Digital Commons Network^™

A Class Of Benzofuranoindoline-Bearing Heptacyclic Fungal Ripps With Anticancer Activities, Qiuyue Nie, Fanglong Zhao, Xuerong Yu, Mithun C Madhusudhanan, Caleb Chang, Siting Li, Sandipan Roy Chowdhury, Bryce Kille, Andy Xu, Rory Sharkey, Chunxiao Sun, Hongzhi Zeng, Shuai Liu, Dishu Zhou, Xin Yu, Kevin Yang, Sandra A C Figueiredo, Maria Zotova, Zichen Hu, Alan Y Du, Dongyin Guan, Rui Tang, Todd Treangen, Jin Wang, Pedro N Leão, Yang Gao, Junjie Chen, Peng Liu, Hans Renata, Xue Gao

Children’s Nutrition Research Center Staff Publications

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a promising source of new pharmaceuticals, yet the therapeutic potential of fungal RiPPs remains largely underexplored. Here, we report asperigimycins as a distinct class of fungal RiPPs, featuring a unique heptacyclic scaffold consisting of a benzofuranoindoline core and three additional macrocycles, primarily assembled by six distinct fungi-specific DUF3328 oxidases. Inspired by the enhancement of anticancer activity through the N-terminal pyroglutamate in naturally occurring asperigimycins C and D, we chemically modify the inactive asperigimycin B with a series of lipid substitutions at its N-terminus. A derivative with a C-11 linear fatty …

Middle Meningeal Artery Embolization Of Septated Chronic Subdural Hematomas, Juan Carlos Martinez-Gutierrez, Salvatore A D'Amato, Hussein A Zeineddine, Michael I Nahhas, Matthew J Kole, Hyun Woo Kim, Youngran Kim, Bryden H Dawes, Peng Roc Chen, Spiros L Blackburn, Sunil A Sheth, Gary Spiegel, Ching-Jen Chen, Ashutosh Mahapatra, Ryan S Kitagawa, Mark J Dannenbaum

Faculty, Staff and Student Publications

Introduction

Middle meningeal artery embolization (MMAE) has emerged as a promising new treatment for patients with chronic subdural hematomas (cSDH). Its efficacy, however, upon the subtype with a high rate of recurrence—septated cSDH—remains undetermined.

Methods

From our prospective registry of patients with cSDH treated with MMAE, we classified patients based on the presence or absence of septations. The primary outcome was the rate of recurrence of cSDH. Secondary outcomes included a reduction in cSDH thickness, midline shift, and rate of reoperation.

Results

Among 80 patients with 99 cSDHs, the median age was 68 years (IQR 59–77) with 20% females. Twenty-eight …

Healthcare Professionals’ Awareness Of And Barriers To Shared-Clinical-Decision-Making For Hpv Vaccination Among Adults 27–45 Years, Manali Desai, Shreela V Sharma, Joel Fokom Domgue, Onyema Chido-Amajuoyi, Robert Yu, Wenyaw Chan, Charles Darkoh, Sanjay Shete

Faculty, Staff and Student Publications

The Advisory Committee on Immunization Practices recommends human papillomavirus (HPV) vaccination for inadequately vaccinated adults aged 27–45 based on shared clinical decision-making (SCDM). However, little is known about awareness and barriers to SCDM among US healthcare providers (HCPs), especially in Texas, where HPV vaccination rates are below the national average. Between January and April 2021, we conducted a population-based cross-sectional survey (12% response rate) of HCPs licensed in Texas to assess the prevalence and factors associated with awareness of the SCDM recommendation. HCPs were asked if they were aware and if they foresaw any barriers in implementing SCDM for HPV …

Metabolomic Signatures Of Prediabetes In Mexican Americans: The Role Of Genetics And Macronutrients, Shinhye Chung, Charles Evans, Charles F Burant, Han Chen, Bing Yu, David Aguilar, Eric L Brown, Craig L Hanis, Goo Jun

Faculty, Staff and Student Publications

Prediabetes is one of the main health concerns in public health, and various etiological factors contribute to its onset. This study aimed to evaluate genetic associations and gene‐macronutrient interaction with prediabetes‐related metabolites to understand how genetic variation and dietary intake contribute to dysglycemia. We analyzed a total of 482 self‐identified Mexican American participants recruited from Starr County, Texas in 2018‐2019. Untargeted metabolomic profiling was performed using LC‐MS. Nutrient densities of six macronutrients were derived from a 106‐item food frequency questionnaire. Genetic associations for each metabolite were tested using Generalized linear Mixed Model Association Tests (GMMAT). Gene‐macronutrient interactions on prediabetes‐associated metabolites …

