Digital Commons Network^™

Sars-Cov-2 Antibody Responses In Children Exhibit Higher Fcr Engagement And Avidity Than In Adults, Carolyn A Cohen, Ludivine Grzelak, Susan S Chiu, David Sc Hui, Mike Yw Kwan, Owen Ty Tsang, Wai Hung Chan, Yat Sun Yau, Kelly Wk Lee, Masashi Mori, Gaya K Amarasinghe, Samuel Ms Cheng, Leo Lm Poon, Malik Peiris, Sophie A Valkenburg

2020-Current year OA Pubs

As intrinsic differences in humoral immune response to SARS-CoV-2 between children and adults remain unclear, we improved characterisation by defining the kinetics, specificity and function of antibodies to SARS-CoV-2 in children (n = 146, aged 9.4 ± 4.8 years with n = 257 samples) compared to adults (n = 85, aged 39.5 ± 15.2 years with n = 122 samples). We used plasma samples from an infection and vaccination-naive cohort study with RT-PCR confirmed ancestral B.1* SARS-CoV-2 virus infection with asymptomatic or mild disease, collected in Hong Kong between March to December 2020, from acute (0-14 days post infection) to …

Multivariate Protein Landscape Of Host Response In Hospitalised Patients With Suspected Infection In The Emergency Department, Pratik Sinha, Et Al.

2020-Current year OA Pubs

Suspected infection requiring hospitalisation has highly heterogenous presentation. Yet, variances in host response and its implications are largely unknown. In this multicentre cohort of 3802 individual patients presenting to the Emergency Department (ED) with suspected infection requiring hospitalisation, we apply uniform manifold approximation and projections and K-means clustering to 29 plasma proteins to identify biologically discrete host response clusters. In this work, we first describe two large clusters, called "Dysregulated" and "Undifferentiated", with abnormal protein concentrations and adverse outcomes in the former. Through further clustering, we identify 4 sub-clusters in the Dysregulated cluster, each with discrete biological signatures, clinical correlates, …

Racial And Socioeconomic Disparities In Long Term Survival After Surgery And Radiation For Spinal Cord Hemangioblastoma, Abdul Karim Ghaith, Xinlan Yang, Joshua Weinberg, Shaan Bhandarkar, Taha Khalilullah, Abdel-Hameed Al-Mistarehi, Khaled Zaitoun, Meghana Bhimreddy, Arjun K. Menta, Antony A. Fuleihan, Kamel Chebaro, Jawad Khalifeh, Andrew Grossbach, Nicholas Theodore, Daniel Lubelski

Department of Medicine Faculty Papers

Spinal cord hemangioblastomas are rare, benign, intradural tumors that, despite their nonmalignant histopathology, can lead to substantial neurological morbidity. While disparities in outcomes based on race and socioeconomic status have been well-documented in other spinal tumor populations, their role in spinal cord hemangioblastoma remains poorly understood. In this study, we utilize the National Cancer Database (NCDB) to evaluate the influence of race, socioeconomic factors, and healthcare access on survival outcomes in patients with spinal cord hemangioblastoma. Additionally, we explore the utility of machine learning-based survival models to improve individualized risk prediction and to identify key clinical and sociodemographic determinants of …

Does Patient Age Influence Procedural Management Of Kidney Trauma?, Nizar Hakam, Behzad Abbasi, Umar Ghaffar, Kevin D Li, Hiren Patel, Charles P Jones, Joseph Cuschieri, Benjamin N Breyer

2020-Current year OA Pubs

OBJECTIVES: We aimed to examine the association between patient age and procedural intervention, especially nephrectomy, in patients with renal trauma in the National Trauma Data Bank (NTDB).

MATERIALS AND METHODS: We queried the 2013-2020 NTDB for adult renal trauma patients with an American Association for the Surgery of Trauma (AAST) grade. Patients without AAST grade or with no sign of life were excluded. We constructed a multinomial logistic regression model to demonstrate the association between age and procedural interventions (renal angioembolization, renorrhaphy and nephrectomy). Models were adjusted for patient, hospital, and clinical factors.

