Digital Commons Network^™

Biallelic Loss-Of-Function Variants In C19orf44 Lead To Retinal Degeneration, Hafiz Muhammad Jafar Hussain, Wang Meng, Yumei Li, Sabika Firasat, Mark E Pennesi, Michael B Gorin, Bin Guan, Rebecca Lynn Clark, Emma Fale-Olsen, Ranya Al Rawi, Aime Agather, Laryssa A Huryn, Paul Yang, Anna Matynia, Rui Chen

Faculty, Staff and Students Publications

Background: Inherited retinal diseases (IRDs) are a group of disorders often resulting in progressive vision loss, ultimately leading to blindness. A significant portion of their genetic causes remain unresolved, partly due to undiscovered disease-associated genes or variants. This study aimed to identify novel genetic links to IRDs.

Methods: All patients underwent comprehensive ophthalmological evaluation, including retinal imaging (fundus autofluorescence and macular optical coherence tomography) and electroretinogram testing. Whole exome sequencing and whole genome sequencing were performed on patients with clinically unsolved IRD, and data were analysed using an in-house pipeline to identify causal variants. Subsequently, Sanger sequencing was performed to …

Global Age-Sex-Specific All-Cause Mortality And Life Expectancy Estimates For 204 Countries And Territories And 660 Subnational Locations, 1950–2023: A Demographic Analysis For The Global Burden Of Disease Study 2023, Gbd 2023 Demographics Collaborators

Faculty, Staff and Students Publications

BACKGROUND: Comprehensive, comparable, and timely estimates of demographic metrics-including life expectancy and age-specific mortality-are essential for evaluating, understanding, and addressing trends in population health. The COVID-19 pandemic highlighted the importance of timely and all-cause mortality estimates for being able to respond to changing trends in health outcomes, showing a strong need for demographic analysis tools that can produce all-cause mortality estimates more rapidly with more readily available all-age vital registration (VR) data. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) is an ongoing research effort that quantifies human health by estimating a range of epidemiological quantities of …

The Fast And The Very Fast: High-Frequency Oscillations In Alzheimer's Disease, Manuel Silva-Pérez, Jeannie Chin

Faculty, Staff and Students Publications

Alzheimer's disease increases the risk of developing epilepsy together with cognitive decline. Early diagnosis or prediction of parameters associated with epileptic activity can greatly help in managing disease outcomes. Network hyperexcitability is a candidate of interest as a neurophysiological biomarker of Alzheimer's disease. High-frequency oscillations are increasingly recognized as potential biomarkers of hyperexcitability and epileptic activity. However, they have not yet been identified in Alzheimer's disease. In this study, we measured high-frequency oscillations via magnetoencephalography recordings in Alzheimer's disease patients with and without epileptic activity, as part of a Phase 2a randomized, double blind clinical trial of the efficacy of …

Cep76 Impairment At The Centrosome-Cilium Interface Contributes To A Spectrum Of Ciliopathies, Kamal Khan, Erika Tavares, Katherine Bishara, Aysegul Ozanturk, Leila Qebibo, Stephan Frangakis, Daniel G Calame, Isabelle Meunier, Béatrice Bocquet, Rafal Ploski, Mohammad Ayman Al Khateeb, Dana Marafi, Luke Mansard, Lena Damaj, Richard A Lewis, Farid Ullah, Thomas Arbogast, Jackson P Ogden, Madeleine Harion, Marjolaine Willems, Maha S Zaki, Tobias Bartolomaeus, Anne-Françoise Roux, James R Lupski, Malgorzata Rydzanicz, Rami Abou Jamra, Francis Ramond, Elise Heon, Lydie Burglen, Erica E Davis

