Digital Commons Network^™

Activin A Secretion By Muscle-Repairing Macrophages Induces Heterotopic Ossification In Mice, Wenqiang Yin, Kazuo Okamoto, Asuka Terashima, Warunee Pluemsakunthai, Takehito Ono, Taku Ito-Kureha, Shizuo Akira, Yoshinobu Hashizume, Roland Baron, Satoshi Ueha, Kouji Matsushima, Martin M Matzuk, Yuji Mishina, Hiroshi Takayanagi

Faculty, Staff and Students Publications

The immune system is not only essential for host defense, but it is also involved in tissue maintenance and disease pathogenesis. Macrophages play a key role in tissue repair, fibrosis, and tumorigenesis, but the mechanisms underlying their multifunctionality have not been fully explored. Here, we identified Mrep (Ly6ChiCX3CR1loPDPN+CD9+) as a crucial subset of macrophages for muscle regeneration after muscle injury. Muscle regeneration required Mrep-derived activin A, which was produced via the TLR4/TIR domain-containing adapter-inducing interferon-β/TANK-binding kinase 1/interferon regulatory factor 3/7 signaling pathway in response to muscle injury. Mrep exerted pathological effects by secreting activin A in a model of genetically …

Regulating Ai In Pediatrics-Is Transparency Enough?, R Brandon Hunter, Kolaleh Eskandanian, Chester J Koh

Faculty, Staff and Students Publications

No abstract provided.

Consolidation Enfortumab Vedotin And Pembrolizumab After Cisplatin Induction In Metastatic Urothelial Cancer: Outcomes Of Complete Response And Bladder Preservation, Kok Hoe Chan, Putao Cen, Tung Shu, Steven Canfield, Hui Zhao, Anneliese Gonzalez, Julie Rowe, Varaha Tammisetti, Hajar Ayoub, Angel Blanco, Mark Amsbaugh, Nizar Tannir

Faculty, Staff and Student Publications

Bladder preservation remains a highly desirable therapeutic goal in urothelial carcinoma, particularly when durable survival can be achieved. Radical cystectomy is the standard treatment for muscle-invasive disease; however, it results in irreversible bladder loss and significant morbidity. Among patients with locally advanced or metastatic urothelial carcinoma, recurrence rates after standard therapy remain high. Consolidation therapy with enfortumab vedotin and pembrolizumab following cisplatin-based induction chemotherapy has demonstrated promising efficacy, with substantial complete response rates and improved bladder preservation. This single-center retrospective analysis evaluated the efficacy and safety of enfortumab vedotin plus pembrolizumab as consolidation therapy in 11 patients with metastatic urothelial …

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, …

Physical And Occupational Therapist Evaluations For Fall Prevention In The Emergency Department: A Geriatric Ed Guidelines 2.0 Systematic Review, Lauren T Southerland, Pedro K Curiati, Richard D Shih, Alexander X Lo, Kristie Harper, Ian Tarnovsky, Alexis Brengartner, Luna Ragsdale, Neha Raukar, Suzanne Ryer, Katherine M Hunold, Fabrice Mowbray, Charles L Maddow, Christopher R Carpenter, Shan W Liu

Faculty, Staff and Student Publications

Background: Older adults are at high risk for severe injuries and death from falls. Physical therapist (PT) and occupational therapist (OT) evaluations have been introduced into Emergency Department (ED) care to assist with fall risk evaluation and fall prevention care. An evaluation of current evidence was undertaken to inform the Geriatric ED Guidelines 2.0.

Methods: Systematic review of physical and/or occupational therapy evaluation for fall prevention in the ED. The intervention was evaluation by a rehabilitation therapist (PT, OT, or both) for fall prevention, fall assessment, or mitigation of fall risk factors. Studies that did not perform the evaluation during …

Histologic Analysis Of Peri-Implant Soft Tissue Around External Hexagon And Morse Taper Implant Connections, Daniel Sartorelli Marques De Castro, Jefferson David Melo De Matos, Jozely Francisca Mello Lima, Guilherme Da Rocha Scalzer Lopes, Mário Alexandre Coelho Sinhoreti, Daher Antonio Queiroz, Carlos Do Reis Pereira De Araújo

Faculty, Staff and Student Publications

Background: Twenty patients rehabilitated with screw-retained full-arch implant-supported prostheses functioning for at least one year were included.