RESULTS: Our cohort was comprised of 49,884 …

Prefrontal Cortex Astrocytes Modulate Distinct Neuronal Populations To Control Anxiety-Like Behavior, Eunyoung Kim, Hairuo Du, Yanqi Tan, Brandon L Brown, Yaowen Chang, Blanca Díaz-Castro, Jonathan V Sweedler, Xinzhu Yu

Faculty, Staff and Student Publications

Accumulating evidence has supported diverse regulatory functions of astrocytes in different neural circuits as well as various aspects of complex behaviors. However, little is known about how astrocytes regulate different neuronal subpopulations that are linked to specific behavioral aspects within a single brain region. Here, we show that astrocytes in the medial prefrontal cortex (mPFC) encode anxiogenic environmental cues in freely behaving mice. Silencing mPFC astrocyte Ca

Organizational Climate And Decision Aid Sustainability In Lupus Care: Mixed Methods Study, Aizhan Karabukayeva, Larry R Hearld, Nathan W Carroll, Reena Kelly, Jasvinder A Singh

Faculty, Staff and Students Publications

Background: Digital decision aids (DAs) are increasingly used in health care to support shared decision-making and promote patient engagement. In the context of systemic lupus erythematosus (SLE), a complex autoimmune disease characterized by diverse symptoms and uncertain prognoses, DAs offer guidance to patients in navigating treatment risks and benefits. Although numerous studies have examined the initial implementation of evidence-based tools, there is limited evidence on the organizational factors that influence their long-term sustainability in clinical practice. This gap is particularly salient for digital interventions, where integration into routine workflows and ongoing use require alignment with clinic readiness and culture. This …

Modeling The Importance Of Life Exposure Factors On Memory Performance In Diverse Older Adults: A Machine Learning Approach, Evan Fletcher, Marianne Chanti-Ketterl, Emily Hokett, Yi Lor, Umesh Venkatesan, Ruijia Chen, Omonigho M. Bubu, Rachel Whitmer, Paola Gilsanz, Zvinka Z. Zlatar

Moss-Magee Rehabilitation Papers

INTRODUCTION: Many health life exposure factors (LEFs) influence cognitive decline and dementia incidence, but their relative importance to episodic memory (an early indicator of cognitive decline) among diverse older adults is unclear. We used machine learning to rank LEFs for memory performance in a large and diverse US cohort.

METHODS: Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) and Study of Healthy Aging in African Americans (STAR), participants underwent neuropsychological testing and answered questionnaires about multiple LEFs. XGBoost and Shapley Additive exPlanation values ranked the importance of factors influencing cross-sectional episodic memory in the full sample and by sex and …

Dexamethasone-Eluting Cochlear Implants Reduce Inflammation And Foreign Body Response In Human And Murine Cochleae, Muhammad Taifur Rahman, Keiko Hirose, Et Al.

2020-Current year OA Pubs

The inflammatory foreign body response (FBR) following cochlear implantation (CI) can negatively impact CI outcomes, including increased electrode impedances. This study aims to investigate the long-term efficacy of dexamethasone-eluting cochlear implant and locally delivered dexamethasone, a potent anti-inflammatory glucocorticoid, on the intracochlear FBR and electrical impedance post-implantation in a murine model. Preliminary impedance data in humans are also provided as a complement to the murine data to illustrate generalizability and reinforce implications related to clinical application. The left ears of CX3CR1

Deep Phenotyping Of Obesity: Electronic Health Record-Based Temporal Modeling Study, Xiaoyang Ruan, Shuyu Lu, Liwei Wang, Andrew Wen, Sameer Murali, Hongfang Liu

Faculty, Staff and Student Publications

Background: Obesity affects approximately 40% of adults and 15%-20% of children and adolescents in the United States, and poses significant economic and psychosocial burdens. Currently, patient responses to any single antiobesity medication (AOM) vary significantly, making obesity deep phenotyping and associated precision medicine important targets of investigation.

Objective: This study aimed to evaluate the potential of electronic health records (EHR) as a primary data source for obesity deep phenotyping. We conducted an in-depth analysis of the data elements and quality available from obesity patients prior to pharmacotherapy and applied a multimodal longitudinal deep autoencoder to investigate the feasibility, data requirements, …

Germline Structural Variations Involving The Pediatric Brain Tumor Transcriptome Include Disease-Relevant And Ancestry-Related Genes, Fengju Chen, Yiqun Zhang, Luis F Paulin, Fritz J Sedlazeck, Chad J Creighton

Faculty, Staff and Students Publications

Background: Germline Structural Variants (SVs) represent an important source of genetic diversity, in large part due to their influence on gene transcription. It is necessary to systematically catalog germline SVs and their associated impacted genes across different cohorts and tissue and cellular contexts, including pediatric brain or Central Nervous System (CNS) tumors.

