Digital Commons Network^™

Short-Stay Units Vs Routine Admission From The Emergency Department In Patients With Acute Heart Failure: The Ssu-Ahf Randomized Clinical Trial, Peter S Pang, Douglas Char, Et Al.

2020-Current year OA Pubs

IMPORTANCE: More than 80% of patients who present to the emergency department (ED) with acute heart failure (AHF) are hospitalized. With more than 1 million annual hospitalizations for AHF in the US, safe and effective alternatives are needed. Care for AHF in short-stay units (SSUs) may be safe and more efficient than hospitalization, especially for lower-risk patients, but randomized clinical trial data are lacking.

OBJECTIVE: To compare the effectiveness of SSU care vs hospitalization in lower-risk patients with AHF.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter randomized clinical trial randomly assigned low-risk patients with AHF 1:1 to SSU or hospital admission …

Prospective Study To Characterize Adalimumab Exposure In Pediatric Patients With Rheumatic Diseases, Tatjana Welzel, Klervi Golhen, Andrew Atkinson, Verena Gotta, David Ternant, Jasmin B Kuemmerle-Deschner, Christine Michler, Gilbert Koch, Johannes N Van Den Anker, Marc Pfister, Andreas Woerner

2020-Current year OA Pubs

BACKGROUND: In pediatric rheumatic diseases (PRD), adalimumab is dosed using fixed weight-based bands irrespective of methotrexate co-treatment, disease activity (DA) or other factors that might influence adalimumab pharmacokinetics (PK). In rheumatoid arthritis (RA) adalimumab exposure between 2-8 mg/L is associated with clinical response. PRD data on adalimumab is scarce. Therefore, this study aimed to analyze adalimumab PK and its variability in PRD treated with/without methotrexate.

METHODS: A two-center prospective study in PRD patients aged 2-18 years treated with adalimumab and methotrexate (G

RESULTS: Twenty-eight patients (14 per group), diagnosed with juvenile idiopathic arthritis (71.4%), non-infectious uveitis (25%) or chronic recurrent …

Digital Clock And Recall Is Superior To The Mini-Mental State Examination For The Detection Of Mild Cognitive Impairment And Mild Dementia, Ali Jannati, Claudio Toro-Serey, Joyce Gomes-Osman, Russell Banks, Marissa Ciesla, John Showalter, David Bates, Sean Tobyne, Alvaro Pascual-Leone

Faculty, Staff and Students Publications

Background: Disease-modifying treatments for Alzheimer's disease highlight the need for early detection of cognitive decline. However, at present, most primary care providers do not perform routine cognitive testing, in part due to a lack of access to practical cognitive assessments, as well as time and resources to administer and interpret the tests. Brief and sensitive digital cognitive assessments, such as the Digital Clock and Recall (DCR™), have the potential to address this need. Here, we examine the advantages of DCR over the Mini-Mental State Examination (MMSE) in detecting mild cognitive impairment (MCI) and mild dementia.

Methods: We studied 706 participants …

Patient Priorities-Aligned Care For Older Adults With Multiple Conditions: A Nonrandomized Controlled Trial, Mary E Tinetti, Ardeshir Hashmi, Henry Ng, Margaret Doyle, Toyomi Goto, Jessica Esterson, Aanand D Naik, Lilian Dindo, Fan Li

Faculty, Staff and Student Publications

IMPORTANCE: Older adults with multiple conditions receive health care that may be burdensome, of uncertain benefit, and not focused on what matters to them. Identifying and aligning care with patients' health priorities may improve outcomes.

OBJECTIVE: to assess the association of receiving patient priorities care (PPC) vs usual care (UC) with relevant clinical outcomes.

