Digital Commons Network^™

Pregnancy, Cancer, And Radiation-A Modern Refresher, Kelly Kisling, Sandra M Meyers, Rebecca Milman, Susan Richardson, Christina Chapman, Justine Dupere, Grace Eliason, Suzanne Evans, Titania Juang, Young Lee, Jeffrey Masten, Julia Maues, Rachel Newman, Mike Silosky, Catherine Song, Catheryn Yashar, Sara Thrower

Faculty, Staff and Student Publications

Cancer occurs in ∼1 per 1000 pregnancies; thousands of patients may require radiation procedures for diagnosis and treatment each year in the United States alone. This rare but high-risk scenario, coupled with fear of radiation, has created ambiguity in the ideal management of pregnant patients. Without a comprehensive guide for the use of radiation in imaging and treatment for pregnant cancer patients, it is difficult for providers to offer optimal patient-centered care without introducing disparities. The goal of this paper is to provide guidance on the use of radiation for screening, diagnosis, staging, and treatment of cancer, while highlighting gaps …

Proteomic Profiling Of Pulmonary Function And Cardiovascular Disease Risk In The Atherosclerosis Risk In Communities Study, Yura Lee, Astrid M Manuel, Ngoc Quynh H Nguyen, Christine Ladd-Acosta, Alanna C Morrison, Kari E North, Eric Boerwinkle, Amil M Shah, Zhongming Zhao, Stephanie J London, Bing Yu

Faculty, Staff and Student Publications

Background: Pulmonary function is linked to cardiovascular disease risk; however, the underlying mechanisms remain unclear. We aimed to identify protein biomarkers associated with pulmonary function and examine their impact on incident chronic obstructive pulmonary disease, coronary heart disease, heart failure, and all-cause mortality.

Methods: Data from White and Black Americans in the Atherosclerosis Risk in Communities study (visit 2: N=11 354, mean age=57 years; visit 5: N=3517, mean age=75 years), a prospective cohort, were analyzed. Linear regression assessed associations between protein levels and pulmonary function measures, including forced expiratory volume in 1 second and forced vital capacity. The impact of …

Clinical Validation Of Perfusion Imaging With Pulmonary Function Test Data Using Voronoi-Based Discretization, Jorge Cisneros, Caleb J. Herrera, Yi-Kuan Liu, Lisa V. Du, Yevgeniy Vinogradskiy, Richard Castillo, Girish Nair, Edward Castillo

Department of Medicine Faculty Papers

Objective.Accurate lung function assessment is essential for diagnosing and managing diseases like chronic obstructive pulmonary disorder, pulmonary emboli, and lung cancer. Single-photon emission computed tomography (SPECT) provides valuable 3D functional imaging of ventilation and perfusion, but is limited by low spatial resolution, availability, additional radiation, and cost. Alternative methods, including CT-based perfusion (CT-P) and deep learning models, require large datasets to validate results that are often scarce. Pulmonary function tests (PFTs) offer rapid and noninvasive global lung function measures and are clinically widely used. While ventilation correlates well with PFTs, perfusion imaging presents challenges due to complex blood flow and …

Association Between Functional Status And Cardiac Function In Chronic Heart Failure: Insights From The C-Mic Ii Trial., Marat Fudim, Tamara Kovacevic-Preradovic, Marija Zdravkovic, Sasko Jovev, Nermir Granov, Tanja Popov, Igor Rudez, Petar Vukovic, Velibor Ristic, Annette Holtdirk, Muhammad Shahzeb Khan, Faouzi Kallel, Miodrag Peric, Javed Butler, Stefan D. Anker, Dragana Kosevic, J. Eduardo Rame

Department of Medicine Faculty Papers

INTRODUCTION: Relationship between changes in cardiac function, functional capacity, and patient-reported health status in heart failure (HF) remains incompletely defined, which may help inform endpoint selection and clarify how distinct clinical domains reflect treatment response.

