Medicine and Health Sciences Commons^™

Outcomes Following Matched Sibling Donor Transplantation For Severe Combined Immunodeficiency: A Report From The Pidtc, Ahmad Rayes, Jeffrey J Bednarski, Et Al.

2020-Current year OA Pubs

The Primary Immune Deficiency Treatment Consortium performed a retrospective analysis of 133 patients with severe combined immunodeficiency (SCID) receiving matched sibling donor (MSD) hematopoietic cell transplantation (HCT) between 1980 and 2023 at 30 North American institutions. In this largest cohort of MSD outcomes in patients with SCID to date, we examined the impact of conditioning regimen and graft-versus-host disease (GVHD) prophylaxis on survival and immune recovery. Outcomes after MSD HCT for SCID were excellent. Patients without an active infection or failure to thrive (FTT) at the time of HCT had 5-year overall survival superior to those with infection or FTT. …

Myokine Sirpα Exacerbates Kidney Disease In Diabetes, Jiao Wu, Elisa Russo, Daniela Verzola, Qingtian Li, Helena Zhang, Bhuvaneswari Krishnan, David Sheikh-Hamad, Zhaoyong Hu, William E Mitch, Sandhya S Thomas

Faculty, Staff and Students Publications

Mechanisms responsible for skeletal muscle kidney crosstalk have not been defined. We have determined that a circulating mediator, signal regulatory protein α (SIRPα), impairs intracellular insulin-mediated functions. To elucidate the effect of myokine SIRPα on diabetic kidney disease (DKD), flox mice and muscle-specific (m-specific) SIRPα-KO mice were subjected to an obesity-induced model of diabetes, high-fat diet (HFD; 60%) or insulin-deficient hyperglycemia model, streptozotocin (STZ), and were subsequently exposed to anti-SIRPα monoclonal antibodies. In the obesity-induced diabetic mice, serum SIRPα increased. Genetic deletion of muscle SIRPα protected against obesity and improved intracellular insulin signaling in muscle and adipose tissue, with reduced …

Fractionated Radiotherapy Adjuvant To Surgery Of Who-2 Meningioma With And Without Gross Total Resection: A Multicenter, Retrospective Cohort Study Of 1,452 Patients, Christian Mirian, Lasse Rehné Jensen, Adam Gorm Hoffmann, Tareq A Juratli, Andrea Daniela Maier, Pernilla Lindner, Anders Broechner, Sverre H Torp, Helen A Shih, Ramin A Morshed, Jacob S Young, Stephen T Magill, Walter Stummer, Dorothee Cäcilia Spille, Benjamin Brokinkel, Martin Proescholdt, Yasuhiro Kuroi, Konstantinos Gousias, Matthias Simon, Ricardo Prat-Acin, Stéphane Goutagny, Johannes Wach, Erdem Güresir, Junkoh Yamamoto, Young Zoon Kim, Joo Ho Lee, Daniel W Kim, Matthew Koshy, Donald M Cannon, Dennis C Shrieve, Chang-Ok Suh, Jong Hee Chang, Maria Kamenova, Sven Straumann, Jehuda Soleman, Ilker Y Eyüpoglu, Tony Catalan, Austin Lui, Philip V Theodosopoulos, Michael W Mcdermott, Pedro Góes, Fang Wang, Luis Souhami, Marie-Christine Guiot, Tamás Csonka, Toshiki Endo, Tejpal Gupta, Akash J Patel, Tiemo J Klisch, Jun Won Kim, Francesco Maiuri, Valeria Barresi, María Dolores Tabernero, Simon Skyrman, Mechthild Krause, Ian Law, Bjarne Winther Kristensen, Tina Nørgaard Munch, Torstein Meling, Kåre Fugleholm, Paul Blanche, Tiit Mathiesen

Faculty, Staff and Students Publications

Purpose

The role of adjuvant fractionated radiotherapy (aFRT) after gross total resection (GTR) of WHO-2 meningiomas remains unclear. We aimed to estimate the effect of aFRT on recurrence risk and survival following GTR and subtotal resection (STR).