Faculty, Staff and Students Publications

Dysfunction at the centrosome-cilium interface underlies a broad range of ciliopathies. Here, we identify biallelic variants in CEP76, encoding a centrosomal protein, in eight unrelated individuals presenting with neurodevelopmental, ocular, and variable additional multisystem features. Proband-derived fibroblasts and CEP76-depleted RPE1 cells display ciliary deficits, including impaired cilium formation and length, disrupted transition zone architecture, and impaired IFT88-mediated anterograde intraflagellar transport. Zebrafish cep76 mutants recapitulate key clinical phenotypes, and in vitro complementation assays confirm pathogenicity for all tested human disease-associated variants. Proteomics analysis identifies CEP76 interactors, including known partners CCP110 and CEP97, and highlights clinically and functionally relevant candidates, including …

A Case Study Of Ai-Enabled Software As A Medical Device Cleared By The Fda For Assessing Hemorrhage Risk Index (Appraise-Hri) After Trauma, Andrew Frock, Jeffrey T Robbins, Francisco G Vital-Lopez, Valmik Desai, Gheorghe Doros, Barry E Sands, Arunkumar Prabhakaran, Christopher Nemeth, Gregory T Rule, Jason L Sperry, Francis X Guyette, Stephen R Wisniewski, Ernest E Moore, Martin Schreiber, Bellal Joseph, Chad T Wilson, Bryan Cotton, Daniel Ostermayer, Brian G Harbrecht, Mayur B Patel, Suzanne Tamang, Sanjay Malunjkar, David A Spain, Andrew T Reisner, Jonathan D Stallings, Jaques Reifman

Faculty, Staff and Student Publications

Hemorrhage is the leading cause of preventable death on the battlefield, yet combat medics lack clinical decision support systems to help stratify hemorrhage risk in trauma casualties. We previously trained the Automated Processing of the Physiological Registry for Assessment of Injury Severity - Hemorrhage Risk Index (APPRAISE-HRI) software to associate patterns in vital signs (heart rate and blood pressure) collected from trauma patients with three HRI levels: I (low), II (average), or III (high). To independently validate APPRAISE-HRI and obtain U.S. Food and Drug Administration (FDA) clearance, we collected trauma registry and continuous vital sign data from 5895 trauma patients …

A Pooled Sample Study Of Opioid Use Disorder Treatment Wait Time Among A Pregnant Population In New York, Stanley Nkemjika, Gulshan Begum, Bolaji Yoade, Vaibhav Vyas, Henry Onyeaka, Olubusola Olatunji, Olaniyi Olayinka, Ayana Jordan

Faculty, Staff and Student Publications

Background and Aim: Opioid use disorder (OUD) during pregnancy has become a major public health issue, with its prevalence rising significantly in recent years. The incidence of neonatal abstinence syndrome (NAS) has also surged, from 1.5 cases per 1000 hospital births in 1999 to 6.0 cases per 1000 in 2013. This study aims to identify and analyze the concerns faced by pregnant people in accessing OUD treatment on time, specifically focusing on New York.

Methods: The pooled sample of 225,275 individuals represents pregnant patients with OUD who received treatment at substance use disorder (SUD) facilities across New York State between …

Equal Survival For Black Americans With Multiple Myeloma When Appropriately Matched To White Americans, David E Mery, Guido Tricot, Samer Al Hadidi, Yihao Zhan, Cody Ashby, Clyde Bailey, Eric R Siegel, Daisy V Alapat, Hongwei Xu, Sandra Mattox, Caroline Schinke, Maurizio Zangari, Sharmilan Thanendrarajan, Qing Yi, Robert Z Orlowski, Frits Van Rhee, John D Shaughnessy, Fenghuang Zhan

Faculty, Staff and Student Publications

No abstract provided.

Dietary Patterns For Weight And Glycemic Management In Persons With Type 1 Diabetes: A Meta-Analysis Of Clinical Trials, Daria Igudesman, Laura M Nally, Alyssa A Grimshaw, Craig G Gunderson, Elizabeth G Considine, Laura M Jacobsen, Mustafa Tosur, Peter A Gottlieb, Irl B Hirsch, Lori M Laffel, Jennifer L Sherr, Chantal Mathieu, Richard E Pratley

Children’s Nutrition Research Center Staff Publications

Background: Medical nutrition therapy is fundamental for managing glycemia and weight in type 1 diabetes, yet dietary guidance specific to this population and relevant subgroups is lacking.

