Digital Commons Network^™

Mif/Nr3c2 Axis Regulates Glucose Metabolism Reprogramming In Pancreatic Cancer Through Mapk-Erk And Ap-1 Pathways, Shouhui Yang, Wei Tang, Azadeh Azizian, Jochen Gaedcke, Yuuki Ohara, Helen Cawley, Nader Hanna, Michael Ghadimi, Trisha Lal, Subrata Sen, Chad J Creighton, Jianjun Gao, Nagireddy Putluri, Stefan Ambs, Perwez Hussain

Faculty, Staff and Student Publications

Inflammation and aberrant cellular metabolism are widely recognized as hallmarks of cancer. In pancreatic ductal adenocarcinoma (PDAC), inflammatory signaling and metabolic reprogramming are tightly interwoven, playing pivotal roles in the pathogenesis and progression of the disease. However, the regulatory functions of inflammatory mediators in metabolic reprogramming in pancreatic cancer have not been fully explored. Earlier, we demonstrated that pro-inflammatory mediator macrophage migration inhibitory factor (MIF) enhances disease progression by inhibiting its downstream transcriptional factor nuclear receptor subfamily 3 group C member 2 (NR3C2). Here, we provide evidence that MIF and NR3C2 interactively regulate metabolic reprogramming, resulting in MIF-induced cancer growth …

Personalized Neoantigen Vaccines As Early Intervention In Untreated Patients With Lymphoplasmacytic Lymphoma: A Non-Randomized Phase 1 Trial, Szymon J Szymura, Lin Wang, Tiantian Zhang, Soung-Chul Cha, Joo Song, Zhenyuan Dong, Aaron Anderson, Elizabeth Oh, Vincent Lee, Zhe Wang, Sapna Parshottam, Sheetal Rao, Jasper B Olsem, Brandon N Crumpton, Hans C Lee, Elisabet E Manasanch, Sattva Neelapu, Larry W Kwak, Sheeba K Thomas

Faculty, Staff and Student Publications

Lymphoplasmacytic lymphoma (LPL) is an incurable low-grade lymphoma with no standard therapy. Nine asymptomatic patients treated with a first-in-human, neoantigen DNA vaccine experienced no dose limiting toxicities (primary endpoint, NCT01209871). All patients achieve stable disease or better, with one minor response, and median time to progression of 72+ months. Post-vaccine single-cell transcriptomics reveal dichotomous antitumor responses, with reduced tumor B-cells (tracked by unique B cell receptor) and their survival pathways, but no change in clonal plasma cells. Downregulation of human leukocyte antigen (HLA) class II molecules and paradoxical upregulation of insulin-like growth factor (IGF) by the latter suggest resistance mechanisms. …

Proximity Analysis Of Native Proteomes Reveals Phenotypic Modifiers In A Mouse Model Of Autism And Related Neurodevelopmental Conditions, Yudong Gao, Daichi Shonai, Matthew Trn, Jieqing Zhao, Erik J Soderblom, S Alexandra Garcia-Moreno, Charles A Gersbach, William C Wetsel, Geraldine Dawson, Dmitry Velmeshev, Yong-Hui Jiang, Laura G Sloofman, Joseph D Buxbaum, Scott H Soderling

Faculty, Staff and Students Publications

One of the main drivers of autism spectrum disorder is risk alleles within hundreds of genes, which may interact within shared but unknown protein complexes. Here we develop a scalable genome-editing-mediated approach to target 14 high-confidence autism risk genes within the mouse brain for proximity-based endogenous proteomics, achieving the identification of high-specificity spatial proteomes. The resulting native proximity proteomes are enriched for human genes dysregulated in the brain of autistic individuals, and reveal proximity interactions between proteins from high-confidence risk genes with those of lower-confidence that may provide new avenues to prioritize genetic risk. Importantly, the datasets are enriched for …

Mitochondrial Permeability Transition Dictates Mitochondrial Maturation Upon Switch In Cellular Identity Of Hematopoietic Precursors, Sandeep P Dumbali, Paulina D Horton, Travis I Moore, Pamela L Wenzel

