Digital Commons Network^™

Sustained Lung Inflammation Post-Sars-Cov-2 Infection In Mice Is Associated With Increased Pulmonary T Cells., Sophie Y Guan, Patricia P Ogger, Ana Farias, Minerva Garcia Martín, Joy Nakawesi, Olivia Bedard, Candice N Baker, Nadia Rosenthal, Cecilia Johansson

Faculty Research 2025

Many SARS-CoV-2 patients experience chronic pulmonary symptoms and long-term inflammation despite viral clearance. While these clinical manifestations have been linked to the dysregulation of the adaptive immune response, the underlying immunopathology remains poorly understood due to a lack of suitable animal models. To investigate long-term pulmonary consequences of SARS-CoV-2 infection, we used a genetic cross of 129 mice and C57BL/6 (B6)-K18-hACE2 transgene mice, a model previously shown to survive infection. 129xB6-K18-hACE2 mice or littermate controls were infected with a low dose (5 × 10² PFU) of ancestral SARS-CoV-2. Complete viral clearance and full recovery from weight loss …

Use Of Cognitive-Behavioral Therapy In A Nation-Wide Veterans Health Administration Sample: The Role Of Clinic, Therapist, And Patient Factors., Alan Mcguire, Mindy Flanagan, Madison E Stout, Jessica Coffing, Marina Kukla, Morgan Traylor, Laura Myers, Nancy Henry, Jessica Carter, Marianne Matthias

Health Services and Informatics Research

OBJECTIVE: To examine the use of CBT-CP (Cognitive-behavioral therapy for chronic pain) by CBT-CP-trained therapists to treat patients with pain over a five-year period (October 2015-February 2020).

DATA SOURCES AND STUDY SETTING: CBT-CP is a core evidence-based practice that is central to multidisciplinary chronic pain care. However, research suggests that CBT-CP is underused. The current study used national Veterans Health Administration data to examine the use of CBT-CP by CBT-CP-trained therapists to treat patients with pain over a five-year period.

STUDY DESIGN: Multilevel modeling was used to evaluate clinic, therapist, and patient-level factors as predictors of CBT-CP receipt.

DATA COLLECTION: …

Association Of Epigenetic Aging With Plasma Cbiomarkers Of Amyloid, Tau, Neurodegeneration, And Neuroinflammation In Hispanic/Latino Adults, Myriam Fornage, Wassim Tarraf, Martha L Daviglus, Charles Decarli, Kevin A Gonzalez, Carmen R Isasi, Sayaka Kuwayama, Melissa Lamar, Bonnie E Levin, Humberto Parada, Alberto R Ramos, Tatjana Rundek, Bharat Thyagarajan, Hector M González

The Brown Foundation: Institute of Molecular Medicine

Background: Blood-based biomarkers hold significant promise for the early detection and diagnosis of Alzheimer's disease (AD) and other dementias. Age-related changes in blood levels of AD biomarkers are well-documented but poorly understood. Epigenetic clocks are mathematical models based on DNA methylation patterns that reflect various aspects of the multidimensional aging process. We investigated the associations of epigenetic aging with five blood-based AD biomarkers in 2656 Hispanic/Latino adults (mean age 62.5 years; 65% females) from the Hispanic Community Health Study/Study of Latinos. We used multivariable linear regression models to estimate the associations of acceleration in each of five epigenetic clocks with …

American College Of Rheumatology Guidance Statements For Addressing Mental Health Concerns In Youth With Pediatric Rheumatologic Diseases., Natoshia R. Cunningham, Ashley N. Danguecan, Samantha L. Ely, Yaa Amponsah, Alaina Davis, Suzanne Edison, Julia G. Harris, Jordan T. Jones, Alana Goldstein-Leever, Alison Manning, Anne Mchugh, Crystal Mui, Ekemini Ogbu, Nikki Reitz, Martha Rodriguez, Natalie Rosenwasser, Alyse Tankanow, Erin Treemarcki, Katherine Winner, Tamar B. Rubinstein, Andrea M. Knight, Carra Mental Health Workgroup

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Pediatric rheumatologic diseases (PRDs) are characterized by high rates of anxiety and depression known to impact health-related outcomes. We present guidance statements to assess and manage mental health concerns for youth with PRDs in pediatric rheumatology practice.

