Medicine and Health Sciences Commons^™

Daily Diagnostic Quality Computed Tomography-On-Rails (Ctor) Image Guidance For Abdominal Stereotactic Body Radiation Therapy (Sbrt), Rachael M Martin-Paulpeter, P James Jensen, Luis A Perles, Gabriel O Sawakuchi, Prajnan Das, Eugene J Koay, Albert C Koong, Ethan B Ludmir, Joshua S Niedzielski, Sam Beddar

Faculty, Staff and Student Publications

BACKGROUND/OBJECTIVES: Stereotactic body radiation therapy (SBRT) for abdominal targets faces a variety of challenges, including motion caused by the respiration and digestion and a relatively poor level of contrast between the tumor and the surrounding tissues. Breath-hold treatments with computed tomography-on-rails (CTOR) image guidance is one way of addressing these challenges, allowing for both the tumor and normal tissues to be well-visualized. Using isodose lines (IDLs) from CT simulations as a guide, the anatomical information can be used to shift the alignment or trigger a replan, such that normal tissues receive acceptable doses of radiation.

METHODS: This study aims to …

Unlocking Intracellular Oncology Targets: The Unique Role Of Antibody-Based T-Cell Receptor Mimic (Tcrm) Therapeutics In T-Cell Engagers (Tces) And Antibody-Drug Conjugates (Adcs), Jeffrey Molldrem, Dongxing Zha

Faculty, Staff and Student Publications

Effectively targeting intracellular tumor-associated proteins presents a formidable challenge in oncology, as they are traditionally considered inaccessible to conventional antibody-based therapies and CAR-T cell therapies. However, recent advancements in antibody engineering have revolutionized this field, offering promising new strategies to combat cancer. This review focuses on the innovative use of T-cell receptor mimic (TCRm) antibodies within the therapeutic frameworks of T-cell engagers (TCE) and antibody-drug conjugates (ADCs). TCRm antibodies, designed to recognize peptide-MHC complexes rather than cell surface proteins, integrate the capacity of T-cells to reach intracellular targets with the unique strengths of antibodies. When incorporated into T-cell engaging therapeutics, …

The Rna Receptor Rig-I Binding Synthetic Oligodeoxynucleotide Promotes Pneumonia Survival, Yongxing Wang, Vikram V Kulkarni, Jezreel Pantaleóngarcía, Michael K Longmire, Mathilde Lethier, Stephen Cusack, Scott E Evans

Faculty, Staff and Student Publications

Pneumonia is a worldwide threat to public health, demanding novel preventative and therapeutic strategies. The lung epithelium is a critical environmental interface that functions as a physical barrier to pathogen invasion while also actively sensing and responding to pathogens. We have reported that stimulating lung epithelial cells with a combination therapeutic consisting of a diacylated lipopeptide and a synthetic CpG oligodeoxynucleotide (ODN) induces synergistic pneumonia protection against a wide range of pathogens. We report here that mice deficient in TLR9, the previously described receptor for ODN, still displayed partial ODN-induced protection. This prompted us to seek an alternate ODN receptor, …

Modeling Antisense Oligonucleotide Therapy In Mecp2 Duplication Syndrome Human Ipsc-Derived Neurons Reveals Gene Expression Programs Responsive To Mecp2 Levels, Sameer S Bajikar, Yehezkel Sztainberg, Alexander J Trostle, Harini P Tirumala, Ying-Wooi Wan, Caroline L Harrop, Jesse D Bengtsson, Claudia M B Carvalho, Davut Pehlivan, Bernhard Suter, Jeffrey L Neul, Zhandong Liu, Paymaan Jafar-Nejad, Frank Rigo, Huda Y Zoghbi