Faculty, Staff and Student Publications

The mitochondrial permeability transition pore (mPTP) is a supramolecular channel that regulates exchange of solutes across cristae membranes, with executive roles in mitochondrial function and cell death. The contribution of the mPTP to normal physiology remains debated, although evidence implicates the mPTP in mitochondrial inner membrane remodeling in differentiating progenitor cells. Here, we demonstrate that strict control over mPTP conductance shapes metabolic machinery as cells transit toward hematopoietic identity. Cells undergoing the endothelial-to-hematopoietic transition (EHT) tightly control chief regulatory elements of the mPTP. During EHT, maturing arterial endothelium restricts mPTP activity just prior to hematopoietic commitment. After transition in cellular …

The Dna Methylome Of Pediatric Brain Tumors Appears Shaped By Structural Variation And Predicts Survival, Fengju Chen, Yiqun Zhang, Lanlan Shen, Chad J Creighton

Faculty, Staff and Students Publications

Structural variation heavily influences the molecular landscape of cancer, in part by impacting DNA methylation-mediated transcriptional regulation. Here, using multi-omic datasets involving >2400 pediatric brain and central nervous system tumors of diverse histologies from the Children's Brain Tumor Network, we report hundreds of genes and associated CpG islands (CGIs) for which the nearby presence of somatic structural variant (SV) breakpoints is recurrently associated with altered expression or DNA methylation, respectively, including tumor suppressor genes ATRX and CDKN2A. Altered DNA methylation near enhancers associates with nearby somatic SV breakpoints, including MYC and MYCN. A subset of genes with SV-CGI methylation associations …

Video And Phone Visit Use Differed By Language Preference Among Us Latino And Chinese Adults During The First 9 Months Of The Covid-19 Pandemic: A Cross-Sectional Electronic Health Record Study, Nancy P Gordon, Teresa Y Lin, Antonia Torreblanca, Mary E Reed

Faculty, Staff and Student Publications

BACKGROUND: During the first nine months of the COVID-19 emergency, patients were encouraged to use virtual versus clinic visits if in-person care was not deemed necessary by clinical staff. This study examined the association of spoken language preference and ethnicity with use of video versus phone virtual visits by US Latino and Chinese adult patients who got care in the same healthcare system.

METHODS: We analyzed electronic health record data for four groups of adults aged 26-85y who had ≥ 1 primary or specialty care outpatient clinician visits during April-December 2020: 80,869 Latino adults preferring Spanish (LEP Latino); 214,765 Latino …

Cefiderocol Heteroresistance Associated With Mutations In Tonb-Dependent Receptor Genes In Pseudomonas Aeruginosa Of Clinical Origin, Stephanie L Egge, Samie A Rizvi, Shelby R Simar, Manuel Alcalde, Jose R W Martinez, Blake M Hanson, An Q Dinh, Rodrigo P Baptista, Truc T Tran, Samuel A Shelburne, Jose M Munita, Cesar A Arias, Morgan Hakki, William R Miller

Faculty, Staff and Student Publications

The siderophore-cephalosporin cefiderocol (FDC) presents a promising treatment option for carbapenem-resistant (CR) P. aeruginosa (PA). FDC circumvents traditional porin and efflux-mediated resistance by utilizing TonB-dependent receptors (TBDRs) to access the periplasmic space. Emerging FDC resistance has been associated with loss of function mutations within TBDR genes or the regulatory genes controlling TBDR expression. Further, difficulties with antimicrobial susceptibility testing (AST) and unexpected negative clinical treatment outcomes have prompted concerns for heteroresistance, where a single lineage isolate contains resistant subpopulations not detectable by standard AST. This study aimed to evaluate the prevalence of TBDR mutations among clinical isolates of P. aeruginosa …

Stroke Severity, Caregiver Feedback, And Cognition In The Regards-Cares Study, Jason A Blake, D Leann Long, Amy J Knight, Burel R Goodin, Michael Crowe, Suzanne E Judd, J David Rhodes, David L Roth, Olivio J Clay

2020-Current year OA Pubs

BACKGROUND: Cognitive impairment after stroke is common and is present in up to 60% of survivors. Stroke severity, indicated by both volume and location, is the most consequential predictor of cognitive impairment, with severe strokes predicting higher chances of cognitive impairment. The current investigation examines the associations of 2 stroke severity ratings and a caregiver-report of poststroke functioning with longitudinal cognitive outcomes.