METHODS: Development of the guidance statements was initiated in 2019 and concluded in November 2023. It included (1) the formation of a task force (including pediatric rheumatologists, pediatric behavioral health providers, patients, and parents) led by two licensed pediatric psychologists and two board-certified pediatric rheumatologists, (2) iterative drafting of statements and rating of evidence based on the Oxford Centre for Evidence-Based Medicine …

Biomechanical Analysis Of 3d Correction And Bone-Screw Forces As A Function Of Rod Insertion Sequence And Orientation Relative To The Sagittal Plane In Adolescent Idiopathic Scoliosis Instrumentation., Camille Pillot, Xiaoyu Wang, Alexandria Mallinos, Todd Ritzman, Lorena Floccari, Richard M. Schwend, Carl-Eric Aubin

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: In adolescent idiopathic scoliosis instrumentation, rods are typically aligned with the sagittal plane during the initial translation maneuver. Surgeons often empirically orient the rod slightly opposite to the scoliotic curve, but the optimal orientation and insertion sequence, as well as their influence on 3D correction and forces, remain unclear. This study investigates the biomechanical influence of these rod parameters on scoliosis correction.

METHODS: Patient-specific multi-body biomechanical models were developed for 30 adolescent idiopathic scoliosis patients (11 hypo-, 12 normo-, 7 hyper-kyphotic thoracic curves) to simulate posterior instrumentation with a primary segmental translation correction maneuver. Rod insertion was tested in …

Vascular Risk Factors And 1-Year Cognitive Change Among Individuals With Traumatic Brain Injury, Andrea L. C. Schneider, Katherine Hunzinger, Benjamin L. Brett, Danielle K Sandsmark, Sonia Jain, Xiaoying Sun, Raquel C. Gardner, Geoffrey T. Manley, Ramon Diaz-Arrastia, Lindsay D. Nelson, Patrick Belton, Shawn Eagle, Shankar Gopinath, Ramesh Grandhi, C. Dirk Keene, Vijay Krishnamoorthy, Christine Mac Donald, Michael Mccrea, Randall Merchant, Pratik Mukherjee, Laura B. Ngwenya, David Okonkwo, Claudia Robertson, David Schnyer, Sabrina R. Taylor, John K. Yue, Ross Zafonte

Department of Exercise Science Faculty Papers

IMPORTANCE: Traumatic brain injury (TBI) and vascular risk factors are associated with cognitive impairment, but it is unknown if individuals with vascular risk factors experience worse cognitive outcomes after TBI.

OBJECTIVE: To evaluate cognitive function among patients with TBI with vs without comorbid preinjury vascular risk factors.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study examined individuals with TBI enrolled in the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) Study between February 26, 2014, and August 8, 2018, with a 1-year follow-up. Analyses were conducted February 26, 2024, to May 29, 2025.

EXPOSURES: Vascular risk factors (ie, hypertension, diabetes, …

Chronic Cluster Headache Is A Rare Disease: Implications For Diagnosis, Treatment And Public Health, Hsiangkuo Yuan, Jan Hoffmann, Elena Ruiz De La Torre, Michael J. Marmura, Mario F. P. Peres

Department of Jefferson Headache Center Papers and Presentations

Cluster headache (CH) is a rare and painful primary headache disorder characterized by severe unilateral pain and cranial autonomic symptoms. This perspective examines the epidemiological evidence supporting the classification of chronic cluster headache (CCH) as a rare disease, noting a prevalence of CH of approximately 124 per 100,000 individuals, with only 3.5-13.7% manifesting CCH. This prevalence meets criteria established by both the US Food and Drug Administration and European Medicines Agency for rare disease designation. The rarity of CCH creates substantial clinical and research challenges, including prolonged diagnostic delays, limited research funding and a dearth of approved treatments. The economic …

The Impact Of Gender, Training Year, Medical Specialty And The Covid-19 Pandemic On Resident Wellness, Sara Beachy, Jessica Luzier, Chantel Weisenmuller, Kathleen Bors, Mary Ann Maurer, Amna Anees, Tiffany Lasky, Lisa Calderwood

Department of Family & Community Medicine Faculty Papers

INTRODUCTION: Data are limited as to which factors most strongly impact medical trainees' well-being, and few studies have assessed trainee's wellness at multiple time points during the COVID-19 pandemic. Additionally, much research has not taken an intersectional approach to understanding the ways in which different facets of a resident's identity impact their wellness. Thus, more person-centred, probability-driven statistical approaches that can produce distinct heterogenous groups of individuals are warranted to understand the way in which different identities are associated with resident wellness scores.