Faculty, Staff and Students Publications

Genomic copy-number variations (CNVs) that can cause neurodevelopmental disorders often encompass many genes, which complicates our understanding of how individual genes within a CNV contribute to pathology. MECP2 duplication syndrome (MDS or MRXSL in OMIM; OMIM#300260) is one such CNV disorder caused by duplications spanning methyl CpG-binding protein 2 (MECP2) and other genes on Xq28. Using an antisense oligonucleotide (ASO) to normalize MECP2 dosage is sufficient to rescue abnormal neurological phenotypes in mouse models overexpressing MECP2 alone, implicating the importance of increased MECP2 dosage within CNVs of Xq28. However, because MDS CNVs span MECP2 and additional genes, we generated human …

Tumor-Associated Edema In Children With Kaposi Sarcoma: 14 Years' Experience At Kamuzu Central Hospital, Lilongwe, Malawi, Fatsani Rose Manase, Allison Silverstein, William Kamiyango, Jimmy Villiera, Clement Dziwe, Claudia Wallrauch, Tom Heller, Mark Zobeck, Tamiwe Tomoka, Michael E Scheurer, Carl E Allen, Nmazuo Ozuah, Rizine Mzikamanda, Nader Kim El-Mallawany, Casey L Mcatee

Center for Medical Ethics and Health Policy Staff Publications

Background/objectives: Kaposi sarcoma (KS) is a common lymphatic endothelial cancer among children with and without HIV in central and eastern Africa. Despite its clinical heterogeneity, its various clinical phenotypes are often grouped together in staging and treatment algorithms. Patients with KS tumor-associated edema, referring to hard, non-pitting lesions which often lead to chronic disability, represent a unique, understudied subgroup of children with KS. To continue our work defining the distinct phenotypes of pediatric KS, this study aimed to assess the clinical progression and outcomes of KS edema in children.

Methods: A retrospective cohort study was conducted at Kamuzu Central Hospital …

Transcutaneous Electrical Nerve Stimulation For Fibromyalgia-Like Syndrome In Patients With Long-Covid: A Pilot Randomized Clinical Trial, Alejandro Zulbaran-Rojas, Rasha O Bara, Myeounggon Lee, Miguel Bargas-Ochoa, Tina Phan, Manuel Pacheco, Areli Flores Camargo, Syed Murtaza Kazmi, Mohammad Dehghan Rouzi, Dipaben Modi, Fidaa Shaib, Bijan Najafi

Faculty, Staff and Students Publications

This study investigated the effect of Transcutaneous Electrical Nerve Stimulation (TENS) for fibromyalgia-like symptoms including chronic widespread musculoskeletal pain, fatigue, and/or gait impairment in twenty-five individuals with long-COVID. Participants were randomized to a high dose (intervention group, IG) or low dose (placebo group, PG) TENS device. Both groups received daily 3-5 h of TENS therapy for 4-weeks. The Brief Pain Inventory assessed functional interference from pain (BPI-I), and pain severity (BPI-S). The global fatigue index (GFI) assessed functional interference from fatigue. Wearable technology measured gait parameters during three 30-feet consecutive walking tasks. At 4-weeks, the IG exhibited a greater decrease …

Genomic Insights For Personalised Care In Lung Cancer And Smoking Cessation: Motivating At-Risk Individuals Toward Evidence-Based Health Practices, Tony Chen, Giang Pham, Louis Fox, Nina Adler, Xiaoyu Wang, Jingning Zhang, Jinyoung Byun, Younghun Han, Gretchen R B Saunders, Dajiang Liu, Michael J Bray, Alex T Ramsey, James Mckay, Laura J Bierut, Christopher I Amos, Rayjean J Hung, Xihong Lin, Haoyu Zhang, Li-Shiun Chen

Faculty, Staff and Students Publications

BACKGROUND: Lung cancer and tobacco use pose significant global health challenges, necessitating a comprehensive translational roadmap for improved prevention strategies such as cancer screening and tobacco treatment, which are currently under-utilised. Polygenic risk scores (PRSs) may further motivate health behaviour change in primary care for lung cancer in diverse populations. In this work, we introduce the GREAT care paradigm, which integrates PRSs within comprehensive patient risk profiles to motivate positive health behaviour changes.

