Digital Commons Network^™

Modulating Alternative Splicing Of Mecp2 Is A Potential Therapeutic Strategy For Rett Syndrome, Harini P Tirumala, Li Wang, Yan Li, Sameer S Bajikar, Ashley G Anderson, Wei Wang, Alexander J Trostle, Mahla Zahabiyon, Aleksandar Bajic, Jean J Kim, Hu Chen, Zhandong Liu, Huda Y Zoghbi

Faculty, Staff and Students Publications

Rett syndrome (RTT) is a neurological disorder caused by loss-of-function mutations in methyl CpG binding protein 2 (MECP2), a transcriptional regulator essential for maintenance of normal neuronal function. The current FDA-approved treatment for RTT, Trofinetide, mildly alleviates some symptoms. In contrast, re-introducing MeCP2 or increasing its amount through transgenesis in mouse RTT models improves most neurological phenotypes and enhances survival. Here, we devised a therapeutic strategy to moderately increase MeCP2 protein by modulating the alternative splicing of MECP2 to switch the less efficiently translated e2 to the more efficiently translated e1 isoform. We deleted Mecp2 exon 2 (unique …

Influence Of Body Composition On The Efficacy Of Nivolumab Plus Ipilimumab For Metastatic Clear Cell Renal Cell Carcinoma, Kabir Grewal, Maria Julia Moura Nascimento Santos, Pankaj Kumar Chauhan, Kai Yu, Nizar M Tannir, Sagar S Mukhida, Neha Venkatesh, Amishi Y Shah, Amado J Zurita, Andrew C Johns, Matthew T Campbell, Sangeeta Goswami, Jianjun Gao, Eric Jonasch, Jennifer L Mcquade, Omar Alhalabi, Pavlos Msaouel, Andrew W Hahn

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitor therapy (ICI) with nivolumab+ipilimumab is a first-line (1L) standard for metastatic clear cell renal cell carcinoma (ccRCC), yet outcomes remain heterogeneous. Increasing evidence suggests that host factors influence the tumor microenvironment and response to ICI. Although higher body mass index (BMI) has been associated with improved outcomes in several malignancies, BMI is an imprecise surrogate for underlying adipose and muscle compartments. We evaluated the association between body composition and outcomes with 1L nivolumab+ipilimumab in metastatic ccRCC.

Methods: We retrospectively analyzed patients with mccRCC treated with 1L nivolumab+ipilimumab at MD Anderson Cancer Center between June 2015 and …

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 …

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 …

Mechanometabolism Instructs Hematopoietic Stem Cell Specification, Paulina D Horton, Alina Syed, Michelle Winkler, Abishek B Vaidya, Michael Rariden, Neha Arora, Yong Zhou, Michihiro Kobayashi, Momoko Yoshimoto, Hyun Jung Lee, Hyun-Eui Kim, John P Hagan, Catherine Denicourt, Travis I Moore, Pamela L Wenzel

Faculty, Staff and Student Publications

Mechanical force generated by blood flow stimulates emergence of the first hematopoietic stem cells (HSCs) that populate the blood system. Force drives the transition of HSC precursors from an endothelial to hematopoietic identity, yet the molecular regulation of this fate switch remains poorly understood. We report that shear stress triggers adaptation in mitochondrial composition, ultrastructure, and function, which are essential for hematopoietic fate and engraftment potential. Shear stress remodels mitochondria in hemogenic endothelium by promoting mitochondrial gene transcription and protein synthesis. Laminar flow selectively initiates translation of 5' terminal polypyrimidine (5'TOP) motif-containing transcripts, which commonly encode ribosome and translation machinery. …

Trends In Mammography Use Among Women Aged 40 To 74 Years In The Us, 2002-2022, Syed Mahfuz Al Hasan, Debbie L Bennett, Adetunji T Toriola

2020-Current year OA Pubs

IMPORTANCE: Understanding how prior policies, systemic factors, and public health events have shaped mammography use among US women is essential for interpreting the 2024 US Preventive Services Task Force (USPSTF) recommendation update and identifying gaps to inform equitable public health strategies.