METHODS: A latent profile analysis was conducted using institutional data from resident surveys administered from 2019 to …

Sarcoplasmic Reticulum-Mitochondria Microdomains: Hugging And Kissing In The Heart, Bong Sook Jhun, Jin O-Uchi, Brian Rhee, Ameneh Ahrari, Nathan Demichaelis, Kye-Im Jeon, David M. Booth, Shey-Shing Sheu

Center for Translational Medicine Faculty Papers

Endoplasmic reticulum (ER)-mitochondrial (ER-Mito) interface, termed mitochondrial-ER contacts (MERCs), plays significant roles in the maintenance of bioenergetics and basal cell functions via the exchange of lipids, Ca 2 þ , and reactive oxygen species (ROS) in various cell types/tissues. Genetic deletion of mitofusin 2 (Mfn2), one of the key components of ER-Mito tethering, in cardiomy- ocytes (CMs) in vivo revealed the importance of the microdomains between mitochondria and sarcoplasmic reticulum (SR), a dif- ferentiated form of ER in muscle cells, for maintaining normal mitochondrial Ca 2 þ (mtCa 2 þ ) handling and bioenergetics in the adult heart. However, key …

Family-Level Factors That Influence Physical Activity Among Hispanic Adolescents At Risk For Type 2 Diabetes, Sandra Mihail, Ayleen A Hernandez, Erica G Soltero

Children’s Nutrition Research Center Staff Publications

Objective: Family-based health promotion and disease prevention strategies are recommended as best practice; however, there is limited knowledge regarding the family-level factors that influence modifiable behavior risk factors like physical activity (PA) among Latinx adolescents. This study addressed this knowledge gap by using qualitative methods to identify perceptions of family-level factors that influence PA among Hispanic youth.

Methods: We conducted semistructured, open-ended interviews with 20 Latinx adolescents (14-16 years) with obesity (body mass index ≥95th percentile) to identify their perceptions of how family influences PA. Content analysis was used to identify emergent themes, which were then compared across demographic factors, …

Genetic Study Of Von Willebrand Factor Antigen Levels ≤ 50 Iu/Dl Identifies Variants Associated With Increased Risk Of Von Willebrand Disease And Bleeding, Rachel K Friedman, Adam S Heath, Jennifer E Huffman, James T Baker, Natalie R Hasbani, Sarah A Gagliano Taliun, Ming-Huei Chen, Tom E Howard, Joshua P Lewis, Nathan Pankratz, Snehal Patil, Alex P Reiner, Florian Thibord, Lisa R Yanek, Jie Yao, Hung-Hsin Chen, Joanne E Curran, Nauder Faraday, Xiuqing Guo, Marsha M Wheeler, Kathleen A Ryan, Xiang Zhou, Kelly Cho, Laura Almasy, Paul L Auer, Lewis C Becker, Peter W F Wilson, Eric Boerwinkle, Jeffrey R O'Connell, Stephen S Rich, David C Samuels, National Heart, Lung And Blood Institute (Nhlbi) Trans-Omics For Precision Medicine (Topmed) Consortium, Topmed Hematology & Hemostasis Working Group, Va Million Veteran Program, John Blangero, Myriam Fornage, Charles Kooperberg, Rasika A Mathias, Braxton D Mitchell, Jerome I Rotter, Andrew D Johnson, Nicholas L Smith, Zeynep H Coban-Akdemir, Jennifer E Below, Alanna C Morrison, Jill M Johnsen, Paul S De Vries

Faculty, Staff and Student Publications

Background: von Willebrand disease (VWD) is a common inherited bleeding disorder caused by low levels or activity of circulating von Willebrand factor (VWF). Genetic susceptibility to VWF antigen (VWF:Ag) below normal (≤ 50 IU/dL) in the general population is underexplored.

Objectives: To identify genetic variants influencing VWF:Ag levels ≤ 50 IU/dL.

Methods: We performed a genome-wide association study in 926 cases with VWF:Ag levels ≤ 50 IU/dL and 12 846 controls from 7 studies from the Trans-Omics for Precision Medicine program. We then examined whether significant genome-wide findings were also associated with clinical diagnosis of VWD in 5 biobanks with …

Impaired Rest-Activity Rhythm Characteristics Predict Higher Risk Of Incident Type 2 Diabetes In Uk Biobank Participants, Chris Ho Ching Yeung, Alison K Wright, Daniel P Windred, Angus C Burns, Andrew J K Phillips, Sean W Cain, Martin K Rutter, Qian Xiao

Faculty, Staff and Student Publications

Objective: Circadian rhythms play a key role in metabolic health. Rest-activity rhythms, which are in part driven by circadian rhythms, may be associated with diabetes risk. There is a need for large prospective studies to comprehensively examine different rest-activity metrics to determine their relative strength in predicting risk of incident type 2 diabetes.

Research design and methods: In actigraphy data from 83,887 UK Biobank participants, we applied both parametric and nonparametric algorithms to derive 13 different metrics characterizing different aspects of rest-activity rhythm. Diabetes cases were identified using both self-reported data and health records. We used Cox proportional hazards models …

Linking Chronic Kidney Disease To Incident Heart Failure And Adverse Cardiac Remodeling Through The Plasma Proteome: The Aric Study, Leo F Buckley, Pranav Dorbala, Victoria Lamberson, Brian L Claggett, Yue Ren, Morgan E Grams, Josef Coresh, Kunihiro Matsushita, Ryan T Demmer, Ruth F Dubin, Rajat Deo, Peter Ganz, Christie M Ballantyne, Ron C Hoogeveen, Bing Yu, Amil M Shah

Faculty, Staff and Student Publications

Background: Investigation of circulating plasma proteins may reveal insights into molecular pathways that contribute to the development of heart failure (HF) among people with chronic kidney disease.