METHODS: We developed PRSs using large-scale multi-ancestry genome-wide association studies and standardised PRS distributions across all ancestries. We validated our PRSs in 561,776 individuals of diverse ancestry …

Ephb4-Rasa1 Inhibition Of Piezo1 Ras Activation Drives Lymphatic Valvulogenesis, Di Chen, Yipei Tang, Philip E Lapinski, David Wiggins, Eva M Sevick, Michael J Davis, Philip D King

Faculty, Staff and Student Publications

BACKGROUND: EPHB4 (ephrin receptor B4) and the RASA1 (p120 Ras GTPase-activating protein) are necessary for the development of lymphatic vessel (LV) valves. However, precisely how EPHB4 and RASA1 regulate LV valve development is unknown. In this study, we examine the mechanisms by which EPHB4 and RASA1 regulate the development of LV valves.

METHODS: We used LV-specific inducible EPHB4-deficient mice and EPHB4 knockin mice that express a form of EPHB4 that is unable to bind RASA1 yet retains protein tyrosine kinase activity (EPHB4 2YP) to study the role of EPHB4 and RASA1 in LV valve development in the embryo and LV …

Addressing Practice Effects In Population-Based Studies Of Trends In Late-Life Dementia And Cognitive Impairment, Vicki A Freedman, Mengyao Hu

Faculty, Staff and Student Publications

No abstract provided.

Estimating The Number Of Polygenic Diseases Among Six Mutually Exclusive Entities Of Non-Tumors And Cancer, C I Edvard Smith, Jan A Burger, Rula Zain

Faculty, Staff and Student Publications

In the era of precision medicine with increasing amounts of sequenced cancer and non-cancer genomes of different ancestries, we here enumerate the resulting polygenic disease entities. Based on the cell number status, we first identified six fundamental types of polygenic illnesses, five of which are non-cancerous. Like complex, non-tumor disorders, neoplasms normally carry alterations in multiple genes, including in 'Drivers' and 'Passengers'. However, tumors also lack certain genetic alterations/epigenetic changes, recently named 'Goners', which are toxic for the neoplasm and potentially constitute therapeutic targets. Drivers are considered essential for malignant transformation, whereas environmental influences vary considerably among both types of …

Probabilistic Presurgical Language Fmri Atlas Of Patients With Brain Tumors, Jian Ming Teo, Vinodh A Kumar, Jina Lee, Rami W Eldaya, Ping Hou, Mu-Lan Jen, Kyle R Noll, Peng Wei, Sherise D Ferguson, Sujit S Prabhu, Max Wintermark, Ho-Ling Liu

Faculty, Staff and Student Publications

Background and purpose: Patients with brain tumors have high intersubject variation in putative language regions, which may limit the utility of straightforward application of healthy subject brain atlases in clinical scenarios. The purpose of this study was to develop a probabilistic functional brain atlas that consolidates language functional activations of sentence completion and Silent Word Generation language paradigms using a large sample of patients with brain tumors.

Materials and methods: The atlas was developed using retrospectively collected fMRI data from patients with brain tumors who underwent their first standard-of-care presurgical language fMRI scan at our institution between July 18, 2015, …

Real-World Impact Of Differences In The Who And Icc Classifications Of Non-Hodgkin Lymphoma: A Leo Cohort Study Analysis, Brooj Abro, Matthew J Maurer, Thomas M Habermann, W Richard Burack, Jennifer R Chapman, Jonathon B Cohen, Jonathan W Friedberg, Giorgio Inghirami, Brad S Kahl, Melissa C Larson, Brian K Link, Izidore S Lossos, Peter Martin, Timothy J Mcdonnell, Loretta J Nastoupil, Shaun M Riska, Sergei Syrbu, Francisco Vega, Kiran R Vij, Christopher R Flowers, James R Cerhan, David L Jaye, Andrew L Feldman

Faculty, Staff and Student Publications

Recent introduction of 2 different lymphoma classifications has raised concerns about consistency in diagnosis, management, and clinical trial enrollment. Data from a large cohort reflecting real-world clinical practice suggest that differences between the classifications will affect < 1% of non-Hodgkin lymphomas.