DESIGN, SETTING, AND PARTICIPANTS: In this nonrandomized controlled trial with propensity adjustment, enrollment occurred between August 21, 2020, and May 14, 2021, with follow-up continuing through February 26, 2022. Patients who were aged 65 years or older and with 3 or more chronic conditions were enrolled …

Clonal Hematopoiesis Risk Score And All-Cause And Cardiovascular Mortality In Older Adults, Seyedmohammad Saadatagah, Md Mesbah Uddin, Lachelle D Weeks, Abhishek Niroula, Meng Ru, Koichi Takahashi, Lukasz Gondek, Bing Yu, Alexander G Bick, Benjamin L Ebert, Elizabeth A Platz, Pradeep Natarajan, Christie M Ballantyne

Faculty, Staff and Student Publications

IMPORTANCE: Clonal hematopoiesis (CH) with acquired pathogenic variants in myeloid leukemia driver genes is common in older adults but of unknown prognostic value.

OBJECTIVE: To investigate the prevalence of CH and the utility of the CH risk score (CHRS) in estimating all-cause and disease-specific mortality in older adults with CH.

DESIGN, SETTING, AND PARTICIPANTS: This population-based prospective cohort study involved community-dwelling older adults (aged 67-90 years) without hematologic malignant neoplasms (HMs) who were participants in the Atherosclerosis Risk in Communities Visit 5 at 4 US centers: Forsyth County, North Carolina; Jackson, Mississippi; Minneapolis, Minnesota; and Washington County, Maryland. Samples were …

Continued Treatment With Tirzepatide For Maintenance Of Weight Reduction In Adults With Obesity: The Surmount-4 Randomized Clinical Trial, Louis J Aronne, Naveed Sattar, Deborah B Horn, Harold E Bays, Sean Wharton, Wen-Yuan Lin, Nadia N Ahmad, Shuyu Zhang, Ran Liao, Mathijs C Bunck, Irina Jouravskaya, Madhumita A Murphy, Surmount-4 Investigators

Faculty, Staff and Student Publications

IMPORTANCE: The effect of continued treatment with tirzepatide on maintaining initial weight reduction is unknown.

OBJECTIVE: To assess the effect of tirzepatide, with diet and physical activity, on the maintenance of weight reduction.

DESIGN, SETTING, AND PARTICIPANTS: This phase 3, randomized withdrawal clinical trial conducted at 70 sites in 4 countries with a 36-week, open-label tirzepatide lead-in period followed by a 52-week, double-blind, placebo-controlled period included adults with a body mass index greater than or equal to 30 or greater than or equal to 27 and a weight-related complication, excluding diabetes.

INTERVENTIONS: Participants (n = 783) enrolled in an open-label …

Pediatric Medical Subspecialist Use In Outpatient Settings, Christopher B Forrest, Candice P Chen, Eliana M Perrin, Christopher J Stille, Ruth Cooper, Katherine Harris, Qian Luo, Mitchell G Maltenfort, Lauren E Parlett

Faculty, Staff and Student Publications

Importance

A first step toward understanding whether pediatric medical subspecialists are meeting the needs of the nation’s children is describing rates of use and trends over time.

Objectives

To quantify rates of outpatient pediatric medical subspecialty use.

Design, Setting, and Participants

This repeated cross-sectional study of annual subspecialist use examined 3 complementary data sources: electronic health records from PEDSnet (8 large academic medical centers [January 1, 2010, to December 31, 2021]); administrative data from the Healthcare Integrated Research Database (HIRD) (14 commercial health plans [January 1, 2011, to December 31, 2021]); and administrative data from the Transformed Medicaid Statistical Information …

Cell State Of Origin Impacts Development Of Distinct Endometriosis-Related Ovarian Carcinoma Histotypes, Ian Beddows, Huihui Fan, Karolin Heinze, Benjamin K Johnson, Anna Leonova, Janine Senz, Svetlana Djirackor, Kathleen R Cho, Celeste Leigh Pearce, David G Huntsman, Michael S Anglesio, Hui Shen