Objectives: The authors aimed to identify circulating kidney function-related plasma proteins that are associated with the risk of incident HF.

Methods: The authors studied participants of the ongoing longitudinal ARIC (Atherosclerosis Risk In Communities) study. Relative plasma concentrations of 4,697 unique proteins were measured with the use of an aptamer assay (Somalogic). Each protein was tested for associations with estimated glomerular filtration rate (eGFR), log-transformed urine albumin-to-creatinine ratio (UACR), and incident HF by …

Trends In Glucagon-Like Peptide 1 Receptor Agonist Prescribing Patterns, Maria Ukhanova, Joseph S Wozny, Chau N Truong, Lopita Ghosh, Trudy M Krause

Faculty, Staff and Student Publications

Objective: Obesity affects more than 40% of US adults, increasing risks for cardiovascular disease and type 2 diabetes. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs), initially indicated for diabetes, show promise in weight loss but face coverage issues, high costs, and premature prescribing from physicians. Research is needed to assess prescribing patterns, especially in patients without diabetes.

Study design: We conducted a retrospective, population-based, observational study using the Merative MarketScan Commercial Database and the Merative MarketScan Medicare Supplemental Database, which capture person-specific clinical utilization and expenditures. We analyzed GLP-1 RA prescribing rates from 2018 to 2023, comparing semaglutide with other …

Autoantibody Profiling To Predict Response To The Anti-Pd-1 Therapy, Pembrolizumab, In Rare Tumors, M H Derbala, J Hajjar, B Stephen, S A Gurses, E Kwiatkowski, P Budde, H-D Zucht, M Bräutigam, A-S Lindemann, B A Abhari, M A Gouda, L Castillo, A Zarifa, J A How, E Rodriguez, J T Moyers, D S Hong, S Fu, F Meric-Bernstam, A Naing

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitors (ICIs) have limited response rates in selected patients and can cause potentially life-threatening immune-related adverse events (irAEs). This underscores the urgent need for the development of biomarkers predictive of ICI response. Pre-existing autoantibodies (AAbs) have been linked with responses to ICIs and the development of irAEs. We conducted AAb profiling to assess associations between baseline AAbs and clinical benefit (CB) in patients with rare tumors treated with anti-programmed cell death protein 1-based therapy.

Patients and methods: We conducted AAb profiling using Oncimmune's SeroTag multiplex antibody discovery technology and immune oncology array containing 1168 antigens. The study …

Racial Disparities In The Receipt Of Therapies For Cancer, Hypertension, And Diabetes, And In Mortality In A Large Population-Based Cohort Of Older Men With Prostate Cancer, Zhuoyun Li, Xianglin L Du

Faculty, Staff and Student Publications

Background: Racial disparities in treatment and mortality were widely studied among prostate cancer patients; however, few studies considered the prevalence of hypertension and diabetes and their treatment status.

Objectives: To determine whether there are racial discrepancies in the use of anti-cancer, antihypertensive, and antidiabetic drugs in a cohort of long-term survivors of prostate cancer diagnosed in 2007-2015; and to examine racial disparities in mortality after adjustments for their differences in those treatments.

Methods: We used the SEER (Surveillance, Epidemiology, and End Results)-Medicare linked database and included records for patients with prostate cancer at age 65 years or older diagnosed from …

Principles And Practice In Pediatric Vascular Trauma: Part 1: Scope Of Problem, Team Structure, Multidisciplinary Dynamics, And Solutions, Matthew T Harting, Natalie A Drucker, Mary T Austin, Matthew R Greives, Bryan A Cotton, S Keisin Wang, Derrick P Williams, Joseph J Dubose, Charles S Cox

The Brown Foundation: Institute of Molecular Medicine

As of 2020, penetrating injuries became the leading cause of death among children and adolescents ages 1-19 in the United States. For the patients who initially survive and receive advanced medical care, vascular injuries are a significant cause of morbidity and additionally trigger notable trauma team angst. Moreover, penetrating injuries can lead to life-threatening hemorrhage and/or limb-threatening ischemia if not addressed promptly. Vascular injury management demands timely and unique expertise, particularly for pediatric patients. As the frequency of vascular injuries requiring operative management increases, it becomes clear that an ad hoc approach is not ideal. An integrated team would provide …