Total Retinal Thickness Is An Important Factor In Evaluating Diabetic Retinal Neurodegeneration, Noor-Us-Sabah Ahmad, Kristen Staggers, Kyungmoo Lee, Nitish Mehta, Amitha Domalpally, Benjamin J Frankfort, Yao Liu, Roomasa Channa

Faculty, Staff and Students Publications

OBJECTIVE: Macular retinal nerve fibre layer (mRNFL) and ganglion cell-inner plexiform layer thickness (GC-IPL) measurements are important markers of diabetic retinal neurodegeneration (DRN). In this cross-sectional study, we aimed to quantify the contribution of total retinal thickness (TRT) and other factors in the variation of mRNFL and GC-IPL thickness among participants with diabetes.

METHODS AND ANALYSIS: We used macular-centred spectral domain-optical coherence tomography scans from participants with diabetes in the UK Biobank. Two multiple linear regression models (prior to and after adjusting for TRT) were used to determine factors associated with mRNFL and GC-IPL thicknesses. A p value of less …

Large-Scale Application Of Clingen-Insight Apc-Specific Acmg/Amp Variant Classification Criteria Leads To Substantial Reduction In Vus, Xiaoyu Yin, Marcy Richardson, Andreas Laner, Xuemei Shi, Elisabet Ognedal, Valeria Vasta, Thomas V O Hansen, Marta Pineda, Deborah Ritter, Johan De Dunnen, Emadeldin Hassanin, Wencong Lyman Lin, Ester Borras, Karl Krahn, Margareta Nordling, Alexandra Martins, Khalid Mahmood, Emily Nadeau, Victoria Beshay, Carli Tops, Maurizio Genuardi, Tina Pesaran, Ian M Frayling, Gabriel Capellá, Andrew Latchford, Sean V Tavtigian, Carlo Maj, Sharon E Plon, Marc S Greenblatt, Finlay A Macrae, Isabel Spier, Stefan Aretz

Faculty, Staff and Students Publications

Pathogenic constitutional APC variants underlie familial adenomatous polyposis, the most common hereditary gastrointestinal polyposis syndrome. To improve variant classification and resolve the interpretative challenges of variants of uncertain significance (VUSs), APC-specific variant classification criteria were developed by the ClinGen-InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel (VCEP) based on the criteria of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP). A streamlined algorithm using the APC-specific criteria was developed and applied to assess all APC variants in ClinVar and the International Society for Gastrointestinal Hereditary Tumours (InSiGHT) international reference APC Leiden Open Variation …

Homozygous Variants In Wdr83os Lead To A Neurodevelopmental Disorder With Hypercholanemia, Scott Barish, Sheng-Jia Lin, Reza Maroofian, Alper Gezdirici, Hamoud Alhebby, Aurélien Trimouille, Marta Biderman Waberski, Tadahiro Mitani, Ilka Huber, Kristian Tveten, Øystein L Holla, Øyvind L Busk, Henry Houlden, Ehsan Ghayoor Karimiani, Mehran Beiraghi Toosi, Reza Shervin Badv, Paria Najarzadeh Torbati, Fatemeh Eghbal, Javad Akhondian, Ayat Al Safar, Abdulrahman Alswaid, Giovanni Zifarelli, Peter Bauer, Dana Marafi, Jawid M Fatih, Kevin Huang, Cassidy Petree, Daniel G Calame, Charlotte Von Der Lippe, Fowzan S Alkuraya, Sami Wali, James R Lupski, Gaurav K Varshney, Jennifer E Posey, Davut Pehlivan

Faculty, Staff and Students Publications

WD repeat domain 83 opposite strand (WDR83OS) encodes the 106-aa (amino acid) protein Asterix, which heterodimerizes with CCDC47 to form the PAT (protein associated with ER translocon) complex. This complex functions as a chaperone for large proteins containing transmembrane domains to ensure proper folding. Until recently, little was known about the role of WDR83OS or CCDC47 in human disease traits. However, biallelic variants in CCDC47 were identified in four unrelated families with trichohepatoneurodevelopmental syndrome, characterized by a neurodevelopmental disorder (NDD) with liver dysfunction. Three affected siblings in an additional family share a homozygous truncating WDR83OS variant and a phenotype of …