METHODS: This post hoc analysis of the randomized cardiac microcurrent (C-MIC) II trial, which evaluated the efficacy and safety of C-MIC therapy in patients with chronic HF with reduced ejection fraction on optimal guideline-directed medical therapy, included 65 ambulatory patients with non-ischaemic dilated cardiomyopathy, New York Heart Association (NYHA) Class III-IV symptoms, and baseline left ventricular ejection fraction (LVEF) 25-35%. Correlations between changes in Kansas …

Pd-L1 Positivity Predicts A Unique Hyperaggressive Tumor Group Within Meng C Meningiomas, Vijay Nitturi, Shervin Hosseingholi Nouri, Collin English, Hsiang-Chih Lu, Elizabeth Ledbetter, Diego Rojas, Sean Lau, Malcolm Mcdonald, Jacob J Mandel, Abdul Basit Khan, Arif O Harmanci, Akdes S Harmanci, Tiemo Klisch, Akash J Patel

Duncan NRI Faculty and Staff Publications

Molecular profiling has identified 3 groups of meningiomas, with MenG C tumors exhibiting the vast majority of recurrences. Efforts to find effective treatments for recurrent meningiomas have remained elusive. Higher WHO-grade meningiomas have exhibited greater Programmed Death Ligand 1 (PD-L1) expression through various methods, but the prognostic value of PD-L1 expression has not been described in the context of molecular profiling. Additionally, trials investigating PD-1/PD-L1-targeted immunotherapies have produced disappointing results. Here, we find that PD-L1 positivity, while prevalent in MenG C tumors, does not predict recurrence in the benign MenG A and B tumors. PD-L1 positivity also occurs independently of …

Circulating Ketone Bodies And Incident Cardiovascular Outcomes And Mortality: Insights From The Uk Biobank, Parag Anilkumar Chevli, Saeid Mirzai, Richard Kazibwe, Jeff Kingsley, Alexis C Wood, Joseph Yeboah, Leandro Slipczuk, Anurag Mehta, Harpreet S Bhatia, Ambarish Pandey, Michael D Shapiro

Children’s Nutrition Research Center Staff Publications

Background: Ketone bodies (KB) are endogenous energy sources synthesized by the liver in response to metabolic stress. Their associations with atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and mortality and their potential beneficial or harmful effects have yet to be determined. This study aimed to examine the association between KB and incident cardiovascular outcomes and mortality in a large general population cohort free from ASCVD and HF at baseline.

Methods: This analysis included 90 987 participants (mean age 56.4 ± 8.1 years; 54.7% women) from the UK Biobank without prevalent ASCVD or HF. KB were measured by nuclear magnetic resonance …

An Ai Approach To Differentiating Lung Squamous Cell Carcinoma From Metastases Of Other Origins, Mark G Evans, Jennifer Ribeiro, Todd Maney, Anthony Helmstetter, Jennifer Johnson, Anthony Karnezis, Casey Bales, George Sledge, David Spetzler, Ari Vanderwalde, Matthew Oberley, Balazs Halmos, Hossein Borghaei, Farah Abdulla, David Bryant, Fred Hirsch, Hassan Ghani

Department of Medical Oncology Faculty Papers

IMPORTANCE: Distinguishing primary lung squamous cell carcinoma (SCC) from squamous metastases to the lung is a clinical challenge due to histopathologic similarities. Accurate diagnosis is essential to guide treatment decisions.

OBJECTIVE: To assess the utility of an artificial intelligence (AI) approach that includes evaluation of key orthogonal evidence in distinguishing primary lung SCCs from metastatic tumors of other tissue origins.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used GPSai, a tissue-of-origin AI model run automatically on each sample submitted for molecular profiling, to flag potential misdiagnoses among research-eligible cases submitted as lung SCC. Molecularly profiled cases within the Caris Life …

Shifts In Antipsychotic Prescribing By Clinician Type For Medicare Part D Beneficiaries, 2013-2023, Youngran Kim, Xuan Zhou, Shilei Du, Trudy M Krause, Rafael Samper-Ternent, Antonio L Teixeira

Faculty, Staff and Student Publications

Importance: Despite safety warnings, antipsychotics remain commonly prescribed to older adults, particularly those with dementia, and for off-label indications. However, little is known about how prescribing patterns vary by clinician type over time.

Objective: To examine trends in antipsychotic prescribing by clinician type among Medicare beneficiaries from 2013 to 2023.

Design, setting, and participants: This repeated cross-sectional study used the Medicare Part D Prescribers by Provider and Drug dataset from 2013 to 2023. Participants included Medicare beneficiaries enrolled in Medicare Part D. Analyses were performed between November 2024 and June 2025.

Exposure: Prescribing clinician type, categorized as psychiatrist, primary care …

Population Analysis And Immunologic Landscape Of Melanoma In People Living With Hiv, Lindsay Barger, Derek Wang, Ashley Saravia, Valeria Mezzano, Gyles Ward, Cynthia Loomis, Carly Feldman, Madalina Tuluc, Rino Seedor, Peter Gaskill, Anna Coghill, Gita Suneja, Iman Dehzangi, Jennifer Hope, George Jour, Gabriele Romano

Department of Medical Oncology Faculty Papers

PURPOSE: To dissect the clinical and immunologic features of people living with human immunodeficiency virus (HIV; PLWH) diagnosed with melanoma, who have consistently shown worse outcomes than HIV-negative individuals (PLw/oH) with the same cancer.