The Global Neurodegeneration Proteomics Consortium: Biomarker And Drug Target Discovery For Common Neurodegenerative Diseases And Aging, Farhad Imam, Rowan Saloner, Jacob W Vogel, Varsha Krish, Gamal Abdel-Azim, Muhammad Ali, Lijun An, Federica Anastasi, David Bennett, Alexa Pichet Binette, Adam L Boxer, Martin Bringmann, Jeffrey M Burns, Carlos Cruchaga, Jeff L Dage, Amelia Farinas, Luigi Ferrucci, Caitlin A Finney, Mark Frasier, Oskar Hansson, Timothy J Hohman, Erik C B Johnson, Mika Kivimaki, Roxanna Korologou-Linden, Agustin Ruiz Laza, Allan I Levey, Inga Liepelt-Scarfone, Lina Lu, Niklas Mattsson-Carlgren, Lefkos T Middleton, Kwangsik Nho, Hamilton Se-Hwee Oh, Ronald C Petersen, Eric M Reiman, Oliver Robinson, Jeffrey D Rothstein, Andrew J Saykin, Artur Shvetcov, Chad Slawson, Bart Smets, Marc Suárez-Calvet, Betty M Tijms, Maarten Timmers, Fernando Vieira, Natalia Vilor-Tejedor, Pieter Jelle Visser, Keenan A Walker, Laura M Winchester, Tony Wyss-Coray, Chengran Yang, Niranjan Bose, Simon Lovestone, The Global Neurodegeneration Proteomics Consortium (Gnpc)

Faculty, Staff and Student Publications

More than 57 million people globally suffer from neurodegenerative diseases, a figure expected to double every 20 years. Despite this growing burden, there are currently no cures, and treatment options remain limited due to disease heterogeneity, prolonged preclinical and prodromal phases, poor understanding of disease mechanisms, and diagnostic challenges. Identifying novel biomarkers is crucial for improving early detection, prognosis, staging and subtyping of these conditions. High-dimensional molecular studies in biofluids ('omics') offer promise for scalable biomarker discovery, but challenges in assembling large, diverse datasets hinder progress. To address this, the Global Neurodegeneration Proteomics Consortium (GNPC)-a public-private partnership-established one of the …

Associations Between Social Support, Social Control, And Stage Of Change With Self-Reported And Objectively Assessed Physical Activity In Adult Latino Dyads, Jemima C John, Minjae Lee, Soo K Park, Lorna H Mcneill, Deanna M Hoelscher, Susan M Schembre, Belinda M Reininger, Larkin L Strong

Faculty, Staff and Student Publications

Health behaviors such as physical activity (PA) are socially influenced, such that individuals from shared social networks or living environments may exhibit similar habits. This cross-sectional study examined associations of social support, social control, and family member stage of change with moderate-to-vigorous self-reported and objective PA in dyads of adult Hispanic family members. We used the Godin Leisure-Time Physical Activity Questionnaire to assess self-reported PA and accelerometry for objective PA. Validated scales assessed social support, social control, and stage of change. We performed multivariable multilevel analysis using generalized estimating equations (GEE) to account for within-dyad correlations. We conducted multivariable negative …

