Medicine and Health Sciences Commons^™

Trait-Like Visual Cortical Hyperactivity In Trait Anxiety, Zhaohan Wu, Yuqi You, Joshua A Brown, Raymond J Dolan, Wen Li

Faculty, Staff and Student Publications

Sensory processing varies across individuals, with some traits-particularly sensory hypersensitivity to basic non-valenced stimuli-linked to emotional traits and psychiatric risk. Traditional accounts attribute this sensory-emotion linkage to limbic or prefrontal modulation, but empirical support is limited. Growing evidence suggests sensory cortex itself flexibly encodes value beyond labeled-line analysis. Across four high-density EEG experiments with multi-wave assessments, we identified reliable visual cortical hyperactivity in high trait anxiety. The effect emerged as early as 46 ms, localized to V1/V2, and was specific to the parvocellular pathway. It was reproducible across arousal states, stimulus valence, extended intervals, and paradigms, and evident for both …

Development Of A Procedure For Prion Surveillance In The Laboratory Setting, Damian Gorski, Isaac Schauer, Kane Spicker, Ananya Tupaki-Sreepurna, Fei Wang, Claudio Soto, Sandra Pritzkow

Faculty, Staff and Student Publications

Infectious prions readily adhere to common surfaces, retain infectivity, and are highly resistant to conventional decontamination, posing significant biosafety challenges in the medical and research environments. Recent occupational exposures underscore the urgency of improving safety measures. Here, we describe an approach combining foam-swab surface sampling and protein misfolding cyclic amplification to enhance prion surveillance. Our results demonstrate the ability to detect prions most relevant to human health directly from contaminated surfaces, even at 100 million-fold dilutions of the brain. We applied our method to assess the completeness of prion decontamination and show that high prion quantities can resist even approved …

The Common Cold Is Associated With Protection From Sars-Cov-2 Infections, Camille M Moore, Katherine Rivera-Spoljaric, Et Al.

2020-Current year OA Pubs

BACKGROUND: Adults and children often respond differently to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, with adults facing a higher risk of symptomatic and severe illness. We hypothesize that children's protection from symptomatic SARS-CoV-2 may be due to more frequent respiratory viral infections, which prime their airway antiviral defenses.

METHODS: Using case-cohort and case-control analyses in the Human Epidemiology and Response to SARS-CoV-2 cohort, we evaluated whether infection with common respiratory viruses protects against SARS-CoV-2 infections and investigated airway molecular mechanisms by which this protection is achieved. We tested 10 493 longitudinal nasal swabs from 1156 participants for 21 …

Impact Of Adhesive Curing Mode And Dentin Sealing On Bond Strength Of Cad/Cam Resin Composite, Sara Adel Botros, Mohamed Fouad Haridy, Nermin Mohieldin Abdelmohssen

Dentistry

No abstract provided.

Multi Agent Large Language Models For Biomedical Hypothesis Generation In Drug Combination Discovery, Qidi Xu, Claudio Soto, Mohammad Shahnawaz, Xiaozhong Liu, Xiaoqian Jiang, Yejin Kim

Faculty, Staff and Student Publications

Recent advancements in large language models (LLMs) have demonstrated their potential in scientific reasoning, but their ability to open-ended hypotheses in data-scarce domains remains underexplored. Here, we introduce Combinatorial Alzheimer’s Disease Therapeutic Efficacy Decision (Coated-LLM), an AI-driven framework that is inspired by scientific collaboration to predict efficacious combinatorial therapy when data-driven prediction is infeasible. Coated-LLM employs multiple specialized LLM agents—Researcher, Reviewers, and Moderator—to systematically generate and evaluate hypotheses through several in-context learning techniques. Using Alzheimer’s disease (AD) as a test case, Coated-LLM outperformed traditional knowledge-based methods (accuracy: 0.74 vs. 0.52), with external validation achieving an …

Beyond Precision: Ambiomic Survivorship In Childhood And Aya Cancer., Juan Antonio Ortega-García, Omar Shakeel, Nicole Wood, Antonio Pérez-Martínez, Jose Luís Fuster-Soler, Mark D. Miller