Methods

We analyzed 1452 patients with WHO-2 from our international, multicenter database (followed between 1989 and 2019). Outcomes were recurrence (10-year follow-up) and death (5-year follow-up). Risk estimates were obtained using competing risks and survival analysis. Average treatment effects were estimated by G-computation, adjusted for potential confounding by age, sex, Simpson grade, Ki-67 proliferation index, location, country group (universal healthcare or not), …

Dupilumab Beyond The Airway: Decreased Morbidity In A Real-World Analysis, Emma J. Anisman, Spencer Short, Emma Tam, Benjamin F. Bitner, Abdulghafoor Alani, Marc Rosen, Mindy Rabinowitz, Damaris Pena Evertz, Elina Toskala, Gurston G. Nyquist

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Background: Post hoc analyses of clinical trials have characterized dupilumab's adverse effects, yet the real-world impact in chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma is not well described. This study aims to characterize the risks of lymphoma, cardiovascular events, eosinophilia, joint pain, inflammatory arthritis, and sleep apnea in dupilumab-treated CRSwNP and/or asthma patients compared to those not taking dupilumab, and to other biologics.

Methods: This retrospective cohort study used TriNetX, a de-identified database containing over 100 million patient records. Demographics and adverse effects associated with immunotherapy use were collected.

Results: We identified 21,249 dupilumab-treated CRSwNP and/or asthma patients. After …

Defining Clinically Relevant Responses In Erectile Function: An Smsna Position Statement, Landon Trost, Faysal Yafi, Alan Shindel, Mohit Khera, Raymond C Rosen, Petar Bajic, Helen Bernie, Martin Gross, Johanna Hannan, Sevann Helo, Lawrence Jenkins Ii, Carol Podlasek, Daniel Watter, Matthew Ziegelmann, Tobias Köhler

Faculty, Staff and Students Publications

Background: To date, no scoring system has adequately defined clinical efficacy of erectile dysfunction (ED) therapies when evaluating differences between cohorts or in meta-analytic studies.

Aim: To outline the minimal criteria required for any therapy to be considered clinically effective in the treatment of ED.

Methods: An analytic review was performed of standardized ED questionnaires, with a particular emphasis placed on the International Index of Erectile Function, Erectile Function Domain (IIEF-EFD), and the minimally clinically important difference (MCID) concept. The data were used to create a societal position statement and recommendations on best practices within clinical trials to determine treatment …

Improving Prediction Accuracy Of Radiation-Induced Temporal Lobe Injury In Nasopharyngeal Carcinoma Using Adc-Based Deep Learning And Dosiomics, Li Wang, Yang Li, Ting Qiu, Junyi Liu, Jiawei Zhou, Han Gao, Hongliang Yu, Yinsu Zhu, Baozhou Sun, Guanyu Yang, Shengfu Huang, Lirong Wu, Li Sun, Xia He

Faculty, Staff and Students Publications

Background: To investigate the potential of apparent diffusion coefficient (ADC) map-based deep learning and dose distribution-based dosiomics in predicting radiation-induced temporal lobe injury (RTLI) in nasopharyngeal carcinoma (NPC).

Methods: This retrospective study included 3578 NPC patients from Jiangsu Cancer Hospital receiving intensity-modulated radiation therapy (IMRT). Ninety-four RTLI patients were recruited based on inclusion criteria and matched 1:1 with 97 control subjects using propensity scores. Patients were randomly assigned to the training cohort (n = 135) and the validation cohort (n = 59). Deep transfer learning (DTL) features and dosiomics features were extracted from ADC map and three-dimensional dose distribution, respectively. …

Human Papillomavirus Vaccine Perceptions Among Noncollege Young Adults And Tiktok Influencers: Qualitative Study, Amelia Burke-Garcia, Dasha Afanaseva, Erin Cutroneo, Kayla Madden, Angela Sustaita-Ruiz, Estefany Rivera Sanchez, Amy Leader

Department of Medical Oncology Faculty Papers

BACKGROUND: Human papillomavirus (HPV) vaccination is a proven and effective tool for preventing several types of cancers, yet vaccination rates among young adults remain suboptimal, particularly among those not enrolled in 4-year colleges. This population can be more difficult to reach due to fewer established institutional touchpoints, limited engagement with campus-based health services, and greater variability in access to preventive care. At the same time, social media has become a dominant source of information for young adults, with TikTok (ByteDance) emerging as one of the most widely used platforms. Approximately 41% of TikTok's users are between the ages of 16 …