METHODS AND RESULTS: One hundred fifty-seven caregivers and stroke survivor dyads participated in the CARES (Caring for Adults Recovering From the Effects of Stroke) project, an ancillary study of the REGARDS (Reasons for Geographic and Racial Differences in …

Pkd1 Mutant Clones Within Cirrhotic Livers Inhibit Steatohepatitis Without Promoting Cancer, Min Zhu, Yunguan Wang, Tianshi Lu, Jason Guo, Lin Li, Meng-Hsiung Hsieh, Purva Gopal, Yi Han, Naoto Fujiwara, Darren P Wallace, Alan S L Yu, Xiangyi Fang, Crystal Ransom, Sara Verschleisser, David Hsiehchen, Yujin Hoshida, Amit G Singal, Adam Yopp, Tao Wang, Hao Zhu

Faculty, Staff and Student Publications

Somatic mutations in non-malignant tissues are selected for because they confer increased clonal fitness. However, it is uncertain whether these clones can benefit organ health. Here, ultra-deep targeted sequencing of 150 liver samples from 30 chronic liver disease patients revealed recurrent somatic mutations. PKD1 mutations were observed in 30% of patients, whereas they were only detected in 1.3% of hepatocellular carcinomas (HCCs). To interrogate tumor suppressor functionality, we perturbed PKD1 in two HCC cell lines and six in vivo models, in some cases showing that PKD1 loss protected against HCC, but in most cases showing no impact. However, Pkd1 haploinsufficiency …

Large-Scale Mutational Analysis Identifies Unc93b1 Variants That Drive Tlr-Mediated Autoimmunity In Mice And Humans., Victoria E. Rael, Julian A. Yano, John P. Huizar, Leianna C. Slayden, Madeleine A. Weiss, Elizabeth A. Turcotte, Jacob M. Terry, Wenqi Zuo, Isabelle Thiffault, Tomi Pastinen, Emily G. Farrow, Janda L. Jenkins, Mara L. Becker, Stephen C. Wong, Anne M. Stevens, Catherine Otten, Eric J. Allenspach, Devon E. Bonner, Jonathan A. Bernstein, Matthew T. Wheeler, Robert A. Saxton, Undiagnosed Diseases Network, Bo Liu, Olivia Majer, Gregory M. Barton

Manuscripts, Articles, Book Chapters and Other Papers

Nucleic acid-sensing Toll-like receptors (TLR) 3, 7/8, and 9 are key innate immune sensors whose activities must be tightly regulated to prevent systemic autoimmune or autoinflammatory disease or virus-associated immunopathology. Here, we report a systematic scanning-alanine mutagenesis screen of all cytosolic and luminal residues of the TLR chaperone protein UNC93B1, which identified both negative and positive regulatory regions affecting TLR3, TLR7, and TLR9 responses. We subsequently identified two families harboring heterozygous coding mutations in UNC93B1, UNC93B1+/T93I and UNC93B1+/R336C, both in key negative regulatory regions identified in our screen. These patients presented with cutaneous tumid lupus and juvenile idiopathic arthritis plus …

Epigenetic Associations With Neonatal Age In Infants Born Very Preterm, Particularly Among Genes Involved In Neurodevelopment., Kenyaita M. Hodge, Amber A. Burt, Marie Camerota, Brian S. Carter, Jennifer Check, Karen N. Conneely, Jennifer Helderman, Julie A. Hofheimer, Anke Hüls, Elisabeth C. Mcgowan, Charles R. Neal, Steven L. Pastyrnak, Lynne M. Smith, Sheri A. Dellagrotta, Lynne M. Dansereau, T Michael O'Shea, Carmen J. Marsit, Barry M. Lester, Todd M. Everson