Methods: We combined RNA with whole genome sequencing across 1430 pediatric brain or CNS tumor patients from the Children's Brain Tumor Network. We set out to systematically identify genes for which the proximity of germline SVs was recurrently and significantly associated with differential expression in the tumor sample …

Multi-Ancestral Genome-Wide Association Study Of Clinically Defined Nicotine Dependence Reveals Strong Genetic Correlations With Other Substance Use Disorders And Health-Related Traits, Emma C Johnson, Jared V Balbona, Alexander S Hatoum, David A A Baranger, Louis Fox, Paul W Jeffries, Laura J Bierut, Andrew C Heath, Pamela A Madden, Elliot C Nelson, Arpana Agrawal, Et Al.

2020-Current year OA Pubs

BACKGROUND: Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement.

METHODS: We conducted a genome-wide association study (GWAS) of nicotine dependence defined using the Diagnostic and Statistical Manual of Mental Disorders (DSM-NicDep) in 61,861 individuals (47,884 of European ancestry [EUR], 10,231 of African ancestry, and 3,746 of East Asian ancestry) and compared the results to other nicotine-related phenotypes.

RESULTS: We replicated the well-known association at the

CONCLUSIONS: Our results suggest that combining the wide availability of diagnostic EHR data with nuanced criterion-level analyses of DSM tobacco use disorder may produce new insights into the genetics …

Dissatisfaction And Residual Symptoms In Younger And Older Adult Patients After Total Knee Arthroplasty, Nicholas Pohl, Parker Brush, Adrian Santana, Sebastian Fras, Eleanor Jenkins, Arjun Saxena

Department of Orthopaedic Surgery Faculty Papers

INTRODUCTION: Total knee arthroplasty (TKA) is an increasingly used treatment option for younger patients with osteoarthritis. Previous research has found only 66% patients < 60 years who underwent TKA postoperatively reported that their knees felt normal. However, the prior studies did not compare underlying causes for dissatisfaction based on age. This study compared the satisfaction and residual symptom rates between patients ages < 60 and ≥60 years and identified specific reasons for their dissatisfaction between the age groups.

METHODS: Patients who underwent unilateral TKA for osteoarthritis from 2014 to 2016 were electronically sent a 15-question survey pertaining to surgery satisfaction. Following patient identification and survey completion, patient demographics, medical history, surgical time, and length of stay were collected through manual review of medical records. Patients who completed surveys were grouped by age (< 60 years or ≥60 years) for analysis.

RESULTS: In total, 1189 ≥ 60-year-old patients and 388 < 60-year-old patients were included. Most patients in both cohorts reported satisfaction with overall knee function (< 60: 68.6%; ≥60: 71.8%; P = 0.175). Fewer < 60-year patients reported normal knee function (66.5% vs. 75.2%; P < 0.001). The most common residual symptom in both cohorts was continued pain.

CONCLUSION: Patients younger than 60 years reported less satisfaction with performing normal activities …

Revisiting The Effect Of Udenafil On Exercise Performance In Patients With Fontan Circulation: Results Of A Post Hoc Analysis Of The Fuel Trial., David J. Goldberg, Victor Zak, Chenwei Hu, Adam M. Lubert, Rahul H. Rathod, Daniel J. Penny, Robert Whitehill, Kurt R. Schumacher, Salil Ginde, Michelle Ploutz, Gi Beom Kim, Todd T. Nowlen, Michael V. Dimaria, Benjamin P. Frischhertz, Jonathan B. Wagner, Kimberly E. Mchugh, Brian W. Mccrindle, Mark J. Cartoski, Jon Detterich, Anji T. Yetman, Anitha S. John, Marc E. Richmond, Matthew Files, R Mark Payne, Andrew S. Mackie, Christopher K. Davis, William B. Orr, Ruchira Garg, Kevin D. Hill, Jennifer S. Yauck, Michael G. Mcbride, James Yeager, Gail D. Pearson, Stephen M. Paridon, Bryan H. Goldstein

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: In the FUEL (Fontan Udenafil Exercise Longitudinal) trial, a positive treatment effect was identified for outcomes at the ventilatory anaerobic threshold but not for the primary outcome, oxygen consumption (Vo₂ in participants with near-normal baseline exercise performance.

