rates of change with 95% confidence intervals. Associations of change from baseline to 4 years between BCVA, FST, ERG, and other metrics were assessed …

Longitudinal Host Transcriptional Responses To Sars-Cov-2 Infection In Adults With Extremely High Viral Load, Vasanthi Avadhanula, Chad J Creighton, Laura Ferlic-Stark, Divya Nagaraj, Yiqun Zhang, Richard Sucgang, Erin G Nicholson, Anubama Rajan, Vipin Kumar Menon, Harshavardhan Doddapaneni, Donna Marie Muzny, Ginger A Metcalf, Sara Joan Javornik Cregeen, Kristi Louise Hoffman, Richard A Gibbs, Joseph F Petrosino, Pedro A Piedra

Faculty, Staff and Students Publications

Current understanding of viral dynamics of SARS-CoV-2 and host responses driving the pathogenic mechanisms in COVID-19 is rapidly evolving. Here, we conducted a longitudinal study to investigate gene expression patterns during acute SARS-CoV-2 illness. Cases included SARS-CoV-2 infected individuals with extremely high viral loads early in their illness, individuals having low SARS-CoV-2 viral loads early in their infection, and individuals testing negative for SARS-CoV-2. We could identify widespread transcriptional host responses to SARS-CoV-2 infection that were initially most strongly manifested in patients with extremely high initial viral loads, then attenuating within the patient over time as viral loads decreased. Genes …

Goldenbraid20 E Coli: A Comprehensive And Characterized Toolkit For Enterics, Matthew B Cooke, Kobie T Welch, Laura D Ramirez, Alice X Wen, David C Marciano, Christophe Herman

Faculty, Staff and Students Publications

Modular cloning systems streamline laboratory workflows by consolidating genetic 'parts' into reusable and modular collections, enabling researchers to fast-track strain construction. The GoldenBraid 2.0 modular cloning system utilizes the cutting property of type IIS restriction enzymes to create defined genetic 'grammars', which facilitate the reuse of standardized genetic parts and assembly of genetic parts in the right order. Here, we present a GoldenBraid 2.0 toolkit of genetic parts designed to accelerate cloning in the model bacterium

The Dna Demethylase Tet1 Modifies The Impact Of Maternal Folic Acid Status On Embryonic Brain Development, Lehua Chen, Bernard K Van Der Veer, Qiuying Chen, Spyridon Champeris Tsaniras, Wannes Brangers, Harm H M Kwak, Rita Khoueiry, Yunping Lei, Robert Cabrera, Steven S Gross, Richard H Finnell, Kian Peng Koh

Faculty, Staff and Students Publications

Folic acid (FA) is well known to prevent neural tube defects (NTDs), but we do not know why many human NTD cases still remain refractory to FA supplementation. Here, we investigate how the DNA demethylase TET1 interacts with maternal FA status to regulate mouse embryonic brain development. We determined that cranial NTDs display higher penetrance in non-inbred than in inbred Tet1−/− embryos and are resistant to FA supplementation across strains. Maternal diets that are either too rich or deficient in FA are linked to an increased incidence of cranial deformities in wild type and Tet1+/− offspring and to …