Manuscripts, Articles, Book Chapters and Other Papers

The time from conception through the first year of life is the most dynamic period in human development. This time period is particularly important for infants born very preterm (< 30 weeks gestation; VPT), as they experience a significant disruption in the normal developmental trajectories and are at heightened risk of experiencing developmental impairments and delays. Variations in the epigenetic landscape during this period may reflect this disruption and shed light on the interrelationships between aging, maturation, and the epigenome. We evaluated how gestational age (GA) and age since conception in neonates [post-menstrual age (PMA)], were related to DNA methylation in buccal cells collected at NICU discharge from VPT infants (n = 538). After adjusting for confounders and applying Bonferroni correction, we identified 2,366 individual CpGs associated with GA and 14,979 individual CpGs associated with PMA, as well as multiple differentially methylated regions. Pathway enrichment analysis identified pathways involved in axonogenesis and regulation of neuron projection development, among many other growth and developmental pathways (FDR q < 0.001). Our findings align with prior work, and also identify numerous novel associations, suggesting that genes important in growth and development, particularly neurodevelopment, are subject to substantial epigenetic changes during early development among children born VPT.

Disability In Cluster Headache Is More Than Attack Frequency – Results From And Validation Of The English Version Of The Cluster Headache Impact Questionnaire (Chiq), Katharina Kamm, Andreas Straube, Mark Burish, Ruth Ruscheweyh

Faculty, Staff and Student Publications

BACKGROUND: Cluster headache (CH) is associated with high disability. The Cluster Headache Impact Questionnaire (CHIQ) is a short, disease-specific disability questionnaire first developed and validated in German. Here, we validated the English version of this questionnaire.

METHODS: The CHIQ was assessed together with nonspecific headache-related disability questionnaires in CH patients from a tertiary headache center and an American self-help group.

RESULTS: 155 active episodic and chronic CH patients were included. The CHIQ showed good internal consistency (Cronbach's α = 0.91) and test-retest reliability (ICC = 0.93, n = 44). Factor analysis identified a single factor. Convergent validity was shown by …

Tumour-Intrinsic Endomembrane Trafficking By Arf6 Shapes An Immunosuppressive Microenvironment That Drives Melanomagenesis And Response To Checkpoint Blockade Therapy, Yinshen Wee, Junhua Wang, Emily C Wilson, Coulson P Rich, Aaron Rogers, Zongzhong Tong, Evelyn Degroot, Y N Vashisht Gopal, Michael A Davies, H Atakan Ekiz, Joshua K H Tay, Chris Stubben, Kenneth M Boucher, Juan M Oviedo, Keke C Fairfax, Matthew A Williams, Sheri L Holmen, Roger K Wolff, Allie H Grossmann

Faculty, Staff and Student Publications

Tumour-host immune interactions lead to complex changes in the tumour microenvironment (TME), impacting progression, metastasis and response to therapy. While it is clear that cancer cells can have the capacity to alter immune landscapes, our understanding of this process is incomplete. Herein we show that endocytic trafficking at the plasma membrane, mediated by the small GTPase ARF6, enables melanoma cells to impose an immunosuppressive TME that accelerates tumour development. This ARF6-dependent TME is vulnerable to immune checkpoint blockade therapy (ICB) but in murine melanoma, loss of Arf6 causes resistance to ICB. Likewise, downregulation of ARF6 in patient tumours correlates with …

Lipid Droplet-Associated Hydrolase Mobilizes Stores Of Liver X Receptor Sterol Ligands And Protects Against Atherosclerosis, Young-Hwa Goo, Janeesh Plakkal Ayyappan, Francis D Cheeran, Sushant Bangru, Pradip K Saha, Paula Baar, Sabine Schulz, Todd A Lydic, Bernhard Spengler, Andreas H Wagner, Auinash Kalsotra, Vijay K Yechoor, Antoni Paul