Manuscripts, Articles, Book Chapters and Other Papers

Background: Survival among children and adolescents and young adults (AYA) with cancer has improved substantially over recent decades; however, dominant survivorship models remain reactive-activated post-treatment and anchored to static exposure- and organ-based screening. This design underuses the anticipatory window at diagnosis and overlooks environmental and social determinants that modulate outcomes across the life course. Methods: We narratively reviewed international frameworks including the Children's Oncology Group (COG), the International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG), the Pan-European Network for Care of Survivors after Childhood and Adolescent Cancer (PanCare) and the National Comprehensive Cancer Network (NCCN), and synthesized evidence …

Protocol For Nucleo-Cytoplasmic Fractionation Of Mammalian Cells To Study Protein Translocation Via Immunoblotting, Adhikarimayum Lakhikumar Sharma, Eddy Zhu, Rithika Padyala, Kavya Parikh, Mudit Tyagi

Center for Translational Medicine Faculty Papers

Studying protein translocation is essential for understanding protein function and regulatory mechanisms, including the activity of transcription factors. Here, we present a protocol for isolating high-quality cytoplasmic and nuclear protein fractions from mammalian cells. We describe steps for separating cytoplasmic proteins, washing nuclei, and extracting nuclear proteins. We then detail procedures for quantifying proteins and analyzing their distribution by immunoblotting within a single immunoblot. This protocol is applicable to both suspension and adherent cell types. For complete details on the use and execution of this protocol, please refer to Sharma et al.

Long Covid Incidence Across Sars-Cov-2 Lineages And Identification Of Conserved Spike Targets For Multivalent Vaccines, Grace J. Kim, Md Ashad Alam, Judy S. Crabtree, Rebecca Rose, Susanna L. Lamers, San Chu, Ronald Horswell, Daniel Fort, Lucio Miele

School of Graduate Studies Faculty Publications

Background: Long COVID remains poorly characterized at the genomic level. The primary aim of this study was to examine the relationship between viral sequences and the incidence of Long COVID at a tertiary care center in Louisiana between April 2020 and December 2022. A secondary aim was analysis of the Spike protein to identify conserved regions for multivalent vaccine targets. Method: To estimate Long COVID incidence across variants, we linked 4,789 SARS-CoV-2 sequences to 3,090 de-identified patient electronic health record information. The base population was defined as any patient with an International Classification of Diseases-10-Clinical Modification COVID-19 diagnosis code (U07.1) …

Adaptive Neuromodulation Dialogues: Navigating Current Challenges And Emerging Innovations In Neuromodulation System Development, Frederik Lampert, Matthew R Baker, Michael A Jensen, Amir H Ayyoubi, Christian Bentler, Jessica L Bowersock, Rosana Esteller, Jeffrey A Herron, Graham W Johnson, Daryl R Kipke, Christopher K Kovach, Vaclav Kremen, Filip Mivalt, Joseph S Neimat, Theoden I Netoff, Enrico Opri, Alexander Rockhill, Joshua M Rosenow, Kristin K Sellers, Nathan P Staff, Chandra Prakash Swamy, Ashwin Viswanathan, Gerwin Schalk, Timothy Denison, Dora Hermes, Nuri F Ince, Peter Brunner, Gregory A Worrell, Kai J Miller

Faculty, Staff and Students Publications

Adaptive neuromodulation systems and implantable brain-computer interfaces have made notable strides in recent years, translating experimental prototypes into clinical applications and garnering substantial attention from the public. This surge in interest is accompanied by increased scrutiny related to the safety, efficacy, and ethical implications of these systems, all of which must be directly addressed as we introduce new neurotechnologies. In response, we have synthesized the insights resulting from discussions between groups of experts in the field and summarized them into five key domains essential to therapeutic device development: (1) analyzing current landscape of neuromodulation devices and translational platforms (2) identifying …

P-15 Peptide Enhanced Bone Graft Improves Time To Fusion In Transforaminal Lumbar Interbody Fusion: A Randomized, Controlled, Investigational Device Exemption Study, James S. Harrop, Michael P. Steinmetz, John E. O'Toole, Christopher D Chaput, Rick C. Sasso, K. Brandon Strenge, Greg Maislin, Jeffrey P. Mullin, Thomas B. Freeman, Anthony Guanciale, Howard Lantner, Michael E. Janssen, David G. Schwartz, John M. Small, Wellington K. Hsu, Paul M. Arnold

Department of Neurosurgery Faculty Papers

STUDY DESIGN: Prospective, multicenter, single-blind, randomized, and controlled pivotal study.