EXPERIMENTAL DESIGN: We analyzed electronic health records from 1,087 PLWH and 394,437 PLw/oH with melanoma. Demographic and clinical characteristics were compared. Spatial immune transcriptomics (72 immune-related genes) was performed on melanoma tumor samples (n = 11), with downstream validation using multiplex immunofluorescence (mIF; n = 15 PLWH, n = 14 PLw/oH).

RESULTS: PLWH were diagnosed at a younger age, had a greater representation of Hispanic and …

The Development Of Ace-Iii Performance Validity Tests For Dementia Screening, Donnchadh Murphy, Rupert Noad

Peninsula Medical School

Objective: Performance validity tests (PVTs) are an essential component of a neuropsychological evaluation. There is a lack of brief validated PVTs for use alongside cognitive screening assessments for dementia. The current study sought to develop and evaluate a series of brief PVTs, which could be embedded into the Addenbrooke’s Cognitive Examination (ACE-III) and used in a dementia clinic. Method: This study used a diagnostic accuracy design to compare the performance of 31 individuals with Alzheimer’s disease dementia and 26 healthy older adults who simulated having Alzheimer’s disease. Participants were asked to complete ACE-III, the Test of Memory Malingering (TOMM), and …

Poly(Adp-Ribose) Glycohydrolase Enforces P21 Degradation Via Deparylation To Promote Gastric Cancer Progression, Yangchan Hu, Qimei Bao, Yixing Huang, Yan Wang, Xin Zhao, Junjun Nan, Yuxin Meng, Mingcong Deng, Yuancong Li, Zirui Zhuang, Hanyi He, Dan Zu, Yuke Zhong, Chunkai Zhang, Bing Wang, Ran Li, Yanhua He, Qihan Wang, Min Liu, John A Tainer, Yin Shi, Xiangdong Cheng, Ji Jing, Zu Ye

Faculty, Staff and Student Publications

Dysregulation of cell cycle checkpoints is a cancer hallmark, with ubiquitination-controlled protein stability playing a pivotal role. Although p21, a key cyclin-dependent kinase inhibitor, is tightly regulated by ubiquitin-mediated degradation, the key upstream modulators of its ubiquitination remain incompletely defined. Here, we identify poly(ADP-ribose) glycohydrolase (PARG) as a regulator of p21 stability in gastric cancer (GC) cells. We show that PARG expression is markedly upregulated in GC tissues and correlates with poor patient prognosis. Functional assays revealed that genetic depletion of PARG triggers G2/M phase arrest and impairs GC cell proliferation. Mechanistically, we demonstrate that PARG loss enhances p21 PARylation, …

Continuous Vs Intermittent Postoperative Vital Sign Monitoring: A Cluster Randomized Crossover Trial, Ashish K Khanna, Nathaniel Sean O'Connell, Amit K Saha, Megan Henley Hicks, Robert S Weller, Lynnette Harris, Bruce D Cusson, Ann Faris, Carolyn S Huffman, Scott Segal, Brian J Wells, Eric S Kirkendall, Daniel I Sessler

Faculty, Staff and Student Publications

Importance: Continuous postoperative monitoring on general nursing units detects vital sign abnormalities that are missed with conventional intermittent monitoring. Early recognition may prompt interventions to limit potentially harmful blood pressure, heart rate, and oxygen saturation perturbations.

Objective: To test the hypothesis that continuous unblinded monitoring of vital signs would decrease blood pressure, heart rate, and oxygen saturation abnormalities compared with intermittent monitoring in patients recovering from noncardiac surgery.

Design, setting, and participants: This multiple crossover randomized cluster trial in 2 postoperative hospital wards included patients recovering from noncardiac surgery and was conducted from October 7, 2020, to October 7, 2021. …

Prevalence And Risk Factors For Non-Hacek Gram-Negative Bacillus Endocarditis: A Retrospective Analysis, Jason H Park, Edwin Chen, Divyia E Joseph, Audrey Wanger, J Alex Viehman, Simi Padival

Faculty, Staff and Student Publications

Background: Infective endocarditis (IE) caused by non-HACEK gram-negative bacilli (GNB) is challenging to diagnose and is associated with high morbidity and mortality. There is growing literature highlighting the differences in IE prevalence amongst various GNB; therefore, there is an impetus to characterize these traditionally "atypical" organisms to accurately risk stratify this complex infectious diagnosis.