Faculty, Staff and Students Publications

Foam cells in atheroma are engorged with lipid droplets (LDs) that contain esters of regulatory lipids whose metabolism remains poorly understood. LD-associated hydrolase (LDAH) has a lipase structure and high affinity for LDs of foam cells. Using knockout and transgenic mice of both sexes, here we show that LDAH inhibits atherosclerosis development and promotes stable lesion architectures. Broad and targeted lipidomic analyzes of primary macrophages and comparative lipid profiling of atheroma identified a broad impact of LDAH on esterified sterols, including natural liver X receptor (LXR) sterol ligands. Transcriptomic analyzes coupled with rescue experiments show that LDAH modulates the expression …

G12/13 Signaling In Asthma, Elizabeth L. Mcduffie, Reynold A Panettieri, Charles P. Scott

Department of Biochemistry and Molecular Biology Faculty Papers

Shortening of airway smooth muscle and bronchoconstriction are pathognomonic for asthma. Airway shortening occurs through calcium-dependent activation of myosin light chain kinase, and RhoA-dependent calcium sensitization, which inhibits myosin light chain phosphatase. The mechanism through which pro-contractile stimuli activate calcium sensitization is poorly understood. Our review of the literature suggests that pro-contractile G protein coupled receptors likely signal through G12/13 to activate RhoA and mediate calcium sensitization. This hypothesis is consistent with the effects of pro-contractile agonists on RhoA and Rho kinase activation, actin polymerization and myosin light chain phosphorylation. Recognizing the likely role of G12/13 signaling in the pathophysiology …

Znf397 Deficiency Triggers Tet2-Driven Lineage Plasticity And Ar-Targeted Therapy Resistance In Prostate Cancer, Yaru Xu, Yuqiu Yang, Zhaoning Wang, Martin Sjöström, Yuyin Jiang, Yitao Tang, Siyuan Cheng, Su Deng, Choushi Wang, Julisa Gonzalez, Nickolas A Johnson, Xiang Li, Xiaoling Li, Lauren A Metang, Atreyi Mukherji, Quanhui Xu, Carla R Tirado, Garrett Wainwright, Xinzhe Yu, Spencer Barnes, Mia Hofstad, Yu Chen, Hong Zhu, Ariella B Hanker, Ganesh V Raj, Guanghui Zhu, Housheng H He, Zhao Wang, Carlos L Arteaga, Han Liang, Felix Y Feng, Yunguan Wang, Tao Wang, Ping Mu

Faculty, Staff and Students Publications

Cancer cells exhibit phenotypical plasticity and epigenetic reprogramming that allows them to evade lineage-dependent targeted treatments by adopting lineage plasticity. The underlying mechanisms by which cancer cells exploit the epigenetic regulatory machinery to acquire lineage plasticity and therapy resistance remain poorly understood. We identified zinc finger protein 397 (ZNF397) as a bona fide coactivator of the androgen receptor (AR), essential for the transcriptional program governing AR-driven luminal lineage. ZNF397 deficiency facilitates the transition of cancer cell from an AR-driven luminal lineage to a ten-eleven translocation 2 (TET2)-driven lineage plastic state, ultimately promoting resistance to therapies inhibiting AR signaling. Intriguingly, our …

Mucosal Immunization With Chad-Sars-Cov-2-S Prevents Sequential Transmission Of Sars-Cov-2 To Unvaccinated Hamsters, Tamarand L Darling, Houda H Harastani, Astha Joshi, Traci L Bricker, Nadia Soudani, Kuljeet Seehra, Ahmed O Hassan, Michael S Diamond, Adrianus C M Boon