METHODS: Participants were divided into subgroups by baseline predicted peak Vo₂ (< 80% versus ≥80%). Treatment effect was evaluated in those with a baseline peak Vo2 < 80% predicted and linear regression was performed to examine the interaction between subgroup and response to therapy for the primary and secondary outcomes.

RESULTS: Of the 379 participants with paired exercise data, 302 (80%) had a baseline peak Vo₂ < 80% predicted. In this subgroup, the primary outcome of peak Vo₂ improved significantly after 6 months of udenafil treatment, when compared with placebo (0.23±4.17 mL/kg per min versus -0.90±3.74 mL/kg per min; P=0.021). Secondary outcome measures, including Vo₂ at …

Dna Methylation Signatures Of Cardiovascular Health Provide Insights Into Diseases, Madeleine Carbonneau, Yi Li, Yishu Qu, Yinan Zheng, Alexis C Wood, Mengyao Wang, Chunyu Liu, Tianxiao Huan, Roby Joehanes, Xiuqing Guo, Jie Yao, Kent D Taylor, Russell P Tracy, Peter Durda, Yongmei Liu, W Craig Johnson, Wendy S Post, Tom Blackwell, Jerome I Rotter, Stephen S Rich, Susan Redline, Myriam Fornage, Jun Wang, Hongyan Ning, Lifang Hou, Donald Lloyd-Jones, Kendra Ferrier, Yuan-I Min, April P Carson, Laura M Raffield, Alexander Teumer, Hans J Grabe, Henry Völzke, Matthias Nauck, Marcus Dörr, Arce Domingo-Relloso, Amanda Fretts, Maria Tellez-Plaza, Shelley A Cole, Ana Navas-Acien, Meng Wang, Joanne M Murabito, Nancy L Heard-Costa, Brenton Prescott, Vanessa Xanthakis, Dariush Mozaffarian, Daniel Levy, Jiantao Ma

Faculty, Staff and Students Publications

Background: The association of overall cardiovascular health (CVH) with changes in DNA methylation (DNAm) has not been well characterized.

Methods: We calculated the American Heart Association's Life's Essential 8 score to reflect CVH in 5 cohorts with diverse backgrounds (mean age 54 years, 55% women, and enrollment year ranging from 1989 to 2012). Epigenome-wide association studies (EWAS) for Life's Essential 8 score were conducted, followed by bioinformatic analyses. DNAm loci significantly associated with Life's Essential 8 score were used to calculate a CVH DNAm score. We examined the association of the CVH DNAm score with incident cardiovascular disease (CVD), cardiovascular …

Trpc4 Regulates Limbic Behavior And Neuronal Development By Stabilizing Dendrite Branches Through Actomyosin-Driven Integrin Activation, Jaepyo Jeon, Travis I Moore, Insuk So, Marc Freichel, Veit Flockerzi, Lutz Birnbaumer, Michael X Zhu

Faculty, Staff and Student Publications

Transient Receptor Potential Canonical 4 (TRPC4) channels have been implicated in multiple neurological functions, including anxiety and sociability. TRPC4 variants were also found in patients with autism. However, the contributions of TRPC4 to neurodevelopment remain undefined. Here, we show that neurobehavioral deficits appear early in young TRPC4 knockout (Trpc4^−/−) mice immediately after weaning, manifesting as alterations in multiple, limbic-related behaviors, such as nesting, marble burying, burrowing, self-grooming, and social interactions. Hippocampal neurons of Trpc4−/− mice exhibit reduced dendritic arborization both in vivo and in vitro. Mechanistically, we found that TRPC4 expression in dendrites surged at the …

