Digital Commons Network^™

Mepolizumab Improves Outcomes In Patients With Crswnp With One Or More Prior Nasal Polyp Surgeries, Joseph K. Han, Joaquim Mullol, Martin Wagenmann, Laura Walrave, Lingjiao Zhang, Ana R. Sousa, Peter Howarth, Claire Hopkins

Department of Otolaryngology (ENT) Faculty Publications

BACKGROUND: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) often undergo multiple nasal surgeries. The Phase III SYNAPSE study (GSK ID:205687; NCT0308579) demonstrated that mepolizumab reduces the need for repeat surgery. We explored whether outcomes differed based on the number of prior surgeries. METHODOLOGY: This post hoc analysis of SYNAPSE stratified patients by history of 1 or more than 1 prior surgery. Patients were randomised to receive mepolizumab or placebo every 4 weeks, alongside standard of care, for 52 weeks. Outcomes included change from baseline in endoscopic nasal polyp (NP) score, visual analogue scale (VAS) scores for nasal obstruction, loss …

Educational Interventions To Prepare Undergraduate Students For Out-Of-Hours Practice As A Newly Qualified Doctor In The United Kingdom: A Scoping Review, Alex Gordon, Molly Parkinson, Rosanna Watts, Kamal El-Badawi, Erin Dawson, Rohan Chiktara, Lorna Burns, Nicola Brennan

Peninsula Dental School

Background: In the United Kingdom (UK), newly qualified doctors are routinely responsible for out-of-hours (OOH) care, often managing acutely unwell patients with limited supervision. Despite national recommendations encouraging OOH experience during medical school training, there is no formal curriculum for OOH practice. Objectives: This scoping review aimed to identify the range of educational interventions designed to prepare UK medical students for OOH clinical responsibilities and assess their reported effects on perceived and actual preparedness. Methods: Following Joanna Briggs Institute methodology, a systematic search of seven databases and grey literature sources was conducted. Eligible studies involved UK-based medical students and reported …

Seeing Anxiety: Ecological Video Ethnography And Simulation To Understand Anxiety And Decision-Making In Dental Care, Mona Nasser, Hannah Drayson, Sally Hanks, Nicholas Peres, Michael Punt

Peninsula Dental School

BACKGROUND: Dental anxiety is a widespread barrier to care, often contributing to appointment avoidance, treatment disruption, and emotional strain for both patients and clinicians. While extensively studied as a psychological trait, less attention has been paid to how anxiety manifests situationally and relationally, through non-verbal, affective, and spatial cues within clinical encounters. Moreover, in certain contexts, such affective signals can intersect with decision-making processes, shaping how patients interpret, engage with, or withdraw from clinical choices.

OBJECTIVE: To explore how anxiety manifests within the micro-choreography of dental encounters, develop a taxonomy of 'anxious tells', and assess the utility of ecological video …

Chronobiology Of Meal Timing In Early-Stage Hypertension: A Controlled Feeding Pilot Study Investigating The Effects On Renal And Vascular Function, Natalie J. Bohmke, Brittany Barton, Patrice Wiecek, Paula Rodriguez-Miguelez, Dave L. Dixon, Youngdeok Kim, Salvatore Carbone, Danielle L. Kirkman

EVMS School of Health Professions Faculty Publications

Lifestyle intervention is critical for young adults with early-stage hypertension. A Western diet has negative effects on kidney function and blood pressure; however, time-of-day effects are understudied. We hypothesized that consumption of a Western-style meal that is misaligned with the endogenous circadian rhythm would have adverse effects on blood pressure, kidney function, and vascular function. Ten young adults with elevated blood pressure or stage 1 hypertension (means ± SD: 26 ± 8 yr, 50% female) underwent a randomized crossover, isocaloric controlled feeding intervention. Participants were allocated to receive a Western-style meal high in sodium, sugar, and saturated fat in the …

The Treatment Of Obesity In The Context Of The Obesity Paradox In Patients With Heart Failure: A Narrative Review, Pamela L. Alebna, Sarah Martey, Anurag Mehta, Carl J. Lavie, Salvatore Carbone

EVMS School of Health Professions Faculty Publications

Purpose of review

While excess adiposity is a known risk factor for incident heart failure ( HF), once the condition is established, observational data suggest that increased body mass index (BMI) may confer a survival advantage. This paradox has emphasized the underlying roles of cardiorespiratory fitness (CRF), and body composition, particularly lean mass (LM), in influencing clinical outcomes.