Clinical And Genomic Characterization Of Serratia Bloodstream Infections, Roberta Monardo, Lawrence P Park, Felicia Ruffin, Phillip Cox, An Q Dinh, Rachel E Korn, Parisa Farahani, Marco Ripa, Antonella Castagna, Blake M Hanson, Vance G Fowler, Joshua T Thaden, Stacey A Maskarinec

Faculty, Staff and Student Publications

Background: Previously considered a rare opportunistic pathogen, Serratia is now an emerging cause of bacteremia. We compared the risk factors and outcomes of patients with Serratia bacteremia relative to other Enterobacterales in a cohort of hospitalized patients.

Methods: Patients were prospectively enrolled from 2002-2021 at Duke University. Characteristics and outcomes were compared among bacteremic patients due to Serratia and other Enterobacterales. Regression models were used to determine features associated with outcomes. Whole genome sequencing (WGS) was performed to characterize the phylogenetic diversity of Serratia isolates associated with device infections.

Results: Of 2676 patients, 173 (6.5%) had Serratia bacteremia. Among patients …

A Qualitative Study Of Health Priorities Of People With Dementia And Care Partners In Emergency Department And Hospital Care In A Public Safety-Net Setting, Anita Chary, Sumin Yoon, Victor Lara, Annika Bhananker, Michelle Suh, Kei Ouchi, Maura Kennedy, Aanand D Naik

Faculty, Staff and Student Publications

Background: Over half of the people with dementia visit the emergency department (ED) each year. Little is known about how people with dementia and their care partners conceptualize or communicate about health outcome goals or care preferences during acute care episodes.

Participants and setting: We conducted interviews with 14 Hispanic people with dementia and 19 care partners recruited from a public safety net hospital system in the southeastern United States. Participants were community-dwelling and had recently visited the ED.

Methods: We used a qualitative study design informed by phenomenology and guided by the patient priorities care (PPC) framework. Interviews elicited …

The "Woundosome" Concept And Its Impact On Procedural Outcomes In Patients With Chronic Limb-Threatening Ischemia, Lorenzo Patrone, Edoardo Pasqui, Michael S Conte, Alik Farber, Roberto Ferraresi, Matthew Menard, Joseph L Mills, John Rundback, Peter Schneider, August Ysa, Kumar Abhishek, George L Adams, Naseer Ahmad, Irfan Ahmed, Vlad A Alexandrescu, Max Amor, David Alper, Martin Andrassy, Christopher Attinger, Andy Baadh, Hashem Barakat, Lukla Biasi, Theodosios Bisdas, Zagum Bhatti, Erwin Blessing, Marc P Bonaca, Stefano Bonvini, Michel Bosiers, Andrew W Bradbury, Robert Beasley, Christian-Alexander Behrendt, Marianne Brodmann, Gonzalo Cabral, Roberto Cancellieri, Andrea Casini, Venita Chandra, Emiliano Chisci, Omar Chohan, Edward T C Choke, Patrick F S Chong, Giacomo Clerici, Raphael Coscas, Mary Costantino, Luca Dalla Paola, Sabeen Dand, Robert S M Davies, Mario D'Oria, Athanasios Diamantopoulos, Sebastian Debus, Koen Deloose, Costantino Del Giudice, Gianmarco De Donato, Brian De Rubertis, Jean Paul De Vries, Nuno V Dias, Larry Diaz-Sandoval, Florian Dick, Konstantinos Donas, Anahita Dua, Fabrizio Fanelli, Stefano Fazzini, Mazin Foteh, Roberto Gandini, Mauro Gargiulo, Luca Garriboli, Elizabeth A Genovese, Edward Gifford, Yann Goueffic, Peter Goverde, Prem Chand Gupta, Robert Hinchliffe, Andrew Holden, Kim C Houlind, Dominic Pj Howard, Bella Huasen, Giacomo Isernia, Konstantinos Katsanos, Barry Katzen, Philippe Kolh, Igor Koncar, Grigorios Korosoglou, Prakash Krishnan, Thomas Kroencke, Miltiadis Krokidis, Arun Kumarasamy, Paul Hayes, Osamu Iida, Enrique Alejandre Lafont, Ralf Langhoff, Alexandre Lecis, Mark Lessne, Hady Lichaa, Michael Lichtenberg, Marta Lobato, Alice Lopes, Giorgio Loreni, Pierleone Lucatelli, Sreekumar Madassery, Lieven Maene, Marco Manzi, Martin Maresch, Jay Santhosh Mathews, James Mccaslin, Antonio Micari, Stefano Michelagnoli, Bruno Migliara, Robert Morgan, Luis Morelli, Daniele Morosetti, Nicolas Mouawad, Paul Moxey, Stefan Müller-Hülsbeck, Jihad Mustapha, Tatsuya Nakama, Bahaa Nasr, Zola N'Dandu, Richard Neville, Elias Noory, Joakim Nordanstig, Katariina Noronen, Luis Mariano Palena, Gianbattista Parlani, Ashish S Patel, Parag Patel, Rafiuddin Patel, Sanjay Patel, Costantino Pena, Drazen Perkov, Mark Portou, Giovanni Pratesi, Christos Rammos, Jim Reekers, Vicente Riambau, Trisha Roy, Kenneth Rosenfield, Maria Antonella Ruffino, Fadi Saab, Athanasios Saratzis, Paolo Sbarzaglia, Andrej Schmidt, Eric Secemsky, Michael Siah, Henrik Sillesen, Gioele Simonte, Marc Sirvent, Jill Sommerset, Sabine Steiner, Ahmed Sakr, Dierk Scheinert, Mehdi Shishebor, Stavros Spiliopoulos, Alessio Spinelli, Konstantinos Stravoulakis, Gergana Taneva, Desarom Teso, Joerg Tessarek, Selva Theivacumar, Anish Thomas, Shannon Thomas, Narayan Thulasidasan, Giovanni Torsello, Ramesh Tripathi, Nicola Troisi, Srini Tummala, Venkat Tummala, Christopher Twine, Raman Uberoi, Alessandro Ucci, Domenico Valenti, Jos Van Den Berg, Daniel Van Den Heuvel, Isabelle Van Herzeele, Ramon Varcoe, Melina Vega De Ceniga, Frank J Veith, Maarit Venermo, Badri Vijaynagar, Sanjiv Virdee, Conrad Von Stempel, Michiel T Voûte, Kak Khee Yeung, Thomas Zeller, Hany Zayed, Miguel Montero Baker