Material and methods: This clinical study included 20 patients rehabilitated with screw-retained full-arch implant-supported prostheses in function for at least 1 year. Participants were allocated into two groups according to the implant-abutment connection design: external hexagon (EH; n = 10) and Morse taper (MT; n = 10). One peri-implant soft tissue biopsy specimen was obtained from each patient and processed for hematoxylin-eosin staining. Histological evaluation assessed epithelial hyperplasia, epithelial organization, inflammatory infiltrate intensity, and connective tissue fibrosis. Data normality was assessed using the …

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 …

The Role Of Top-Down Appetite Self-Regulation In The Development Of Healthy Eating Behaviors Among Children: A Narrative Review And Socialization Framework, David J Bridgett, Sheryl O Hughes, Matthew Broussard, Daniela Mccourt, Christina M Croce, Jennifer O Fisher

Children’s Nutrition Research Center Staff Publications

Appetite self-regulation (ASR) among children is thought to have a fundamental role in shaping the development of healthy eating behaviors, dietary intake, and growth during childhood. Parallel to developmental frameworks for understanding "general" self-regulation among children, ASR has been described as involving children's use of "top-down" cognitive processes to moderate "bottom-up" biological drives around food approach and avoidance in the interest of achieving desired eating behaviors or outcomes. Whereas bottom-up ASR processes during early childhood are well characterized, particularly in the context of dysregulation and obesity risk, the role of top-down ASR processes in the development of healthy eating behaviors …

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 …

Post-Dobbs Realities: Ethical Imperatives For Data Transparency And Trust In Maternal Health Care, Faith E Fletcher, Sophie L Schott, Kelley Akhiemokhali, Kari White

Center for Medical Ethics and Health Policy Staff Publications

No abstract provided.

Brief Report: Long-Acting Injectable Prep Can Substantially Reduce Hiv Incidence In Los Angeles County: A Simulation Study, Aditya Khanna, Francis Lee, Katrina Schrode, Daniel Sheeler, Anna Hotton, John Schneider, Kayo Fujimoto, Siri Chirumamilla, Ekow Kwa Sey, Nina T Harawa

Faculty, Staff and Student Publications

Background: Although oral pre-exposure prophylaxis (PrEP) has been instrumental in decreasing HIV incidence, its daily dosing regimen poses adherence challenges. Using an agent-based network model informed by empirical data, we simulate the impact of introducing long-acting injectable (LAI) PrEP among young Black men who have sex with men (YBMSM) in Los Angeles County, a group disproportionately affected by HIV.

Setting: Computer simulations using an agent-based network model.

Methods: We modeled HIV transmission among YBMSM over 10 years under scenarios varying the proportion of PrEP users opting for LAI instead of oral medications and adherence levels to LAI retention. The model …

Preferences For Game-Based Elements To Increase Preexposure Prophylaxis And Hiv Prevention Engagement Among Latino Men Who Have Sex With Men: South Florida, 2022, Lacey Despres, Edda Rodriguez, Ross Shegog, Stephanie Diez, Susanne Doblecki-Lewis, Kayo Fujimoto, Suzanne Randolph Cunningham, Mariano Kanamori

Faculty, Staff and Student Publications

We explored gaming elements as a tool to promote engagement in HIV prevention services among Latino men who have sex with men. We conducted thematic content analysis of semistructured interview data that we collected from 12 Latino men who have sex with men (April-August 2022) in South Florida. Themes emerged related to intervention delivery, components, and perceptions. Our findings will guide the development of a game-based intervention to improve preexposure prophylaxis and HIV prevention engagement among Latino men who have sex with men.

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, …

Intraoperative Blood Pressure Management In Noncardiac Surgery: A Narrative Review Based On Current Evidence, Alexandre Joosten, Michelle S Chew, Emmanuel Futier, Anatole Harrois, Matthias Jacquet-Lagreze, Matthieu Legrand, Antonio Messina, Paul S Myles, Bernd Saugel, Daniel I Sessler, Denise P Veelo, Jean-Luc Fellahi

Faculty, Staff and Student Publications

Purpose: Blood pressure is closely monitored during anaesthesia, yet the optimal intraoperative target remains uncertain. This narrative review synthesizes contemporary observational and randomized evidence and explores emerging strategies for individualized haemodynamic management.