Recent findings

In this review, we explore the multifaceted nature of the obesity paradox in HF, with a focus on emerging anti-obesity incretin-mimetic therapies, such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists. These agents …

First-Generation Medical School Applicants: A Quantitative Study Designed To Identify Areas Of Educational Support, Bethsabe Romero, Amanda K. Burbage

EVMS School of Health Professions Faculty Publications

First-generation (First Gen) students are unique medical school applicants. Due to their lived experience, they approach patient care by prioritizing trust, comfort and understanding. They have proven ability to overcome obstacles and were found to be more resilient than their continuing generation (Cont Gen) peers. Despite these notable attributes, they face unique challenges in gaining medical school acceptance. There are very few quantitative studies examining this student subpopulation, and our study identifies characteristics of first-generation medical school applicants while highlighting areas of needed support. This cross-sectional study used deidentified Application and Matriculating Student Questionnaire survey data that was obtained from …

Crossing The Theory Threshold: The Pedagogical Potential Of Generative Artificial Intelligence In Educational Research, Amanda Burbage, Jennifer L. Styron

EVMS School of Health Professions Faculty Publications

Purpose

This paper presents findings from an educational research graduate course in which generative artificial intelligence (AI) was incorporated to strengthen learners' understanding of threshold concepts related to theoretical frameworks. Medical and health professionals often struggle with the transition from a clinical role into the educational research role.

Methods

The study posits that the use of generative AI will help learners understand and apply theoretical frameworks beyond a superficial level, furthering their understanding, constructing new knowledge, and strengthening their ability to develop sound educational research studies. Journal and AI transcripts were analyzed for 37 participants.

Results

Open-ended codes were grouped …

Formulation Development Of Topical Inserts Containing Doxycycline And Doxycycline Combined With Tenofovir Alafenamide And Elvitegravir For The Prevention Of Sexually Transmitted Infections, Vivek Agrahari, M. Melissa Peet, Jasmin Monpara, Rijo John, Sriramakamal Jonnalagadda, Pardeep K. Gupta, Meredith R. Clark, Gustavo F. Doncel

CONRAD Publications

Despite advances in oral and injectable HIV prevention options and oral prophylaxis for sexually transmitted infections (STIs) of bacterial origin, there remains a critical need for effective on-demand topical (vaginal and rectal) products for pre- and post-exposure prophylaxis (PrEP and PEP). To fill this gap, we have developed single and first-in-kind multi-active topical inserts for bacterial STIs and HIV/STIs prevention. We have formulated two different inserts, one containing doxycycline (DOX) at 10, 50, and 100 mg doses for bacterial STI prevention, and a multipurpose prevention product (TED insert) that combines DOX (10 mg) with the antiretrovirals tenofovir alafenamide (TAF; 20 …

Micrornas Regulated By Pregnancy Target Antiviral And Cancer Immunity Overlapping With The Hiv Interactome, Paula F. T. Cezar-De-Mello, Jonathan M. Dreyfuss, Pai-Lien Chen, Hidemi Yamamoto, Xiaoming Gao, Hui Pan, Charles Morrison, Gustavo F. Doncel, Robert L. Barbieri, Raina N. Fichorova

CONRAD Publications

Innate immunity predictors of HIV-1 risk and pathogenesis vary with reproductive hormones, pregnancy, and lactation, yet the underlying mechanisms remain unclear. We hypothesized that pregnancy-associated physiological adaptations alter systemic microRNA (miRNA) expression, thereby regulating immunity, pathogenesis and susceptibility to infection. We analyzed 174 serum samples from 88 participants in a longitudinal cohort from Uganda and Zimbabwe across pre-pregnancy (PP), pregnancy (P), and postpartum breastfeeding (BF). Cell-free peripheral blood miRNAs (n = 2083) were profiled using HTG EdgeSeq. Pregnancy-specific miRNAs were identified by intersecting differentially expressed (DE) miRNAs from P vs. PP and P vs. BF comparisons. miRNA targets and pathways …