A Large-Scale Genome-Wide Study Of Gene-Sleep Duration Interactions For Blood Pressure In 811,405 Individuals From Diverse Populations, Pavithra Nagarajan, Thomas W Winkler, Amy R Bentley, Clint L Miller, Aldi T Kraja, Karen Schwander, Songmi Lee, Wenyi Wang, Michael R Brown, John L Morrison, Ayush Giri, Jeffrey R O'Connell, Traci M Bartz, Lisa De Las Fuentes, Valborg Gudmundsdottir, Xiuqing Guo, Sarah E Harris, Zhijie Huang, Mart Kals, Minjung Kho, Christophe Lefevre, Jian'an Luan, Leo-Pekka Lyytikäinen, Massimo Mangino, Yuri Milaneschi, Nicholette D Palmer, Varun Rao, Rainer Rauramaa, Botong Shen, Stefan Stadler, Quan Sun, Jingxian Tang, Sébastien Thériault, Adriaan Van Der Graaf, Peter J Van Der Most, Yujie Wang, Stefan Weiss, Kenneth E Westerman, Qian Yang, Tabara Yasuharu, Wei Zhao, Wanying Zhu, Drew Altschul, Md Abu Yusuf Ansari, Pramod Anugu, Anna D Argoty-Pantoja, Michael Arzt, Hugues Aschard, John R Attia, Lydia Bazzanno, Max A Breyer, Jennifer A Brody, Brian E Cade, Hung-Hsin Chen, Yii-Der Ida Chen, Zekai Chen, Paul S De Vries, Latchezar M Dimitrov, Anh Do, Jiawen Du, Charles T Dupont, Todd L Edwards, Michele K Evans, Tariq Faquih, Stephan B Felix, Susan P Fisher-Hoch, James S Floyd, Mariaelisa Graff, Charles Gu, Dongfeng Gu, Kristen G Hairston, Anthony J Hanley, Iris M Heid, Sami Heikkinen, Heather M Highland, Michelle M Hood, Mika Kähönen, Carrie A Karvonen-Gutierrez, Takahisa Kawaguchi, Setoh Kazuya, Tanika N Kelly, Pirjo Komulainen, Daniel Levy, Henry J Lin, Peter Y Liu, Pedro Marques-Vidal, Joseph B Mccormick, Hao Mei, James B Meigs, Cristina Menni, Kisung Nam, Ilja M Nolte, Natasha L Pacheco, Lauren E Petty, Hannah G Polikowsky, Michael A Province, Bruce M Psaty, Laura M Raffield, Olli T Raitakari, Stephen S Rich, Renata L Riha, Lorenz Risch, Martin Risch, Edward A Ruiz-Narvaez, Rodney J Scott, Colleen M Sitlani, Jennifer A Smith, Tamar Sofer, Maris Teder-Laving, Uwe Völker, Peter Vollenweider, Guanchao Wang, Ko Willems Van Dijk, Otis D Wilson, Rui Xia, Jie Yao, Kristin L Young, Ruiyuan Zhang, Xiaofeng Zhu, Jennifer E Below, Carsten A Böger, David Conen, Simon R Cox, Marcus Dörr, Mary F Feitosa, Ervin R Fox, Nora Franceschini, Sina A Gharib, Vilmundur Gudnason, Sioban D Harlow, Jiang He, Elizabeth G Holliday, Zoltan Kutalik, Timo A Lakka, Deborah A Lawlor, Seunggeun Lee, Terho Lehtimäki, Changwei Li, Ching-Ti Liu, Reedik Mägi, Fumihiko Matsuda, Alanna C Morrison, Brenda Wjh Penninx, Patricia A Peyser, Jerome I Rotter, Harold Snieder, Tim D Spector, Lynne E Wagenknecht, Nicholas J Wareham, Alan B Zonderman, Kari E North, Myriam Fornage, Million Veteran Program, Adriana M Hung, Alisa K Manning, James Gauderman, Han Chen, Patricia B Munroe, Dabeeru C Rao, Diana Van Heemst, Susan Redline, Raymond Noordam, Heming Wang

Faculty, Staff and Student Publications

Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discovered 22 novel gene-sleep duration interaction loci for blood pressure, mapped to 23 genes. Investigating these genes' functional implications shed light on neurological, thyroidal, bone metabolism, and hematopoietic pathways that necessitate future investigation for blood pressure management that caters to sleep health …

Chance Or Strategy? Assessing The Unanticipated Policy Window For Active Transportation During The Covid-19 Pandemic: A Systematic Review, Katja Siefken, Michael Pratt, Juliana Mejía-Grueso, Adrian Bauman, Deborah Salvo, Catherine B Woods, Wanda Wendel-Vos, Justin Richards, J Jaime Miranda, Pedro C Hallal, Andrea Ramírez Varela

Faculty, Staff and Student Publications

Physical activity (PA) policy is essential for promoting population-level PA by coordinating efforts across various sectors. Global crises like the COVID-19 pandemic can open policy windows, enabling rapid implementation of innovative policies. This study examined how policy windows shaped active transportation (AT) policies during the pandemic, resulting in infrastructural changes.

Methods: A systematic review using PubMed, Scopus, ProQuest-Coronavirus Research Database, Web of Science, WHO COVID-19 Research Database, PsycInfo, and SPORTDiscus conducted to characterize AT policy during the pandemic (2020-2023). Descriptive analyses were conducted in Stata. PROSPERO registration number: CRD42025644930.

Results: The search retrieved 3879 articles; 1162 were duplicates, leaving 2716 …

Accelerometer-Measured Chronoactivity And Type 2 Diabetes Risk: A Prospective Study In Uk Biobank Participants, Qiuyu Feng, Gali Albalak, Ko Willems Van Dijk, Jeroen H P M Van Der Velde, Qian Xiao, Raymond Noordam, Diana Van Heemst

Faculty, Staff and Student Publications

Objective: We assessed whether timing of physical activity, independent from the total activity amount, - which we refer to as chronoactivity - is associated with type 2 diabetes (T2D) risk.