Methods: We reviewed major observational cohort studies, randomized controlled trials (RCTs), consensus statements, and recent technological developments addressing intraoperative hypotension, MAP thresholds, and strategies to prevent perioperative organ injury in adult noncardiac surgery.

Results: Large observational datasets consistently demonstrate graded, duration-dependent associations between intraoperative MAP 60-70 mmHg and postoperative myocardial injury, acute kidney injury, and mortality . These findings have informed international recommendations to avoid MAP below 60-65 …

Learn More About Article Processing Waivers And Discounts, Joanne Romano

TMC Library Newsletter (2015-)

Analysis of the Library’s Publishing Support program reveals over 300 authors benefitted from waivers and discounts from 2023-2025, saving members and institutions around $845,000. Learn more and check your eligibility for this program at the guide Publishing Support at the TMC Library.  The list of participating publishers and details for each agreement are available in the guide. The newest publisher agreement added for 2026 is Springer Nature.

Lunch & Learn Webinar Series, Katie Prentice

TMC Library Newsletter (2015-)

We are so excited to bring this series to you and look forward to seeing you in 2026!

Check our institutional repository for presentation and resources guides of archived classes since 2025.

Behavioral Health Resources At The Tmc Library, Joanne Romano

TMC Library Newsletter (2015-)

No abstract provided.

Barriers To Occupational And Physical Therapy Utilization For Children With Cancer, Maria C Swartz, Shiming Zhang, Donna Kelly, Clark R Andersen, Keri Schadler, Alakh P Rajan, Eduardo Gonzalez Villarreal, Stephanie J Wells, Amy Heaton, Karen Moody

Faculty, Staff and Student Publications

Introduction: Occupational and physical therapy (OT/PT) referrals and utilization barriers for childhood cancer patients have not been adequately examined. The current study investigated factors influencing referrals to and utilization of OT/PT services among children with cancer at an NIH-designated cancer center.

Methods: This retrospective cohort study included pediatric cancer patients (up to 18.99 years) presenting to the center over a 33.5-month period. Variables that could influence referrals to OT/PT were extracted from the electronic medical record (EMR) including OT and PT referrals (inpatient and outpatient), OT and PT consult completion, age at diagnosis, cancer type, sex, race/ethnicity, insurance, cancer treatment, …

Physical Activity In Osteosarcoma Patients During And Post Therapy: A Single Site Prospective Observational Study, Elysia R Cohen, Clark Andersen, Karen Moody, Maria C Swartz, Michael C Robertson, Alakh Rajan, Theresa Honey, Sandra Lugo, Grace Waterman, Keri Schadler

Faculty, Staff and Student Publications

PURPOSE: Osteosarcoma is the most common primary bone tumor in childhood and adolescence. Many patients face long-term impairments in their mobility and function after treatment, leading to a decrease in their quality of life. Exercise has been shown to improve functional recovery and improve quality of life in patients with cancer, though data specific to children with osteosarcoma are sparse. Exercise has also been shown to be feasible in patients undergoing chemotherapy, with numerous potential benefits to health and quality of life. To design the most effective exercise interventions for children and adolescents with osteosarcoma, we must first understand the …

Sexual Toxicity After Chemoradiation For Anal Cancer Among Men Who Have Sex With Men: A Mixed-Methods Analysis, Beck O Gold, Angie Arzola, Benjamin R Schrank, Van K Morris, Christophe Marques, Jaime Gilliland, Thomas M Atkinson, Emma B Holliday

Faculty, Staff and Student Publications

Purpose: Chemoradiation (CRT) is the standard of treatment for localized anal squamous cell carcinoma (SCCA). Although cure rates are high, acute and late toxicities are common. There are increasing published data regarding vaginal stenosis and erectile dysfunction; however, the nature and impact of holistic sexual dysfunction after pelvic radiation, particularly among men who have sex with men (MSM), remains poorly characterized. This study aimed to: (1) explore patient-reported sexual health outcomes among MSM as measured by existing patient-reported outcome tools, and (2) assess the applicability of these existing tools for this population.