Predicting Oral Hiv Pre-Exposure Prophylaxis Efficacy In Cisgender Women Across Pregnancy And Postpartum, Yifan Yu, Kristina M. Brooks, Gustavo F. Doncel, Brookie M. Best, Mark A. Marzinke, Mark Mirochnick, Peter L. Anderson, Landon Myer, Connie Celum, Renee Heffron, Jenell Coleman, Dvora L. Joseph Davey, Lanxin Zhang, Max Von Kleist, Craig W. Hendrix, Jeremiah D. Momper, Robert Bies, Rachel K. Scott

CONRAD Publications

Cisgender women face an increased risk of HIV acquisition during pregnancy and postpartum. Oral pre-exposure prophylaxis (PrEP) with emtricitabine and tenofovir disoproxil fumarate (F/TDF) is recommended in pregnancy despite limited published pharmacokinetic (PK) and efficacy data during pregnancy. Altered PK during pregnancy may reduce prophylactic efficacy and necessitate higher adherence. Tenofovir alafenamide (TAF) is a newer tenofovir prodrug with higher tenofovir diphosphate (TFV-DP) exposure in peripheral blood mononuclear cells (PBMCs), but the prophylactic efficacy of F/TAF across different reproductive stages in women is understudied. We adapted a multiscale modeling framework to predict the prophylactic efficacy of F/TDF and F/TAF across …

Stim1-Dependent Treg Dysfunction Promotes Cardiometabolic Hfpef: Insights From Patients And Animal Studies, Balaji Srinivas, Alluri Kiran, Hongmei Peng, Jiang Xu, Paula Fortuno, Jennifer May, Ismail El Moudden, Nour-Eddine Rhaleb, John M. Herre, Raymond L. Benza, Khalid Matrougui

Department of Biomedical and Translational Sciences Faculty Publications

Background

Heart failure with preserved ejection fraction (HFpEF) arises from chronic cardiometabolic and vascular stress and is increasingly recognized as an inflammatory syndrome with immune dysregulation. Regulatory T cells (Tregs) are critical modulators of cardiovascular inflammation, yet the mechanisms driving Treg dysfunction in HFpEF remain poorly defined. stromal interaction molecule 1 (STIM1)-dependent calcium signaling is a key stress-responsive pathway in immune cells; however, its role in Treg maladaptation during HFpEF remains unknown.

Methods

Circulating Tregs from patients with and without HFpEF were analyzed for abundance, STIM1 expression, and stress-associated signaling pathways. To establish causality, mice with Treg-specific deletion of STIM1 …

Exploring The Acceptability Of Integrating Dietitians Into Primary Care Dental Services For Children, Lauren Hallewell, Raul Bescos, Zoe Brookes, Tracey Parkin, Robert Witton, Patricia Casas-Agustench

School of Health Professions

BACKGROUND: Dental caries is a common childhood non-communicable disease strongly associated with high sugar intake. Beyond oral health, a poor diet can affect children's growth, development, and overall well-being. While dietary advice is central to preventive dental care, some primary care dental clinics have introduced body mass index (BMI) assessments and further dietary advice to address wider nutritional concerns in children. However, these efforts are often constrained by limited nutrition training, time constraints and concerns about sensitivity. Integrating dietitians into primary dental care may help overcome these barriers by enhancing dietary guidance, supporting broader nutritional needs and facilitating structured BMI …

Ex Vivo Assessment Of Keratinocytic Carcinomas Using A Fast Mid-Infrared Probe., Maria G Vazquez De Vasquez, Rebecca C Bradley, Charles L Hitchcock, Angela S Casey, Austin Cusick, James V Coe, Ronald Siegle

Ambulatory and Primary Care Articles

A fast mid-infrared spectral probe was used to record infrared (IR) spectra of fresh skin tissue removed from patients with biopsy-proven keratinocytic cancer (KC) during Mohs surgery. A 150-patient library of IR spectral data was obtained to see if KC on the epidermal side (outside) of tissue samples can be differentiated from adjacent nonmalignant tissue and normal skin. A linear support vector machine model minimized overtraining predicting the contributions to decisions at each step in the spectrum. Training with an equal cost for KC and nontumor cases samples demonstrated a KC sensitivity of 93% ± 5% and specificity 82% ± …