Methods: We included UK Biobank participants with valid accelerometry data (UK, exposure measurement: 2013-2015, follow-up till November 2023) and without diabetes mellitus at baseline (N = 89,439; mean age: 61.7 [SD:7.9] years). Relative hourly physical activity was calculated by dividing the average hourly clock time physical activity by the average hourly physical activity in a week. Participants were categorized into different chronoactivity clusters using k-means cluster analysis on relative hourly …

Evaluating The Antimicrobial Properties Of Different Dental Cleaning Tablets Against S Aureus Grown On Two Denture Base Materials, Sindi Vishaj, Alissa Villhauer, Mandi Morris, Donald M Belles, Daher Antonio Queiroz, Maria D Gonzalez, Ransome Van Der Hoeven

Faculty, Staff and Student Publications

Objectives: This study aimed to evaluate the antimicrobial efficacy of three commercially available denture cleaning tablets Efferdent, Polident, and Val-clean against Staphylococcus aureus biofilms formed on two denture base materials: milled polymethyl methacrylate (PMMA) and 3D printed denture resin.

Material and methods: Eighty samples were fabricated, with 40 specimens per denture base material: CAD/CAM milled PMMA (Lucitone Digital Fit LT; Dentsply Sirona, Charlotte, NC, USA) and 3D printed resin (Denture Base Resin; Formlabs Inc., Somerville, MA, USA). Each group was divided into four subgroups (n = 10), Efferdent, Polident, Val-clean, and deionized water (control). Surface roughness was measured using a …

Genome-Wide Approaches To Bacterial Strain Typing: A History And Review Of Recent Methodological Advances, William C Shropshire, Blake M Hanson, Samuel A Shelburne

Faculty, Staff and Student Publications

Purpose of review: Whole genome sequencing (WGS) has transformed bacterial strain typing, an essential tool for outbreak detection, antimicrobial resistance surveillance, and tracking clonal emergence across clinical, research, and public health settings. Herein, we will review recent advances in WGS-based bacterial strain typing methods for purposes of comparison and classification with a focus on improvements in variant identification, strain classification, and transmission assessment.

Recent findings: Advances in sequencing technologies as well as variant calling methodologies and parameter optimization have enhanced the precision and accuracy of single nucleotide variant identification. Hierarchical clustering of gene-by-gene strain typing, combined with novel data management …

Pain Acceptance In Chronic Postoperative Pain: Concept Analysis, Sajini M Thekkel, Constance M Johnson, Meagan Whisenant, Deniz Dishman

Faculty, Staff and Student Publications

Purpose: Chronic postoperative pain (CPOP) is a potential outcome of otherwise successful surgery that can persist for months, with its prevalence varied by surgical type, genetic predispositions, and psychosocial factors. Pain acceptance offers better outcomes to these patient populations by fostering a willingness to experience pain without resistance. This analysis examines how pain acceptance contributes to psychological well-being, helps reduce opioid misuse, and enhances quality of life, even in the presence of CPOP.

Design: The concept analysis approach follows Walker and Avant's framework (2019).

Methods: A literature search across PubMed, Web of Science, and CINAHL yielded 276 articles, of which …

Isolation And Functional Properties Of Highly-Purified N-Terminal Domain Of Human Napi2b By Scalable “Resin Overload” Technique, Daria Savenkova, Irina Makarenko, Daria Nedorezova, Ramziya Kiyamova, Mikhail Bogdanov

Faculty, Staff and Student Publications

Despite the enthusiasm and advances in the purification of native and engineered full-length membrane proteins, little attention has been paid to their fragments which could serve as attractive inspiration for function, regulation, or targeting of full-length membrane protein with therapeutic antibodies (Abs). Production of recombinant fragments of "therapeutic" membrane proteins for early-stage discovery research requires their purification to near homogeneity. It is important not only for the production of biotherapeutic antibodies but also for structural and functional studies of competitive protein-Abs, protein-protein, and lipid-protein interactions which heavily rely on the purity and quality of the isolated protein fragment of interest. …

2025 European Leukemianet Recommendations For The Management Of Chronic Myeloid Leukemia, Jane F Apperley, Dragana Milojkovic, Nicholas C P Cross, Henrik Hjorth-Hansen, Andreas Hochhaus, Hagop Kantarjian, Jeffrey H Lipton, Hemant Malhotra, Dietger Niederwieser, Jerald Radich, Philippe Rousselot, Susanne Saussele, Charles A Schiffer, Richard Silver, Simona Soverini, Leif Stenke, Anna Turkina, Luis Felipe Casado, Fausto Castagnetti, Francisco Cervantes, Richard E Clark, Jorge Cortes, Michael Deininger, Timothy P Hughes, Jeroen Janssen, Qian Jiang, Dong-Wook Kim, Richard A Larson, Francois X Mahon, Michael Mauro, Jiri Mayer, Franck E Nicolini, Fabrizio Pane, Delphine Rea, Johan Richter, Gianantonio Rosti, Giuseppe Saglio, Rüdiger Hehlmann