Methods: This investigation was a retrospective cohort study conducted at 2 health care institutions in the USA. All hospitalized adult patients with bloodstream infection with a prespecified GNB (Enterobacter cloacae, Escherichia coli, Klebsiella aerogenes, Klebsiella pneumoniae, Klebsiella oxytoca, Pseudomonas aeruginosa, and Serratia marcescens) between January 1, …

Effect Of Dental Treatments On Reduction Of Preterm Birth: A Systematic Review And Meta-Analysis, Camille Thomas, Shakil Ahmed, Vincenzo Berghella, Romina Brignardello-Petersen, Mohamed El-Rabbany, Catherine Devion, Stefania Ronzoni

Department of Obstetrics and Gynecology Faculty Papers

OBJECTIVE: Periodontal disease is associated with increased risk of preterm birth. Effective management during pregnancy may reduce preterm birth, though clinical trial evidence has been inconsistent. This study aimed to assess whether treating dental disease during pregnancy reduces preterm birth.

DATA SOURCES: A systematic search was performed of EMBASE, MEDLINE, PubMed, Cochrane Library, and trial registries up to December 2023 and re-run in January 2025.

STUDY ELIGIBILITY CRITERIA: Randomized controlled trials (RCTs) enrolling pregnant persons with any dental disease randomized to receive dental treatment vs no treatment were included. No language restriction was applied.

STUDY APPRAISAL AND SYNTHESIS METHODS: Data …

Apoe And Plasma Ad Biomarkers: The Role Of Genetic Ancestry In Hispanics/Latinos, Caitlin Cheung, Natasha Z Anita, Paola Filigrana, Myriam Fornage, Kevin A Gonzalez, Linda C Gallo, Carmen R Isasi, Robert C Kaplan, Xihao Li, Freddie Márquez, Humberto Parada, Krista M Perreira, Alberto R Ramos, Tatjana Rundek, Wassim Tarraf, Fernando D Testai, Charles Decarli, Hector M González, Tamar Sofer

Faculty, Staff and Student Publications

Background: Apolipoprotein E (APOE) alleles are well-established genetic risk factors for Alzheimer's disease (AD), but their effects on AD biomarkers (amyloid beta [Aβ]42/40, phosphorylated tau [p-tau]181, neurofilament light chain [NfL], and glial fibrillary acidic protein [GFAP]) may vary across populations due to ancestry-, age-, and sex-related differences. We hypothesized that these effects vary across Hispanic/Latino background groups with distinct ancestral admixture.

Methods: We analyzed ε2 and ε4 allele associations with AD biomarkers using survey-weighted linear regression models, adjusting for demographic covariates. Secondary analyses examined genetic analysis group- and ancestry-specific effects.

Results: ε4 was associated with lower Aβ42/40 and higher p-tau181and …

Perceptions And Use Of Behaviour Change Interventions For Physical Activity In Chronic Respiratory Disease In The Republic Of Ireland, Ciara Hanrahan, Joseph G Mcveigh, Terence M O'Connor, Thierry Troosters, Julie Broderick

Children’s Nutrition Research Center Staff Publications

Objectives: Behaviour change interventions may support physical activity behaviour in people with chronic respiratory disease. The most effective interventions for long-term physical activity behaviour change in this cohort remains unclear. This aim of this study was to explore the use and perceptions of behaviour change interventions by both providers of physical activity programmes for people with chronic respiratory disease and by people living with chronic obstructive pulmonary disease (COPD) in The Republic of Ireland.

Design: Two anonymous online and paper-copy cross-sectional surveys, piloted and mapped to the COM-B model of behaviour change, were distributed via social media and relevant gate-keepers …