OBJECTIVE: Compare time-to-fusion in patients treated with P-15L (PearlMatrix TM P-15 peptide enhanced bone graft) versus local autograft over 24 months and evaluate changes in pain and quality of life at 24 months relative to baseline.

SUMMARY OF BACKGROUND DATA: P-15L, an FDA-designated breakthrough device, is a composite bone graft with P-15, a 15-amino acid polypeptide that promotes cellular adhesion, proliferation, and differentiation to support bone formation.

METHODS: Patients (22-80 y) with degenerative disc disease were randomized to the investigational (P-15L) or control (local autograft) group during single-level transforaminal lumbar …

A Systematic Characterization Of Fibroblast Subtypes And Heterogeneity, Xiuli Zhu, Hongen Kang, Zhongming Zhao, Peilin Jia

Faculty, Staff and Student Publications

Fibroblasts are essential components in development, disease, and treatment response, yet their diversity and function remain incompletely understood. Here, we constructed a comprehensive fibroblast landscape by integrating large-scale single-cell and single-nucleus RNA sequencing datasets spanning 60 major human organs and tissues across various developmental stages and biological conditions. We identified 16 fibroblast subtypes and systematically characterized their tissue specificities, transcriptional heterogeneity, and cell states. Further analyses revealed distinct fibroblast subtypes associated with pluripotency and senescence across tissues. Leveraging the well-defined fibroblast atlas, we demonstrated that different fibroblast subtypes were associated with various complex traits such as anthropometric and immune diseases. …

Evaluating The Accuracy Of Point Of Care Testing Compared To Standard Laboratory Testing Among Inborn Infants In The Neonatal Intensive Care Unit, Isha Parikh, Sepideh Saroukhani, Matthew Rysavy, Brian Chang, Mar Romero-Lopez, Lindsay F Holzapfel

Faculty, Staff and Student Publications

Objective: Point-of-care (POC) testing offers expedited results with lower blood volume requirements than central laboratory (CL) tests, particularly for low-birth-weight infants.

Methods: A retrospective cohort included 118 patients with paired POC and CL tests within one hour in the first 14 postnatal days. Differences and agreement were assessed using linear mixed-effect models that account for within and between-subject variations.

Results: Compared to CL, POC testing underestimated sodium (6.0 mEq/L), potassium (0.1 mEq/L), chloride (5.1 mEq/L), and glucose (2.3 mg/dL), and overestimated hemoglobin (0.08 g/dL) and hematocrit (0.8%). Differences (CL- POC) varied by postnatal age and sample type, with larger differences …

Baseline Exposure-Response Assessment Of Metals From Dried Blood Spots And Personal Household Air Pollution Concentrations Among Pregnant Women In Rwanda: Household Air Pollution Intervention Network Trial, Adolphe Ndikubwimana, Lisa De Las Fuentes, Victor G Dávila-Román, Et Al.

2020-Current year OA Pubs

BACKGROUND: Exposure to metals from the combustion of biomass via inhalation may result in negative health outcomes affecting a variety of organs and systems. Pregnant women cooking with biomass fuels may be exposed to metals, such as lead (Pb) and cadmium (Cd), and have unique risks for adverse health effects with potential impacts on the growing fetus. We assessed the associations between household air pollution and metals detected in dried blood spots from pregnant women at baseline in Rwanda.