Purpose: We synthesized the interventional literature investigating diet patterns for glycemic and weight management in youth and adults with type 1 diabetes, with attention to interindividual variation that suggests the need for precision approaches. The protocol was prospectively registered (CRD42024519941).

Data sources: AMED, CINAHL, Cochrane Library, Ovid MEDLINE, Ovid Embase, Google Scholar, and Web of Science Core Collection were searched from January 2011 to June 2024.

Study selection: Clinical trials ≥4 weeks with …

Introducing Mcodegpt As A Zero-Shot Information Extraction From Clinical Free Text Data Tool For Cancer Research, Kai Zhang, Tongtong Huang, Bradley A Malin, Travis Osterman, Qi Long, Xiaoqian Jiang

Faculty, Staff and Student Publications

Background: The vast amount of natural language clinical notes about patients with cancer presents a challenge for efficient information extraction, standardization, and structuring. Traditional NLP methods require extensive annotation by domain experts for each type of named entity and necessitate model training, highlighting the need for an efficient and accurate extraction method.

Methods: This study introduces a tool based on the Large Language Model (LLM) for zero-shot information extraction from cancer-related clinical notes into structured data aligned with the minimal Common Oncology Data Elements (mCODE™) structure. We utilize the zero-shot learning capabilities of LLMs for information extraction, eliminating the need …

Strategies For Addressing Covid-19 Vaccine Equity With Intermediaries, Prevention Research Centers, And The Vaccine Confidence Network, Kelianne K Hara-Hubbard, Allison Beaulieu, Anais Mendiola, Pooja Gandhi, Nicole Kuiper, Richard Quartarone, Jinni Tang, Olivia Dominguez, Maritza Bond, Dorothy Cohen, Margaret Goetz, Nasra Mohamed, Paula Cuccaro, Peggy A Hannon, Maria E Fernandez, Jackson Higginbottom, Rafael Pérez-Escamilla, Bárbara Baquero

Faculty, Staff and Student Publications

In April 2021, the CDC provided supplemental funding to all 26 Prevention Research Centers (PRCs) to create the PRC Vaccine Confidence Network (VCN) to increase COVID-19 vaccine confidence and uptake in communities disparately impacted by COVID-19 and/or in vaccine hesitant populations. A key strategy to building vaccine confidence was engaging with intermediaries (i.e., mutually trusted community and practice-based organizations conducting community outreach and intervention activities) to address barriers for our shared communities of focus. These intermediaries were key in building community trust, addressing community needs and concerns, and in turn, building vaccine confidence and demand in areas and communities disproportionately …

Stereoelectroencephalography Reveals Neural Signatures Of Multisensory Integration In The Human Superior Temporal Sulcus During Audiovisual Speech Perception, Yue Zhang, John F Magnotti, Xiang Zhang, Zhengjia Wang, Yingjia Yu, Kathryn A Davis, Sameer A Sheth, H Isaac Chen, Daniel Yoshor, Michael S Beauchamp

Faculty, Staff and Students Publications

Human speech perception is multisensory, integrating auditory information from the talker's voice with visual information from the talker's face. BOLD fMRI studies have implicated the superior temporal gyrus (STG) in processing auditory speech and the superior temporal sulcus (STS) in integrating auditory and visual speech, but as an indirect hemodynamic measure, fMRI is limited in its ability to track the rapid neural computations underlying speech perception. Using stereoelectroencephalography (sEEG) electrodes, we directly recorded from the STG and STS in 42 epilepsy patients (25F, 17M). Participants identified single words presented in auditory, visual, and audiovisual formats with and without added auditory …