Multi-Omics To Study Chronic Respiratory Diseases And Viral Infections, Sobia Idrees, Hao Chen, Tayyaba Sadaf, Saima Firdous Rehman, Matt D Johansen, Keshav Raj Paudel, Gang Liu, Yuting Wang, Malte D Luecken, Elinor Hortle, Ashleigh S Philp, Kurtis F Budden, Matthew O'Rourke, Gerard E Kaiko, Sionne E M Lucas, Joanne L Dickinson, Peter C Allen, Joseph E Powell, Lai-Ying Zhang, Daniel C Chambers, Tamera Corte, Gaetano Caramori, Maor Sauler, Peter A Wark, Janine Gote-Schniering, Mareike Lehmann, Thomas M Conlon, Theodore S Kapellos, Ali Önder Yildirim, Rosa Faner, Shyamali C Dharmage, Craig E Wheelock, Maarten Van Den Berge, Martijn C Nawijn, Francesca Polverino, Gabrielle T Belz, Sanjay H Chotirmall, Leopoldo N Segal, Alen Faiz, Philip M Hansbro

Faculty, Staff and Students Publications

Integrating omics layers reveals complex biological systems, unveiling vital insights into chronic respiratory diseases and COVID-19. This holistic approach is crucial for developing more effective treatments and understanding intricate relationships. https://bit.ly/3VKFzJH

Non-Congenital Hsv-1 Keratitis In An Immunocompetent 9-Month-Old Infant, Caleb A Casanova, Stephanie Trejo Corona, Stephen F Pflugfelder

Faculty, Staff and Students Publications

Isolated, non-congenital herpes simplex virus type 1 (HSV-1) keratitis in immunocompetent infants is exceedingly rare and may be easily misdiagnosed, leading to delays in appropriate antiviral therapy. This case is unique in that it describes HSV-1 keratitis in a healthy 9-month-old infant presenting without systemic illness, initially treated as bacterial conjunctivitis. The patient presented with unilateral eye pain, redness, and corneal opacification. Subsequent evaluation revealed HSV-1 keratitis, and the patient was treated with intravenous acyclovir in combination with topical moxifloxacin and topical ganciclovir, resulting in complete resolution of symptoms within one week. This case adds to the limited literature on …

Highly Variable Expressivity Of A Cnv Deletion Involving Tbx4 In Three Deceased Siblings With Lung Developmental Disorder And Their Mildly Affected Mother And Grandfather, Przemyslaw Szafranski, Tomasz Gambin, Michal Kadlof, Michał Denkiewicz, Dariusz Plewczynski, Hyun Jeong Kim, Gail Deutsch, Nahir Cortes-Santiago, Salmo Raskin, Paweł Stankiewicz

Faculty, Staff and Students Publications

Single nucleotide variants (SNVs) and copy-number variant (CNV) deletions involving TBX4 have been associated with pulmonary arterial hypertension, ischiocoxopodopatellar syndrome, and lethal lung developmental disorders (LLDDs). Thus far, all large CNV deletions encompassing entire TBX4 have been found to have arisen de novo. Here, we present a three-generation family with three neonate siblings who died within 35-66 days due to histopathologically diagnosed LLDD. Whole-genome sequencing identified an ~108-kb CNV deletion encompassing TBX4 in all three infants. The deletion was also found in their mother with a history of pneumonia and persistent thick upper airway secretions and in the maternal grandfather …

Noradrenergic Innervation Across Brain Regions Is Altered By Aging And By Disease Progression In A Mouse Model Of Alzheimer’S Disease Neuropathology, Nicole M Hernandez, Manuel Silva-Pérez, Jeannie Chin

Faculty, Staff and Students Publications

Norepinephrine plays critical roles in modulating arousal and attention, is highly dynamic in awake, behaving individuals, and has anti-inflammatory and neuroprotective actions. Notably, the locus coeruleus (LC), the primary source of norepinephrine in the central nervous system, is among the first brain regions to show pathological alterations in early stages of Alzheimer's disease (AD). LC neuronal loss and associated reductions in norepinephrine in the brain have therefore been postulated to play a key role in AD pathophysiology. LC neurons and their axons have been studied in several mouse models of AD-related neuropathology to investigate their contribution to brain dysfunction in …