2020-Current year OA Pubs

COVID-19 vaccines have successfully reduced severe disease and death after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Nonetheless, COVID-19 vaccines are variably effective in preventing transmission and symptomatic SARS-CoV-2 infection. Here, we evaluated the impact of mucosal or intramuscular vaccine immunization on airborne infection and transmission of SARS-CoV-2 in Syrian hamsters. Immunization of the primary contact hamsters with a mucosal chimpanzee adenoviral-vectored vaccine (ChAd-CoV-2-S), but not intramuscular messenger RNA (mRNA) vaccine, reduced infectious virus titers ~100-fold and 100,000-fold in the upper and lower respiratory tract of the primary contact hamster following SARS-CoV-2 exposure. This reduction in virus titer in …

Renal Mass Imaging Modalities: Does Body Mass Index (Bmi) Matter?, Young Son, Mark E. Quiring, Raeann M. Dalton, Brian Thomas, Noah Davidson, Dayna Devincentz, Collin Payne, Sahil H. Parikh, Benjamin A. Fink, Thomas Mueller, Gordon Brown

Jefferson Health - New Jersey Papers

PURPOSE: Accurate measurement of renal mass size is crucial in the management of renal cancer. With the burdensome cost of imaging yet its need for management, a better understanding of the variability among patients when determining mass size remains of urgent importance. Current guidelines on optimal imaging are limited, especially with respect to body mass index (BMI). The aim of this study is to discern which modalities accurately measure renal mass size and whether BMI influences such accuracy.

METHODS: A multi-institutional chart review was performed for adult patients undergoing partial or radical nephrectomy between 2018 and 2021, with 236 patients …

Assessing The Reproducibility Of Research Based On The Food And Drug Administration Manufacturer And User Facility Device Experience Data, Xinyu Li, Yubo Feng, Yang Gong, You Chen

Faculty, Staff and Student Publications

Objective: This article aims to assess the reproducibility of Manufacturer and User Facility Device Experience (MAUDE) data-driven studies by analyzing the data queries used in their research processes.

Methods: Studies using MAUDE data were sourced from PubMed by searching for "MAUDE" or "Manufacturer and User Facility Device Experience" in titles or abstracts. We manually chose articles with executable queries. The reproducibility of each query was assessed by replicating it in the MAUDE Application Programming Interface. The reproducibility of a query is determined by a reproducibility coefficient that ranges from 0.95 to 1.05. This coefficient is calculated by comparing the number …

A Cell Cycle-Aware Network For Data Integration And Label Transferring Of Single-Cell Rna-Seq And Atac-Seq, Jiajia Liu, Jian Ma, Jianguo Wen, Xiaobo Zhou

Faculty, Staff and Student Publications

In recent years, the integration of single-cell multi-omics data has provided a more comprehensive understanding of cell functions and internal regulatory mechanisms from a non-single omics perspective, but it still suffers many challenges, such as omics-variance, sparsity, cell heterogeneity, and confounding factors. As it is known, the cell cycle is regarded as a confounder when analyzing other factors in single-cell RNA-seq data, but it is not clear how it will work on the integrated single-cell multi-omics data. Here, a cell cycle-aware network (CCAN) is developed to remove cell cycle effects from the integrated single-cell multi-omics data while keeping the cell …

Patient-Centered Clinical Decision Support Challenges And Opportunities Identified From Workflow Execution Models, Dean F Sittig, Aziz Boxwala, Adam Wright, Courtney Zott, Nicole A Gauthreaux, James Swiger, Edwin A Lomotan, Prashila Dullabh

Faculty, Staff and Student Publications

OBJECTIVE: To use workflow execution models to highlight new considerations for patient-centered clinical decision support policies (PC CDS), processes, procedures, technology, and expertise required to support new workflows.

METHODS: To generate and refine models, we used (1) targeted literature reviews; (2) key informant interviews with 6 external PC CDS experts; (3) model refinement based on authors' experience; and (4) validation of the models by a 26-member steering committee.