Correction: Román-Ríos Et Al., Gabriel Román-Ríos, Gabriel Rosario-Ortiz, Marcos J Ramos-Benitez, Ricardo A Mosquera, Wilfredo De Jesús-Rojas

Faculty, Staff and Student Publications

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Sub-Ciliary Localization Of Cep290 And Effects Of Its Loss In Mouse Photoreceptors During Development, Abigail R. Moye, Michael A. Robichaux, Melina A. Agosto, Alexandre P. Moulin, Alexandra Graff-Meyer, Carlo Rivolta, Theodore G. Wensel

Faculty, Staff and Students Publications

No abstract provided.

Resilience And Vulnerabilities Of Tumor Cells Under Purine Shortage Stress, Jianpeng Yu, Chen Jin, Cheng Su, David Moon, Michael A Sun, Hong Zhang, Xue Jiang, Fan Zhang, Nomi Tserentsoodol, Michelle L Bowie, Christopher J Pirozzi, Daniel J George, Robert Wild, Xia Gao, David M Ashley, Yiping He, Jiaoti Huang

Faculty, Staff and Students Publications

Purpose: Purine metabolism is a promising therapeutic target in cancer; however, how cancer cells respond to purine shortage, particularly their adaptation and vulnerabilities, remains unclear.

Experimental design: Using the recently developed purine shortage-inducing prodrug DRP-104 and genetic approaches, we investigated the responses in prostate, lung, and glioma cancer models.

Results: We demonstrate that when de novo purine biosynthesis is compromised, cancer cells employ microtubules to assemble purinosomes, multiprotein complexes of de novo purine biosynthesis enzymes that enhance purine biosynthesis efficiency. Although this process enables tumor cells to adapt to purine shortage stress, it also renders them more susceptible to the …

Predictors Of Long-Term Follow-Up Clinic Attendance And Continued Engagement Among Survivors Of Cancer In Childhood And Adolescence, Ji Yun Tark, Kayla L Foster, Shawki L Qasim, Omar Shakeel, Alicia Howell, Mary C Shapiro, Abiodun Oluyomi, Zoann E Dreyer, Ashley M Butler, Austin L Brown, Maria M Gramatges

Faculty, Staff and Students Publications

Purpose: Survivorship care is vital to screen for and manage late effects, yet follow-up remains suboptimal. We examined factors associated with long-term survivor clinic (LTSC) nonattendance, delayed initiation, and disengagement at a large, diverse pediatric cancer center.

Methods: We analyzed outcomes in 1138 survivorship-eligible childhood cancer survivors diagnosed between 2011 and 2019. Outcomes included (1) LTSC nonattendance (no visit ≥ 2 years post-treatment), (2) delayed LTSC visit initiation (first visit > 5 years from end of treatment), and (3) LTSC visit disengagement (no follow-up after initial LTSC visit). Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for factors associated with …

Alterations Of The Upper Respiratory Microbiome Among Children Living With Hiv Infection In Botswana, Sweta M Patel, John Farirai, Mohamed Z Patel, Sifelane Boiditswe, Leabaneng Tawe, Shimane Lekalake, Mogomotsi Matshaba, Andrew P Steenhoff, Tonya Arscott-Mills, Kristen A Feemster, Samir S Shah, Nathan Thielman, Coleen K Cunningham, Lawrence A David, David M Murdoch, Matthew S Kelly

Faculty, Staff and Students Publications

Children living with HIV (CLWH) are at high risk of colonization and infection by respiratory pathogens, though this risk can be reduced by other microbes in the upper respiratory microbiome. The impact of HIV infection on the pediatric upper respiratory microbiome is poorly understood, and we sought to address this knowledge gap by identifying associations between HIV infection and the nasopharyngeal microbiomes of Batswana children. We enrolled Batswana CLWH (< 5 years) and age- and sex-matched HIV-exposed, uninfected and HIV-unexposed, uninfected children in a cross-sectional study. We used shotgun metagenomic sequencing to compare nasopharyngeal microbiomes by HIV status. Among the 143 children in this study, HIV and HIV-associated immunosuppression were associated with alterations in nasopharyngeal microbiome composition, including lower abundances of Corynebacterium species associated with resistance to bacterial pathogen colonization. These findings suggest that the upper respiratory microbiome may contribute to the high risk of respiratory infections among CLWH.