Frontline Aspiration Versus Stent Retriever Thrombectomy For M2 Occlusions: Insights From The Star Registry, Michael Gaub, Rahim Abo Kasem, Ilko Maier, Ansaar Rai, Pascal Jabbour, Joon-Tae Kim, Brian Howard, Ali Alawieh, Stacey Quintero Wolfe, Robert M Starke, Marios-Nikos Psychogios, Amir Shaban, Nitin Goyal, Justin Dye, Ali Alaraj, Mohamad Ezzeldin, Shinichi Yoshimura, David Fiorella, Omar Tanweer, Daniele G Romano, Pedro Navia, Hugo Cuellar, Isabel Fragata, Adam Polifka, Joshua Osbun, Fazeel Siddiqui, Mark Moss, Kaustubh Limaye, Maxim Mokin, Charles Matouk, Min S Park, Waleed Brinjikji, Ergun Daglioglu, Richard Williamson, David J Altschul, Christopher S Ogilvy, Roberto Crosa, Michael R Levitt, Benjamin Gory, Alexandra Paul, Peter Kan, Walter Casagrande, Shakeel Chowdhry, Michael F Stiefel, Ramesh Grandhi, Alejandro Spiotta, Justin Mascitelli

Faculty, Staff and Students Publications

Background: Recent trials have furthered uncertainty regarding the endovascular benefit for medium vessel occlusions (MeVO). Stent retrievers (SR) were employed in the first attempt in most interventional arm participants. We sought to compare outcomes in acute MCA M2 occlusions between frontline aspiration and SR, and to delineate procedural and anatomical covariates associated with differential treatment effect.

Methods: Retrospective analysis of a multicenter stroke thrombectomy cohort identified cases of MT for M2 occlusions. Unmatched and propensity score-matched (PSM) cohorts were generated comparing frontline aspiration to standalone and combined SR. The primary outcome was functional independence (mRS 0-2) at 90 days. Recanalization, …

Comparing Rotational Thromboelastometry And Standard Coagulation Assays For Predicting Intraoperative Bleeding In Pediatric Liver Transplantation, Kirby Deshotels, Trung Nguyen, Jun Teruya, Muhammed Umair M Mian, Kelby Fuller, Sanjiv Harpavat, Anna Banc-Husu, Amir Navaei, John Goss, Moreshwar Desai, Arun Saini

Faculty, Staff and Students Publications

Background: Utility of preoperative rotational thromboelastometry (ROTEM) over standard coagulation assays (SCAs) in predicting intraoperative bleeding during orthotopic liver transplantation (OLT) in children with liver failure (LF) remains unclear.

Methods: In this single-center retrospective cohort of pediatric OLT recipients, we compared the predictive values of preoperative ROTEM parameters (intrinsic pathway (INTEM) maximum clot firmness (MCF), extrinsic pathway (EXTEM) clotting time (CT), INTEM CT, and fibrinogen-based (FIBTEM) MCF) and the corresponding SCAs (platelet count, international normalized ratio (INR), activated partial thromboplastin time (aPTT), and fibrinogen level, respectively) for significant intraoperative bleeding (blood loss of > 22 mL/kg; i.e., ≥ 85th percentile for …

Organ Chips And Translational Research: Identifying And Examining New Ethical Issues, Melanie Jeske

Center for Medical Ethics and Health Policy Staff Publications

Organ chips, also known as organ-on-a-chip devices, tissue chips, or microphysiological systems, have emerged over the last decade as a promising translational technology amidst growing concern about the translational crisis between laboratory research and patient bedside. Pointing to high rates of failure between nonhuman animal models and safety and efficacy in humans, organ chips and similar new approach methods have attracted substantial public and private investment. As human-cell-based alternatives to animal models, organ chips promise more predictive, efficient, and ethical platforms for pharmaceutical and toxicity testing. Engineered cultivation systems that enable cells to assemble into tissue-like structures (e.g. kidney, brain, …

Anything But Endo: Diagnostic Buck-Passing In Endometriosis Diagnosis, Rita Dexter, Megan Kitts, Heather Welty, Melanie Jeske

Center for Medical Ethics and Health Policy Staff Publications

People living with endometriosis, a disease in which tissue similar to the lining of the uterus grows elsewhere in the body, often experience prolonged diagnostic journeys because of symptom variability, normalisation of period pain and other symptoms, and lack of awareness of the condition. In this article, we analyse the endometriosis diagnostic journey through the lens of epistemic injustice. Drawing on in-depth interviews with 52 people living with endometriosis in the United States, we introduce the concept of diagnostic buck-passing to characterise the phenomenon wherein individuals who seek treatment for their symptoms end up stuck in a cycle of seeing …

Differences Between Government, Consortium, And Private Database Stewards Impacting The Genomic Data Market: A Survey Of U.S. Academic Genetic Researchers., Amanda K Greene, J Denard Thomas, Kaitlyn Jaffe, Luyun Chen, Kerry A Ryan, Brian J Zikmund-Fisher, J Scott Roberts, Amy L Mcguire, Katherine Hendy, Kayte Spector-Bagdady

Center for Medical Ethics and Health Policy Staff Publications

Background: Despite major shifts in U.S. federal government data sharing requirements, their impact, and relation to researcher choice of database, are underexplored. This study surveyed genetic researchers regarding trends, priorities, perceptions of quality, impact on research outcomes, and genomic data sharing and use across government, consortium, and private databases.