Faculty, Staff and Student Publications

Clear cell ovarian carcinoma (CCOC) and endometrioid ovarian carcinoma (ENOC) are ovarian carcinoma histotypes, which are both thought to arise from ectopic endometrial (or endometrial-like) cells through an endometriosis intermediate. How the same cell type of origin gives rise to two morphologically and biologically different histotypes has been perplexing, particularly given that recurrent genetic mutations are common to both and present in nonmalignant precursors. We used RNA transcription analysis to show that the expression profiles of CCOC and ENOC resemble those of normal endometrium at secretory and proliferative phases of the menstrual cycle, respectively. DNA methylation at the promoter of …

Time To Continuous Renal Replacement Therapy Initiation And 90-Day Major Adverse Kidney Events In Children And Young Adults, Katja M Gist, Shina Menon, Pilar Anton-Martin, Amee M Bigelow, Gerard Cortina, Akash Deep, Sara De La Mata-Navazo, Ben Gelbart, Stephen Gorga, Isabella Guzzo, Kenneth E Mah, Nicholas J Ollberding, H Stella Shin, Sameer Thadani, Amanda Uber, Huaiyu Zang, Michael Zappitelli, David T Selewski, We-Rock Investigators

Faculty, Staff and Students Publications

IMPORTANCE: In clinical trials, the early or accelerated continuous renal replacement therapy (CRRT) initiation strategy among adults with acute kidney injury or volume overload has not demonstrated a survival benefit. Whether the timing of initiation of CRRT is associated with outcomes among children and young adults is unknown.

OBJECTIVE: To determine whether timing of CRRT initiation, with and without consideration of volume overload (VO;

DESIGN, SETTING, AND PARTICIPANTS: This multinational retrospective cohort study was conducted using data from the Worldwide Exploration of Renal Replacement Outcome Collaborative in Kidney Disease (WE-ROCK) registry from 2015 to 2021. Participants included children and young …

Clonal Hematopoiesis And Incident Heart Failure With Preserved Ejection Fraction, Art Schuermans, Michael C Honigberg, Laura M Raffield, Bing Yu, Mary B Roberts, Charles Kooperberg, Pinkal Desai, April P Carson, Amil M Shah, Christie M Ballantyne, Alexander G Bick, Pradeep Natarajan, Joann E Manson, Eric A Whitsel, Charles B Eaton, Alexander P Reiner

Faculty, Staff and Student Publications

IMPORTANCE: Clonal hematopoiesis of indeterminate potential (CHIP), the age-related clonal expansion of hematopoietic stem cells with leukemogenic acquired genetic variants, is associated with incident heart failure (HF).

OBJECTIVE: To evaluate the associations of CHIP and key gene-specific CHIP subtypes with incident HF with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF).

DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study included participants from 2 racially diverse prospective cohort studies with uniform HF subtype adjudication: the Jackson Heart Study (JHS) and Women's Health Initiative (WHI). JHS participants were enrolled during 2000 to 2004 and followed up through 2016. WHI participants were …

C1q Is Elevated During Chronic Staphylococcus Epidermidis Central Nervous System Catheter Infection, Matthew K. Beaver, Lara Bergdolt, Anna Dunaevsky, Tammy Kielian, Gwenn Skar

Journal Articles: Pathology and Microbiology

INTRODUCTION: Significant neurologic morbidity is caused by pediatric cerebrospinal fluid (CSF) shunt infections. The underlying mechanisms leading to impaired school performance and increased risk of seizures are unknown, however, a better understanding of these mechanisms may allow us to temper their consequences. Recent evidence has demonstrated important roles for complement proteins in neurodevelopment and neuroinflammation.