Generative Modeling For Interpretable Anomaly Detection In Medical Imaging: Applications In Failure Detection And Data Curation, Mckell E Woodland, Mais Altaie, Caleb S O'Connor, Austin H Castelo, Olubunmi C Lebimoyo, Aashish C Gupta, Joshua P Yung, Paul E Kinahan, Clifton D Fuller, Eugene J Koay, Bruno C Odisio, Ankit B Patel, Kristy K Brock

Faculty, Staff and Students Publications

This work aims to leverage generative modeling-based anomaly detection to enhance interpretability in AI failure detection systems and to aid data curation for large repositories. For failure detection interpretability, this retrospective study utilized 3339 CT scans (525 patients), divided patient-wise into training, baseline test, and anomaly (having failure-causing attributes—e.g., needles, ascites) test datasets. For data curation, 112,120 ChestX-ray14 radiographs were used for training and 2036 radiographs from the Medical Imaging and Data Resource Center for testing, categorized as baseline or anomalous based on attribute alignment with ChestX-ray14. StyleGAN2 networks modeled the training distributions. Test images were reconstructed with backpropagation and …

Understanding The Nutrition Ecology And Related Distal And Proximal Research Gaps Impacting School-Aged Children's And Adolescents' Functioning-A Report From The "Biomarkers Of Nutrition For Development: Knowledge Indicating Dietary Sufficiency (Bond-Kids)" Project Working Group 2., Maureen M Black, Meg M Bruening, Amy Carroll-Scott, Jayna M Dave, Kristie L Ebi, Lora L Iannotti, Susan L Johnson, Lorrene D Ritchie, Elizabeth Y Jimenez, Alison L Steiber, Daniel J Raiten

Children’s Nutrition Research Center Staff Publications

Nutrition is critical to the health, development, and well-being of children and adolescents, operating through nutrients and the social and physical influences of dietary behaviors. Child and adolescent growth and development depend on complex biological systems interacting with the nutrition ecology. In this review, we focus on bidirectional interactions with the multilevel nutrition ecology, including distal systems (climate, geopolitical, and food systems) and proximal systems (community food options; health, social, and food services; and school policies and programs), all mediated by the family. Thus, the impact of nutrition on children's and adolescents' functional outcomes is dependent on understanding the multilevel …

Inhibition Of Osteosarcoma Lung Metastases By Β-Glucan And Cd40 Agonist Is Mediated By Activation Of Macrophages And Nk Cells, Pradeep Shrestha, Rejeena Shrestha, Eugenie S Kleinerman

Faculty, Staff and Student Publications

Background: Osteosarcoma (OS) lung metastases remain a significant therapeutic challenge. Innate immune activation is a promising therapeutic approach. Innate immune agonists can modulate the tumor immune microenvironment and improve therapeutic response.

Methods: Using an experimental syngeneic OS lung metastasis BALB/c mouse model with K7M3-luc OS cells, we evaluated the antitumor effects of yeast-derived particulate β-glucan in prevention and therapeutic settings. We then assessed whether the CD40 agonist (CD40a) in combination with β-glucan increased therapeutic response in two different immune-competent mouse models of OS lung tumor burden.