Proteogenomic Characterization Unveils Biomarkers Associated With Chemoresistance In Muscle-Invasive Bladder Cancer, Matthew V Holt, Yongchao Dou, Meggie N Young, Alexander B Saltzman, Meenakshi Anurag, Jonathan T Lei, Antrix Jain, Mei Leng, Beom-Jun Kim, Lacey E Dobrolecki, Stefanie F Faucher, Sara Savage, Chenwei Wang, Zhiao Shi, Hugo Villanueva, Karoline Kremers, Kyle D Drinnon, Patricia D Castro, Michael M Ittmann, Mehak Mehboob Khatani, Sung Han Kim, Matthew J Ellis, Bing Zhang, Anna Malovannaya, Seth P Lerner

Faculty, Staff and Students Publications

To explore potential chemoresistance mechanisms and identify therapeutic opportunities in muscle-invasive bladder cancer (MIBC), we conduct comprehensive proteogenomic characterization of 46 pre- and 14 post-treatment MIBC tumors incorporating genomics, transcriptomics, proteomics, and phosphoproteomics. Multi-omics clustering not only recapitulated established molecular subtypes but also revealed subtypes associated with chemotherapy sensitivity. Protein isoform level analysis identifies protein abundance of a short isoform of ATAD1 and RAF family proteins as biomarkers of chemosensitivity. Integration of proteomic and phosphoproteomic data reveals Wnt signaling via GSK3B-S9 phosphorylation and the JAK/STAT pathway as potential targets to overcome chemoresistance. Correlations between PD-L1 and TROP-2/NECTIN-4 indicate an additive …

Corticotropin-Releasing Hormone Modulates Nrem Sleep Consolidation Through The Thalamic Reticular Nucleus, Loredana Cumpana, Olivia Zanoletti, Dinesh Kankanamge, Bryan Copits, Carmen Sandi, Simone Astori

2020-Current year OA Pubs

Corticotropin-releasing hormone (CRH) is a peptide associated with stress and anxiety that acts as a potent modulator throughout the nervous system. The thalamic reticular nucleus (TRN) displays high expression of the CRH receptor 1 (CRHR1), but whether CRH modulates key TRN functions, such as sleep spindle rhythmogenesis, remained unexplored. Combining polysomnographic and photometric recordings in mice, we show that CRH release in TRN during non-rapid-eye movement sleep (NREMS) oscillates with a ~50-s periodicity, anti-correlating with sleep spindle dynamics. Optogenetic manipulations of CRH release in TRN modulated NREMS fragmentation through microarousals with corresponding changes in sigma and delta power. In ex-vivo …

Experience-Dependent Intrinsic Plasticity In Layer Iv Of Barrel Cortex At Whisking Onset, Molly C Shallow, Lucy Tian, Bryan T Higashikubo, Hudson Lin, Katheryn B Lefton, Siyu Chen, Joseph D Dougherty, Joe P Culver, Mary E Lambo, Keith B Hengen

2020-Current year OA Pubs

The development of motor control over sensory organs is a critical milestone, enabling active exploration and shaping of the sensory environment. Whether the onset of sensory organ motor control directly influences the development of corresponding sensory cortices remains unknown. Here, we confirm and exploit the late onset of whisking behavior in mice to address this question in the somatosensory system. Using ex vivo electrophysiology, we describe a transient increase in the intrinsic excitability of excitatory neurons in layer IV of the barrel cortex, which processes whisker input, immediately following the onset of active whisking on postnatal days 13 and 14. …

Revisiting The Effect Of Udenafil On Exercise Performance In Patients With Fontan Circulation: Results Of A Post Hoc Analysis Of The Fuel Trial, David J Goldberg, William B Orr, Et Al.

2020-Current year OA Pubs

BACKGROUND: In the FUEL (Fontan Udenafil Exercise Longitudinal) trial, a positive treatment effect was identified for outcomes at the ventilatory anaerobic threshold but not for the primary outcome, oxygen consumption (Vo

METHODS: Participants were divided into subgroups by baseline predicted peak Vo

RESULTS: Of the 379 participants with paired exercise data, 302 (80%) had a baseline peak Vo

CONCLUSIONS: In this post hoc subgroup analysis, after exclusion of patients with Fontan circulation with near-normal baseline peak Vo

REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT0274115.