Methods and materials: MSM who are at least …

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 …

Glutamatergic Dysfunction Of Astrocytes In Paraventricular Nucleus Of Thalamus Contributes To Adult Anxiety Susceptibility In Adolescent Ethanol Exposed Mice, Aubrey Bennett, Hyunjung Kim, David Thomas, Peter Biggs, Roxan Ara, Asamoah Bosomtwi, Seungwoo Kang

The Brown Foundation: Institute of Molecular Medicine

Repeated ethanol exposure during adolescence increases adult anxiety risk, but the underlying mechanisms remain unclear. The paraventricular nucleus of the thalamus (PVT) has been considered a hub for controlling anxiety and is affected by experiences from early life. Thus, this study investigated how adolescent intermittent repeated ethanol exposure (AIE) affects the PVT activities and anxiety-related behaviors in adulthood. We found that AIE triggers anxiety-like behaviors and parallelly exhibited elevated firing rates and increased calcium signaling in the PVT neurons compared to control counterpart mice. Chemogenetic inhibition of PVT neurons reduced anxiety-like behaviors in AIE-treated animals, confirming PVT's role in adolescent …

Lipids Grease The Chain Of Cancer Progression, Joseph Rupert, Pham Hong Anh Cao, Daniel E Frigo, Mikhail G Kolonin

The Brown Foundation: Institute of Molecular Medicine

The role of lipids in cancer progression has become a fervent area of exploration. The crosstalk of tumors with adipose tissue is a complex but well-regulated orchestration of signaling pathways, lipid transporters, and enzymes. They regulate fatty acid synthesis, their deposition into lipid droplets (LDs) as triglycerides, induction of lipolysis, shuttling lipids across cells, and their systemic trafficking, modification, and catabolism. For the latter, lipid oxidation has emerged as a metabolic process of particular clinical importance. Products of lipid processing can become secondary messengers, contribute to reactive oxygen species (ROS) generation, stimulate the production of antioxidants, and, if left unchecked, …

Neutralization Of Sars-Cov-2 By Igm-14 Via Engagement Of Two Distinct Spike Epitopes, Yan Wang, Yanping Hu, Zhiqiang Ku, Jason Yeung, Jing Zou, Michael Woodson, Nikolai S Prokhorov, Ekaterina S Knyazhanskaya, Haiqing Zhao, Michael B Sherman, Zhiqiang An, Stephen F Carroll, Pei-Yong Shi, Petr G Leiman, Xuping Xie

The Brown Foundation: Institute of Molecular Medicine

Engineered immunoglobulin M (IgM) antibodies typically exhibit superior neutralization potency and avidity compared to their parental IgG counterparts, primarily due to multivalent binding to repeated epitopes on a targeting antigen. In this study, we characterize the neutralization breadth and mechanism of action of IgM-14, a previously reported intranasally deliverable antibody targeting SARS-CoV-2. IgM-14 demonstrates remarkably potent antiviral activity against all pre-Omicron variants but significantly reduced efficacy against Omicron BA.1, and complete loss of activity against the later subvariant JN.1. Resistance selection identified two key mutations in the receptor-binding domain (RBD), G476D and F486P, which disrupt IgM-14 binding and confer strong …

Early Behavioral And Cognitive Changes In Patients With Pathologically Confirmed Alzheimer Disease, Lewy Body Dementia, And Mixed Dementia, Ming Wang, Hongke Wu, Aaron Bonner-Jackson, Yiming Chen, Wen Tang, Hao Feng, Lijun Zhang, Chixiang Chen, James B Leverenz, Jagan A Pillai

Faculty, Staff and Student Publications

Background and objectives: Alzheimer's disease pathology (ADP) and Lewy body pathology (LBP) are traditionally associated with distinct cognitive profiles. However, growing evidence highlights the role of behavioral and psychological symptoms of dementia (BPSD) in shaping clinical presentations. The combined influence of cognitive and behavioral symptoms across neuropathologically confirmed ADP, LBP, and mixed AD-LBP has not been systematically examined. This study aimed to identify clinically meaningful subtypes by jointly analyzing cognitive performance and BPSD profiles in individuals with autopsy-confirmed dementia pathology.

Methods: This retrospective longitudinal cohort study used data from the National Alzheimer Coordinating Center (NACC), collected across multiple U.S. Alzheimer's …

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 …