METHODS: We examined complement activation throughout

RESULTS: We found that MASP2 predominated early in catheter infection, but that Factor B was elevated at intermediate time points. Unexpectedly C1q was elevated at late timepoints when bacterial burdens were low or undetectable. Based on these findings and …

Potential Prognostic Determinants For Fet::Creb Fusion-Positive Intracranial Mesenchymal Tumor, Frank M. Mezzacappa, Frankie K. Smith, Weiwei Zhang, Andrew Gard, Fatmagul Kusku Cabuk, Ignancio Gonzalez-Gomez, Hector L. Monforte, Jiancong Liang, Omkar Singh, Martha M. Quezado, Kenneth D. Aldape, Murat Gokden, Julia A. Bridge, Jie Chen

Journal Articles: Pathology and Microbiology

Intracranial mesenchymal tumor (IMT), FET::CREB fusion-positive is a provisional tumor type in the 2021 WHO classification of central nervous system tumors with limited information available. Herein, we describe five new IMT cases from four females and one male with three harboring an EWSR1::CREM fusion and two featuring an EWSR1::ATF1 fusion. Uniform manifold approximation and projection of DNA methylation array data placed two cases to the methylation class "IMT, subclass B", one to "meningioma-benign" and one to "meningioma-intermediate". A literature review identified 74 cases of IMTs (current five cases included) with a median age of 23 years (range 4-79 years) and …

Digital Clock Drawing As An Alzheimer's Disease Susceptibility Biomarker: Associations With Genetic Risk Score And Apoe In Older Adults, L I Thompson, M Cummings, S Emrani, David J. Libon, A Ang, C Karjadi, R Au, C Liu

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia in older adults, but most people are not diagnosed until significant neuronal loss has likely occurred along with a decline in cognition. Non-invasive and cost-effective digital biomarkers for AD have the potential to improve early detection.

OBJECTIVE: We examined the validity of DCTclockTM (a digitized clock drawing task) as an AD susceptibility biomarker.

DESIGN: We used two primary independent variables, Apolipoprotein E (APOE) ε4 allele carrier status and polygenic risk score (PRS). We examined APOE and PRS associations with DCTclockTM composite scores as dependent measures.

SETTING: We used existing data …

Safety And Efficacy Of Peptide Receptor Radionuclide Therapy In Neuroendocrine Tumors: A Single Center Experience., Vineeth Sukrithan, Heather Armbruster, Sherise Rogers, Sherry Mori Vogt, Cassandra Grenade, Claire Verschraegen, Ye Zhou, Ashima Goyal, Mona Natwa, Akram Hussein, Hallie Barr, Dramane Konate, Rochelle Batdorf, Andrew Brown, Bonnie Williams, Songzhu Zhao, Lai Wei, Menglin Xu, Manisha H Shah, Bhavana Konda

Oncology Articles

Peptide receptor radionucleotide therapy (PRRT) with 177Lu-dotatate is widely used for the treatment of patients with neuroendocrine tumors (NETs). We analyzed data from 104 patients with NETs treated with 177Lu -dotatate at a US academic center between December 2017 and October 2020 to better understand patterns of long-term efficacy, safety, and toxicity in the real-world setting. 177Lu-dotatate (200 mCi) was administered every eight weeks for four doses. The most common sites of primary disease were small intestine NETs (n = 49, 47%), pancreatic NETs (n = 32, 31%), and lung NETs (n = 7, 7%). Twenty-seven percent had Ki-6720%. The …

Facilitating Factors For Female Leadership In Finance, Haleigh Woloszak

Honors Program Theses

High levels of gender inequity remain in finance leadership positions. This research is interested in the factors that facilitate female leadership in finance roles as opposed to the challenges women face in this industry. Through semi-structured interviews and thematic analysis, this paper explores the education, career development, organizational practices, professional support networks, and personal factors of successful women in finance. Commonalities among interviewee’s responses suggest that capabilities, one’s perspective on their career, personal support and domestic responsibility, and workplace relationships play a role in the success of the women in our sample. Additionally, participants discuss in depth specific organizational and …

Socioeconomic Status And Health Disparities Drive Differences In Accelerometer-Derived Physical Activity In Fatty Liver Disease And Significant Fibrosis, Lucia Tabacu, Sajag Swami, Mark Ledbetter, Mohamad S. Siddiqui, Ekaterina Smirnova

Mathematics & Statistics Faculty Publications

Background and aims

The cornerstone of clinical management of patients with nonalcoholic fatty liver disease (NAFLD) are lifestyle changes such as increasing physical activity (PA) aimed at improving cardiometabolic risk. To inform NAFLD prevention and treatment guidelines we aimed to: (i) quantify the role of PA on lowering the risk for NAFLD and fibrosis; (ii) characterize NAFLD and fibrosis association with PA in the context of socioeconomic environment.