Pre- And Postnatal Exposure To Pm2.5 And No2 And Blood Pressure In Children: Results From The Echo Cohort, Yu Ni, Andrew Law, Xingyu Gao, Adam A Szpiro, Christine T Loftus, Miranda Jones, Logan C Dearborn, Marnie F Hazlehurst, Allison R Sherris, Sindana Ilango, Kaja Z Lewinn, Nicole R Bush, Qi Zhao, Leonardo Trasande, Joseph T Flynn, Daniel A Enquobahrie, Ruby H N Nguyen, Tom O'Connor, Arpita K Vyas, Mingyu Zhang, Hooman Mirzakhani, Alison Hipwell, Anne Starling, Alicia K Peterson, Akhgar Ghassabian, Assiamira Ferrara, Judy Aschner, Scott Collingwood, Margaret R Karagas, Michelle Katzow, Annemarie Stroustrup, Mehtap Haktnair, Tina V Hartert, Brittney M Snyder, Sophia Jan, Anne Marie Singh, Dana Dabelea, Angela M Malek, Jennifer K Straughen, Carlos A Camargo, Miatta A Buxton, Rosalind Wright, Kecia Carroll, Keia Sanderson, Daphne Koinis Mitchell, Viren D'Sa, Christine Hockett, Anne L Dunlop, Shohreh F Farzen, Sunni L Mumford, Akram N Alshawabkeh, Hudson P Santos, Xueying Zhang, Zhongzheng Niu, Nan Ji, Carrie Breton, Donghai Liang, Catherine J Karr, Echo Cohort Consortium

Children’s Nutrition Research Center Staff Publications

Background: There is growing interest in understanding the link between early life exposures to ambient air pollution and childhood blood pressure; however, existing findings, largely from single site/cohort studies, are inconclusive.

Methods: We examined the association between exposures to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) and blood pressure measured at age 5-12 years in 4863 U.S. children from 20 pregnancy cohorts of the NIH ECHO cohort. Point-based residential exposures were derived from spatiotemporal models with a biweekly resolution and averaged over each trimester, the whole pregnancy, and child age 0-2 years. We converted systolic (SBP) and diastolic blood …

Associations Of Moderate-To-Vigorous Physical Activity Timing With Type 2 Diabetes Incidence In Uk Biobank And Prevalent Glycemic Measures In Nhanes, Qiuyu Feng, Gali Albalak, Linjun Ao, Qian Xiao, Heming Wang, Jeroen H P M Van Der Velde, Jessica C Kiefte-De Jong, Martin K Rutter, Charles E Matthews, Joshua R Freeman, Ko Willems Van Dijk, Diana Van Heemst, Raymond Noordam

Faculty, Staff and Student Publications

Objective: We assessed the association between timing of moderate-to-vigorous physical activity (MVPA) with incident type 2 diabetes (T2D) and glycemic measures.

Research design and methods: Regression models were used to assess associations between accelerometer-derived MVPA timing and incident T2D in UK Biobank (UKB) (n = 84,528, prospective), prevalent diabetes, and glycemic measures in the National Health and Nutrition Examination Survey (NHANES) (n = 6,998, cross-sectional).

Results: In UKB, with early morning (0500-0959) MVPA as reference and before adjustment for total MVPA, "variable-timing" MVPA was associated with the lowest incident T2D risk; while after adjustment, afternoon-evening MVPA (1500-2400) showed the lowest …

Hyperpolypharmacy And Readmission Risk Among Medicare Beneficiaries: The Role Of Postdischarge Care, Maria Ukhanova, Linda D Highfield, Trudy M Krause, Gayla M Ferguson, Robert O Morgan

Faculty, Staff and Student Publications

Objectives: Medication reconciliation post discharge may reduce readmission risk in populations with multimorbidity and polypharmacy. We aimed to evaluate the association between hyperpolypharmacy and 30-day readmissions; determine the impact of postdischarge care on 30-day readmissions; and identify interactions among hyperpolypharmacy, postdischarge care, and 30-day readmissions in 2 Medicare populations: individuals 65 years and older and individuals of any age with a qualifying disability.

Study design: Retrospective observational study using the 5% national sample Medicare fee-for-service claims data from 2016 to 2019.

Methods: We used descriptive statistics and generalized estimating equation models adjusted for covariates to assess the relationships among hyperpolypharmacy, …

Estimating Population Structure Using Epigenome-Wide Methylation Data, Ziqing Wang, Kent D Taylor, Jerome I Rotter, Stephen S Rich, Yinan Zheng, Lifang Hou, Xiuqing Guo, Jan Bressler, Laura M Raffield, Yongmei Liu, Robert Kaplan, Donald M Lloyd-Jones, Alanna C Morrison, Myriam Fornage, Bruce M Psaty, Jennifer A Brody, Tamar Sofer