OBJECTIVE: To analyze mammography use trends in US women aged 40 to 49 and 50 to 74 years from 2002 to 2022 and assess variation by sociodemographic, health care access, behavioral, and geographic factors, including associations with the 2009 USPSTF recommendation and the COVID-19 pandemic.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from the Behavioral Risk Factor …

Improving Vaccination In People With Ckd: Report From A National Kidney Foundation Working Group, Susan F. Massengill, Kenneth A. Andreoni, Keith A. Bellovich, Cheryl Courtlandt, Vimal K. Derebail, David L. Feldman, Gia J. Oh, John W. Sleasman, Kristina A. Bryant, Improving Vaccination In Ckd Working Group

Department of Surgery Faculty Papers

People with chronic kidney disease (CKD) are particularly vulnerable to vaccine-preventable infections. Therefore, the National Kidney Foundation organized a multidisciplinary working group, including people with CKD and family care partners, to develop recommendations to improve vaccination rates, vaccination effectiveness, and health care for the CKD population. A modified Delphi process was used to achieve consensus on the recommendations. Recommendations on vaccination in CKD patients were organized into these categories: (1) patient preferences; (2) assessing the vaccination status of patients with CKD; (3) assessing vaccine response in patients with CKD; (4) vaccination of immunocompromised patients; (5) vaccination in posttransplant patients; (6) …

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 …

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.

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 …

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 …

[Factors Associated With Adhd Medication Adherence And Treatment Outcomes, Hali Temkin, Kerri L Daniel, Diana Martinez, Julia C Bennett, Paris A Nix, Linh Nguyen, Yen-Chi Le, Bruno Kluwe-Schiavon, Cesar A Soutullo

Faculty, Staff and Student Publications

Introduction: Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder that affects 5 to 8% of youth and 2.5 to 4% of adults. Pharmacological treatments are among the most effective when treating ADHD, yet adherence to medication is still sub-optimal. We reviewed the literature on clinical and socio demographic factors that may influence adherence and compared it to our clinical data.

Methods: We conducted a targeted literature review on factors associated with ADHD medication adherence. These factors were compared within our sample of patients aged 3-18 with ADHD at the Child and Adolescent Mood Disorders Program (ChAMP) at (UT Health) - Houston. …

Development And Initial Testing Of An Online Security Prime Writing Intervention During Covid-19, Angie S Leroy, Andreas Weyland, Jade Kanemitsu, Arya Tsay-Jones, Vincent D Lai, E Lydia Wu-Chung, Nyla Vela, Amanda Perozo, Valentina I Maza, Sierra Wickline, Katherine Beach, Robert Suchting

Faculty, Staff and Student Publications

Background and objectives: During the COVID-19 pandemic, we tested the efficacy of a one-week online security prime (SP) writing intervention in reducing distress among 254 adults (60+ years and/or having an underlying health condition). The efficacy of writing interventions can depend on several factors. Attachment orientations, characterized by dimensions of anxiety and avoidance, reflect individuals' tendencies in how they seek proximity to and rely on others for support, and influence how people experience and regulate their emotions.

Design and methods: Participants were randomly assigned to one of three conditions: Security Priming (SP), where people wrote about what made them feel …

Childhood Pulmonary Outcomes After Late Preterm Antenatal Corticosteroids, Cynthia Gyamfi-Bannerman, Rebecca G Clifton, Robert A Wise, Alan T N Tita, Jessica A De Voest, Sharon A Mcgrath-Morrow, Elizabeth C Matsui, Sean C Blackwell, Monica Longo, Sabine Z Bousleiman, Felecia Ortiz, Sankaran Krishnan, Dwight J Rouse, Torri D Metz, George R Saade, Maged M Costantine, Kent D Heyborne, John M Thorp, Kelly S Gibson, Geeta K Swamy, William A Grobman, Yasser Y El-Sayed, George A Macones, Eunice Kennedy Shriver National Institute Of Child Health And Human Development Maternal-Fetal Medicine Units Network And The National Heart, Lung, And Blood Institute

Faculty, Staff and Student Publications

Objective: To evaluate whether antenatal betamethasone affects childhood respiratory impairment.