Methods

A sample of 2648 participants from the NHANES 2003–2006 was selected to develop survey weighted multivariable logistic regression models for predicting NAFLD and significant fibrosis, diagnosed non-invasively via fatty liver index …

Narrative Feature Or Structured Feature? A Study Of Large Language Models To Identify Cancer Patients At Risk Of Heart Failure, Ziyi Chen, Mengyuan Zhang, Mustafa Mohammed Ahmed, Yi Guo, Thomas J George, Jiang Bian, Yonghui Wu

Faculty, Staff and Student Publications

Cancer treatments are known to introduce cardiotoxicity, negatively impacting outcomes and survivorship. Identifying cancer patients at risk of heart failure (HF) is critical to improving cancer treatment outcomes and safety. This study examined machine learning (ML) models to identify cancer patients at risk of HF using electronic health records (EHRs), including traditional ML, Time-Aware long short-term memory (T-LSTM), and large language models (LLMs) using novel narrative features derived from the structured medical codes. We identified a cancer cohort of 12,806 patients from the University of Florida Health, diagnosed with lung, breast, and colorectal cancers, among which 1,602 individuals developed HF …

Predictors Of Utilization Of Preventive Gynecologic Health Services Among Women Veterans, Jennifer Lynn Milore

PCOM Psychology Dissertations

As the number of women veterans in the United States increases, additional attention has been given to understanding their healthcare experiences within the Veterans Health Administration. However, much of the current literature exploring women veterans has been qualitative and little research has examined quantitative relationships between experiences in the VA healthcare system and gynecologic health behaviors and outcomes. The purpose of this study was to evaluate potential factors (health literacy, social problem-solving abilities, and perceived gender discrimination) that may predict gynecologic health behaviors in women veterans. This study included 145 anonymous participants. Participants completed screening questions and demographic and health …

Breathe, Renee J Flores

Faculty and Staff Publications

This is a personal essay about breasts. It focuses on my experiences as a young girl, moving through adolescence to a history of breast cancer in my family, including my mother's breast cancer diagnosis. As a physician, patient, and wife, I reflect on the choices that I have to make and what this means for my identity as a woman and mother.

A Mixed-Method Evaluation Of Implementation Determinants For Chaplain Intervention In A Hospital Setting, Jennifer S Mascaro, Marianne P Florian, Erin Brauer, Patricia K Palmer, Marcia J Ash, Maureen Shelton, Roman Palitsky, Deanna M Kaplan, Shaheen Rana, Cam Escoffery, Charles L Raison, George H Grant

Faculty and Staff Publications

Healthcare chaplains address broad social and emotional dimensions of care within a pluralistic religious landscape. Although the development and evaluation of chaplaincy interventions has advanced the field, little research has investigated factors influencing the implementation of new chaplain interventions. In this mixed-method study, we examined attitudes about evidence-based interventions held by chaplain residents (n = 39) at the outset of an ACPE-accredited residency program in the southeast United States. We also used semi-structured interviews (n = 9) to examine residents' attitudes, beliefs, and decision-making processes after they trained in the delivery of a novel manualized intervention, Compassion-Centered Spiritual Health (CCSH). …

Design Of A Targeted Blood Transcriptional Panel For Monitoring Immunological Changes Accompanying Pregnancy., Tobias Brummaier, Darawan Rinchai, Mohammed Toufiq, Mohammed Y Karim, Tanwir Habib, Jürg Utzinger, Daniel H Paris, Rose Mcgready, Alexandra K Marr, Tomoshige Kino, Annalisa Terranegra, Souhaila Al Khodor, Damien Chaussabel, Basirudeen Syed Ahamed Kabeer

Faculty Research 2024

BACKGROUND: Immunomodulatory processes exert steering functions throughout pregnancy. Detecting diversions from this physiologic immune clock may help identify pregnant women at risk for pregnancy-associated complications. We present results from a data-driven selection process to develop a targeted panel of mRNAs that may prove effective in detecting pregnancies diverting from the norm.