METHODS: We analyzed data from 781 pregnant women aged 18-35 years who resided in rural households using biomass fuel and who …

The Effect Of Glp-1 Receptor Agonists On Reoperation Following Anterior Cervical Discectomy And Fusion, Nicholas C. Bank, Daniel Whittingslow, Sam Duggan, Joshua L. Morningstar, Douglas S. Weinberg

Student Papers, Posters & Projects

BACKGROUND: Pseudarthrosis remains a significant complication of ACDF, contributing to patient morbidity and increased healthcare costs. Glucagon-like peptide-1 receptor agonists (GLP-1RA), widely prescribed for diabetes and obesity, have been shown to reduced odds of pseudoarthrosis after ACDF. However, it remains unclear whether these reductions meaningfully translate to reduced odds of subsequent cervical surgery.

METHODS: The TriNetX United States Collaborative Network was queried for patients who underwent single- or multi-level ACDF between 2013-2023. Patients with perioperative GLP-1RA use and propensity-score-matched controls without GLP-1RA use were compared for subsequent rates of pseudoarthrosis and cervical reoperation at 6-, 12-, and 24-month intervals. Odds …

Single-Nucleus Multiomics Reveals The Disrupted Regulatory Programs In Three Brain Regions Of Sporadic Early-Onset Alzheimer’S Disease, Andi Liu, Citu Citu, Nitesh Enduru, Xian Chen, Chia-Hao Tung, Tirthankar Sinha, Sofia E Sepulveda, Astrid M Manuel, Damian Gorski, Brisa S Fernandes, Meifang Yu, Paul E Schulz, Lukas M Simon, Claudio Soto, Zhongming Zhao

Faculty, Staff and Student Publications

Sporadic early-onset Alzheimer’s disease (sEOAD) represents a substantial but less-studied subtype of Alzheimer’s disease (AD). Here, we generated a single-nucleus multiome atlas derived from the postmortem prefrontal cortex, entorhinal cortex, and hippocampus of nine individuals with or without sEOAD. Comprehensive analyses were conducted to delineate cell type–specific transcriptomic changes and linked candidate cis-regulatory elements (cCREs) across brain regions. We prioritized eight conservative transcription factors in glial cells in multiple brain regions, including RFX4 in astrocytes and IKZF1 in microglia, which are implicated in regulating sEOAD-associated genes. Moreover, we identified the top 25 altered intercellular signaling between glial cells …

Metabolomic Profiling Reveals Brain Lipid Alterations In Pex7-Deficient Models Of Rhizomelic Chondrodysplasia Punctata, Riya Sankhe, Meredith I Williams, Wedad Fallatah, Laura Mackay, Mary Layne Brown, Pranjali Bhagwat, Sarah H Elsea, Nancy Braverman, Michael F Wangler

Duncan NRI Faculty and Staff Publications

Rhizomelic chondrodysplasia punctata type 1 (RCDP1) is a peroxisomal disorder characterized by skeletal shortening, intellectual disability, seizures, cataracts, and reduced lifespans. RCDP1 is caused by biallelic loss-of-function variants in PEX7, which encodes a protein required for importing select enzymes into the peroxisome matrix, including those essential for ether lipid synthesis (e.g., plasmalogens) and the branched-chain fatty acid catabolism. Plasmalogen deficiency is a hallmark of RCDP1 and other peroxisomal disorders, including RCDP types 2-5 (RCDP2-5) and Zellweger spectrum disorders (ZSD). Here, we performed comprehensive metabolomic profiling of clinical samples from RCDP patients and Pex7-deficient mouse models. We identified profound …

Abnormalities In Sensorimotor Brain Function Are Related To Chronicity Of Low Back Pain, Jo Armour Smith, Rongwen Tain, Kelli G. Sharp, Laura M. Glynn, Linda R. Van Dillen, Jesse V. Jacobs, Steven C. Cramer

Physical Therapy Faculty Articles and Research

Maladaptive plasticity in the brain may contribute to chronic low back pain (LBP) and underlie the altered postural control of the lumbopelvic musculature that is evident in some individuals with LBP. We recently described an MRI-compatible leg-raise paradigm to measure brain activity associated with lumbopelvic postural control. The objective of this study was to compare brain function in young adults with and without a history of LBP and to determine relationships between brain function, pain, and postural control characteristics. We recruited 55 participants with a history of LBP, who were asymptomatic when studied, and 30 healthy controls. Postural control during …