Bi-Allelic Variants In Neuronal Adhesion Molecule Astrotactin 1 Gene Astn1 Cause Diverse Neurodevelopmental Disorders, Jesse M Levine, Daniel G Calame, Riccardo Sangermano, Haowei Du, Ahmed Saad, Jasmin Lisfeld, Tatjana Bierhals, Jonas Denecke, Eyyup Uctepe, Merve Yoldas Celik, Ahmet Yesilyurt, Hilal Yildiz Er, Elif Yilmaz Gulec, Aziza Mushiba, Naif Almontashiri, Pawel Gawlinski, Wojciech Wiszniewski, Ender Karaca, Lama Alabdi, Davut Pehlivan, Dana Marafi, Maha S Zaki, Fowzan S Alkuraya, Joseph G Gleeson, Shalini N Jhangiani, Richard A Gibbs, Jennifer E Posey, Kinga M Bujakowska, James R Lupski

Faculty, Staff and Students Publications

ASTN1 encodes astrotactin 1, a neuronal-glial ligand in the developing brain that promotes neuronal migration along radial glia in brain structures with laminar organization, such as the cerebral cortex, hippocampus, and cerebellum. In mouse models, disruption of Astn1 results in neuronal migration deficits, a mild reduction in cerebellar volume, and balance and coordination deficits. In humans, bi-allelic ASTN1 variants have been identified in nine individuals with neurodevelopmental disorders (NDDs) with or without brain malformations. ASTN1 additionally interacts with astrotactin 2 (ASTN2) to implement neuronal migration; ASTN2 deletions associate with NDDs with reduced penetrance. Here, we describe eighteen individuals with NDDs …

Sclerostin Deficiency Sensitizes White Adipocytes To Thermogenic Signals That Induce Beiging In Mice, Gillian M Choquette, Soohyun P Kim, Kevin J Wilkinson, Belen C Avelar, Sushrut Pathy, Zhu Li, Jasmine Wu, Susan Aja, Daniel L J Thorek, Michael J Wolfgang, Ryan C Riddle

2020-Current year OA Pubs

Maintenance of bone mass is coordinated with adipose tissue function through the secretion of hormones and endocrine factors that act on the opposing tissue. Sclerostin, a small glycoprotein produced by osteocytes embedded within the bone matrix, potently suppresses bone formation by antagonizing Wnt/β-catenin signaling while stimulating adipose tissue accumulation via the same mechanism of action. Since sclerostin-deficient mice develop pockets of multilocular adipocytes in subcutaneous adipose, we investigate the influence of sclerostin on thermogenic and β3-adrenergic stimuli-induced white adipose tissue beiging. Here, we report that Sost gene expression in bone and serum sclerostin levels are induced by β3-adrenergic agonists via …

Multiparent Recombinant Inbred Lines Crossed To A Tester Provide Novel Insights Into Sources Of Cis And Trans Regulation Of Gene Expression, Fabio Marroni, Alison M Morse, Adalena V Nanni, Nadja Nolte, Patricka Williams-Simon, Luis G León-Novelo, Rita M Graze, Paul Schmidt, Elizabeth King, Lauren M Mcintyre

Faculty, Staff and Student Publications

To understand the relative importance of cis and trans effects on regulation, we crossed multi-parent recombinant-inbred lines (RILs) to a common tester and measured allele-specific gene expression in the offspring. Testing the difference of allelic imbalance between two RIL × Tester crosses is a test of cis or trans, depending on the RIL alleles compared. The study design also enables to separation of two sources of trans variation, genetic and environmental, detected via interactions with cis effects. We demonstrate the effectiveness of this approach in a long-read RNA-seq experiment in female abdominal tissue at two time points in Drosophila melanogaster. …