The Brown Foundation: Institute of Molecular Medicine

Population stratification is one of the source of inflation in epigenome-wide association studies (EWAS) when not properly accounted for. To address this, we developed methylation population scores (MPSs) to predict genetic principal components (GPCs) using a feature selection approach. We used multi-ethnic DNA methylation data from Illumina EPIC arrays across five cohorts, including MESA (n = 929), CARDIA (n = 1123), JHS (n = 1365), ARIC (n = 2338), and HCHS/SOL (n = 1475), randomly splitting participants into training (85%) and test (15%) sets. Within each cohort, associations between GPCs and CpG sites were estimated using linear regression adjusting for …

Human-Centered Design Of Patient Interviews: Capturing The Experiences Of Patients Recovering From Emergency Abdominal Surgery, Jenna L Marquard, Christie L Martin, Elizabeth C Wick, Amanda C Trofholz, Matthew S Loth, Suhyun Park, Genevieve B Melton

The Brown Foundation: Institute of Molecular Medicine

Objectives: Recognizing the challenges of at-home recovery following a truncated presurgical pathway for emergency laparotomy (EL) patients, we sought to identify barriers and facilitators to optimal recovery. This study aimed to develop a human-centered interview guide to capture the experiences of patients recovering at home after EL.

Methods: We employed an iterative human-centered design (HCD) approach to interview guide development, structured across 3 cycles. Each cycle refined the interview guide based on mock interviews and feedback from an interdisciplinary team. In cycle 1, we focused on creating a patient-centered, understandable guide. In cycle 2, we introduced a preinterview survey to …

Diversity And Immune Dynamics Of Choroid Plexus Macrophages Are Shaped By Distinct Developmental Origins, Siling Du, Khai M Nguyen, Alina Ulezko Antonova, Jose L Fachi, Patrick Fernandes Rodrigues, Alice Verdiani, Martina Molgora, Igor Smirnov, Jasmin Herz, Tornike Mamuladze, Jennifer Ponce, Amanda Swain, Mattia Bugatti, Susan Gilfillan, Marina Cella, William Vermi, Jonathan Kipnis, Marco Colonna, Simone Brioschi

The Brown Foundation: Institute of Molecular Medicine

The choroid plexus forms a key barrier and signaling interface between the brain and peripheral circulation, yet its immune landscape remains incompletely understood. Using single-cell transcriptomics combined with lineage and spatial tracing methods, we identified three biologically distinct populations of choroid plexus macrophages, defined by differential expression of CD163, MHCII or CD9. These subsets arise from separate hematopoietic waves, occupy distinct anatomical niches and differentially rely on CSF1 and IL-34 for survival. We found that TGFβ signaling is essential to maintain their tissue-specific identities, and deletion of Tgfbr2 in these cells induces broad phenotypic reprogramming. During neuroinflammation, choroid plexus macrophages …

Risk Factors For Early-Onset And Late-Onset Dementia: A Prospective Cohort Study, Katherine Giorgio, John J Stephen, Maxwell Mansolf, Elizabeth A Peterson, Alden L Gross, Emily M Briceño, Deborah A Levine, Catherine Helmer, Stéphanie Debette, Aïcha Soumaré, M Arfan Ikram, Frank J Wolters, Sudha Seshadri, Claudia L Satizabal, Jayandra Jung Himali, Lenore J Launer, David Li, Djass Mbangdadji, Donald M Lloyd-Jones, Farzaneh A Sorond, Lihui Zhao, Oscar L Lopez, Suzanne E Judd, Timothy M Hughes, Vilmundur Guðnason, Allison E Aiello, Alison Fohner, Archana Singh-Manoux, Behnam Sabayan, James S Pankow, Paul S De Vries, Kristine Yaffe, Alexa Beiser, Abbas Dehghan, Rachel Zmora, Denise Scholtens, Pamela L Lutsey, Norrina B Allen, Richard Maclehose, Sanaz Sedaghat

Faculty, Staff and Student Publications

Background: Early-onset dementia (onset before age 65 years) is an important health concern, but much of our understanding of its risk factors is inferred from studies of late-onset dementia (onset after age 65 years). We investigated associations between several demographic, clinical, and lifestyle factors with early-onset dementia and compared those estimates against their associations with late-onset dementia.

Methods: Data from five community-based longitudinal cohort studies from the UK and USA were pooled and rigorously harmonised: UK Biobank, Atherosclerosis Risk in Communities Study, Framingham Heart Study, Multi-Ethnic Study of Atherosclerosis, and Whitehall II Study. Dementia was ascertained via hospitalisation and death …

Marginal Dispositions And Shared Decision-Making Among Older Adults In The Ed: A Prospective Cohort Study, Adrian D Haimovich, Anita Chary, Laura Burke, Alexander T Janke, Adam Rodman, Bruce Landon, Nathan I Shapiro, Aanand D Naik, Elizabeth Schoenfeld, Kei Ouchi, Mara A Schonberg

Faculty, Staff and Student Publications

Background: ED disposition decisions for older adults are complex and often uncertain, yet studies rarely capture emergency physicians' real-time perspectives.