Methods: As part of an exploratory sequential mixed methods project, we surveyed 294 U.S.-based genomic academic researchers.

Results: Genetic researchers generally have a choice between databases, which allows them to prioritize data quality. This might explain recent trends toward the use of government and consortium databases away from private ones. Respondents …

Can I Get A Witness? The Ethical Dimensions Of Family Presence In Patient Suffering, Jennifer Blumenthal-Barby, Trevor M Bibler, Holland Kaplan, Adam Omelianchuk, Joanna Smolenski

Center for Medical Ethics and Health Policy Staff Publications

For patients who are suffering, the bedside presence of a family member can provide comfort, and many people hold that there is moral value in being present with a conscious, suffering patient. Yet what is the moral significance of the absence of family members when a patient is minimally conscious or unconscious and not aware of their absence? Clinicians are often troubled when family members and surrogate decision-makers who are able to spend a significant amount of time at an unconscious, seriously ill patient's bedside do not do so. Clinicians feel frustrated that they must bear the burden of witnessing …

Toward Ethical Provenance Tracking: The Ga4gh Model Data Access Agreement (Daa), Alexander Bernier, Bartha Maria Knoppers, Jonathan Lawson, Robyn Mcdougall, Maili Raven-Adams, Vasiliki Rahimzadeh

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Standardizing contractual clauses that govern data access enables research institutions to responsibly steward genomic and related health data while enabling its efficient downstream reuse.

Methods: We describe a document analysis study using both qualitative and comparative law analytical approaches to identify the most common categories of clauses from 29 different data access agreements used by human biomedical research consortia globally. We furthermore characterized the legal positions and standard practices for each common element of the agreement and synthesized across them to develop model clauses. A total of 3 discussion sessions were organized virtually to refine the clauses among members …

Refining Aicardi Syndrome Diagnostic Criteria: An Expert-Based Consensus Using A Modified Delphi Approach, Silvia Masnada, Valentina De Giorgis, Umberto Carugo, Nadia Bahi-Buisson, Mara Cavallin, Mark Corbett, Manuela Formica, Jozef Gecz, Natalia Petros, Emilio Perucca, Anna Pichiecchio, Paolo Fusar Poli, Elliott H Sherr, Ignatia B Van Den Veyver, Federico Zara, Martin Geroldinger, Pierangelo Veggiotti, Alexis Arzimanoglou

Duncan NRI Faculty and Staff Publications

Background and objectives: Aicardi syndrome (AIC) is a rare neurodevelopmental disorder historically characterised by the presence of chorioretinal lacunae, corpus callosum agenesis, infantile spasms and several supporting features that aid in diagnosis. However, the unclear aetiology and evolving diagnostic tools have led to ongoing reconsideration of the criteria, based on individual approaches. Our study aimed to establish, for the first time, an expert-based consensus on diagnostic criteria for AIC by integrating both existing and novel ones.

Methods: A geographically diverse and multidisciplinary group of expert physicians was invited to participate in a modified Delphi study, to achieve consensus on major, …