Manual Therapy In Conjunction With Other Multimodal Interventions In A Patient With Chronic Pain And Hypertension: A Case Report, Craig P. Hensley, Renzo Mendoza, Jennifer Ryan, Emmanuel Yung

Physical Therapy Faculty Articles and Research

Chronic pain and hypertension (HTN) are worldwide epidemics that are difficult to manage and frequently encountered as comorbid conditions in patient care. There is a paucity of information regarding the effect that manual therapy has on blood pressure (BP), particularly in those with chronic pain and HTN. This case report describes the management of a patient with chronic pain and HTN. The patient was a 41-year-old female with chronic multisite pain and multiple comorbidities, including HTN. Her BP at the initial evaluation was 147/78 with an oscillated device and 142/82 with a sphygmomanometer in the right arm and 144/80 in …

Daily Intake Of A Lycopene-Rich Juice Is Associated With Reductions In Inflammatory Markers But Not Increases In Skin Carotenoids In A Pilot Study Among Participants With Obesity, Stephanie B Jilcott Pitts, Qiang Wu, Melissa N Laska, Elizabeth Gates, Megumi H Seese, Katelyn E Senkus, Santiago Carrero Longlax, Alexandra Portillo-Varela, Andrew R Dinardo, Nancy E Moran

Faculty, Staff and Students Publications

Background

Obesity is associated with systemic inflammation, increasing chronic disease risk. Carotenoids possess anti-inflammatory properties, yet the short-term impact of carotenoid-rich juice intake on inflammation in individuals with obesity remains unclear. Therefore, the purpose of this paper was to examine: (1) participant adherence to a 3-week lycopene-rich juice intervention; (2) variance and effect sizes of responses to the dietary intervention; (3) changes in skin and plasma carotenoids, and inflammatory markers among adults with obesity.

Methods

Twenty-five participants with body mass index (BMI) > 30 kg/m2 were recruited and completed the study. Participants drank 4 ounces (118.3 mL) of study-provided tomato juice, …

Comparison Of Cervical Spine Injury Clinical Prediction Rules For Children After Blunt Trauma, Lois K. Lee, Fahd A. Ahmad, Lorin R. Brown, Monica Harding, Lawrence Cook, Kathleen Adelgais, Rebecca K. Burger, Alexander Rogers, Leah Tzimenatos, Lauren C. Riney, Daniel Rubalcava, Caleb E. Ward, Kenneth Yen, Julie C. Leonard

2020-Current year OA Pubs

No abstract provided.

Viral Warriors: Unlocking The Immune System’S Potential With Oncolytic Viruses In Cancer Immunotherapy, Reza Ghavimi, Leila Rahimian, Mohsen Mohammadi, Ojasvi Dutta, Harikrishnan Mohan, Vladimir Chouljenko, Tolulope O. Omolekan, Jean Christopher Chamcheu, Konstantin G. Kousoulas

Faculty Publications

Oncolytic viruses (OVs) represent an exciting avenue in tumor immunotherapy, harnessing the power of viruses to overcome resistance and enhance immune responses. OVs achieve this by selectively targeting and destroying tumor cells. This cell lysis releases tumor-specific antigens (TAAs), effectively creating an in situ vaccine that educates the immune system. Moreover, OVs directly trigger both innate and adaptive immunity and can be genetically engineered to secrete immune-boosting factors. Early studies have shown promising synergistic antitumor effects when OVs are combined with other cancer therapies or immunotherapies. A key advantage of OVs is their capacity to reprogram the tumor microenvironment (TME), …

Status Of Training In The Use Of Lumen-Apposing Metal Stents For Therapeutic Endoscopic Ultrasound During Advanced Endoscopy Fellowship: A Survey Questionnaire, Yasi Xiao, Maham Hayat, Abdul S. Mohammed, Abdullah Abbasi, Sagar Pathak, Saurabh Chandan, Daryl Ramai, Deepanshu Jain, Muhammad K. Hasan, Mustafa A. Arain, Kambiz K. Kadkhodayan, Natalie Cosgrove, Dennis Yang