Early Postnatal Polymerase Chain Reaction Testing In The Identification Of Perinatal Transmission Of Hepatitis C Virus, Mona Prasad, Grecio J Sandoval, George R Saade, Brenna L Hughes, Rebecca G Clifton, Uma M Reddy, Anna Bartholomew, Ashley Salazar, Edward K Chien, Alan T N Tita, John M Thorp, Torri D Metz, Ronald J Wapner, Vishakha Sabharwal, Hyagriv N Simhan, Geeta K Swamy, Kent D Heyborne, Baha M Sibai, William A Grobman, Yasser Y El-Sayed, Brian M Casey, Samuel Parry, George A Macones

Faculty, Staff and Student Publications

In this study, a single hepatitis C virus (HCV) RNA at 2-6 months was sensitive and specific (86.7% and 95% confidence interval [CI], 62.1%-96.3% and 100% and 95% CI, 98.8%-100%, respectively) in identifying perinatal transmission of HCV. No cases of perinatal infection requiring treatment were missed.

Time Trends In The Male To Female Ratio For Autism Incidence: Population Based, Prospectively Collected, Birth Cohort Study, Caroline Fyfe, Henric Winell, Joseph Dougherty, David H Gutmann, Alexander Kolevzon, Natasha Marrus, Kristina Tedroff, Tychele N Turner, Lauren A Weiss, Benjamin H K Yip, Weiyao Yin, Sven Sandin

2020-Current year OA Pubs

OBJECTIVES: To examine changes in the male to female ratio in diagnoses of autism spectrum disorder (ASD) over a 35 year period, providing temporal trends in diagnosis (incidence rate), the male to female ratio, and the age-cohort specific cumulative male to female ratio (cMFR).

DESIGN: Population based, prospectively collected birth cohort study.

PARTICIPANTS: 2 756 779 liveborn children recorded in the Swedish medical birth register between 1985 and 2020.

SETTING: Sweden.

MAIN OUTCOME MEASURE: Age-period cohort analysis investigating associations between ASD and age at diagnosis, calendar period, birth cohort, and sex, quantified by incidence rate ratios and associated two sided …

Heterogeneity In The Association Of Genetic Risk For Ra And Resultant Ra Phenotypes, Thomas R Riley, Iris Lee, Et Al.

2020-Current year OA Pubs

OBJECTIVES: The impact of the genetic risk for RA on resultant disease phenotype in RA is incompletely understood. Using individual genetic variants associated with RA and a polygenic score (PGS), we hypothesized that those with higher genetic risk for RA would demonstrate a more severe disease course.

METHODS: We genotyped participants from the Veterans Affairs RA registry (VARA), a prospective cohort of RA. We evaluated associations between PTPN22 R620W genotype, HLA-DRB1 shared epitope (SE; 0, 1, or 2 copies of a high-risk HLA allele), and a non-HLA PGS with RA disease activity scores and disease characteristics using linear and logistic …

Protocol For Personalised Prediction Of Persistent Postsurgical Pain, Katherine J Holzer, Harutyun Alaverdyan, Ziqi Xu, Madelyn R Frumkin, Karen A Frey, Stephen H Gregory, Thomas L Rodebaugh, Chenyang Lu, Christopher R King, Denise Head, Thomas Kannampallil, Simon Haroutounian

2020-Current year OA Pubs

INTRODUCTION: Persistent postsurgical pain (PPSP) affects up to 15% of patients after major surgery, impairing physical function, quality of life and increasing risk for long-term opioid use. Current PPSP prediction models rely on static or retrospective data and fail to incorporate dynamic perioperative factors. The Personalised Prediction of Persistent Postsurgical Pain (P5) study aims to develop individualised, multimodal prediction models by integrating preoperative behavioural, psychophysical and neurocognitive assessments and high-frequency symptom monitoring.