Faculty, Staff and Student Publications

No abstract provided.

Capsinoids, Non-Pungent Trpv1 Agonists, Induce A Mild Hypothermia That Provides Short- And Long-Term Neuroprotection After Ischemic Stroke, Alexander Andersohn, Alexander Andersohn

Dissertations and Theses (Open Access)

Therapeutic hypothermia (TH) has demonstrated neuroprotection in instances of cardiac arrest and neonatal hypoxia/ischemia but faces different challenges in application to stroke due to the activation of cold defense mechanisms in conscious patients. This dissertation examines the efficacy and specificity of capsinoids (a purified mixture of capsiate and dihydrocapsiate) to induce a sustained mild hypothermia in conscious mice that is neuroprotective after stroke. Capsinoids function as TRPV1 agonists. However, unlike capsaicin, capsinoids are vulnerable to esterase-mediated breakdown, thus significantly restricting their action to the site of delivery. We showed that capsinoids delivered intraperitoneally (IP) to mice induced a TRPV1-dependent drop …

Neural Dynamics Supporting Flexible Cognition, Meredith J. Mccarty

Dissertations and Theses (Open Access)

Flexible cognition enables humans to adapt their behavior to changing circumstances by prioritizing relevant information and filtering out distractions. This process is thought to be supported by the integration of ongoing behavioral goals with incoming sensory information, but how this integration is realized in the human brain remains unclear. It is unknown how high-order sensory cortices can balance specialized processing with flexible integration of changing behavioral goals. In the following investigations, we use intracranial EEG (iEEG) recordings in humans to study the neural dynamics of flexible cognition during high-order sensory processing. First, we validated assumptions about the locality of iEEG …

Orthogonal Comparison Of Nuclear And Mitochondrial Clonal Architectures In Hematologic Malignancies, Nehali Shah

Dissertations and Theses (Open Access)

Acute myeloid leukemia (AML) is a hematologic malignancy characterized by accumulation of mutations that disrupt hematopoietic differentiation and promote clonal expansion. Understanding how these mutations arise and evolve is essential for improving diagnosis, prognosis, and treatment stratification. Current methods are limited by either restricted genomic coverage (targeted panels) or low throughput and high cost (in single-cell whole genome sequencing, scWGS). An emerging alternative is the use of mitochondrial DNA (mtDNA) mutations as clonal markers.