Genome-Wide Gene-Sleep Interaction Study Identifies Novel Lipid Loci In 732,564 Participants, Raymond Noordam, Wenyi Wang, Pavithra Nagarajan, Heming Wang, Michael R Brown, Amy R Bentley, Qin Hui, Aldi T Kraja, John L Morrison, Jeffrey R O'Connel, Songmi Lee, Karen Schwander, Traci M Bartz, Lisa De Las Fuentes, Mary F Feitosa, Xiuqing Guo, Xu Hanfei, Sarah E Harris, Zhijie Huang, Mart Kals, Christophe Lefevre, Massimo Mangino, Yuri Milaneschi, Peter J Van Der Most, Natasha L Pacheco, Nicholette D Palmer, Varun Rao, Rainer Rauramaa, Quan Sun, Yasuharu Tabara, Dina Vojinovic, Yujie Wang, Stefan Weiss, Qian Yang, Wei Zhao, Wanying Zhu, Md Abu Yusuf Ansari, Hugues Aschard, Pramod Anugu, Themistocles L Assimes, John Attia, Laura D Baker, Christie Ballantyne, Lydia Bazzano, Eric Boerwinkle, Brain Cade, Hung-Hsin Chen, Wei Chen, Yii-Der Ida Chen, Zekai Chen, Kelly Cho, Ileana De Anda-Duran, Latchezar Dimitrov, Anh Do, Todd Edwards, Tariq Faquih, Aroon Hingorani, Susan P Fisher-Hoch, J Michael Gaziano, Sina A Gharib, Ayush Giri, Mohsen Ghanbari, Hans Jörgen Grabe, Mariaelisa Graff, C Charles Gu, Jiang He, Sami Heikkinen, James Hixson, Yuk-Lam Ho, Michelle M Hood, Serena C Houghton, Carrie A Karvonen-Gutierrez, Takahisa Kawaguchi, Tuomas O Kilpeläinen, Pirjo Komulainen, Henry J Lin, Gregorio V Linchangco, Annemarie I Luik, Jintao Ma, James B Meigs, Joseph B Mccormick, Cristina Menni, Ilja M Nolte, Jill M Norris, Lauren E Petty, Hannah G Polikowsky, Laura M Raffield, Stephen S Rich, Renata L Riha, Thomas C Russ, Edward A Ruiz-Narvaez, Colleen M Sitlani, Jennifer A Smith, Harold Snieder, Tamar Sofer, Botong Shen, Jingxian Tang, Kent D Taylor, Maris Teder-Laving, Rima Triatin, Michael Y Tsai, Henry Völzke, Kenneth E Westerman, Rui Xia, Jie Yao, Kristin L Young, Ruiyuan Zhang, Alan B Zonderman, Xiaofeng Zhu, Jennifer E Below, Simon R Cox, Michelle Evans, Myriam Fornage, Ervin R Fox, Nora Franceschini, Sioban D Harlow, Elizabeth Holliday, M Arfan Ikram, Tanika Kelly, Timo A Lakka, Deborah A Lawlor, Changwei Li, Ching-Ti Liu, Reedik Mägi, Alisa K Manning, Fumihiko Matsuda, Alanna C Morrison, Matthias Nauck, Kari E North, Brenda Wjh Penninx, Michael A Province, Bruce M Psaty, Jerome I Rotter, Tim D Spector, Lynne E Wagenknecht, Ko Willems Van Dijk, Lifelines Cohort Study, Million Veteran Program, Cashell E Jaquish, Peter Wf Wilson, Patricia A Peyser, Patricia B Munroe, Paul S De Vries, W James Gauderman, Yan V Sun, Han Chen, Clint L Miller, Thomas W Winkler, Dabeeru C Rao, Susan Redline, Diana Van Heemst

Faculty, Staff and Student Publications

Background and aims: Deviations from the population mean in sleep duration have been associated with increased risk for developing dyslipidemia and atherosclerotic cardiovascular disease, but the mechanism of effect is poorly characterized. We performed large-scale genome-wide gene-sleep interaction analyses of lipid levels to identify genetic variants underpinning the biomolecular pathways of sleep-associated lipid disturbances and to suggest possible druggable targets.

Methods: We collected data from 55 cohorts with a combined sample size of 732,564 participants (87 % European ancestry) with data on lipid traits (high-density lipoprotein [HDL-c] and low-density lipoprotein [LDL-c] cholesterol and triglycerides [TG]). Short (STST) and long (LTST) …

Alternative Polyadenylation Signatures Distinguish Maladaptive Right Ventricular Remodeling In Pulmonary Hypertension: Implications For Rna-Based Diagnostics And Therapeutics, Janani Subramaniam, Venkata Jonnakuti, Scott D Collum, Sandra Martineau, Kai-Lieh Huang, Sandra Breuils-Bonnet, Andrea L Frump, Bindu H Akkanti, Jayeshkumar A Patel, Manish K Patel, Ismael Salas De Armas, Isabella N Lefebvre, Rajko Radovancevic, Elvin Blanco, Eric J Wagner, Igor Gregoric, Sriram Nathan, Biswajit Kar, Steeve Provencher, Sebastien Bonnet, François Potus, Hari Krishna Yalamanchili, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