METHODS AND ANALYSIS: P5 is a prospective, single-centre cohort study enrolling 2500 adults aged 18-75 undergoing major surgery at a tertiary academic hospital. Participants complete baseline surveys, cognitive …

Two Faces Of Mitral Stenosis: Uncovering Structural And Hemodynamic Signatures Of Rheumatic And Mitral Annular Calcification-Induced Disease, Mohammad S. Hashemi, Peter Abdelmaseeh, Atif Nehvi, Gregg S. Pressman, Arash Kheradvar

Einstein Health Papers

BACKGROUND: Mitral annular calcification (MAC) is common and associated with increased cardiovascular risk and, when severe, mitral stenosis (MS). MAC-related MS differs anatomically and hemodynamically from rheumatic MS (RMS), challenging standard diagnostic methods. This study compares structural and flow characteristics, including  kinetic energy losses, across MAC-related MS, RMS, and normal mitral valves, and evaluates the applicability of conventional diagnostic metrics in MAC.

METHODS: Three-dimensional transesophageal echocardiographic data sets from 70 patients (22 normal mitral valves, 26 RMS valves, 22 MAC valves) were used to obtain linear, area, and volumetric measurements for valve comparison. Representative valves from each group were converted …

Epidemiology Of Healthcare-Associated Ventriculitis And Meningitis (Hcavm) And Community-Acquired Meningitis/Encephalitis And Evaluation Of An Off-Label Pcr Panel For Hcavm Diagnosis, Jaime Nassur, Katarina Schnell, Christine Dolon, Laura Walters, Devin Weber, Matthew Pettengill

Department of Medicine Faculty Papers

Healthcare-associated ventriculitis and meningitis (HCAVM) is associated with high morbidity and mortality, but rapid diagnostic tests intended to cover microorganisms that typically cause HCAVM are not commercially available. We sought to evaluate the etiology of HCAVM compared to community-acquired meningitis/encephalitis (CAME) at our healthcare system, and to study the utility of repurposing a multiplex molecular panel intended for positive blood cultures for HCAVM cases. Our epidemiologic review demonstrated that HCAVM cases were primarily caused by bacteria and fungi also associated with bloodstream infections, in contrast with CAME cases, which were primarily caused by herpesviruses and Cryptococcus. Eighty-two cerebrospinal fluid …

An Autopsy Case Of Extensive Aortic Thrombosis With Acute Kidney Injury As The Sole Clinical Manifestation, Risa Suenaga, Makoto Fukuda, Atsuhiko Suenaga, Yuki Ikeda, Maki Yoshihara, Megumi Nishiyama, Seiichi Kato, Motoaki Miyazono

Children’s Nutrition Research Center Staff Publications

Aortic thrombosis is a rare but life-threatening condition. It typically presents with abdominal or lower-limb ischemia. Although acute kidney injury (AKI) can accompany aortic thrombosis, AKI as the sole clinical manifestation has not been previously reported. A 69-year-old man with extensive atherosclerotic disease and chronic kidney disease presented with severe oliguria. Initial evaluation, including non-contrast computed tomography (CT), did not reveal any aortic abnormalities. Renal Doppler ultrasonography findings and markedly elevated D-dimer levels prompted contrast-enhanced CT, which demonstrated extensive thrombus formation extending from the descending thoracic aorta to the bilateral iliac arteries, with complete occlusion of both renal arteries and …

Patient-Specific Computational Flow Simulation Reveals Adverse Hemodynamic Factors Associated With Occlusion Of Directional Branches After Fenestrated-Branched Endovascular Aneurysm Repair, Kenneth Tran, Jesse Chait, Emmanuel Tenorio, Weiguang Yang, Alison Marsden, Bernardo Mendes, Jason T Lee, Gustavo S Oderich

Faculty, Staff and Students Publications

Background: Fenestrated and branched endovascular aneurysm repair can be complicated by branch vessel occlusion in the absence of structural stenosis. We hypothesized that computational flow simulation could identify adverse hemodynamic features associated with postfenestrated and branched endovascular aneurysm repair branch occlusion.