Methods: This was a prospective follow-up study of children aged 6 years and older from parents in the ALPS (Antenatal Late Preterm Steroids) trial randomized to betamethasone or placebo from 34 0/7 to 36 6/7 weeks of gestation. Primary outcome composite included the following: 1) abnormal spirometry, forced expiratory volume in 1 second (FEV 1 ) below the lower limit of normal, FEV 1 /forced vital capacity (FVC) below the lower limit of normal, or FVC below the lower limit of normal, defined as below the 5th percentile by the …

A Patient-Derived Organ-On-Chip Platform For Modeling The Tumor Microenvironment And Drug Responses In Pancreatic Cancer, Darbaz Adnan, Natan Roberto De Barros, Luca S Santovito, Xuhong Cheng, Kristi M Lawrence, Mariah K Barnett, Martine D Boetto, Neal Mehta, Ajaypal Singh, Lin Cheng, Xiangsheng Huang, Faraz Bishehsari

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) is a fatal malignancy. Current conventional chemotherapeutics are inadequate in controlling the disease; hence, there is an urgent need for precision medicine. Ex vivo models that replicate the tumor and its microenvironment can advance precision medicine in PDAC. Patient‐derived organoids (PDOs) offer a promising solution by retaining the functional features of the tumor, allowing for individualized study of cancer biology and drug response. However, PDOs fall short in replicating the tumor microenvironment (TME), which includes various stromal and immune cells influencing tumor growth and chemoresistance. We hypothesize that combining PDO technology with organ‐on‐a‐chip (OoC) systems can …

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

Faculty, Staff and Students 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 …

Pharmacodynamics, Efficacy, And Safety Of Intraputaminal Eladocagene Exuparvovec Administered To Pediatric Patients With Aromatic L-Amino Acid Decarboxylase Deficiency Using An Mr-Compatible Cannula: 48 Weeks Of Follow-Up, Daniel J Curry, Phillip L Pearl, Scellig S D Stone, Donald L Gilbert, Sudhakar Vadivelu, Bruria Ben-Zeev, Matthew Vestal, Muhammad Zafar, Chun-Hwei Tai, Sheng-Che Chou, Zion Zibly, Lior Ungar, Mered Parnes, Mariam Hull, Lisa Emrick, Christian Werner, Alexis Krolick, Vinay Penematsa, Antonia Wang, Rezwanur Rahman, Lee Golden, Yin-Hsiu Chien, Paul Wuh-Liang Hwu

Faculty, Staff and Students Publications

Aromatic ʟ‐amino acid decarboxylase (AADC) deficiency is a rare pediatric neurotransmitter disorder that typically necessitates lifelong care, and that carries a risk of childhood mortality. Eladocagene exuparvovec gene therapy is designed to restore AADC production. Study GT‐002 (NCT04903288) is a phase 2, multicenter, open‐label trial assessing the pharmacodynamics, safety, and efficacy of eladocagene exuparvovec administered to the putamen bilaterally in pediatric patients with AADC deficiency using a magnetic resonance (MR)‐compatible cannula. Patients received eladocagene exuparvovec at 1.8 × 1011 vector genomes via the SmartFlow MR‐compatible cannula in a single operative session. Endpoints include the change from baseline in …

How Does Frailty Impact Peri-Operative And Speech Recognition Outcomes For Cochlear Implants In Veterans?, Kaitlyn A Brooks, Benjamin D Lovin, Alex D Sweeney, Angela S Peng, Nathan R Lindquist

Faculty, Staff and Students Publications

Objective: To investigate the association of frailty with post-cochlear implant (CI) admission, morbidity, and CI-aided word recognition outcomes in veterans.

Study design: Retrospective cohort.

Setting: Single-institution tertiary care Veterans Health Administration (VHA) hospital.