High-Grade Glioma With Pleomorphic And Pseudopapillary Features: A Single-Institution Series Of Three Cases, Eric A Goethe, Rasha Alfattal, Subhiksha Srinivasan, Pushan Dasgupta, Vinay Puduvalli, Shiao-Pei Weathers, Leomar Y Ballester, Jeffrey S Weinberg, Sujit Prabhu, Sherise D Ferguson, Maria A Gubbiotti

Faculty, Staff and Students Publications

Introduction: Modern molecular diagnostic techniques such as DNA methylation profiling are leading to the reclassification of several central nervous system malignancies and discovery of novel diagnostic entities, such as high-grade glioma with pleomorphic and pseudopapillary features (HPAP).

Methods: We performed a retrospective chart review of all patients with HPAP confirmed with methylation profiling at a single institution between 2023 and 2025. Demographic, radiographic, surgical, and outcome data were collected.

Results: Three patients were identified: two females and one male with a mean age of 49.7 years (range 25-62). No patients had a prior cancer history. One patient had an incidentally …

Extended Survival With Pancreatic Carcinosarcoma: A Case Report And Literature Review, Tian Xiao, Claire Browne, Morgan Black, Celia Marginean, Elena Tsvetkova

Faculty, Staff and Students Publications

Pancreatic carcinosarcoma is a rare and aggressive malignancy that can mimic pancreatic adenocarcinomas in presentation but often has different disease biology and different responses to conventional treatment for pancreatic adenocarcinoma. Case reports have documented a 5-year overall survival of approximately 13% only if the disease is caught at an earlier stage and is amenable to multi-modality treatment, including surgery, chemotherapy, and radiation. In the advanced stage, treatments do not often provide benefit, and patients may decline rapidly. There are currently no studies demonstrating survival benefits with chemotherapy in patients with metastatic carcinosarcoma, owing to both the rarity and the often …

Old Vs New Local Ancestry Inference In Hchs/Sol: A Comparative Study, Xueying Chen, Hao Wang, Iris Broce, Anders Dale, Bing Yu, Laura Y Zhou, Xihao Li, Maria Argos, Martha L Daviglus, Jianwen Cai, Nora Franceschini, Tamar Sofer

Faculty, Staff and Student Publications

Hispanic/Latino populations are admixed, with genetic contributions from multiple ancestral populations. To uncover genetic associations in these populations, researchers often turn to admixture mapping, which relies on inferred counts of "local" ancestry, i.e. the source ancestral population at a locus. Local ancestries are inferred using external reference panels that represent ancestral populations, making the choice of inference method and reference panel critical. This study used a dataset of Hispanic/Latino individuals from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) to evaluate how updates in local ancestry inference (LAI) affect results, specifically, the 'old' LAI performed using a popular inference method …

Kdm2b Variants In The Cxxc Domain Impair Its Dna-Binding Ability And Cause A Distinct Neurodevelopmental Syndrome, Amber S E Van Oirsouw, Michael A Hadders, Martijn Koetsier, Edith D J Peters, Nurit Assia Batzir, Tahsin Stefan Barakat, Diana Baralle, Adelyn Beil, Marie-Noëlle Bonnet-Dupeyron, Philip M Boone, Arjan Bouman, Deanna Alexis Carere, Benjamin Cogne, Leslie Dunnington, Laura S Farach, Casie A Genetti, Bertrand Isidor, Louis Januel, Aakash Joshi, Nayana Lahiri, Kristen N Lee, Idit Maya, Meriel Mcentagart, Hope Northrup, Mathilde Pujalte, Kate Richardson, Susan Walker, Bobby P C Koeleman, Mariëlle Alders, Richard H Van Jaarsveld, Renske Oegema

Faculty, Staff and Student Publications

Rare variants affecting the epigenetic regulator KDM2B cause a recently delineated neurodevelopmental disorder. Interestingly, we previously identified both a general KDM2B-associated episignature and a subsignature specific to variants in the DNA-binding CxxC domain. In light of the existence of a distinct subsignature, we set out to determine if KDM2B CxxC variants are associated with a unique phenotype and disease mechanism. We recruited individuals with heterozygous CxxC variants and assessed the variants' effect on protein expression and DNA-binding ability. We analyzed clinical data from 19 individuals, including ten previously undescribed individuals with seven novel CxxC variants. The core phenotype of the …

Implementation Of Clinical Practice Guidelines To Prevent Cervical Cancer: Mixed Methods Study, Oliver C Ezechi, Folahanmi T Akinsolu, Olunike R Abodunrin, Oluwabukola M Ola, Chisom Obi-Jeff, Ishak K Lawal, George U Eleje, Joseph D Tucker, Juliet I Iwelunmor

2020-Current year OA Pubs

BACKGROUND: Cervical cancer is a common cause of death among women globally, particularly in Africa. Each year, an average of 7093 women in Nigeria die from cervical cancer. Clinical practice guidelines developed by the Society of Obstetrics and Gynecology of Nigeria (SOGON) aim to prevent cervical cancer. However, the extent of their adoption among gynecologists remains unclear.

