Digital Commons Network^™

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 …

Phase I Study Of Bevacizumab And Temsirolimus Combination Therapy In Advanced Malignancies: Safety, Efficacy, And Ovarian Cancer Expansion, Sarina A Piha-Paul, Chieh Tseng, Emily Thompson, R Jason Stafford, Hung Le, Lei Kang, Siqing Fu, Apostolia Tsimberidou, George Blumenschein, Jordi Rodon Ahnert, John M Slopis, David Hong, Aung Naing, Funda Meric-Bernstam, Chaan S Ng, Shannon Westin, Anil K Sood

Faculty, Staff and Student Publications

Background: Bevacizumab and temsirolimus target angiogenic and mTOR pathways in cancer progression.

Methods: This phase I study enrolled 48 heavily pretreated patients with advanced solid tumors, including an ovarian cancer expansion cohort. Patients received bevacizumab biweekly plus temsirolimus weekly in a 3 + 3 design to assess safety, maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs). Exploratory analyses included tumor genomic profiling and dynamic contrast-enhanced MRI (DCE-MRI).

Results: Patients had a median age of 59 and median four prior therapies. Common tumor types were ovarian (27%) and head and neck (15%). Treatment-related adverse events occurred in 93.8%, with 31.3% ≥grade …

Targeting Pediatric Glioblastomas By Combining Olig2 Inhibitor Ct-179 With Fractionated Radiation In A Panel Of Patient-Derived Orthotopic Xenograft Mouse Models., Holly Lindsay, Yuchen Du, Lin Qi, Huiyuan Zhang, Sibo Zhao, Frank K Braun, Mari Kogiso, Clifford Stephan, Gordon Alton, Gregory Stein, Graham Beaton, Santosh Kesari, Steven Neuhauser, Timothy M Stearns, Jeffrey Chuang, Emily L Jocoy, Carol J Bult, Beverly Teicher, Malcolm A Smith, Xiao-Nan Li

Faculty Research 2026

The poor clinical outcomes of pediatric high-grade glioma (pHGG) highlight the urgent need for new therapies. Oligodendrocyte lineage transcription factor 2 (OLIG2) is a pro-mitotic transcription factor highly expressed in glioma stem cells and may represent a novel therapeutic target. To evaluate the therapeutic efficacy of an OLIG2 inhibitor CT-179 in pHGG, we determined the OLIG2 mRNA expression in 10 patient-derived orthotopic xenograft (PDOX) models. In vitro activities of CT-179 were analyzed in monolayer and neurosphere cells (0–10 µM) with and without radiation (XRT) (0–8 Gy), brain penetration was evaluated in tumor-bearing PDOX mice, and in vivo efficacy was determined …

Targeting Pediatric Glioblastomas By Combining Olig2 Inhibitor Ct-179 With Fractionated Radiation In A Panel Of Patient-Derived Orthotopic Xenograft Mouse Models., Holly Lindsay, Yuchen Du, Lin Qi, Huiyuan Zhang, Sibo Zhao, Frank K Braun, Mari Kogiso, Clifford Stephan, Gordon Alton, Gregory Stein, Graham Beaton, Santosh Kesari, Steven Neuhauser, Timothy M Stearns, Jeffrey Chuang, Emily L Jocoy, Carol J Bult, Beverly Teicher, Malcolm A Smith, Xiao-Nan Li

Faculty Research 2026

The poor clinical outcomes of pediatric high-grade glioma (pHGG) highlight the urgent need for new therapies. Oligodendrocyte lineage transcription factor 2 (OLIG2) is a pro-mitotic transcription factor highly expressed in glioma stem cells and may represent a novel therapeutic target. To evaluate the therapeutic efficacy of an OLIG2 inhibitor CT-179 in pHGG, we determined the OLIG2 mRNA expression in 10 patient-derived orthotopic xenograft (PDOX) models. In vitro activities of CT-179 were analyzed in monolayer and neurosphere cells (0–10 µM) with and without radiation (XRT) (0–8 Gy), brain penetration was evaluated in tumor-bearing PDOX mice, and in vivo efficacy was determined …

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 …

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.