Objective: To assess patient outcomes based on emergency physician-perceived need for admission.

Design: Single-site prospective cohort study conducted between July and November 2024.

Setting: A Boston-area academic tertiary care ED.

Participants: Patients aged 65 and older dispositioned by attending physicians, excluding patients who were handed off, left without being seen, or eloped.

Measurements: Physicians rated admission need using a 5-point Likert scale (2-4 considered marginal). Primary outcome was ED disposition stratified by rating. Secondary outcomes were hospital length-of-stay (LOS), 7-day …

Evaluating The Health Economic Impacts Of Baloxavir Marboxil And Oseltamivir For The Treatment Of Influenza In Adult Outpatients In Hong Kong: A Cost-Effectiveness Analysis, Ruohan Chen, Zengyang Shao, Kaiming Bi, Benjamin John Cowling, Zhanwei Du

Faculty, Staff and Student Publications

Background: Baloxavir marboxil, an antiviral used only in private hospitals in Hong Kong since February 2019 for treating influenza, is recognized for its efficacy against strains resistant to standard antiviral agents, providing an alternative to neuraminidase inhibitors such as oseltamivir.

Methods: This study compares the cost-effectiveness of baloxavir and oseltamivir for influenza treatment in otherwise healthy (OwH) and high-risk (HR) adult outpatients in Hong Kong from the healthcare-payer's perspective. A decision tree was utilized to study the progression of influenza and estimate associated costs and quality-adjusted life-years (QALYs) over 14 days for each antiviral.

Findings: In the general population, the …

Unilateral Online Ultrasound Stimulation Of Early Visual Cortex Suppresses Responses To Contralateral Visual Stimuli, Suraya Dunsford, Keith Murphy, Ema Darrieutort, Elsa Fouragnan, Giorgio Ganis

School of Psychology

INTRODUCTION: Transcranial ultrasound stimulation (TUS) shows great promise for inducing neuroplastic changes that persist long after stimulation. Evidence of stimulation-locked (online) neural changes would enable the development of closed-loop application of TUS. However, such responses have been difficult to distinguish from coincident neural activity caused by auditory and somatosensory effects of TUS.

METHODS: To dissociate genuine online neuromodulatory effects from peripheral confounds, we leveraged the contralateral retinotopic organization of the early visual cortex in nineteen subjects. Using a hemifield visual stimulation paradigm combined with high-precision, functional MRI-guided TUS, we applied TUS to the left early visual cortex while participants viewed …

Real-World Effectiveness Of Second-Line Therapies In Advanced Non-Small Cell Lung Cancer: Insights From Propensity-Weighted Comparative Analyses Of Longitudinal Ehr Data, Gary C N Hettinger, Qi Long, Ravi B Parikh

Faculty, Staff and Student Publications

Background: While substantial research has focused on first-line (1L) therapies for advanced-stage non-small cell lung cancer (aNSCLC), less is known about the effectiveness of second-line (2L) treatments following disease progression on 1L. The poor prognosis after 1L progression, limited guidance for 2L treatment, and constraints of clinical trials in addressing these questions underscore the need for real-world comparative effectiveness research.

Methods: We conducted a retrospective analysis to compare real-world overall survival (rwOS) associated with 2L treatments among patients with disease progression during 1L. Eligible patients were selected from Flatiron Health's nationwide electronic health record (EHR)-derived de-identified database. 1L and 2L …

Impact Of Mutational Landscape And Burden On Rbc Transfusion Response In Patients With Lower-Risk Myelodysplastic Syndromes (Lr-Mds) In The Commands Study, Rami S Komrokji, Sheida Hayati, Manuel Ugidos, Guillermo Garcia-Manero, Matteo Giovanni Della Porta, Amer M Zeidan, Valeria Santini, Uwe Platzbecker, Anita K Gandhi, Rajasekhar N V S Suragani