Faculty, Staff and Student Publications

In this 5th version of the European LeukemiaNet guidance for adult patients, there are important changes in several areas of management based on evidence available since 2020, including the World Health Organisation's reclassification of CML as a biphasic disease. Previous advice to switch the tyrosine kinase inhibitor (TKI) on failure of molecular milestones, is modified to better account for individual patient circumstances. Our recommendations are summarized in tables designed to be read in conjunction with the text which offers justification and additional advice. We describe decision-making for first-line treatment, both in available drugs and their initial dosing. Similarly we elaborate …

Addressing Challenges In Developing Treatments For Inherited Retinal Diseases: Recommendations From The Third Monaciano Symposium, Debra A Thompson, K Thiran Jayasundera, Oleg Alekseev, Robin R Ali, Alessia Amato, Vadim Y Arshavsky, Isabelle S Audo, Alberto Auricchio, James W B Bainbridge, Eyal Banin, Cagri G Besirli, David G Birch, Kari E Branham, Artur V Cideciyan, Stephen P Daiger, Jacque L Duncan, Abigail T Fahim, John G Flannery, Roberto Gattegna, John R Heckenlively, Elise Héon, Alessandro Iannaccone, Naheed W Khan, Samer Khateb, Henry J Klassen, Bart P Leroy, Dario Marangoni, Michel Michaelides, David C Musch, Mark E Pennesi, Simon M Petersen-Jones, Eric A Pierce, Rajesh C Rao, José-Alain Sahel, Paul A Sieving, Enrica Strettoi, Cameron R Strong, Thomas J Wubben, Paul Yang, David N Zacks

Faculty, Staff and Student Publications

Over the past decade, efforts focused on developing genetic therapies for inherited retinal diseases have advanced steadily to clinical trials and the development of a treatment, fueling optimism for the potential of precision medicines to provide safe and effective therapies for these rare conditions. Although several ongoing programs remain poised for success, numerous challenges have negatively impacted the ability to obtain regulatory approvals. The present position paper briefly summarizes recent advances and challenges in developing therapeutics for inherited retinal diseases, and presents a set of recommendations for moving the field forward. The priorities identified are discussed in terms of progress …

Transcriptomic Analysis Of Localized High-Risk Prostate Cancer Improves Prognostication And Identifies Benefit From Adding Docetaxel To Definitive Radiotherapy With Androgen Suppression In The Nrg Oncology/Rtog 0521 Phase 3 Trial, Ryan M Phillips, James A Proudfoot, Elai Davicioni, Yang Liu, Daniel E Spratt, Jeff M Simko, Robert B Den, Alan Pollack, Seth A Rosenthal, A Oliver Sartor, Christopher J Sweeney, Gerhardt Attard, Leslie Longoria, Samir Patel, Michael W Straza, Jason A Efstathiou, Amit B Shah, Karen E Hoffman, Joseph P Rodgers, Howard M Sandler, Felix Y Feng, Phuoc T Tran

Faculty, Staff and Student Publications

Background and objective: NRG/RTOG 0521 randomized men with high-risk localized prostate cancer (PC) to androgen suppression (AS) and definitive radiotherapy (RT) ± docetaxel-based chemotherapy (CT). The overall survival (OS) benefit with CT initially reported was lost on longer follow-up. The Decipher genomic classifier (GC) measures multiple transcripts relevant to docetaxel action. Basal/luminal differentiation portends differential response to AS and CT for high-risk localized and metastatic hormone-sensitive PC. We validated the Decipher GC in pretreatment biopsy samples for risk stratification and examined basal-luminal subtyping to predict docetaxel response.

Methods: Decipher GC scores and basal-luminal cellular subtypes were generated for specimens from …

Efficacy And Safety Of Oral Decitabine/Cedazuridine In The Chronic Myelomonocytic Leukaemia Subpopulations From Phase 2 And 3 Studies, Michael R Savona, Olatoyosi Odenike, Gail J Roboz, Harshad Amin, Amy E Dezern, Elizabeth A Griffiths, Kim-Hien Dao, Amer M Zeidan, Bhavana Bhatnagar, Rena Buckstein, Brian Leber, Mary-Margaret Keating, Somedeb Ball, Aram Oganesian, Yuri Sano, Harold N Keer, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

DNA methyltransferase inhibitors (DNMTis) are commonly used in treating chronic myelomonocytic leukaemia (CMML); however, data from prospective studies of DNMTis in CMML are limited. The present analysis evaluated the efficacy, safety and pharmacodynamics of the oral DNMTi decitabine/cedazuridine in the subset of patients with CMML from the phase 2 and 3 trials, which led to the approval of this agent for myelodysplastic syndromes and CMML in the United States and Canada. Potential prognostic factors also were analysed. In all, 34 patients with CMML were screened and 33 were treated. Most patients (76% [n = 25]) had myelodysplastic type-CMML and 77% …