Results: In the pretreatment settings, mice treated with β-glucan prior to OS cell infusion …

A Safety-Ii Approach To Learn From Practice Variation In The Diagnostic Process In The Emergency Department: An Action Research Study, Rick Roos, Laura Zwaan, Myrthe Maranus, Iwan A Meynaar, Vanessa J Valk, Cees Van Nieuwkoop, Gert-Jan Kamps, Hardeep Singh, Maarten O Van Aken

Faculty, Staff and Students Publications

Objectives: The focus on improving patient safety has mainly been by learning from errors and near misses (Safety-I). We applied a novel Safety-II approach to identify and learn from practice variations in the diagnostic process in the emergency department (ED), and subsequently design and implement practice changes.

Methods: In this single-center study, we used action research (cycles of micro-experiments to study and improve processes with active stakeholder involvement) in the diagnostic process. We used three subsequent observation cycles of the following six steps: observations, gathering of follow-up data, analyses, a co-creation session with involved stakeholders, sharing of best practices, and …

Risk Factors And Clinical Significance Of Urologic Injury In Cesarean Hysterectomy For Placenta Accreta Spectrum, J Connor Mulhall, Kayla E Ireland, John J Byrne, Patrick S Ramsey, Georgia A Mccann, Jessian L Munoz

Faculty, Staff and Students Publications

Background/Objectives: Placenta accreta spectrum (PAS) is an obstetric condition with placental adherence to the underling myometrium characterized by significant surgical morbidity at time of delivery. PAS delivery is most commonly performed by cesarean hysterectomy. The most common morbidities associated with PAS cesarean hysterectomy are blood transfusion, intensive care unit admission and urinary tract injuries. This requires interdisciplinary team management including obstetricians and urologists. Our objective was to identify pre- and intra-operative risk factors for urologic injury in this high-risk condition.

Methods: A retrospective cohort study was performed at a single tertiary center with the Center for the Management …

Advancements In Prenatal Genetic Screening And Testing: Emerging Technologies And Evolving Applications, Mona M Makhamreh, Mei Ling Chong, Ignatia B Van Den Veyver

Duncan NRI Faculty and Staff Publications

Advancements in genomic technologies have transformed prenatal genetic testing, offering more accurate, comprehensive, and noninvasive approaches to reproductive care. This review provides an in-depth overview of current methodologies and emerging innovations, including expanded carrier screening (ECS), cell-free DNA (cfDNA) testing, chromosomal microarray analysis (CMA), and sequencing-based diagnostics. We highlight how next-generation sequencing (NGS) technologies have revolutionized carrier screening and fetal genome analysis, enabling detection of a broad spectrum of genetic conditions. The clinical implementation of cfDNA has expanded from common aneuploidies to include copy number variants (CNVs), and single-gene disorders. Diagnostic testing has similarly evolved, with genome sequencing outperforming traditional …

Genetic Engineering Of Esophageal Organoids: Crispr-Based Knock-In For Cell Lineage Tracing, Kyung-Pil Ko, Jae-Il Park

Faculty, Staff and Student Publications

Esophageal organoids serve as powerful systems to study epithelial lineage hierarchies and cancer biology. Gene manipulation in these organoids has traditionally involved overexpression or knockout strategies. However, CRISPR-/Cas9-based knock-in (KI) approaches now enable precise cell lineage tracing and live imaging. Here, we describe protocols to generate fluorescent KI organoids from murine esophageal epithelium by tagging Krt13 (BFP) and Sox2 (mNeon). These dual-reporter organoids allow direct monitoring of growth dynamics and differentiation trajectories. We outline CRISPR/Cas9 design, donor construction using homology-independent approaches (CRISPaint), delivery into organoid cells, enrichment and single-clone isolation, and validation by fluorescence. For organoids, homology-directed repair (HDR) can …

Establishing Priority Pediatric Antimicrobial Stewardship Interventions In The Us: Findings From A Delphi Consensus Study, Harry Obeng, Emmanuel Tetteh, Sara Malone, Lauren Walsh, Tyler Walsh, Fernando J Bula-Rudas, Ritu Banerjee, Adam W Brothers, Joshua C Herigon, Katie Namtu, Scott Weissman, Daniel Riggsbee, Jared Olson, Debra Lynn Palazzi, Ann Wirtz, Matthew Sattler, Jessica Tansmore, Brittany A Rodriguez, Monica Abdelnour, Joshua R Watson, Alison C Tribble, Jessica Gillon, Mari Nakamura, Sarah Jones, Jason G Newland, Virginia R Mckay