Division of Gastroenterology and Hepatology Faculty Papers

Background and Aims The lumen-apposing metal stent (LAMS) has revolutionized endoscopic ultrasound (EUS). However, there is a paucity of data on the optimal approaches to training on the use of LAMSs. This survey study aimed to evaluate the status of training in LAMSs among advanced endoscopy fellowship (AEF) trainees. Methods AEF (academic year 2023-2024) trainees were invited to complete a 15-question survey on LAMS training. The questions included the following domains: demographics, exposure to LAMSs before AEF, number of observed and hands-on participation using LAMSs for EUS-guided pancreatic fluid collection drainage (EUS-PFCD), choledochoduodenostomy (EUS-CD), gallbladder drainage (EUS-GBD), and gastrojejunostomy (EUS-GJ) …

Omics Approaches To Understand Cardiovascular Disease, Zeeshan Ahmed, Goo Jun

Faculty, Staff and Student Publications

Omics approaches have emerged as indispensable tools in unravelling the intricate molecular landscape of cardiovascular disease (CVD) by providing comprehensive insights into the underlying mechanisms driving CVD pathogenesis, progression, and response to therapy. Integrative omics approaches further enhance our understanding by integrating multi-omics data to explain complex molecular networks and identify novel disease pathways. In this collection of BMC Cardiovascular Disorders, we invited submissions on omics approaches to investigate and understand CVD. Successfully achieving the goals of this collection, we were able to publish some interesting and impactful research articles after a rigorous peer review process.

Transposable Element-Derived Mir-28-5p And Mir-708-5p: Exploring Potential Roles In Lung Cancer, Sergiu Chira, Cornelia Braicu, Stefan Strilciuc, George A Calin, Ioana Berindan-Neagoe

Faculty, Staff and Student Publications

Background: Transposable elements are normally silenced by epigenetic mechanisms; however, during malignant transformation, epigenetic alterations enable transposons to produce functional molecules like miRNAs. Among these, LINE-2 (L2) elements can generate miRNAs capable of regulating key genes, including tumor suppressors. Two L2-derived miRNAs, miR-28 and miR-708, have been linked to lung cancer, yet the mechanisms underlying their dysregulation remain poorly understood. Our study reveals how genomic context contributes to aberrant gene expression through comprehensive bioinformatic analyses.

Methods: Using bioinformatics analysis, we evaluated the expression of miR-28 and miR-708 in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) datasets from TCGA. …

Pooled Randomised Quartet Trials Assessing Effectiveness Of A Single Pill For Hypertension, Simone Marschner, Mark D Huffman, Desi Quintans, Jody Ciolino, Abigail Baldridge, Danielle Lazar, Emily R Atkins, Graham S Hillis, Mark R Nelson, Markus Schlaich, Anthony Rodgers, Clara K Chow

2020-Current year OA Pubs

BACKGROUND: Hypertension is a major cause of premature death worldwide, controlled by only one in five adults. Two trials (Australia and USA) found a single quadpill containing a quarter dosage of four classes of medication effective in reducing blood pressure (BP) among participants with hypertension. By pooling these trials, we can estimate the overall benefit of the quadpill and its heterogeneity across subgroups and two important barriers for BP control: clinician medication inertia and participant medication adherence.

METHODS: In a prespecified pooled individual participant data analysis of two QUARTET randomised, multicentre, double-blinded trials in people with hypertension using ≤1medication, quadpill …

Presence Of Eosinophils May Represent An Earlier Stage In Achalasia Pathogenesis, Andrea Costantini, Chandra Prakash Gyawali, Francesca Forattini, Valentina Angerilli, Matteo Ghisa, Luca Provenzano, Giovanni Capovilla, Loredana Nicoletti, Michele Valmasoni, Matteo Fassan, Edoardo Vincenzo Savarino, Renato Salvador

2020-Current year OA Pubs

BACKGROUND: Intraepithelial eosinophils have been described in patients with esophageal motor disorders. Conversely, motor disorders and even achalasia have been reported in patients with eosinophilic esophagitis (EoE).

OBJECTIVES: This prospective study aimed to further investigate the association between eosinophilia and achalasia.