RESULTS AND DISCUSSION: We identified 7 major issues that provide significant challenges and opportunities for healthcare systems, researchers, administrators, and health IT and app developers. Overcoming these challenges presents opportunities for new …

Privacy-Preserving Model Evaluation For Logistic And Linear Regression Using Homomorphically Encrypted Genotype Data, Seungwan Hong, Yoolim A Choi, Daniel S Joo, Gamze Gürsoy

Faculty, Staff and Student Publications

Objective: Linear and logistic regression are widely used statistical techniques in population genetics for analyzing genetic data and uncovering patterns and associations in large genetic datasets, such as identifying genetic variations linked to specific diseases or traits. However, obtaining statistically significant results from these studies requires large amounts of sensitive genotype and phenotype information from thousands of patients, which raises privacy concerns. Although cryptographic techniques such as homomorphic encryption offers a potential solution to the privacy concerns as it allows computations on encrypted data, previous methods leveraging homomorphic encryption have not addressed the confidentiality of shared models, which can leak …

Automatic Uncovering Of Patient Primary Concerns In Portal Messages Using A Fusion Framework Of Pretrained Language Modelsautomatic Uncovering Of Patient Primary Concerns In Portal Messages Using A Fusion Framework Of Pretrained Language Models, Yang Ren, Yuqi Wu, Jungwei W Fan, Aditya Khurana, Sunyang Fu, Dezhi Wu, Hongfang Liu, Ming Huang

Faculty, Staff and Student Publications

OBJECTIVES: The surge in patient portal messages (PPMs) with increasing needs and workloads for efficient PPM triage in healthcare settings has spurred the exploration of AI-driven solutions to streamline the healthcare workflow processes, ensuring timely responses to patients to satisfy their healthcare needs. However, there has been less focus on isolating and understanding patient primary concerns in PPMs-a practice which holds the potential to yield more nuanced insights and enhances the quality of healthcare delivery and patient-centered care.

MATERIALS AND METHODS: We propose a fusion framework to leverage pretrained language models (LMs) with different language advantages via a Convolution Neural …

Safety And Feasibility Of Third-Party Cytotoxic T Lymphocytes For High-Risk Patients With Covid-19, Dolores Grosso, John L. Wagner, Allyson O'Connor, Kaitlyn Keck, Yanping Huang, Zi-Xuan Wang, Hilary Mehler, Benjamin Leiby, Phyllis Flomenberg, Usama Gergis, Neda Nikbakht, Michael Morris, Julie Karp, Alexis R. Peedin, Neal Flomenberg

COVID-19 Papers, Posters, and Presentations

Cytotoxic T lymphocytes (CTLs) destroy virally infected cells and are critical for the elimination of viral infections such as those caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Delayed and dysfunctional adaptive immune responses to SARS-CoV-2 are associated with poor outcomes. Treatment with allogeneic SARS-CoV-2-specific CTLs may enhance cellular immunity in high-risk patients providing a safe, direct mechanism of treatment. Thirty high-risk ambulatory patients with COVID-19 were enrolled in a phase 1 trial assessing the safety of third party, SARS-CoV-2-specific CTLs. Twelve interventional patients, 6 of whom were immunocompromised, matched the HLA-A∗02:01 restriction of the CTLs and received …

Transformer-Based Deep Learning Prediction Of 10-Degree Humphrey Visual Field Tests From 24-Degree Data, Min Shi, Anagha Lokhande, Yu Tian, Yan Luo, Mohammad Eslami, Saber Kazeminasab, Tobias Elze, Lucy Shen, Louis Pasquale, Sarah Wellik, Carlos Gustavo De Moraes, Jonathan Myers, Nazlee Zebardast, David Friedman, Michael Boland, Mengyu Wang

Wills Eye Hospital Papers

PURPOSE: To predict 10-2 Humphrey visual fields (VFs) from 24-2 VFs and associated non-total deviation features using deep learning.