Methods: Veterans who underwent cochlear implantation between 1998 to 2024 were included. The Modified 5-Item Frailty Index (mFI-5) score was used to characterize preoperative frailty. Outcomes of interest were admission from post-anesthesia care unit (PACU), relative risk (RR) of admission among frail patients, and relationship between frailty and post-CI word recognition score (WRS). Ordinal data were analyzed via logistic regression and Chi square tests; a multivariate linear …

Predictive Validity Of The Obsessive-Compulsive Inventory-4 And Florida Obsessive-Compulsive Inventory-Ii Severity Scale, Eric A Storch, Ryan J Mccarty, Maya Zehavi, Mahnoor Ahmad, Vanessa Zavala Cruz, Dayan Berrones, Josselyn S Muñoz, Diana Obando, Servando Rodriguez Barajas, Renee M Frederick, Jacey L Anderberg, Hannah C Moore, Marcos E Ochoa-Panaifo, Mayra C Martinez Mallen, Ogechi C Onyeka, Andrew D Wiese, Melisa N Sagarnaga, Joseph F Mcguire, Ygor Arzeno Ferrão, Latin American Trans-Ancestry Initiative For Ocd Genomics (Latino), Wayne K Goodman, James J Crowley, Brazilian Obsessive-Compulsive Spectrum Disorder Working Group (Gttoc)

Faculty, Staff and Students Publications

Efficient and accurate screening tools are crucial for improving early identification and treatment outcomes among individuals with obsessive-compulsive disorder (OCD). This study evaluated the sensitivity and specificity of two OCD screening measures: the Obsessive-Compulsive Inventory-4 (OCI-4) and the Florida Obsessive-Compulsive Inventory-II (FOCI-II) severity scale. The measures were administered in a large transnational sample of Spanish speaking Latin American adults (N = 1696) with elevated obsessive-compulsive symptomatology. Participants completed diagnostic interviews (MINI and Y-BOCS) and self-report assessments across 23 sites in 11 countries. Both measures significantly distinguished OCD from non-OCD cases, with the FOCI-II demonstrating somewhat better predictive performance (AUC = …

Incidence Of Cancers Among Children Living With Hiv In Malawi After Widespread Availability Of Antiretroviral Therapy: A Population-Based Study, Casey L Mcatee, Fatsani Manase, William Kamiyango, Jimmy Villiera, Mark Zobeck, Joseph Mhango, Allison Silverstein, Samuel Maloya, Apatsa Matatiyo, Eluness Simwela, Honour Mhango, Desire Hellings, Brigid O'Brien, Claudia Wallrauch, Tom Heller, Matthew Painschab, Kate Westmoreland, Atupele Mpasa, Rizine Mzikamanda, Nmazuo Ozuah, Joseph Lubega, Nader Kim El-Mallawany, Carl E Allen, Michael E Scheurer

Faculty, Staff and Students Publications

Purpose: Few data describe the modern epidemiology of pediatric HIV-associated cancers in sub-Saharan Africa, home to over 80% of the world's children living with HIV. This study evaluated the incidence of cancers among these children over 15 years after widespread antiretroviral therapy (ART) adoption in Malawi.

Methods: We conducted a retrospective population-based cohort study leveraging multiple independent data sources comprehensive of all cancer diagnoses among children living with HIV in Northern and Central Malawi between 2010 and 2024. HIV-associated cancers were defined as those cancers with well-established epidemiologic associations with HIV. Cumulative incidence and average annual percent change were estimated …

Examining Sleep-Related Problems In Youth With Misophonia, Kevin M Wagner, Matti Cervin, Catherine E Rast, Mered Parnes, Nicholas Murphy, Samuel Spencer, Eric A Storch, Andrew G Guzick

Faculty, Staff and Students Publications

The relationship between misophonia and sleep-related problems (SRPs) in youth is underexplored. This paucity of research is concerning because SRPs might be elevated among youth with misophonia. If left untreated, SRPs can contribute to long-term health consequences. Thus, in this study we examined the link between misophonia and SRPs in youth aged 8 to 17. In this study, we compared SRPs in 102 children and adolescents with clinically significant misophonia to SRPs in a normative youth sample and a sample of 94 youth with anxiety disorders. We also examined the extent to which SRPs were associated with misophonia severity. Approximately …

In Vitro Studies Of The Effects Of Antithrombotic Zn-Dipicolylamine-Harboring Liposomes (Dpals) On Serum Albumin And Human Umbilical Vein Endothelial Cells, Michelle Tanujaya, Gianna Cai, Jia Patel, Zana Moldavsky, Yumna Ejaz, Malia Mahazabin Ahmed, Sangsang Duong, Lawrence E. Goldfinger, Koon Y. Pak, Brian D. Gray, Parkson Lee-Gau Chong