Increased pulmonary vascular pressures due to vascular remodeling, elevated vascular resistance, and vasoconstriction characterize Pulmonary Arterial Hypertension (PAH). The narrowing of the pulmonary arteries and obstruction of blood flow increase the Right Ventricular (RV) afterload, forcing the RV to undergo structural and functional changes. While adaptive remodeling leads to RV compensation by maintaining function, maladaptive remodeling leads to RV decompensation, characterized by worsening function and eventual failure. At present, there is no effective treatment for these patients as therapies for left ventricular failure are ineffectual, and there are no therapies specifically targeting the RV. Therefore, there is a clear need …

Access To Digital Health Technologies: Personalized Framework And Global Perspectives, Sanjiv M Narayan, Mina K Chung, Demilade Adedinsewo, Luisa C C Brant, Leslie L Davis, David Duncker, Jennifer L Hall, Janet K Han, Carolyn S P Lam, Eldrin Lewis, Joseph Loscalzo, Manlio F Márquez, Vasiliki Rahimzadeh, Fatima Rodriguez, Prashanthan Sanders, Emma Svennberg, Kenneth Stein, Mintu Turakhia, Clyde Yancy, Antonis A Armoundas

Center for Medical Ethics and Health Policy Staff Publications

The emergence and rapid adoption of digital health technologies (DHT) present unprecedented opportunities to democratize and reduce disparities in health care by monitoring health and disease at the point of care in all patients. However, limited access to DHT is becoming a major obstacle to realizing these goals. Access to DHT is influenced not only by well-recognized social determinants of health, but also by digital determinants of health, such as digital literacy and the need for broad access to digital infrastructure, as well as commercial and economic factors. Addressing these challenges and designing unbiased systems of care are essential to …

Test-Retest Apparent Diffusion Coefficient Reproducibility In Head And Neck Cancer Using A 15-T Mr-Linac, Brigid A Mcdonald, Dina El-Habashy, Renjie He, Sam Mulder, Sarah Mirbahaeddin, Abdallah S R Mohamed, Sara Ahmed, Yao Ding, Jihong Wang, Stephen Y Lai, Alex Dresner, John Christodouleas, Clifton D Fuller

Faculty, Staff and Student Publications

Purpose

To evaluate the reproducibility of apparent diffusion coefficient (ADC) measurements in head and neck squamous cell carcinoma (HNSCC) using a 1.5-T MR-linac (MRI-guided linear accelerator) system.

Materials and Methods

In this retrospective study, conducted between February 2021 and January 2024, patients with HNSCC lesions underwent echo-planar imaging diffusion-weighted MRI on a 1.5-T MR-linac system at two time points before the start of radiation therapy. Mean and median ADC values and volumes were measured for each lesion. Absolute and percent reproducibility coefficients (RCs) were calculated. Linear regression analyses and F tests were performed to determine whether the lesion volume or …

Insulinemic And Inflammatory Dietary Patterns And Colorectal Cancer Risk: A Dietary Data Harmonization Study Of One Million Participants In The Consortium Of Metabolomics Studies (Comets), Ni Shi, Rachel Hoobler, Rhea Harewood, Amanda E Toland, Demetrius Albanes, Emmanouil Bouras, Marc J Gunter, Linda M Liao, Steven C Moore, Fulvio Ricceri, Jerome I Rotter, Rashmi Sinha, Rachael Stolzenberg-Solomon, Anne Tjønneland, Alexis C Wood, Danxia Yu, Mary C Playdon, Fred K Tabung

Children’s Nutrition Research Center Staff Publications

Background: Inflammatory and insulinemic dietary patterns have been associated with colorectal cancer (CRC) risk, but generalizability across diverse populations with heterogeneous food supplies and dietary behaviors has not been established.

Objectives: We harmonized disparate dietary and covariate data on a large scale to compute the reverse Empirical Dietary Index for Hyperinsulinemia (rEDIH), reverse Empirical Dietary Inflammatory Pattern (rEDIP), and Healthy Eating Index (HEI)-2015 scores, and tested their associations with CRC risk.

Methods: We leveraged data among 501,892 women and 407,390 men from 6 cohorts across the United States (NIH-AARP, Multi-Ethnic Study of Atherosclerosis, Prostate, Lung, Colorectal, and Ovarian, SCCS) and …