This study aims to determine whether mitochondrial-derived clonal architectures correlate with nuclear-derived clonal architectures in AML, thereby evaluating mtDNA as a scalable orthogonal tool for lineage …

Maternal Folic Acid Supplement Use, Folate Intake, And Preterm Birth Among Infants With Spina Bifida, Renata H Benjamin, Katherine L Ludorf, Rachel P Allred, Jenil R Patel, Wendy N Nembhard, Gary M Shaw, Suzan L Carmichael, Tania A Desrosiers, Eirini Nestoridi, Eva M Williford, A J Agopian

Faculty, Staff and Student Publications

Background: We sought to assess the extent to which folic acid supplementation and dietary folate intake are associated with preterm delivery among infants with spina bifida.

Methods: We conducted a retrospective population-based study using the National Birth Defects Prevention Study (NBDPS; 1999-2011) and the Birth Defects Study To Evaluate Pregnancy exposureS (BD-STEPS; 2014-2019). We utilized robust Poisson regression to calculate the risk ratio (RR) and 95% confidence interval (CI) for the associations between preterm birth (< 37 weeks) and maternal use of folic acid-containing supplements, dietary folate intake quartile, and a combined variable accounting for supplementation and dietary folate status.

Results: Among 1199 infants with spina bifida (1011 in NBDPS, 188 in BD-STEPS), 217 (18.1%) were born preterm. There were no statistically significant associations …

Tips On The Prisma Flow Diagram & Methods Section Write-Up, Sandra Y. Desjardins, Jenny Stockton

TMC Library Newsletter (2015-)

Clearly communicate your research methodology with a well-crafted PRISMA flow diagram. This 30-minute class provides practical tips and a step-by-step guide to creating a clear and informative methods section for your research papers. Related LibGuide: Where to Publish Your Research by Tracy Ashby. Come learn the foundational skills needed for successful research in a welcoming and practical "Lunch & Learn" environment. Register here to attend the session.

Open Access Fee Waivers And Discounts, Joanne Romano

TMC Library Newsletter (2015-)

Open Access Publishing at No Cost

PubMed Central (PMC) Eligible authors can deposit accepted manuscripts free of charge. Visit the PMC website for details.

TMC Library Publisher Agreements Affiliated authors may qualify for waived or discounted open access fees through select publishers.

Library Holiday Hours, Beatriz Varman

TMC Library Newsletter (2015-)

The TMC Library will observe the following schedule for the winter holidays.

Regular library hours resume on Saturday, January 3rd, 2026. Happy Holidays!

Epidemiological Patterns And Variability In Acute Brain Injury: A Multicenter Registry Analysis In South Korea's Neurocritical Care Units, Heewon Jeong, So Hee Park, Yoon-Hee Choo, Dong-Wan Kang, Yong Soo Kim, Bosco Seong Kyu Yang, Huimahn Alex Choi, Sung-Min Cho, Eun Jin Ha, Jiwoong Oh, Han-Gil Jeong

The Brown Foundation: Institute of Molecular Medicine

Background: Specialized neurocritical care (NCC) improves outcomes in acute brain injury (ABI), but significant variability exists in practices across and hospitals within South Korea's developing national NCC system. This study aims to assess clinical variability among patients with ABI across six tertiary NCC units (NCCUs) in South Korea and evaluate center-specific effects on clinical outcomes.

Methods: A multicenter registry of patients with ABI admitted to NCCUs between April 2023 and April 2024 was analyzed. A descriptive analysis was conducted to evaluate demographic, clinical, and treatment characteristics across centers. Variability across centers was quantified using the average standardized mean difference (SMD) …

Ddt Exposure Induces Microglial Activation And Disease-Associated Microglial Signatures: Relevance To Mechanisms Of Alzheimer’S Disease, Isha Mhatre-Winters, Aseel Eid, Nicole Blum, Yoonhee Han, Ferass M Sammoura, Long-Jun Wu, Jason R Richardson

The Brown Foundation: Institute of Molecular Medicine

Background: Alzheimer's disease (AD) is characterized by the presence of amyloid-β plaques, neurofibrillary tangles, and neuroinflammation. Previously, we reported that serum levels of dichlorodiphenyldichloroethylene (DDE), the primary metabolite of the pesticide dichlorodiphenyltrichloroethane (DDT), were significantly higher in AD patients compared to age-matched controls and that DDT exposure worsened AD pathology in animal models.