Cardeza Foundation for Hematologic Research

Thrombosis remains a leading cause of cardiovascular morbidity and mortality. During thrombosis, activated platelets and endothelial cells expose phosphatidylserine (PS) on their outer membranes, creating a surface that accelerates clot formation. Current antithrombotic therapies, such as heparin and warfarin, carry significant bleeding risks, highlighting the need for safer alternatives. In response, we developed a PS-targeting liposomal formulation composed of Zn-dipicolylamine (DPA)-cyanine-3[22,22] and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (molar ratio 3:97). This DPA-harboring liposome (DPAL) binds selectively to PS-rich surfaces such as activated platelets and has demonstrated efficacy in reducing thrombosis in mouse models, with minimal bleeding. In the present study, we examined the interaction …

Hiv Infection, Neurotoxicity, Inflammation, Premature Aging, And Therapeutic Challenges To Plwh: An Overview, Mudit Tyagi, Ulhas P. Naik, Kratika Tyagi, Madhulika Sharma, Gagan Kaushal, Alok Bhushan, Michael Bukrinsky, Priya Tyagi

Department of Medicine Faculty Papers

HIV infection remains a major global health challenge due to its complex pathogenesis and lifelong persistence in people living with HIV (PLWH). A central barrier to eradication is the virus's ability to establish long-lived latent reservoirs in different tissues, including the central nervous system (CNS), where it evades immune clearance and antiretroviral therapy (ART). These reservoirs, seeded early during infection, fuel viral rebound if ART is interrupted, requiring lifelong treatment. In the CNS, HIV persists despite systemic viral suppression because of limited ART penetration across the blood-brain barrier (BBB), and infection of long-lived cells such as microglia and perivascular macrophages. …

Supporting Evidence-Based Responses To Emotional Needs In Emphysema (Serene): Protocol For A Randomized, Open-Label Mechanistic Trial Comparing Coping Skills Training And Disease-Specific Education For Depressive Symptoms Conducted In United States Health Systems, Joanna L. Hart, Daniel Carter, Chloe Hinton, James Grilli, Lily A. Brown, Nora Brier, Yingying Lu, Casey Whitman, Michael O. Harhay, Michael Sims, Carmen Alvarez, Lisa R. Miller-Matero, C. Virginia O'Hayer

Department of Psychiatry and Human Behavior Faculty Papers

BACKGROUND: Depressive symptoms and anxiety are highly prevalent among people with chronic obstructive pulmonary disease (COPD), strongly associated with poor outcomes, and rarely recognized or treated. Integrating families into interventions may amplify supportive care treatment effects and overcome common challenges, yet this strategy is understudied. The Supporting Evidence-based Responses to Emotional Needs in Emphysema (SERENE) trial's main objective is to identify the mechanisms through which a family-partnered Coping Skills Training (CST) reduces depressive symptoms among patients with COPD, testing five putative mechanisms: family relationship quality, patient and caregiver self-efficacy, patient loneliness, and caregiver psychological distress.

METHODS: SERENE will enroll 375 …

Human Microglia In Brain Assembloids Display Region-Specific Diversity And Respond To Hyperexcitable Neurons Carrying, Jiaxiang Wu, Xiaoling Chen, Jingliang Zhang, Kyle Wettschurack, Morgan Robinson, Weihao Li, Yuanrui Zhao, Ye-Eun Yoo, Brody A Deming, Yue Shu, Akila D Abeyaratna, Zhefu Que, Dongshu Du, Matthew Tegtmeyer, Chongli Yuan, William C Skarnes, Zhong-Yin Zhang, Jean-Christophe Rochet, Long-Jun Wu, Yang Yang

Faculty Research 2026

Microglia critically shape neuronal circuit development and function, yet their region-specific properties and roles in distinct circuits of the human brain remain poorly understood. In this study, we generated region-specific brain organoids (cortical, striatal, and midbrain), each integrated with human microglia, to fill this critical gap. Single-cell RNA sequencing uncovered six distinct microglial subtypes exhibiting unique regional signatures, including a subtype highly enriched for the GABA_B receptor gene within striatal organoids. To investigate the contributions of microglia to neural circuitry, we created microglia-incorporated midbrain-striatal assembloids, modeling a core circuit node for many neuropsychiatric disorders, including autism. Using chemogenetics to …