Faculty, Staff and Students Publications

Background/objectives: Antimicrobial resistance (AMR) is a major global health threat, with children at higher risk due to developmental differences in drug metabolism, limited treatment options and inappropriate antibiotic use. Pediatric antimicrobial stewardship programs (ASPs) face implementation challenges, often relying on adult-based guidelines and limited pediatric-specific evidence. This study aimed to identify and prioritize the most critical areas for pediatric ASP intervention development through a structured, multi-round Delphi consensus process with experts in antimicrobial stewardship and infectious diseases.

Method: A four-round modified Delphi process was conducted to identify and prioritize key pediatric ASP interventions. Experts in antimicrobial stewardship and infectious diseases …

Ligand-Receptor Interactions Induce And Mediate Regulatory Functions Of Batf3+ B Cells, Hui Yan, Rui Wang, Suryavathi Viswanadhapalli, Christian Cervantes, Funan He, Shuai Wu, Azad Khosh, Weiwei Luo, Jingwei Wang, Maria J Fernandez, Uday P Pratap, Mustafa Khan, Karli Hinton, Sai Eashan Vankamamidi, Dariela Perez, Carlos E Rivera, Harshita B Gupta, Fushun Zhang, Zhenqing Ye, Yidong Chen, Xiao-Dong Li, Gangadhara R Sareddy, Hong Zan, Yue Li, Exing Wang, Evelien M Bunnik, Guangming Zhong, Christopher A Hunter, Ross M Kedl, Zhinan Yin, Booki Min, Diako Ebrahimi, Siyuan Zheng, Tyler J Curiel, Yan Xiang, Ratna K Vadlamudi, Paolo Casali, Zhenming Xu

Faculty, Staff and Student Publications

B cells express many protein ligands, yet their regulatory functions are incompletely understood. We profiled ligand expression across murine B sublineage cells, including those activated by defined receptor signals, and assessed their regulatory capacities and specificities through in silico analysis of ligand-receptor interactions. Consequently, we identified a B cell subset that expressed cytokine interleukin-27 (IL-27) and chemokine CXCL10. Through the IL-27–IL-27 receptor interaction, these IL-27/CXCL10-producing B cells targeted CD40-activated B cells in vitro and, upon induction by immunization and viral infection, optimized antibody responses and antiviral immunity in vivo. Also present in breast cancer tumors and retained there through CXCL10-CXCR3 …

Vaccine And Treatment Evaluation Units: A Historical Perspective, Robert B Belshe, David I Bernstein, Kathryn M Edwards, Sharon E Frey, Wendy A Keitel, Myron M Levine, John J Treanor, Peter F Wright

Faculty, Staff and Students Publications

On 27 February 1962, Surgeon General Luther Terry announced a new vaccine development program within the National Institute of Allergy and Infectious Diseases (NIAID). Initially, the plan had three components: (1) special laboratories and facilities for development of prototype vaccines; (2) pilot lot production facilities and preliminary vaccine trial sites; and (3) larger lot production capacity and expanded human testing. Respiratory viruses were targeted as the top priority for vaccine development. Over 5 decades, this program has evolved and expanded to include multiple academic vaccine evaluation sites within the network, now labeled as the Vaccine and Treatment Evaluation Units (VTEUs). …

Just-In-Time Adaptive Intervention To Improve Hiv Prevention And Substance Use In Youth Experiencing Homelessness (My-Ride): Protocol For A Randomized Controlled Trial, Diane Santa Maria, Nikhil Padhye, Michael Businelle, Natasha Slesnick, Stefani Ricondo, Marguerita Lightfoot

Faculty, Staff and Students Publications

Background: Youth who are experiencing homelessness face a higher risk of HIV infection compared to their housed peers, and suicide and overdose remain the leading causes of death among homeless youth. Just-in-Time Adaptive Interventions (JITAIs) are gaining momentum for HIV prevention and substance use research. Yet, most interventions for homeless youth have not addressed modifiable real-time factors.