METHODS: Based on a

RESULTS: We identified 176 transcripts that were complemented with eight housekeeping genes. Changes in transcript abundance were seen in the early stages of pregnancy and similar patterns were observed in both datasets. Functional gene annotation suggested significant changes in the lymphoid, prostaglandin and inflammation-associated compartments, …

Sampler: Unsupervised Representations For Rapid Analysis Of Whole Slide Tissue Images., Patience Mukashyaka, Todd B Sheridan, Ali Foroughi Pour, Jeffrey Chuang

Faculty Research 2024

BACKGROUND: Deep learning has revolutionized digital pathology, allowing automatic analysis of hematoxylin and eosin (H&E) stained whole slide images (WSIs) for diverse tasks. WSIs are broken into smaller images called tiles, and a neural network encodes each tile. Many recent works use supervised attention-based models to aggregate tile-level features into a slide-level representation, which is then used for downstream analysis. Training supervised attention-based models is computationally intensive, architecture optimization of the attention module is non-trivial, and labeled data are not always available. Therefore, we developed an unsupervised and fast approach called SAMPLER to generate slide-level representations.

METHODS: Slide-level representations of …

Investigation Of Setmelanotide, An Mc4r Agonist, For Obesity In Individuals With Smith-Magenis Syndrome, Julia Lazareva, Stephanie R Sisley, Sheila M Brady, Ann C M Smith, Sarah H Elsea, Jeremy J Pomeroy, Christian L Roth, Jennifer E Sprague, Martin Wabitsch, Jill Garrison, Jack A Yanovski

Children’s Nutrition Research Center Staff Publications

Background: Smith Magenis Syndrome (SMS) is a rare genetic disorder caused by RAI1 haploinsufficiency. Obesity in people with SMS is believed partially due to dysfunction of the proximal melanocortin 4 receptor (MC4R) pathway. We therefore studied effects of treatment with the MC4R agonist setmelanotide on obesity and hunger, as well as metabolic, cardiac and safety, in individuals with SMS.

Methods: People with SMS received once-daily setmelanotide injections, with the dose titrated bi-weekly to a maximum of 3 mg over ∼1 month; and a full-dose treatment duration of 3mo. The primary outcome was percent change in body weight. Secondary outcomes included …

Newborn Screening Analytes And Structural Birth Defects Among 27,000 Newborns, Philip J Lupo, Natalie P Archer, Rachel D Harris, Lisa K Marengo, Jeremy M Schraw, Adrienne T Hoyt, Susan Tanksley, Rachel Lee, Margaret Drummond-Borg, Debra Freedenberg, Priya B Shetty, A J Agopian, Charles Shumate, Sonja A Rasmussen, Peter H Langlois, Mark A Canfield

Center for Medical Ethics and Health Policy Staff Publications

Background: Emerging evidence suggests newborn screening analytes may yield insights into the etiologies of birth defects, yet no effort has evaluated associations between a range of newborn screening analytes and birth defects.