Identification Of Atypical Pediatric Diabetes Mellitus Cases Using Electronic Medical Records, Marcela F Astudillo, William E Winter, Liana K Billings, Raymond Kreienkamp, Ashok Balasubramanyam, Maria J Redondo, Mustafa Tosur

Faculty, Staff and Students Publications

INTRODUCTION: There are no established methods to identify children with atypical diabetes for further study. We aimed to develop strategies to systematically ascertain cases of atypical pediatric diabetes using electronic medical records (EMR).

RESEARCH DESIGN AND METHODS: We tested two strategies in a large pediatric hospital in the USA. Strategy 1: we designed a questionnaire to rule out typical diabetes and applied it to the EMR of 100 youth with diabetes. Strategy 2: we built three electronic queries to generate reports of three atypical pediatric diabetes phenotypes: unknown type, type 2 diabetes (T2D) diagnosed(AbNegT1D).

RESULTS: Strategy 1 identified six cases …

Brain Metastases In Sarcomas: A Multicenter Retrospective Cohort Study, Ellen Zhang, Sheima Farag, Hilary Dietz, Daniel Wang, Angela Hirbe, Kristen Ganjoo, Brian Van Tine, Shane Zaid, Aisha Miah, Vicki Keedy, Elizabeth Davis, Nam Bui

Faculty, Staff and Students Publications

Purpose: Brain metastases (BM) in sarcomas occur rarely and are associated with poor prognosis. This study is a large retrospective cohort describing the demographic and clinical characteristics of these patients, treatment strategies, and survival outcomes.

Methods: In total, 81 patients with BM from sarcomas were identified across five sarcoma centers. Demographic data, clinical presentation, and treatment modalities were analyzed.

Results: The most common histologies were leiomyosarcoma (12.3%) and undifferentiated pleomorphic sarcoma (12.3%). The median time from sarcoma diagnosis to brain metastases was 1.9 years. Upon presentation, 88.9% of patients with BM from sarcomas were symptomatic with the most common presenting …

Systematic Review And Meta-Analysis Of Outcomes In Type 1 Thyroplasty Comparing Silastic To Gore-Tex, Dylan G Vance, David Z Allen, Amy B Leming, Madisyn Cox, Sonya E Fogg, Sameer H Siddiqui, Hallie R Wilson, Andrew G Tritter

Library Staff Publications

OBJECTIVE: Type 1 Thyroplasty is a well-established procedure used for medializing an immobile vocal fold. Silastic and Gore-Tex are the two most common materials used to accomplish this, but comparative data on their relative efficacy are scarce. We sought to compare outcomes between Silastic and Gore-Tex implants via systematic review and meta-analysis for unilateral vocal fold immobility.

METHODS: We collected available data from PubMed, Embase, and Web of Science on demographics, maximum phonation time (MPT), voice handicap index (VHI-10/30) score, and any other relevant metrics encountered before comparatively evaluating differences in outcomes.

RESULTS: The search yielded 1,534 records with 55 …

High Incidence And Geographic Distribution Of Cleft Palate In Finland Are Associated With The Irf6 Gene, Fedik Rahimov, Pekka Nieminen, Priyanka Kumari, Emma Juuri, Tiit Nikopensius, Kitt Paraiso, Jakob German, Antti Karvanen, Mart Kals, Abdelrahman G Elnahas, Juha Karjalainen, Mitja Kurki, Aarno Palotie, Estonian Biobank Research Team, Finngen, Arja Heliövaara, Tõnu Esko, Sakari Jukarainen, Priit Palta, Andrea Ganna, Anjali P Patni, Daniel Mar, Karol Bomsztyk, Julie Mathieu, Hannele Ruohola-Baker, Axel Visel, Walid D Fakhouri, Brian C Schutte, Robert A Cornell, David P Rice