Objective: Here, we investigated the effect of DDT on neuroinflammation in primary mouse microglia (PMG) and C57BL/6J mice.

Methods: DDT-induced inflammatory and disease-associated microglial (DAM) gene expression were determined in PMG by qPCR and immunocytochemistry, with and without pretreatment with the sodium channel antagonist tetrodotoxin (TTX). Furthermore, …

Understanding Dental Hygienists’ Knowledge, Attitudes, And Practices Regarding Hpv Vaccination, Paula M Cuccaro, Jihye Choi, Kawtar Zouaidi, Efrat K Gabay, Michael Mackert, Josefine Ortiz Wolfe

Faculty, Staff and Student Publications

The American Dental Association and American Academy of Pediatric Dentistry encourage oral health professionals to strongly recommend human papillomavirus (HPV) vaccination to prevent HPV-associated oropharyngeal cancer. This study examined oral health professionals' knowledge, attitudes, and practices regarding HPV vaccination. We used purposive sampling to recruit participants through state and national oral health societies and social media platforms. Flyers outlining eligibility criteria were distributed, and eligible participants completed an online survey. Primary measures included participants' HPV-related knowledge, attitudes, and practices, and willingness to receive HPV-related training and recommend HPV vaccination to patients, including parents of adolescents. Only responses from dental hygienists …

Combine Ebis: A Novel Collaborative Method For Building Interventions From Existing Evidence-Based Interventions, Justin Knox, Kara Portier, Christopher Magana, Maggie Denning, Christopher M Ferraris, Emily Dove-Medows, Cho-Hee Shrader, Ohemaa Poku, Phil Kreniske, Robert Remien, Efrat Aharonovich, Jennifer C Elliott, Denis Nash, Kathryn Lancaster, Till Baernighausen, Kayo Fujimoto, Adam Carrico, John A Schneider, Alida Bouris, D Scott Batey, Sheree R Schwartz, Jose Bauermeister, Patrick S Sullivan, Joseph G Rosen, Gina Wingood, Milton Wainberg, Deborah Hasin, Elvin Geng, Patrick A Wilson, Stefan D Baral

Faculty, Staff and Student Publications

Purpose: Combining evidence-based interventions (EBIs) is a discrete process from adapting EBIs, and specific guidance for how to combine EBIs could be helpful amidst the proliferation of frameworks that combine and stage EBIs and calls for services to be combined or bundled. To address this gap, we developed and applied the COllaborative Method for Building INterventions from Existing Evidence-Based Interventions (COMBINE-EBIs) approach, a five-step process for combining EBIs.

Methods: The five steps of COMBINE-EBIs are: (1) Identify and Select EBIs, (2) Develop a Shared Conceptual Model, (3) Evaluate the Conceptual Model, (4) Create a Single Combined Protocol, and (5) Refine …

Proteogenomics In Cerebrospinal Fluid And Plasma Reveals New Biological Fingerprint Of Cerebral Small Vessel Disease, Ilana Caro, Daniel Western, Shinichi Namba, Na Sun, Shuji Kawaguchi, Yunye He, Masashi Fujita, Gennady Roshchupkin, Tim D'Aoust, Marie-Gabrielle Duperron, Muralidharan Sargurupremraj, Ami Tsuchida, Masaru Koido, Marziehsadat Ahmadi, Chengran Yang, Jigyasha Timsina, Laura Ibanez, Koichi Matsuda, Yutaka Suzuki, Yoshiya Oda, Akinori Kanai, Pouria Jandaghi, Markus Munter, Daniel Auld, Iana Astafeva, Raquel Puerta, Jerome I Rotter, Bruce M Psaty, Joshua C Bis, W T Longstreth, Thierry Couffinhal, Pablo García-González, Vanesa Pytel, Marta Marquié, Amanda Cano, Mercè Boada, Marc Joliot, Mark Lathrop, Quentin Le Grand, Lenore J Launer, Joanna M Wardlaw, Myriam Heiman, Agustin Ruiz, Paul M Matthews, Sudha Seshadri, Myriam Fornage, Hieab Adams, Aniket Mishra, David-Alexandre Trégouët, Yukinori Okada, Manolis Kellis, Philip L De Jager, Christophe Tzourio, Yoichiro Kamatani, Fumihiko Matsuda, Carlos Cruchaga, Stéphanie Debette