DESIGN: This is a prospective study.

METHODS: A series of 30 consecutive treatment-naïve achalasia patients (mean age: 45.5 years, 53% female) undergoing laparoscopic myotomy were prospectively enrolled. Preoperative demographic and clinical data, radiological findings, and high-resolution manometry (HRM) features were collected. Patients underwent upper endoscopy with biopsy sampling before surgery, and two samples of distal esophageal muscle were obtained …

Acceptance And Commitment Therapy: A Treatment Option For Substance Use Disorders, Miriam N. Mukasa, Ashley Yaugher, Ty Aller

All Current Publications

There are many evidence-based treatments for individuals experiencing substance use disorders (SUDs) that support both individuals and families. Psychological treatments are effective for a wide range of SUDs, making them a key approach for helping people with differing needs. This fact sheet provides information on treatments and provides more detail about acceptance and commitment therapy as a SUD treatment support.

Genomic Characterization Of Colorectal Tumors: Insights Into Significantly Mutated Genes, Pathways, And Survival Outcomes, Tabitha A Harrison, Yin Cao, Et Al.

2020-Current year OA Pubs

BACKGROUND: Identifying significantly mutated genes in tumors aids in understanding disease etiology and survival and may aid in the discovery of new drug targets. We aimed to detect and characterize mutated genes from a large, well-characterized group of colorectal cancers.

METHODS: In tumor and paired normal samples from 6,111 colorectal patients, we sequenced 199 genes identified from whole exome sequencing of over 1,100 tumors. Analyses focused on non-silent mutations. We classified significantly mutated genes after stratification by hypermutation status, and estimated associations of mutated genes/pathways with disease-specific (DS)-survival using Cox regression, adjusting for age, sex, mutation burden, hypermutation status, and …

Life-Threatening Bradycardia In Anti-Nmda-Receptor Encephalitis And A Novel Use For Permanent Pacing, Sarah Tucker, Abhijit Das, Andres Jimenez, Areeba Basit, Yike Jiang, Emily A Smitherman, Heather Van Mater, Taylor Howard, Alexander J Sandweiss, Kristen S Fisher

Faculty, Staff and Students Publications

Background: Pediatric anti-NMDA receptor encephalitis (pNMDARE) is an autoantibody-mediated disorder that can cause severe autonomic dysfunction, including symptomatic bradycardia and asystole. Dysautonomia can last for years, making it very challenging to manage.

Objective: To describe outcomes of 5 pNMDARE patients with life-threatening bradycardic and/or asystolic events who were managed with permanent or semi-permanent pacemaker implantation.

Methods: We performed a retrospective chart review of 5 patients from multiple institutions. We included patients with a diagnosis of pNMDARE (confirmed by positive cerebrospinal fluid and/or serum anti-NMDAR antibodies) who had a permanent or semi-permanent pacemaker placed due to symptomatic bradycardia, sinus pauses, and/or …

Mechanistic And Functional Characterization Of Abtb2 As A Novel Target For Pancreatic Cancer Therapy, Nan Lyu, Olamide T Olaoba, Qiongling Wang, Harinarayanan Janakiraman, Xinjian Liu, Ernest Ramsay Camp, Kun Cheng, Eric T Kimchi, Yi Miao, Kevin F Staveley-O'Carroll, Guangfu Li

Faculty, Staff and Students Publications

BTB/POZ domain-containing proteins are increasingly recognized for their context-dependent roles in cancer, acting as either tumor suppressors or oncogenic drivers depending on the cancer type. Among them, the function of ankyrin repeat and BTB domain-containing protein 2 (ABTB2) in pancreatic ductal adenocarcinoma (PDAC), a highly lethal malignancy, has remained unexplored. In this study, we employed comprehensive functional genomics approaches—siRNA/shRNA knockdown, CRISPR-Cas9 knockout, plasmid-based overexpression, and a Cre-LoxP transgenic mouse model—to systemically modulate ABTB2 expression in human and murine PDAC cell lines, as well as in the KPC mouse model of PDAC. Our gain- and loss-of-function studies revealed that ABTB2 plays …