Comparing Community-Based Monitoring To Hospital-Based Care Of Patients With Quiescent Age-Related Macular Degeneration: A Qualitative Study Of Patient And Practitioner Perspectives On Acceptability And Access, Sofia Vougioukalou, Simon M Read, Judit Katalin Csontos, Aled Jones, Alijazy Jaber, Anitta Sharma, Konstantinos Balaskas

School of Nursing and Midwifery

Objectives This process evaluation explores patient and healthcare professional acceptability of community-based monitoring versus hospital-based care for patients with quiescent neovascular age-related macular degeneration (QnAMD). Design Qualitative process evaluation was conducted as part of a randomised controlled trial. Setting Six hospitals and six community-based practices. Participants 25 patients and 16 healthcare professionals (ophthalmologists and optometrists). This approach helped differentiate between common issues and those specific to community-based monitoring. Intervention The Quality-Assured Follow-Up of QnAMD by non-medical practitioners trial aimed to examine whether non-medical practitioners follow-up patients with QnAMD in the community in a safe and clinically and cost-effective way. The …

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 …

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 …

Immunogenicity And Efficacy Of A Rabies-Based Vaccine Against Highly Pathogenic Influenza H5n1 Virus, Nir Paran, Christoph Wirblich, Randy Albrecht, Leila Zabihi Diba, Alessandro Tarquinio, Drishya Kurup, Charalambos C. Solomides, Adolfo García-Sastre, Matthias J. Schnell

Department of Microbiology and Immunology Faculty Papers

The recent spillover of highly pathogenic influenza A/H5N1 (HPAI-H5N1) viruses to cattle, other mammals, and humans poses a major risk to animal and human health. Virus adaptation to new species highlights the need for effective vaccines for animals and humans. We recently developed a rabies virus-based H5 vaccine encoding the HPAI-H5 antigen and presenting it on the surface of the rabies virus particle. To test the immunogenicity and efficacy of the vaccine in eliciting systemic and mucosal immune response, we vaccinated mice intramuscularly or intranasally with either live or inactivated and adjuvanted vaccine. The vaccine elicited neutralizing antibodies against RABV …

Nci-Designated Cancer Centers' Policies And Practices With Regard To Alcohol And Cancer: A Call To Lead, Ernest T Hawk, Stephanie L Martch, Meghan Si, Sanjay Shete

Faculty, Staff and Student Publications

Background: Alcohol, a known carcinogen since 1988, increases risk of cancers of the mouth, pharynx, larynx, esophagus, liver, breast, and colorectum. More than one half of US adults consume alcohol whereas about two thirds are unsure whether or unaware that alcohol intake is linked to cancer risk.

Methods: Our objective was to survey awareness, beliefs, intentions, policies, practices, and goals/perceived responsibilities related to establishing/promoting actions to reduce alcohol-related cancer risks from leaders of 72 NCI-Designated Cancer Centers.

Results: Sixty-one percent responded. Forty-three percent either believed in or were uncertain about alcohol's purported health benefits. Nevertheless, 86% considered it part of …

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 …

Generational Trends In Reproductive Factors Among Women In The Us: Implications For Breast Cancer Incidence, Lin Yang, Adetunji T Toriola

2020-Current year OA Pubs

BACKGROUND: Reproductive factors are key breast cancer risk factors, yet contemporary generational patterns remain unclear. We aimed to evaluate trends in reproductive factors among US women born between 1910 and 2000.

METHODS: We conducted a serial, cross-sectional analysis of reproductive factors using data from the US National Health and Nutrition Examination Survey (NHANES) collected between 1999 and 2020. Female participants were grouped by birth cohorts (1910-1930, then by 10-year to 2000). Self-reported data were used to derive age at menarche, prevalence of age at menarche <  12 years, age at natural menopausal, prevalence of first live birth after age 30, and lifetime number of live births.

RESULTS: Data on 28,481 US women were analyzed. From birth cohort 1910-1930 to 1990-2000, the …

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 …

Cd8+ T Cells In The Tumor Microenvironment Modulate The Response To Endocrine Therapy In Breast Cancer, Fabiana Napolitano, Yunguan Wang, Dhivya R Sudhan, Paula I Gonzalez-Ericsson, Luigi Formisano, Nisha Unni, Shahbano Shakeel, James Z Zhu, Khushi Ahuja, Lei Guo, María Rosario Chica-Parrado, Yuki Matsunaga, Pamela Luna, Chang-Ching A Lin, Yasuaki Uemoto, Kyung-Min Lee, Hongli Ma, Nathaniel J Evans, Alberto Servetto, Saurabh Mendiratta, Spencer D Barnes, Roberto Bianco, Yisheng V Fang, Lin Xu, Jeon Lee, Tao Wang, Justin M Balko, Gordon B Mills, Marilyne Labrie, Ariella B Hanker, Carlos L Arteaga