METHODS: We included 5189 reliable 24-2 and 10-2 VF pairs from 2236 patients, and 28,409 reliable pairs of macular OCT scans and 24-2 VF from 19,527 eyes of 11,560 patients. We developed a transformer-based deep learning model using 52 total deviation values and nine VF test features to predict 68 10-2 total deviation values. The mean absolute error, root mean square error, and the R2 were evaluation metrics. We further evaluated whether the predicted 10-2 VFs can improve the structure-function relationship …

A Content Analysis Of Self-Report Child Anxiety Measures, Minjee Kook, Jane W Clinger, Eric Lee, Sophie C Schneider, Eric A Storch, Andrew G Guzick

Faculty, Staff and Students Publications

A clear understanding of the item content of psychological assessments is critical but often overlooked. This study describes the content overlap of seven commonly used and psychometrically validated measures of anxiety among children and adolescents. Symptom codes were created for all items across measures and items were sorted by these codes, which all fell into specific symptom categories. We conducted two analyses of all items: a "bottom-up" content categorization approach, which used symptom categories that were developed during this study, and a "top-down" DSM-5 categorization which mapped items onto symptoms of anxiety disorders in the DSM-5. Findings reveal a weak …

Fathers In The United States Are Getting Older, Larry I Lipshultz, Blair T Stocks

Faculty, Staff and Students Publications

No abstract provided.

Sensory Symptoms Across The Lifespan In People With Cerebral Palsy, Ariel M Lyons-Warren, Danielle Guez-Barber, Sruthi P Thomas, Evelyne K Tantry, Aditya Mahat, Bhooma Aravamuthan

Faculty, Staff and Students Publications

Background: To estimate the prevalence of sensory symptoms in people with cerebral palsy (CP) across the lifespan.

Methods: In this cross-sectional study, the self-reported Sensory Processing Scale Inventory (SPS-I) was administered via Research Electronic Data Capture (REDCap) between February 1, 2022, and August 15, 2022, to people with CP or their caregivers enrolled in the online MyCP Community Registry. We determined the association between SPS-I scores and age (Pearson correlation) and functional status as assessed using five validated functional classification systems for CP (analysis of variance [ANOVA]). We hypothesized that sensory symptoms would differ between younger and older individuals with …

Amoxicillin And Penicillin G Dosing In Pediatric Community-Acquired Pneumococcal Pneumonia In The Era Of Conjugate Pneumococcal Vaccines, Dustin Huynh, Norint Tung, Quang Dam, Tri Tran, Kristina G Hulten, Christopher J Harrison, Sheldon L Kaplan, Allison Nguyen, Tyler H Do, Amartya Setty, Jennifer Le

Faculty, Staff and Students Publications

Background: Parenteral penicillin G (PENG) and oral amoxicillin (AMOX) are recommended as treatment for pediatric community-acquired pneumonia (CAP). With recent epidemiologic penicillin susceptibility data for Streptococcus pneumoniae, the most common etiology of CAP, the objective of this study was to evaluate optimal dosing regimens of PENG and AMOX based on population pharmacokinetics linked to current susceptibility data.

Methods: Using NONMEM v7.3, Monte Carlo simulations (N = 10,000) were conducted for AMOX 15 mg/kg/dose PO every 8 h (standard-dose), AMOX 45 mg/kg/dose PO every 12 h (high-dose), and PENG 62,500 units/kg/day IV every 6 h using six virtual subjects with ages …

The Role Of The Cerebellum In Learning To Predict Reward: Evidence From Cerebellar Ataxia, Jonathan Nicholas, Christian Amlang, Chi-Ying R Lin, Leila Montaser-Kouhsari, Natasha Desai, Ming-Kai Pan, Sheng-Han Kuo, Daphna Shohamy

Faculty, Staff and Students Publications

Recent findings in animals have challenged the traditional view of the cerebellum solely as the site of motor control, suggesting that the cerebellum may also be important for learning to predict reward from trial-and-error feedback. Yet, evidence for the role of the cerebellum in reward learning in humans is lacking. Moreover, open questions remain about which specific aspects of reward learning the cerebellum may contribute to. Here we address this gap through an investigation of multiple forms of reward learning in individuals with cerebellum dysfunction, represented by cerebellar ataxia cases. Nineteen participants with cerebellar ataxia and 57 age- and sex-matched …