OBJECTIVE: This study aimed to assess Nigerian gynecologists' awareness, understanding, and incorporation of the SOGON clinical practice guidelines for cervical cancer prevention in their clinical practices.

METHODS: A convergent parallel mixed methods design was used. Quantitative data were collected via a web-based and …

Exploring Young Adults' Experiences And Beliefs In Asthma Medication Management: Pilot Qualitative Study Comparing Human And Multiple Ai Thematic Analysis, Ruth Ndarake Jeminiwa, Caroline Popielaski, Amber King

College of Pharmacy Faculty Papers

BACKGROUND: Young adults take their asthma maintenance medication 67% of the time or less. Understanding the specific needs and behaviors of young adults with asthma is essential for developing targeted interventions to improve disease self-management. Artificial intelligence (AI) has demonstrated its utility in summarizing and identifying patterns in qualitative research and may support or augment human coding efforts. However, there is pause literature to support this assertion.

OBJECTIVE: The objective of this study is to begin to explore the medication management-related needs of young adults with asthma via a pilot feasibility study. We aim to understand how to best assist …

Outcomes Of Patients With Newly Diagnosed Acute Myeloid Leukemia With Flt3-Tyrosine Kinase Domain Mutations: Prognostic Implications Of Npm1 Co-Mutation, Sankalp Arora, Wei-Ying Jen, Musa Yilmaz, Indraneel Deshmukh, Jayastu Senapati, Sanam Loghavi, Ghayas C Issa, Nicholas J Short, Tapan M Kadia, Courtney D Dinardo, Gautam Borthakur, Joseph Jabbour, Naveen Pemmaraju, Michael Andreeff, Koichi Takahashi, Kapil Bhalla, Uday Popat, Elizabeth J Shpall, Betul Oran, Hussein A Abbas, Guillermo Garcia-Manero, Farhad Ravandi, Hagop Kantarjian, Naval Daver

Faculty, Staff and Student Publications

Background: The prognostic impact of Fms-like tyrosine kinase 3 (FLT3)-tyrosine kinase domain (TKD) mutation in patients with acute myeloid leukemia (AML) is not well defined. The authors described outcomes of one of the largest cohorts of patients with FLT3-TKD mutated (FLT3-TKDmut) AML to date.

Methods: This retrospective study included patients with newly diagnosed AML who received frontline treatment at The University of Texas MD Anderson Cancer Center from January 2012 to March 2024 divided into two cohorts: FLT3-TKDmut AML and nucleophosmin-mutated (NPM1mut)/FLT3-TKD wild-type (FLT3-TKDwt) AML. Patients with FLT3 internal tandem duplication mutations were excluded.

Results: In total, 2922 patients were …

Lipidomic And Proteomic Insights From Extracellular Vesicles In The Postmortem Dorsolateral Prefrontal Cortex Reveal Substance Use Disorder-Induced Brain Changes, Chioma M Okeoma, Wasifa Naushad, Bryson C Okeoma, Carlos Gartner, Yulica Santos-Ortega, Calvin Vary, Savio Lima-Bastos, Victor Corasolla Carregari, Martin R Larsen, Alessio Noghero, Consuelo Walss-Bass, Rodrigo Grassi-Oliveira

Faculty, Staff and Student Publications

Substance use disorder (SUD) significantly increases the risk of neurotoxicity, inflammation, oxidative stress, and impaired neuroplasticity. The activation of inflammatory pathways by substances may lead to reactive astrogliosis and chronic neuroinflammation, potentially mediated by the release of extracellular particles (EPs), such as extracellular condensates (ECs) and extracellular vesicles (EVs). These particles, which reflect the physiological, pathophysiological, and metabolic states of their cells of origin, might carry molecular signatures indicative of SUD. In particular, our study investigated neuroinflammatory signatures in SUD patients by isolating EVs from the dorsolateral prefrontal cortex (dlPFC) Brodmann's area 9 (BA9) from postmortem subjects. We isolated BA9-derived …