Methods: Patients undergoing 4-vessel fenestrated and branched endovascular aneurysm repair for Extent II to IV thoracoabdominal aortic aneurysms were retrospectively reviewed. Branches that occluded without identifiable kinking or stenosis on computed tomography were included, along with an equal cohort of anatomy-matched patent controls. Patient-specific pulsatile rigid-wall simulations were performed using SimVascular with individualized geometries and boundary conditions. Abnormal time-averaged …

Rapid Urinary Lipoarabinomannan Test With Laboratory-Level Sensitivity For Tuberculosis Detection: A Performance Evaluation, Qisheng Jiang, Harisha Ramachandraiah, Carolyn Duncan, Sumanth Gandra, Ige A George, Jingyi Luan, Marcos Perez, Lorraine Lillis, David S Boyle, Scott Crick, Morten Ruhwald, Srikanth Singamaneni

2020-Current year OA Pubs

UNLABELLED: Developing rapid, non-sputum-based tests is a global priority to improve the diagnosis and timely treatment of tuberculosis (TB). In this study, we evaluated the detection limit, precision, stability, and lot-to-lot variation of a next-generation rapid diagnostic test (RDT), the plasmonic fluor (PF)-enhanced urinary lipoarabinomannan lateral flow assay (PF-LAM). We also assessed the diagnostic performance of PF-LAM, Alere Determine TB LAM Ag (AlereLAM), and electrochemiluminescence LAM assay (EclLAM), a highly sensitive laboratory-based test by comparing with microbiology reference standard (MRS) that includes molecular testing (Xpert MTB/RIF) and culture. Two sub-studies were conducted using banked urine samples. First, a preclinical study …

Anxiety Or Depression Trends By Disability Status And Demographic Intersections In Us Adults, 2019-2023, David Adzrago, Kayo Fujimoto, J Michael Wilkerson, Typhanye V Dyer, Faustine Williams

Faculty, Staff and Student Publications

Importance: Mental health problems, particularly anxiety and depression, remain among the leading causes of disease burden in the US. However, trends in anxiety and depression across disability status and demographics remain understudied.

Objective: To examine trends in anxiety and depression prevalence among US adults from 2019 to 2023 by disability status and demographic characteristics.

Design, setting, and participants: This cross-sectional study used national population-based data from the National Health Interview Surveys from 2019 to 2023. Data were collected from household probability samples of noninstitutionalized US civilian adults aged at least 18 years. Data analyses were performed from December 6, 2024, …

Clinician Perceptions Of Barriers And Strategies To Improve Pediatric Hypertension Detection, Abbas H. Zaidi, Erica D. Sood, Sarah De Ferranti, Fabliha Khurshan, Samuel Gidding, Varsha Zadokar, Jonathan M Miller, Anne E Kazak

Department of Pediatrics Faculty Papers

IMPORTANCE: Pediatric hypertension remains underrecognized despite its high prevalence (approximately 5%) and long-term cardiovascular implications. Although guidelines for screening and diagnosis exist, less than 25% of affected children are diagnosed, and more than half do not receive timely follow-up care. Clinician-specific implementation barriers and directly informed strategies, which may alleviate this gap, are insufficiently described.

OBJECTIVE: To identify clinician-reported barriers and actionable recommendations to improve pediatric hypertension detection and follow-up in primary care using the Consolidated Framework for Implementation Research.

DESIGN, SETTING, AND PARTICIPANTS: Semistructured qualitative interviews were conducted between November 1, 2022, and March 31, 2023, with health care …

Demographic And Clinicopathologic Factors Associated With Colorectal Adenoma Recurrence, Usman Ayub Awan, Qingyuan Song, Kristen K Ciombor, Adetunji T Toriola, Jungyoon Choi, Timothy Su, Xiao-Ou Shu, Kamran Idrees, Kay M Washington, Wei Zheng, Wanqing Wen, Zhijun Yin, Xingyi Guo

2020-Current year OA Pubs

IMPORTANCE: Current colorectal surveillance guidelines emphasize adenoma characteristics but overlook temporal, racial, and sex-based heterogeneity in recurrence risk, a gap that limits equitable and personalized care.

OBJECTIVE: To evaluate the associations of demographic factors, obesity, and adenoma features with recurrence risk over time in a large longitudinal surveillance cohort.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included adults who underwent their first colonoscopic polypectomy between January 1990 and July 2024 at a tertiary medical center.

EXPOSURES: Demographic variables included race and ethnicity, sex, obesity (body mass index >30), family history of colorectal cancer (CRC) or polyps, and age at …

Longitudinal Multiomic Signatures Of Ards And Sepsis Inflammatory Phenotypes Identify Pathways Associated With Mortality, Narges Alipanah-Lechner, Pratik Sinha, Et Al.