Faculty, Staff and Student Publications

The COMMANDS trial established luspatercept as a first‐line treatment for anemia in transfusion‐dependent lower‐risk (LR) myelodysplastic syndromes (MDS). Here we report red blood cell (RBC) transfusion response analysis based on somatic mutations profile and disease risk for patients treated with luspatercept or epoetin alfa in the COMMANDS trial. Of 350 evaluable patients, 238 (68.0%) had MDS with multiple lineage dysplasia and ring sideroblasts (RS) according to World Health Organization 2016 criteria, and 320 (91.4%) had somatic mutations in ≥ 1 gene (median, 2) with median variant allele frequencies (VAF) of 2%–59%. Mutation profiles were similar in the treatment groups. Luspatercept …

Clinicopathologic And Molecular Characteristics Of High-Grade Appendiceal Mucinous Neoplasms, Ashlee N Seldomridge, Michael G White, Christopher Scally, Richard E Royal, Mark Routbort, Jbryan Iorgulescu, Michael J Overman, Sun Mi Lee, Wai Chin Foo, Melissa W Taggart, Yun Song, Paul F Mansfield, Keith F Fournier, John Paul Shen, Beth A Helmink

Faculty, Staff and Student Publications

Background: Although 2016 consensus guidelines defined high-grade appendiceal mucinous neoplasms (HAMNs) as a distinct histologic entity, their clinical course and optimal management remain poorly characterized. Comparative data with low-grade appendiceal mucinous neoplasms (LAMNs) are limited. This study aims to detail the clinical management and outcomes of patients with HAMN and those with LAMN.

Methods: This retrospective cohort study was conducted at a large academic cancer center. An internal database was queried to identify patients with LAMN or HAMN who underwent appendectomy between 2016 and 2024. Kaplan-Meier survival analyses were used to assess the impact of primary tumor type and peritoneal …

Classification Of Major Depressive Disorder Using Vertex-Wise Brain Sulcal Depth, Curvature, And Thickness With A Deep And A Shallow Learning Model, Roberto Goya-Maldonado, Tracy Erwin-Grabner, Ling-Li Zeng, Christopher R K Ching, Andre Aleman, Alyssa R Amod, Zeynep Basgoze, Francesco Benedetti, Bianca Besteher, Katharina Brosch, Robin Bülow, Romain Colle, Colm G Connolly, Emmanuelle Corruble, Baptiste Couvy-Duchesne, Kathryn Cullen, Udo Dannlowski, Christopher G Davey, Annemiek Dols, Jan Ernsting, Jennifer W Evans, Lukas Fisch, Paola Fuentes-Claramonte, Ali Saffet Gonul, Ian H Gotlib, Hans J Grabe, Nynke A Groenewold, Dominik Grotegerd, Tim Hahn, J Paul Hamilton, Laura K M Han, Ben J Harrison, Tiffany C Ho, Neda Jahanshad, Alec J Jamieson, Andriana Karuk, Tilo Kircher, Bonnie Klimes-Dougan, Sheri-Michelle Koopowitz, Thomas Lancaster, Ramona Leenings, Meng Li, David E J Linden, Frank P Macmaster, David M A Mehler, Susanne Meinert, Elisa Melloni, Bryon A Mueller, Benson Mwangi, Igor Nenadić, Amar Ojha, Yasumasa Okamoto, Mardien L Oudega, Brenda W J H Penninx, Sara Poletti, Edith Pomarol-Clotet, Maria J Portella, Joaquim Radua, Elena Rodríguez-Cano, Matthew D Sacchet, Raymond Salvador, Anouk Schrantee, Kang Sim, Jair C Soares, Aleix Solanes, Dan J Stein, Frederike Stein, Aleks Stolicyn, Sophia I Thomopoulos, Yara J Toenders, Aslihan Uyar-Demir, Eduard Vieta, Yolanda Vives-Gilabert, Henry Völzke, Martin Walter, Heather C Whalley, Sarah Whittle, Nils Winter, Katharina Wittfeld, Margaret J Wright, Mon-Ju Wu, Tony T Yang, Carlos Zarate, Dick J Veltman, Lianne Schmaal, Paul M Thompson, Enigma Major Depressive Disorder Working Group

Faculty, Staff and Student Publications

Major depressive disorder (MDD) is a complex psychiatric disorder that affects the lives of hundreds of millions of individuals around the globe. Even today, researchers debate if morphological alterations in the brain are linked to MDD, likely due to the heterogeneity of this disorder. The application of deep learning tools to neuroimaging data, capable of capturing complex non-linear patterns, has the potential to provide diagnostic and predictive biomarkers for MDD. However, previous attempts to demarcate MDD patients and healthy controls (HC) based on segmented cortical features via linear machine learning approaches have reported low accuracies. In this study, we used …