Faculty, Staff and Student Publications

In Finland, the frequency of isolated cleft palate (CP) is higher than that of isolated cleft lip with or without cleft palate (CL/P). This trend contrasts to that in other European countries but its genetic underpinnings are unknown. We conducted a genome-wide association study in the Finnish population and identified rs570516915, a single nucleotide polymorphism highly enriched in Finns, as strongly associated with CP (P = 5.25 × 10-34, OR = 8.65, 95% CI 6.11-12.25), but not with CL/P (P = 7.2 × 10-5), with genome-wide significance. The risk allele frequency of rs570516915 parallels the regional variation of CP prevalence …

Skn-1 Activation During Infection Of Caenorhabditis Elegans Requires Cdc-48 And Endoplasmic Reticulum Proteostasis, Carolaing Gabaldón, Ozgur Karakuzu, Danielle A Garsin

Faculty, Staff and Student Publications

During challenge of Caenorhabditis elegans with human bacterial pathogens such as Pseudomonas aeruginosa and Enterococcus faecalis, the elicited host response can be damaging if not properly controlled. The activation of Nrf (nuclear factor erythroid-related factor)/CNC (Cap-n-collar) transcriptional regulators modulates the response by upregulating genes that neutralize damaging molecules and promote repair processes. Activation of the C. elegans Nrf ortholog, SKN-1, is tightly controlled by a myriad of regulatory mechanisms, but a central feature is an activating phosphorylation accomplished by the p38 mitogen-activated kinase (MAPK) cascade. In this work, loss of CDC-48, an AAA+ ATPase, was observed to severely compromise SKN-1 …

Test Smart, Treat Smart-Using Clinician Feedback To Adapt A Catheter-Associated Urinary Tract Infection Intervention For Spinal Cord Injury, Hilary Touchett, Kelley Arredondo, Casey Hines-Munson, Ivy Poon, Sally Ann Holmes, Barbara W Trautner, Felicia Skelton

Faculty, Staff and Students Publications

Background: Catheter-associated urinary tract infection (CAUTI) prevention is a major target for hospital quality metrics because it is linked to increased morbidity, mortality, and health care costs. Health care systems use strict protocols surrounding catheterization and maintenance, which often disregard the clinical needs of special populations (eg, spinal cord injury [SCI]). However, for populations that rely on chronic instrumentation of the bladder, asymptomatic (ie, nonpathogenic) bacterial colonization in the bladder is common but not linked to adverse outcomes. Additionally, alterations in neurologic and sensory function after SCI make it difficult for clinicians to discern asymptomatic bacteriuria from acute urinary tract …

Automatically Extracting Social Determinants Of Health For Suicide: A Narrative Literature Review, Annika M Schoene, Suzanne Garverich, Iman Ibrahim, Sia Shah, Benjamin Irving, Clifford C Dacso

Faculty, Staff and Students Publications

Suicide is a complex phenomenon that is often not preceded by a diagnosed mental health condition, therefore making it difficult to study and mitigate. Artificial Intelligence has increasingly been used to better understand Social Determinants of Health factors that influence suicide outcomes. In this review we find that many studies use limited SDoH information and minority groups are often underrepresented, thereby omitting important factors that could influence risk of suicide.

Gpr56: Gpcr As A Guardian Against Ferroptosis, Yuelong Yan, Li Zhuang, Boyi Gan

Faculty, Staff and Student Publications

Transmembrane receptor proteins are proficient in sensing external signals and initiating downstream pathways to control cell survival. Lin et al. demonstrated that GPR56, a G-protein-coupled receptor, can be activated by its agonist to suppress ferroptosis-a form of cell death-and effectively mitigate ferroptosis-associated liver damage.