Human Microglia In Brain Assembloids Display Region-Specific Diversity And Respond To Hyperexcitable Neurons Carrying, Jiaxiang Wu, Xiaoling Chen, Jingliang Zhang, Kyle Wettschurack, Morgan Robinson, Weihao Li, Yuanrui Zhao, Ye-Eun Yoo, Brody A Deming, Yue Shu, Akila D Abeyaratna, Zhefu Que, Dongshu Du, Matthew Tegtmeyer, Chongli Yuan, William C Skarnes, Zhong-Yin Zhang, Jean-Christophe Rochet, Long-Jun Wu, Yang Yang

Faculty Research 2026

Microglia critically shape neuronal circuit development and function, yet their region-specific properties and roles in distinct circuits of the human brain remain poorly understood. In this study, we generated region-specific brain organoids (cortical, striatal, and midbrain), each integrated with human microglia, to fill this critical gap. Single-cell RNA sequencing uncovered six distinct microglial subtypes exhibiting unique regional signatures, including a subtype highly enriched for the GABA_B receptor gene within striatal organoids. To investigate the contributions of microglia to neural circuitry, we created microglia-incorporated midbrain-striatal assembloids, modeling a core circuit node for many neuropsychiatric disorders, including autism. Using chemogenetics to …

Human Microglia In Brain Assembloids Display Region-Specific Diversity And Respond To Hyperexcitable Neurons Carrying Scn2a Mutation, Jiaxiang Wu, Xiaoling Chen, Jingliang Zhang, Kyle Wettschurack, Morgan Robinson, Weihao Li, Yuanrui Zhao, Ye-Eun Yoo, Brody A Deming, Yue Shu, Akila D Abeyaratna, Zhefu Que, Dongshu Du, Matthew Tegtmeyer, Chongli Yuan, William C Skarnes, Zhong-Yin Zhang, Jean-Christophe Rochet, Long-Jun Wu, Yang Yang

The Brown Foundation: Institute of Molecular Medicine

Microglia critically shape neuronal circuit development and function, yet their region-specific properties and roles in distinct circuits of the human brain remain poorly understood. In this study, we generated region-specific brain organoids (cortical, striatal, and midbrain), each integrated with human microglia, to fill this critical gap. Single-cell RNA sequencing uncovered six distinct microglial subtypes exhibiting unique regional signatures, including a subtype highly enriched for the GABAB receptor gene within striatal organoids. To investigate the contributions of microglia to neural circuitry, we created microglia-incorporated midbrain-striatal assembloids, modeling a core circuit node for many neuropsychiatric disorders, including autism. Using chemogenetics to activate …

Nci9673 (Part B): Etctn Randomized Phase Ii Study Of Nivolumab With Or Without Ipilimumab In Refractory, Metastatic Squamous Cell Carcinoma Of The Anal Canal, Van K Morris, Kristen K Ciombor, Lianchun Xiao, Joshua K Ochieng, Enrica Marmonti, Blase Polite, Benjamin A Weinberg, John C Krauss, John Hays, Sarbajit Mukherjee, Olivia Aranha, Syma Iqbal, Tony Shields, Al B Benson, Syed Kazmi, Christopher Lieu, Howard Hochster, Jennifer Whisenant, Cara Haymaker, Cathy Eng

Faculty, Staff and Student Publications

Purpose: In the previously completed NCI9673 (part A) single-arm study, the antiprogrammed death (PD)-ligand-1 antibody nivolumab demonstrated efficacy for patients with metastatic anal cancer. In NCI9673 (Part B), we evaluated the anticytotoxic T-cell lymphocyte antigen-4 (CTLA-4) antibody ipilimumab in combination with nivolumab for patients with incurable anal cancer.

Methods: In this phase II NCI ETCTN trial, 100 patients with refractory, incurable anal cancer were randomly assigned to receive nivolumab (480 mg IV once every 4 weeks) alone or with ipilimumab (1 mg/kg IV once every 8 weeks). The primary end point was progression-free survival (PFS). Secondary endpoints included radiographic response, …