Faculty, Staff and Student Publications

Cerebral small vessel disease (cSVD) is a leading cause of stroke and dementia with no specific treatment, of which molecular mechanisms remain poorly understood. To identify potential biomarkers and therapeutic targets, we applied Mendelian randomization to examine over 2,500 proteins measured in plasma and, uniquely, cerebrospinal fluid, in relation to magnetic resonance imaging (MRI) markers of cSVD in more than 40,000 individuals. Here we show that 49 proteins are associated with MRI markers of cSVD, most prominently in cerebrospinal fluid. We highlight associations that are consistent across platforms and ancestries, and supported by complementary observational analyses, and we explore differences …

Effect Of Material And Processing Lag Time On Radiant Energy Penetration And Modulus Of 3d-Printed Indirect Bonding Jig Materials, Megan Meyer, Kamal Awad, Baylie Subjeck, Joe C Ontiveros, Venu G Varanasi, F Kurtis Kasper

Faculty, Staff and Student Publications

Objective: To investigate the effect of the time between 3D printing and post-print processing (lag time) on the modulus and radiant energy penetration of 3D-printed indirect bonding jig materials.

Materials and methods: Three 3D-printed resins (Formlabs IBT Resin, SprintRay IDB 2, Pro3dure GR-18.1 IB) were tested for three lag times (0, 16 and 64 h; n = 10 per group). Radiant energy penetration was measured using a power meter, and Vickers hardness was assessed for composites cured through the samples. Mechanical properties were evaluated using uniaxial testing and three-point bending.

Results: Both the resin type and lag time significantly affected …

High-Risk Medications In Pediatric Dentistry: Patterns, Outcomes, And Clinical Implications, Yilei Liu, Kawtar Zouaidi, Colin C Hubbard, Muhammad F Walji, Matthew R Cooke, Donald B Rindal, Kristin N Ray, Elsbeth Kalenderian, Katie J Suda

Faculty, Staff and Student Publications

Background: High-risk medications such as opioids and benzodiazepines are frequently prescribed in pediatric dental care, yet their prescribing patterns and associated adverse outcomes remain poorly understood. The aim of this study was to determine the extent of such prescribing to pediatric patients and factors associated with adverse outcomes.

Methods: MarketScan data for patients younger than 18 years with a dental visit from 2014 through 2019 were analyzed. High-risk medications included benzodiazepines, barbiturates, and opioids. Composite outcomes included hospitalization, emergency department visit, or urgent care visit within 7 days after the dental visit. Opioid-attributable outcomes included opioid-related overdose within 7 days …

Alk5 Inhibitor Impact On Bleomycin-Induced Systemic Sclerosis Mouse Model Via Multifunctional Optical Coherence Tomography, Pavel V Nikitin, Harshdeep S Chawla, Jessica Gutierrez, Geethangili Madamanchi, Manmohan Singh, Salavat R Aglyamov, Minghua Wu, Jerry Alonso, Matthew Fronheiser, Juliana Coculo, Shuyan Du, Shervin Assassi, Kirill V Larin

Faculty, Staff and Student Publications

Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by fibrosis, vascular dysfunction, and immune dysregulation, leading to significant morbidity and mortality. Noninvasive imaging techniques are critical for monitoring disease progression and evaluating therapeutic interventions. This study investigates the technical feasibility of multifunctional optical coherence tomography (OCT)-based methods for longitudinal assessment of skin thickness, stiffness, and microvasculature in a murine SSc model as a translational, noninvasive, and quantitative method to study disease progression and treatment response. Our findings demonstrate significant structural, biomechanical, and vascular changes in the skin's stiffness, indicative of fibrosis, a hallmark of SSc. The application of SB …

Fam13a Polymorphism Is Associated With A Usual Interstitial Pneumonia Pattern In Patients With Systemic Sclerosis-Associated Interstitial Lung Disease, Elana J Bernstein, Francesco Boin, Brett Elicker, Yiming Luo, Yawen Ren, Meng Zhang, John Varga, Shervin Assassi

Faculty, Staff and Student Publications

Objectives: The MUC5B promoter single nucleotide polymorphism (SNP) rs35705950 has been associated with idiopathic pulmonary fibrosis (IPF) and RA-related interstitial lung disease (ILD), but not with SSc-ILD. We hypothesized that the MUC5B promoter polymorphism or other IPF susceptibility loci are associated with an increased risk for the uncommon SSc-usual interstitial pneumonia (UIP) endophenotype, rather than SSc-ILD in general.