Randomised, Placebo-Controlled Trial Of Oral Hymecromone In Adults With Pulmonary Hypertension, Kathryn Czepiel, Nadine Nagy, Tamera Panjalingam, Anissa Kalinowski, Adam R Frymoyer, Harry Karmouty-Quintana, Bo Gu, Haley Hedlin, Gernot Kaber, Sylvie Dobrota Lai, Joelle I Rosser, Paul L Bollyky, Vinicio De Jesus Perez, Roham T Zamanian

Faculty, Staff and Student Publications

Background: Pulmonary hypertension (PH) is a progressive cardiopulmonary condition associated with increased morbidity and mortality. The extracellular matrix component hyaluronan (HA) is linked to vascular remodelling and interstitial fibrosis in PH. We hypothesised that inhibition of HA synthesis with hymecromone could serve as a reverse-remodelling therapy in PH.

Methods: We performed a proof-of-concept phase IIa randomised, double-blind, placebo-controlled study in adults with pulmonary arterial hypertension and PH associated with interstitial lung disease (PH-ILD). Patients were randomised to a 5:3 ratio and stratified by PH group to receive oral hymecromone or placebo two times per day over 24 weeks. The primary …

Clinical, Tumor, And Product Features Associated With Outcomes After Axicabtagene Ciloleucel Therapy In Follicular Lymphoma, Soumya Poddar, Jiali Yan, Gayatri Tiwari, Darawan Rinchai, Justin Budka, Wangshu Zhang, Weixin Peng, Shruti Salunkhe, Madison Davis, Qinghua Song, Sara Beygi, Harry Miao, Mike Mattie, Rhine S Shen, Caron A Jacobson, Davide Bedognetti, Simone Filosto, Sattva S Neelapu

Faculty, Staff and Student Publications

Background: Axicabtagene ciloleucel (axi-cel), anti-CD19 chimeric antigen receptor (CAR) T cell therapy, demonstrated remarkable efficacy with manageable toxicity in relapsed/refractory indolent B cell lymphomas in the ZUMA-5 trial.

Methods:Here, we report associations of product attributes, serum biomarkers, clinical features, and tumor characteristics with outcome in 124 patients with follicular lymphoma (FL).

Results: In univariate and multivariate analyses, pretreatment inflammatory markers, including TNF-α and IL-12p40, as well as total metabolic tumor volume (TMTV), associated with disease progression. Conversely, T-naive–like product phenotype associated with improved outcome, particularly in patients with high TMTV. These covariates improved risk stratification when combined with the …

Contemporary Outcomes Of Octa-Nonagenarians With Newly Diagnosed Acute Myeloid Leukemia, Jayastu Senapati, Hagop M Kantarjian, Tapan M Kadia, Jeannot Kekedjian, Gautam Borthakur, Naval Daver, Courtney D Dinardo, Elias Jabbour, Prithviraj Bose, Nicholas J Short, Musa Yilmaz, Nitin Jain, Naveen Pemmaraju, Hussein A Abbas, Ghayas C Issa, Abhishek Maiti, Guillermo Montalban Bravo, Indraneel Deshmukh, Elizabeth Shpall, Partow Kebriaei, Uday Popat, Sanam Loghavi, Beenu Thakral, Guilin Tang, Fadi G Haddad, Yesid Alvarado, Guillermo Garcia Manero, Farhad Ravandi

Faculty, Staff and Student Publications

Background: Octa-nonagenarians with acute myeloid leukemia (AML) represent a high-risk group due to frequently poor performance status, adverse genomics (e.g., TP53 mutations, complex karyotype), a high incidence of secondary AML, and inability to undergo an allogeneic stem cell transplantation. Evaluating their outcomes with modern treatment approaches is important.

Methods: This retrospective study analyzed outcomes of patients ≥80 years old with newly diagnosed AML treated at our center from 2013-2023.

Results: A total of 289 patients (median age, 83 years; range, 80-95 years) were included. Venetoclax containing low-intensity therapy was administered to 107 patients (37.0%). AML subtypes included de novo (123, …