Mitral Annular Disjunction In Heritable Thoracic Aortic Disease: Insights From The Montalcino Aortic Consortium, Kishan L Asokan, Jennifer R Landes, Wannes Renders, Laura Muiño Mosquera, Julie De Backer, David W Jantzen, Anji T Yetman, Gisela Teixido-Tura, Arturo Evangelista, Richmond Jeremy, Edward G Jones, Shaine Morris, Tam Doan, Maral Ouzonian, Alan Braverman, Guillaume Jondeau, Olivier Milleron, Dianna M Milewicz, Siddharth K Prakash

Faculty, Staff and Student Publications

Background: Mitral annular disjunction (MAD), posterior displacement of the mitral valve leaflet hinge point, predisposes to arrhythmias or sudden cardiac death. We evaluated the burden of MAD, mitral valve prolapse (MVP), and mitral regurgitation (MR) by heritable thoracic aortic disease gene in a cross-sectional analysis of 2014-2023 data in the Montalcino Aortic Consortium registry.

Methods and results: MAD was determined by direct measurement of echocardiographic images. MR and MVP were defined according to current clinical guidelines. Associations were evaluated using χ2 or Fisher exact tests. MR and MVP were enriched in Montalcino Aortic Consortium participants (672) with pathogenic variants (PV) …

White Matter Hyperintensities And Mild Tbi In Post-9/11 Veterans And Service Members, David F Tate, Erin D Bigler, Gerald E York, Mary R Newsome, Brian A Taylor, Andrew R Mayer, Mary Jo Pugh, Angela P Presson, Zhining Ou, Elizabeth S Hovenden, Josephine Dimanche, Tracy J Abildskov, Rajan Agarwal, Heather G Belanger, Aaron M Betts, Timothy Duncan, Blessen C Eapen, Carlos A Jaramillo, Michael Lennon, Jennifer E Nathan, Randall S Scheibel, Matthew B Spruiell, William C Walker, Elisabeth A Wilde

Faculty, Staff and Student Publications

Introduction: The neurobehavioral significance of white matter hyperintensities (WMHs) seen on magnetic resonance imaging after traumatic brain injury (TBI) remains unclear, especially in Veterans and Service Members with a history of mild TBI (mTBI). In this study, we investigate the relation between WMH, mTBI, age, and cognitive performance in a large multisite cohort from the Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium.

Materials and methods: The neuroimaging and neurobehavioral assessments for 1,011 combat-exposed, post-9/11 Veterans and Service Members (age range 22-69 years), including those with a history of at least 1 mTBI (n = 813; median …

Gene Discovery From Microbial Gene Libraries I: Protection Against Reactive Oxygen Species-Driven Dna Damage, John C Taylor, Carmen Gu Liu, James D Chang, Brianna E Thompson, Anthony W Maresso

Faculty, Staff and Students Publications

Reactive oxygen species (ROS) pose a lethal risk for all life forms by causing damage to cell processes, genome-wide DNA damage-driving mutation, replicative instability, and death. Thus, the development of mechanisms to resist or repair ROS-induced DNA damage is critical for the reliable replication of nucleic acids. DNA repair and protection mechanisms have been discovered in all forms of life. However, the vast array of microbes that may harbor novel repair or protection mechanisms, especially bacterial viruses, have not been adequately assessed. Here, we screened a microbial gene library composed primarily of phage open reading frames (ORFs) to uncover elements …

Activation Of A Gpcr, Orl1 Receptor: A Novel Therapy To Prevent Heart Failure Progression, Saliha S Pathan, Aarthi Pugazenthi, Beverly R E A Dixon, Theodore G Wensel, Todd K Rosengart, Megumi Mathison

Faculty, Staff and Students Publications

The number of ischemic heart failure (HF) patients is growing dramatically worldwide. However, there are at present no preventive treatments for HF. Our previous study showed that Gata4 overexpression improved cardiac function after myocardial infarction in rat hearts. We also found that Gata4 overexpression significantly increased the expression of a Pnoc gene, an endogenous ligand for the cell membrane receptor ORL1. We hypothesized that the activation of the ORL1 receptor would suppress HF in a rat ischemic heart model. Adult Sprague Dawley rats (8 weeks old, six males and six females) underwent left anterior descending coronary artery ligation. Three weeks …