Methods: We performed a cross-sectional study of SSc-ILD patients from four US Scleroderma Programs to investigate the frequency of MUC5B rs35705950 and 12 additional IPF susceptibility loci. SSc-ILD patients were stratified by high resolution chest CT (HRCT) imaging findings into UIP and …

Nocturnal Oxygen Therapy For Central Sleep Apnea In Patients With Heart Failure: A Multisite, Double-Blind, Sham-Controlled Randomized Clinical Trial (Loft-Hf), Susan Redline, Dongdong Li, Shahrokh Javaheri, Sanjay R Patel, Sairam Parthasarathy, James C Fang, Lee K Brown, Mark Dunlap, M Safwan Badr, Neomi Shah, Luqi Chi, Ruckshanda Majid, Mihaela Teodorescu, Garrick Stewart, Eileen Hsich, Tamar Polonsky, Justin Vader, Maryl R Johnson, Dennis Auckley, Henry Klar Yaggi, Andrew Kao, Ali Azarbarzin, Raichel Alex, Michael Rueschman, Lisa Wolfe, Daniel J Gottlieb, Scott A Sands, Phyllis C Zee, Reena Mehra, Babak Mokhlesi, Rami Khayat, Eldrin F Lewis, William T Abraham, Rui Wang

Faculty, Staff and Student Publications

Rationale: There are insufficient data to inform the management of central sleep apnea (CSA) in patients with heart failure with reduced ejection fraction (HFrEF). Nocturnal oxygen therapy (NOT) has been postulated to benefit CSA patients with HFrEF but has not been rigorously studied. Objectives: To compare NOT with sham NOT (control) in heart failure (HF) patients receiving guideline-based HF therapy on the composite outcome of first occurrence of either mortality due to any cause, a lifesaving cardiovascular intervention, or an unplanned hospitalization for worsening HF, together with other secondary outcomes.

Methods: A multisite, double-blind, sham-controlled randomized clinical trial was conducted …

Combining Pirfenidone With Mycophenolate Mofetil For Systemic Sclerosis-Related Interstitial Lung Disease (Scleroderma Lung Study Iii): An Investigator-Initiated, Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial, Dinesh Khanna, Cathie Spino, Donald P Tashkin, Elana J Bernstein, Jonathan Goldin, Eric C Kleerup, Airi Harui, Grace Ibrahim, Grace Hyun J Kim, Suiyuan Huang, Richard Mclain, Yi-Hsuan Tu, Vivek Nagaraja, Richard M Silver, Virginia D Steen, S Samuel Weigt, Joyce S Lee, Aryeh Fischer, Mary Beth Scholand, Jessica K Gordon, Paul F Dellaripa, Ivan O Rosas, Gary M Hunninghake, Marcin A Trojanowski, Robert W Simms, Jane E Dematte, Vivien M Hsu, Robyn T Domsic, Ganesh Raghu, Maureen D Mayes, Ryan D Boente, Michael D Roth

Faculty, Staff and Student Publications

Objective: Mycophenolate mofetil (MMF) can stabilize or improve lung function in systemic sclerosis-related interstitial lung disease (SSc-ILD). We hypothesized that combining MMF with pirfenidone (PFD) would produce a significantly more rapid and/or greater improvement in lung function.

Methods: A randomized (1:1), double-blind, placebo (PLA)-controlled phase 2 trial was conducted in SSc-ILD in which patients received PFD or PLA (801 mg three times daily) along with MMF (1,500 mg twice daily) for 18 months. The primary outcome was change in percent predicted forced vital capacity (FVC-%). Linear mixed-effects models assessed treatment differences in a modified intention-to-treat population.

Results: Only fifty-one of …

Revisiting Soluble Guanylate Cyclase Pharmacology: Additive Potential Of Stimulators And Activators, Alexandra Petraina, Mahmoud H Elbatreek, Christopher T Neullens, Theodora Saridaki, Vu Thao-Vi Dao, Rebecca D Szepanowski, Emil Martin, Wolfgang Sippl, Ana I Casas, Harald H H W Schmidt

Faculty, Staff and Student Publications

Nitric oxide (NO) is a key gasotransmitter that binds to soluble guanylate cyclase (sGC), thereby stimulating cGMP production. Under disease conditions, reactive oxygen species disrupt this signaling by either: (1) scavenging NO, or (2) promoting heme-free, NO-insensitive apo-sGC due to impaired heme incorporation or oxidative damage. To counteract these conditions, two pharmacological approaches have emerged: sGC stimulators, which allosterically enhance sGC sensitivity to low NO levels; and sGC activators, which directly activate apo-sGC (heme-free sGC) by binding to its empty heme pocket, inducing a conformation that mimics NO-bound sGC. Thus, sGC stimulators are thought to target only sGC. Instead, we …