Methods: This population-based study pooled statewide data on birth defects, birth certificates, and newborn screening analytes from Texas occurring between January 1, 2007 and December 31, 2009. Associations between a panel of thirty-six newborn screening analytes, collected by the statewide Texas Newborn Screening Program, and the presence of a birth defect, defined as at least one of 39 birth defects diagnoses recorded by the Texas Birth Defects Registry, …

The Seroprevalence Of Sars-Cov-2-Specific Antibodies In Australian Children: A Cross-Sectional Study, Archana Koirala, Jocelynne Mcrae, Philip N Britton, Marnie Downes, Shayal A Prasad, Suellen Nicholson, Noni E Winkler, Matthew V N O'Sullivan, Fatima Gondalwala, Cecile Castellano, Emma Carey, Alexandra Hendry, Nigel Crawford, Ushma Wadia, Peter Richmond, Helen S Marshall, Julia E Clark, Joshua R Francis, Jeremy Carr, Adam Bartlett, Brendan Mcmullan, Justin Skowno, Donald Hannah, Andrew Davidson, Britta S Von Ungern-Sternberg, Paul Lee-Archer, Laura L Burgoyne, Edith B Waugh, John B Carlin, Zin Naing, Nicole Kerly, Alissa Mcminn, Guillian Hunter, Christine Heath, Natascha D'Angelo, Carolyn Finucane, Laura A Francis, Sonia Dougherty, William Rawlinson, Theo Karapanagiotidis, Natalie Cain, Rianne Brizuela, Christopher C Blyth, Nicholas Wood, Kristine Macartney

Staff and Researcher Publications

Background: Following reduction of public health and social measures concurrent with SARS-CoV-2 Omicron emergence in late 2021 in Australia, COVID-19 case notification rates rose rapidly. As rates of direct viral testing and reporting dropped, true infection rates were most likely to be underestimated.

Objective: To better understand infection rates and immunity in this population, we aimed to estimate SARS-CoV-2 seroprevalence in Australians aged 0-19 years.

Methods: We conducted a national cross sectional serosurvey from June 1, 2022, to August 31, 2022, in children aged 0-19 years undergoing an anesthetic procedure at eight tertiary pediatric hospitals. Participant questionnaires were administered, and …

Efficacy And Safety Of Zuranolone Co-Initiated With An Antidepressant In Adults With Major Depressive Disorder: Results From The Phase 3 Coral Study, Sagar V Parikh, Scott T Aaronson, Sanjay J Mathew, Gustavo Alva, Charles Debattista, Stephen Kanes, Robert Lasser, Amy Bullock, Mona Kotecha, Jungah Jung, Fiona Forrestal, Jeff Jonas, Theresa Vera, Bridgette Leclair, James Doherty

Staff and Researcher Publications

Major depressive disorder (MDD) is a mental health disorder that can cause disability and functional impairment that standard-of-care (SOC) antidepressant therapies (ADTs) can take weeks to treat. Zuranolone is a neuroactive steroid and positive allosteric modulator of synaptic and extrasynaptic γ-aminobutyric acid (GABA) type A receptors approved as an oral, once-daily, 14-day treatment course in adults with postpartum depression and under investigation in adults with MDD. The phase 3 CORAL Study (NCT04476030) evaluated the efficacy and safety of zuranolone 50 mg co-initiated with SOC ADT (zuranolone+ADT) vs placebo co-initiated with SOC ADT (placebo+ADT) in adults with MDD. Patients were randomized …

Polygenic And Transcriptional Risk Scores Identify Chronic Obstructive Pulmonary Disease Subtypes In The Copdgene And Eclipse Cohort Studies, Matthew Moll, Julian Hecker, John Platig, Jingzhou Zhang, Auyon J. Ghosh, Katherine A. Pratte, Rui-Sheng Wang, Davin Hill, Iain R. Konigsberg, Joe W. Chiles, Craig P. Hersh, Peter J. Castaldi, Kimberly Glass, Jennifer G. Dy, Don D. Sin, Ruth Tal-Singer, Majd Mouded, Stephen I. Rennard, Gary P. Anderson, Gregory L. Kinney, Russell P. Bowler, Jeffrey L. Curtis, Merry-Lynn Mcdonald, Edwin K. Silverman, Brian D. Hobbs, Michael H. Cho

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Genetic variants and gene expression predict risk of chronic obstructive pulmonary disease (COPD), but their effect on COPD heterogeneity is unclear. We aimed to define high-risk COPD subtypes using genetics (polygenic risk score, PRS) and blood gene expression (transcriptional risk score, TRS) and assess differences in clinical and molecular characteristics.