Trends In Transcatheter Versus Surgical Aortic Valve Replacement Outcomes In Patients With Low-Surgical Risk: A Systematic Review And Meta-Analysis Of Randomized Trials, Sina Kazemian, Parisa Fallahtafti, Mohammad Sharifi, Negin Sadat Hosseini Mohammadi, Hamidreza Soleimani, Arman Soltani Moghadam, Elaheh Karimi, Yaser Sattar, Yaser Jenab, Mehdi Mehrani, Alimohammad Hajizeinali, Mina Iskander, Mehrshad Fathian Sabet, Negar Salehi, Karim Al-Azizi, Diaa Hakim, Mahboob Alam, Kaveh Hosseini

Faculty, Staff and Students Publications

Background: Limited data exist on long-term outcomes after transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR). This meta-analysis aims to elucidate outcome trends following TAVR versus SAVR in patients with severe aortic stenosis and low-surgical risk.

Methods and results: A systematic search was conducted in PubMed, Embase, Scopus, and the Cochrane Library databases from inception until May 2024, to identify studies comparing TAVR versus SAVR in patients with low-surgical risk (Society of Thoracic Surgeons predicted risk of mortality score < 4%). The primary outcome was all-cause mortality. Secondary outcomes included cardiovascular mortality, stroke, disabling stroke, rehospitalization, myocardial infarction, aortic valve reintervention, permanent pacemaker implantation, and new-onset atrial fibrillation. Binary random-effects models were used to compare the risk of each outcome across various follow-up intervals and the risk of bias was assessed using the Cochrane Collaboration's Risk of Bias-2 tool. The meta-analysis included 6 randomized trials including 4682 patients. TAVR was associated with a lower risk of all-cause mortality than SAVR in the 30-day (hazard ratio [HR: 0.45] [95% CI: 0.26-0.77], I2: 0%) and 30-day to 1-year (HR: 0.55 [95% CI: 0.37-0.81], I2: 16%) follow-ups. However, the …

Nepali Oral Microbiomes Reflect A Gradient Of Lifestyles From Traditional To Industrialized, Erica P Ryu, Yoshina Gautam, Diana M Proctor, Dinesh Bhandari, Sarmila Tandukar, Meera Gupta, Guru Prasad Gautam, David A Relman, Ahmed A Shibl, Jeevan Bahadur Sherchand, Aashish R Jha, Emily R Davenport

Faculty, Staff and Student Publications

Background: Lifestyle plays an important role in shaping the gut microbiome. However, its contributions to the oral microbiome remain less clear, due to the confounding effects of geography and methodology in investigations of populations studied to date. Furthermore, while the oral microbiome seems to differ between foraging and industrialized populations, we lack insight into whether transitions to and away from agrarian lifestyles shape the oral microbiota. Given the growing interest in so-called "vanishing microbiomes" potentially being a risk factor for increased disease prevalence in industrialized populations, it is important that we distinguish lifestyle from geography in the study of microbiomes …

Federally Qualified Health Centers And Performance Of Medicare Accountable Care Organizations, Kun Li, Yucheng Hou, Frank Mcstay, Jonathan Gonzalez-Smith, Robert S Saunders

Faculty, Staff and Student Publications

IMPORTANCE: Federally qualified health centers (FQHCs) have increasingly participated in the Medicare Shared Savings Program (MSSP) accountable care organizations (ACOs), one of the most widespread value-based programs. Although FQHCs may strengthen ACOs' ability to provide affordable care to diverse Medicare beneficiaries, evidence on ACOs' performance by FQHC participation is limited.

OBJECTIVES: To compare beneficiary characteristics, utilization, expenditure, and quality between ACOs with and without FQHC participation and assess changes in ACO performance after including first FQHCs.

DESIGN, SETTING, AND PARTICIPANTS: Using MSSP public use files, this cross-sectional study compared performance of ACOs that always had FQHC participation with ACOs that …