A Urine-Based Point-Of-Care Test For Factor Xa Inhibitors In Acute Stroke Management, Prasen R Marella, Jacob A Sambursky, Kriti Bhayana, Asha P Jacob, Varsha Muddasani, Murli Mishra, Alexandra L Czap, James C Grotta

Faculty, Staff and Student Publications

Background: For stroke patients with history of possible Direct Acting Oral Anticoagulant use, clinicians must make treatment decisions without knowledge of whether the patient is therapeutically anticoagulated. A urine-based point-of-care test might help guide these emergency decisions.

Methods: We prospectively enrolled patients with suspected recent factor-Xa-inhibitor (Xai) use being evaluated for acute stroke therapy in an urban teaching hospital. We obtained the urine test and plasma anti-Xa level in parallel with usual clinical management; the treating clinician did not use test results for decision-making but recorded treatment they would have given had they known the urine test was accurate. The …

Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells For Parkinson's Disease: A Randomized Trial., Mya C Schiess, Jessika Suescun, Juan D Martinez-Lemus, Charles Green, Tia S Thomas, Mohammad Shahnawaz, Emily Tharp, Nikunj B Satani, Jerome G Saltarrelli, Christopher Adams, Marie-Francoise Doursout, Vanessa Thyne, Rula Abuamouneh, Elsa M Rodarte, Sean I Savitz, Timothy M Ellmore

Faculty, Staff and Student Publications

Background: Neuroinflammation contributes to Parkinson's disease (PD) progression and motor dysfunction. Allogeneic human mesenchymal stem cells (allo-hMSCs) may reduce neuroinflammation and improve motor symptoms.

Objectives: To evaluate the efficacy of repeated intravenous doses of 10 × 106/kg allo-hMSCs in improving motor symptoms in patients with PD (PwP).

Methods: In this phase 2, randomized, placebo-controlled trial (November 2020-July 2023), mild-to-moderate PwP received either three allo-hMSC infusions, one placebo followed by two allo-hMSC infusions, or three placebo infusions at 18-week intervals. Follow-up lasted 88 weeks. The primary outcome was a >70% posterior probability (PP) of a difference in the proportion of participants …

Prospective Trial Of Cerebrospinal Fluid Filtration After Aneurysmal Subarachnoid Hemorrhage Via Lumbar Catheter Extension (Pillar-Xt), Spiros L Blackburn, Marc A Babi, Andrew W Grande, Omar A Choudhri, Erik F Hauck, Christopher P Kellner, Michael C Giordano, Shivanand P Lad, Aaron R Mccabe

Faculty, Staff and Student Publications

Background: There is a growing consensus that blood in the cerebrospinal fluid (CSF) is deleterious to outcomes in patients with aneurysmal subarachnoid hemorrhage. The extracorporeal filtration of subarachnoid hemorrhage via spinal catheter extension study evaluated the safety, tolerability, and filtration curve of blood and its lysis products from hemorrhagic CSF using the Neurapheresis CSF Management System.

Methods: After aneurysm repair, a dual-lumen intrathecal catheter was inserted into the study participant's spinal canal. CSF was extracorporeally filtered for up to 72 h, removing blood products from the lumbar cistern, and reintroducing filtered CSF to the thoracic subarachnoid space. Neurological examinations were …

Short-Term Preeclampsia Prediction: Cutoff Variations For Sflt-1/Plgf In U.S. Patients With Or Without Hypertensive Disorders, Yaxin Li, Kristen Cagino, Jim Yee, Caroline Andy, Dajana Borova, Ayush Shah, Isla Racine, Tracy B Grossman, Zhen Zhao

Faculty, Staff and Student Publications

Background: Preeclampsia (PE) is a complex disorder with significant maternal and fetal risks. The soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) ratio shows promise as a diagnostic tool, but its adoption in the U.S. remains limited due to the lack of accessible testing platforms, U.S.-based studies, and evidence-based implementation guidelines.

Patients/materials and methods: We conducted a cohort study to evaluate the sFlt-1/PlGF ratio for predicting PE within two weeks among pregnant individuals ≥18 years, ≥20 weeks gestation. Serum samples were obtained from routine prenatal visits or triage evaluations. sFlt-1/PlGF ratios were measured using Roche Elecsys assays, and …