2020-Current year OA Pubs

BACKGROUNDCritically ill patients with acute respiratory distress syndrome (ARDS) and sepsis exhibit distinct inflammatory phenotypes with divergent clinical outcomes, but the underlying molecular mechanisms remain poorly understood. These phenotypes, derived from clinical data and protein biomarkers, were associated with metabolic differences in a pilot study.METHODSWe performed integrative multiomics analysis of blood samples from 160 patients with ARDS in the ROSE trial, randomly selecting 80 patients from each latent class analysis-defined inflammatory phenotype (hyperinflammatory and hypoinflammatory) with phenotype probability greater than 0.9. Untargeted plasma metabolomics and whole-blood transcriptomics at day 0 and day 2 were analyzed using multimodal factor analysis (MEFISTO). …

Amyloidosis Of Bridging Veins Is A Pathologic Feature Of Alzheimer's Disease, Leon C D Smyth, Daan Verhaege, Elio Standen-Bloom, Yue Wu, Steffen E Storck, Pavle Boskovic, Benjamin A Plog, Tornike Mamuladze, Jose A Mazzitelli, Zhuoying Wang, Daniel D Lee, Gwendalyn J Randolph, Katherine E Schwetye, Song Hu, Jonathan Kipnis, Et Al.

2020-Current year OA Pubs

Alzheimer's disease (AD) is characterized by the accumulation of extracellular aggregated amyloid beta, resulting from impaired waste clearance. We recently identified new cerebrospinal fluid (CSF) efflux structures termed arachnoid cuff exit (ACE) points and speculated that these may be impacted in AD, leading to impaired waste clearance function. Using 5XFAD mice, we found progressive amyloidosis of bridging veins at ACE points. Indeed, in 5XFAD mice, there is impaired CSF efflux to the dura mater, impaired CSF flow along bridging veins, and impaired blood flow through bridging veins. These observations suggest that ACE point amyloidosis plays a role in waste clearance …

Estimated Effectiveness Of 2024-2025 Covid-19 Vaccination Against Severe Covid-19, Kevin C Ma, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

IMPORTANCE: As SARS-CoV-2 JN.1 lineage descendants continue to evolve, evaluating COVID-19 vaccine effectiveness (VE) against severe COVID-19 remains important to guide vaccination strategies.

OBJECTIVE: To estimate the VE of the 2024-2025 COVID-19 vaccines against COVID-19-associated hospitalization and severe in-hospital outcomes overall and by time since dose (7-89, 90-179, and ≥180 days), JN.1 descendant lineage (KP.3.1.1, XEC, LP.8.1), and spike protein mutations associated with immune evasion.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter, test-negative, case-control study conducted by the Investigating Respiratory Viruses in the Acutely Ill Network included adult patients (aged ≥18 years) hospitalized between September 1, 2024, and April 30, 2025, …

Costs Of Single Maintenance And Reliever Therapy Vs Traditional Therapy For Asthma, Tri Pham, Abigail R Barker, Sarah A Eisenstein, Eliot Jost, Anna Volerman, Krutika Chauhan, Ross C Brownson, Timothy Mcbride, Mark D Huffman, Kaharu Sumino, Lynn B Gerald, Mario Castro, Anne E Dixon, James G Krings

2020-Current year OA Pubs

IMPORTANCE: Despite strong guideline support, single maintenance and reliever therapy (SMART) for asthma is underused in the US. Limited insurance coverage of SMART-compatible inhalers remains a major barrier to its adoption.

OBJECTIVE: To compare the annual asthma management costs of SMART vs traditional therapy from a US health care payer perspective.