METHODS: We defined high-risk groups based on PRS and TRS quantiles by maximising differences in protein biomarkers in a COPDGene training set and identified these groups in COPDGene and ECLIPSE test sets. We tested multivariable associations of subgroups with clinical outcomes and compared protein-protein interaction networks and drug repurposing …

Spop Downregulation Promotes Bladder Cancer Progression Based On Cancer Cell-Macrophage Crosstalk Via Stat3/Ccl2/Il-6 Axis And Is Regulated By Vezf1., Meiqian Li, Yangyan Cui, Qi Qi, Jiakuan Liu, Jiaxuan Li, Guifang Huang, Jiale Yang, Jingya Sun, Zhihui Ma, Shengjie Liang, Dianzheng Zhang, Jun Jiang, Rujian Zhu, Qiuli Liu, Ruimin Huang, Jun Yan

PCOM Scholarly Works

Background: Cancer cells are intimately intertwined with tumor microenvironment (TME), fostering a symbiotic relationship propelling cancer progression. However, the interaction between cancer cells and tumor-associated macrophages (TAMs) in urothelial bladder cancer (UBC) remains poorly understood. Methods: UBC cell lines (5637, T24 and SW780), along with a monocytic cell line (U937) capable of differentiating into macrophage, were used in a co-culture system for cell proliferation and stemness by MTT, sphere formation assays. VEZF1/SPOP/STAT3/CCL2/ IL-6 axis was determined by luciferase reporter, ChIP, RNA-seq, co-IP, in vitro ubiquitination, RT-qPCR array and ELISA analyses. Results: We observed the frequent downregulation of SPOP, an E3 …

Acceptance-Based Process Variables On Postpartum Well-Being And Distress: The Mediating Role Of Psychological Flexibility., Alexa Bonacquisti, Emily C Woodworth, Maria Diaz, Victoria A Grunberg

PCOM Scholarly Works

OBJECTIVE: Although up to 20% of women experience postpartum depression and/or anxiety, current interventions are limited. Identifying the processes that impact outcomes can inform and enhance interventions. Our study aims to examine: (1) whether acceptance-based process variables (awareness, acceptance, cognitive defusion, psychological flexibility) were associated with postpartum outcomes; and (2) whether psychological flexibility mediated the relationship between treatment engagement and postpartum outcomes.

METHOD: Postpartum women (N = 266) were recruited online using snowball sampling via social media (i.e., Facebook). They completed a cross-sectional survey of validated and reliable quantitative measures assessing their well-being, emotional distress, and acceptance-based processes.

RESULTS: Hierarchical …

Biodegradable Nanoparticles Targeting Circulating Immune Cells Reduce Central And Peripheral Sensitization To Alleviate Neuropathic Pain Following Spinal Cord Injury., Michael N. Saunders, Kate V. Griffin, Irina Kalashnikova, Daniel Kolpek, Dominique R. Smith, Eiji Saito, Brian J. Cummings, Aileen J. Anderson, Lonnie D. Shea, Jonghyuck Park

Pharmaceutical Sciences Faculty Publications

Neuropathic pain is a critical source of comorbidity following spinal cord injury (SCI) that can be exacerbated by immune-mediated pathologies in the central and peripheral nervous systems. In this article, we investigate whether drug-free, biodegradable, poly(lactide- co -glycolide) (PLG) nanoparticle treatment mitigates the development of post-SCI neuropathic pain in female mice. Our results show that acute treatment with PLG nanoparticles following thoracic SCI significantly reduces tactile and cold hypersensitivity scores in a durable fashion. Nanoparticles primarily reduce peripheral immune-mediated mechanisms of neuropathic pain, including neuropathic pain-associated gene transcript frequency, transient receptor potential ankyrin 1 nociceptor expression, and MCP-1 (CCL2) chemokine …