Objective: This paper describes the development and implementation of a randomized attention-controlled trial to assess the efficacy of motivating youth to reduce infections, disconnections, and emotional dysregulation (MY-RIDE), a JITAI to improve HIV prevention and substance use in homeless youth.

Methods: This study …

The Role Of Traumatic Brain Injury On Intimate Partner Violence And Changes In Mental Health From Late Adolescence To Young Adulthood, Eric J Connolly, Elizabeth Baumler, Deborah M Little, Meghan L Royle, Anne C Wingert, Leila Wood, Jeff R Temple

Faculty, Staff and Student Publications

Purpose: Intimate partner violence (IPV) victimization and traumatic brain injury (TBI) are common correlates of mental health problems in adolescence. However, research has yet to investigate whether IPV victimization is related to developmental changes in mental health, as well as the contributing role that TBI may play in conditioning this association. We address this gap by analyzing longitudinal data with well-validated measures of mental health from an ethnically diverse sample of adolescents.

Methods: Prospective data from the Dating it Safe sample (n = 699) were used to measure IPV victimization, depression, post-traumatic stress, binge drinking, and TBI from 2015 to …

Germline Determinants Of Toxicity And Efficacy In Patients With Large B-Cell Lymphoma Treated With Car T-Cell Therapy, Paolo Strati, Amanda Brandt, Anath C Lionel, Jared Henderson, Jason R Westin, Sherry Adkins, Elizabeth J Shpall, Partow Kebriaei, Jeremy Ramdial, Neeraj Saini, Sairah Ahmed, Christopher Flowers, Sattva S Neelapu, Michelle A T Hildebrandt

Faculty, Staff and Student Publications

Background: Recent data have suggested that germline genetic aberrations can affect outcomes in patients with large B-cell lymphoma (LBCL) treated with chimeric antigen receptor T-cell therapy (CART). However, a comprehensive analysis of germline determinants of response and toxicity after CART has not yet been described.

Methods: Genome-wide genotyping was performed in 170 patients with LBCL treated with standard of care axicabtagene ciloleucel. Polygenic risk score instruments for blood cell traits and inflammatory markers were obtained from the PGS Catalog and analyzed using PRSice-2. Exploratory gene-based and genome-wide association study analyses were performed. Genetic ancestry of the patients with LBCL was …

Sers And Seira Detection Of Polycyclic Aromatic Hydrocarbons And Their Derivatives In Murine Tissues: Bioaccumulation And Clearance, Oara Neumann, Andrés B Sánchez-Alvarado, Weiwu Jiang, Guo Dong Zhou, Sachin B Jorveka, Parmeet Dhindsa, Nagireddy Putluri, Peter Nordlander, Melissa A Suter, Bhagavatula Moorthy, Naomi J Halas

Faculty, Staff and Students Publications

The toxicological effects of polycyclic aromatic hydrocarbons (PAHs) and polycyclic aromatic compounds (PACs) have attracted considerable research interest due to their known bioaccumulation. However, time-resolved and longitudinal studies that examine in vivo bioaccumulation and clearance remain limited. Here we use Surface-Enhanced Raman Scattering (SERS) and Surface-Enhanced Infrared Absorption (SEIRA) spectroscopies to detect and track the presence of two PAHs: pyrene, benzo[a]pyrene, and one PAC: 5,12-naphthacenequinone, in murine organ tissues. Mice were exposed to a three-component mixture of these three chemicals, then their organs were collected at 24-, 48-, and 72- hours post-exposure. The accumulation of each of these chemicals in …