DESIGN, SETTING, AND PARTICIPANTS: This economic evaluation used a probabilistic decision-tree model with Monte Carlo simulations to compare the total asthma management costs for patients prescribed SMART vs traditional therapy, conducting analyses from September 1, 2024, to March 13, 2025. Input data were extracted through a systematic review of …

Insomnia In Stimulant Use Disorders: Prevalence And Associations With Negative Affect, Isabella G Bourtin, Constanza De Dios, Jessica Vincent, Joy M Schmitz, Scott D Lane, Heather E Webber

Faculty, Staff and Student Publications

Research suggests that sleep disturbances are common among people who use psychostimulants, including cocaine use and methamphetamine use. These sleep disturbances hinder recovery, heighten relapse risk, and worsen physical and mental health outcomes. This study aimed to estimate the prevalence and severity of insomnia among individuals who use cocaine and methamphetamine and to explore potential psychological factors that are associated with more severe insomnia. The sample included participants who completed in-person screening assessments for ongoing studies at an outpatient research clinic. As a part of this screening, participants completed the Insomnia Severity Index (ISI) and validated assessments of psychological domains …

The Long-Term Effectiveness Of The Anti-Obesity Medication Phentermine (Leap) Trial: Rationale, Design, And Baseline Characteristics, Caroline Blackwell Young, Emily Rives, Kimberly A Gudzune, Byron C Jaeger, Courtney G Simmons, Brian N White, Stephanie A Hooker, Deborah B Horn, Deborah R Young, Jennifer Vesely, Amanda Velazquez, Catherine Price, Shelly D Cook, Katy Martin-Fernandez, Galina Inzhakova, Nicholas M Pajewski, Jamy D Ard, Kristina H Lewis

Faculty, Staff and Student Publications

Background: Current clinical practice guidelines support the long-term use of pharmacotherapy for obesity treatment. Historically, phentermine has been one of the most prescribed obesity medications (OMs), however, its long-term efficacy and safety have never been evaluated in a randomized trial as its market approval predates such requirements. Here we describe the design, rationale, and baseline characteristics for a 24-month, double-blind, randomized controlled trial evaluating the efficacy, cardiovascular risk, and safety of phentermine in adults with overweight or obesity.

Methods: This multicenter trial will compare outcomes among participants randomized to phentermine 24 mg daily versus placebo for 24 months. All participants …

Population-Scale Sequencing Resolves Determinants Of Persistent Ebv Dna, Sherry S Nyeo, Erin M Cumming, Oliver S Burren, Meghana S Pagadala, Jacob C Gutierrez, Thahmina A Ali, Laura C Kida, Yifan Chen, Hoyin Chu, Fengyuan Hu, Xueqing Zoe Zou, Benjamin Hollis, Margarete A Fabre, Stewart Macarthur, Quanli Wang, Leif S Ludwig, Kushal K Dey, Slavé Petrovski, Ryan S Dhindsa, Caleb A Lareau

Duncan NRI Faculty and Staff Publications

Epstein–Barr virus (EBV) is an endemic herpesvirus implicated in autoimmunity, cancer and neurological disorders. Although primary infection is often subclinical, persistent EBV infection can drive immune dysregulation and long-term complications. Despite the ubiquity of infection, the determinants of EBV persistence following primary exposure remain poorly understood, although human genetic variation partially contributes to this phenotypic spectrum1–3. Here we demonstrate that existing whole genome sequencing (WGS) data of human populations can be used to quantify persistent EBV DNA. Using WGS and health record data from the UK Biobank (n = 490,560) and All of Us ( …

Dolichocolon Is Common In Pediatric Gastroenterology Patients With Constipation And Associated Complaints, David Simon, Donovan Berens, Raul Zambrana Valenzuela, Arvind Mohan, Partha Chakraborty, Timot Kellermayer, Eric H Chiou, Craig L Jensen, Ricardo A Arbizu, Marla B K Sammer, Richard Kellermayer

Faculty, Staff and Students Publications

Objectives: Dolichocolon (DC), classified under International Classification of Diseases, Tenth Revision (ICD-10) code Q43.8 ("Other specified congenital malformations of intestine"), refers to an elongated or redundant large intestine. Recent studies in adults indicate a role for dolichocolon in constipation and disorders of gut-brain interaction. Contrast enema (CE) imaging is commonly used to identify DC, typically defined as a sigmoid colon extending above, or a transverse colon descending below, the iliac crest line. Despite its potential relevance, the prevalence and clinical significance of DC in pediatric gastroenterology remain poorly understood.

Methods: This retrospective study assessed the prevalence of DC in pediatric …