Faculty, Staff and Student Publications

The role of the tumor immune microenvironment (TIME) in modulating responses to antiestrogen therapy in hormone receptor-positive (HR+) breast cancers remains unclear. We analyzed pre- and on-treatment biopsies from patients with HR+ breast cancer treated with letrozole to induce estrogen deprivation (ED). Stromal tumor-infiltrating lymphocytes, assessed by H&E staining, and immune-related gene sets, including IFN-γ signaling genes, measured by RNA-Seq, were increased in ED-resistant tumors. Cyclic immunofluorescence and spatial transcriptomics revealed an abundance of CD8+ T cells and enhanced antigen processing and immune gene signatures in ED-resistant tumors. In this group, the expression of CXCL9, CXCL10, and CXCL11 - chemokine …

Women's Preferences For Home-Based Self-Sampling Or Clinic-Based Testing For Cervical Cancer Screening, Joël Fokom Domgue, Monalisa Chandra, Olajumoke Oladoyin, Manali Desai, Robert Yu, Sanjay Shete

Faculty, Staff and Student Publications

Importance: While home-based self-sampling for cervical cancer screening is an evidence-based strategy proven to increase screening access and uptake, it is not currently recommended in the US despite recent Food and Drug Administration approval of the first at-home self-sampling device. Little nationally representative research has examined preference for and drivers of home-based self-sampling over clinic-based testing (the standard of care).

Objective: To assess women's perspectives about, reasons for considering, and factors associated with preferring at-home self-sampling for cervical cancer screening.

Design, setting, and participants: This population-based cross-sectional study used data from the 2024 Health Interview National Trends Survey (HINTS 7), …

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 …

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 …

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). …

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 …

Effects Of Dual-Eligible Integrated Care Plans On Medicaid Enrollment And Retention: Evidence From The Implementation Of Medicare-Medicaid Plans, Eric T Roberts, Eliza Macneal, Kenton J Johnston, José F Figueroa

2020-Current year OA Pubs

Medicare and Medicaid are separate programs that together cover 13 million low-income older adults and people with disabilities, known as dual-eligible individuals. Concern about a lack of coordination across Medicare and Medicaid has prompted the development of Integrated Care Programs (ICPs). Although the primary goal of ICPs is to coordinate financing and care across Medicare and Medicaid, ICPs may also influence whether low-income individuals obtain or keep Medicaid. We evaluated whether the rollout of Medicare-Medicaid Plans (MMPs)-one of the largest ICPs-was associated with changes in Medicaid take-up and retention among Medicare beneficiaries residing in high-poverty zip codes. Using a stacked …

Life-Extending Interventions Do Not Necessarily Result In Compression Of Morbidity: A Case Example Offering A Robust Statistical Approach., Deependra K Thapa, Wasiuddin Najam, Erik S Parker, Xi Rita Wang, Daniel L Smith, Ufuk Beyaztas, James F Nelson, Steven N Austad, Gary Churchill, David B Allison

Faculty Research 2026

Despite extensive research on life-extending interventions, rigorous statistical techniques to determine their impact on compression of morbidity (CoM) are rarely used. We present a case example of an analytical method for examining the effect of life-extending dietary interventions on CoM by comparing the rates of decline in vitality and survival toward the end of life. Using data from previous experimental studies in mice, we calculated the average rate of vitality decline by fitting exponential decay models to individual vitality trajectories and compared this rate with the rate of survival decline estimated from Cox proportional hazards model. The results showed that, …

Life-Extending Interventions Do Not Necessarily Result In Compression Of Morbidity: A Case Example Offering A Robust Statistical Approach., Deependra K Thapa, Wasiuddin Najam, Erik S Parker, Xi Rita Wang, Daniel L Smith, Ufuk Beyaztas, James F Nelson, Steven N Austad, Gary Churchill, David B Allison

Faculty Research 2026

Despite extensive research on life-extending interventions, rigorous statistical techniques to determine their impact on compression of morbidity (CoM) are rarely used. We present a case example of an analytical method for examining the effect of life-extending dietary interventions on CoM by comparing the rates of decline in vitality and survival toward the end of life. Using data from previous experimental studies in mice, we calculated the average rate of vitality decline by fitting exponential decay models to individual vitality trajectories and compared this rate with the rate of survival decline estimated from Cox proportional hazards model. The results showed that, …