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Characterizing Phosphorus Removal And Recovery Performance Of A 3d Printed Iron-Embedded Polylactic Acid Composite, Colin B. Wilson, Anthony J. Parolari, Andrew Hiestand, Brooke K. Mayer, Allison Murray Feb 2025

Characterizing Phosphorus Removal And Recovery Performance Of A 3d Printed Iron-Embedded Polylactic Acid Composite, Colin B. Wilson, Anthony J. Parolari, Andrew Hiestand, Brooke K. Mayer, Allison Murray

Civil and Environmental Engineering Faculty Research and Publications

Green infrastructure (GI) has been heralded as a solution for reducing phosphorus (P) pollution through increasing stormwater runoff infiltration and improving water quality. Despite its global implementation, GI struggles to improve the effluent water quality discharged from these systems consistently. This research evaluates the P removal performance and recovery potential of iron-embedded polylactic acid (PLA) composites through a novel application of three-dimensional (3D) printed representative unit cells (RUC) that could be used to improve effluent quality in GI. The RUC required chemical oxidation to convert the embedded iron to hematite (Fe2⁢O3) to facilitate P adsorption. Batch …


Respuesta A Una Crítica Política Y A Un Ataque Personal Contra Un Informe De Las Naciones Unidas Que Presenta Nueva Evidencia Sobre La Prostitución Como Causa Y Consecuencia De La Violencia Contra Las Mujeres Y Las Niñas, Reem Alsalem Feb 2025

Respuesta A Una Crítica Política Y A Un Ataque Personal Contra Un Informe De Las Naciones Unidas Que Presenta Nueva Evidencia Sobre La Prostitución Como Causa Y Consecuencia De La Violencia Contra Las Mujeres Y Las Niñas, Reem Alsalem

Dignity: A Journal of Analysis of Exploitation and Violence

Reem Alsalem, Relatora Especial de las Naciones Unidas sobre la violencia contra las mujeres y las niñas, sus causas y consecuencias, responde a las acusaciones falsas y infundadas y a los ataques personales sobre su informe sobre Prostitución y Violencia contra la Mujer, presentado ante la 56ª sesión del Consejo de Derechos Humanos de las Naciones Unidas en Ginebra, 2024. Presenté nueva evidencia sobre la relación entre la violencia contra las mujeres y las niñas y la prostitución. Utilizando el derecho de los derechos humanos, el informe describe la prostitución como un sistema de abuso, explotación y violencia contra las …


A Switch Protein Adapter For Anti-Lilrb4 Car-T Cells, Ryan Huang, Heyu Chen, Jingjing Xie, Qi Lou, Lingxiao Tan, Ningyan Zhang, Zhiqiang An, Samuel John, Cheng Cheng Zhang Feb 2025

A Switch Protein Adapter For Anti-Lilrb4 Car-T Cells, Ryan Huang, Heyu Chen, Jingjing Xie, Qi Lou, Lingxiao Tan, Ningyan Zhang, Zhiqiang An, Samuel John, Cheng Cheng Zhang

The Brown Foundation: Institute of Molecular Medicine

Chimeric antigen receptor-T cell (CAR-T) immunotherapy has shown remarkable results for the treatment of certain hematologic malignancies. A redirection strategy that utilizes clinically relevant CAR-T cells in combination with adapter proteins may be an effective strategy to target other hematologic and solid cancers. We established a fusion antibody-based strategy with flexibility to target multiple tumor types in combination with a novel anti-leukocyte immunoglobulin-like receptor-B 4 (LILRB4) CAR-T cell. Specifically, we engineered switch protein (SwP) adapters containing the LILRB4 extracellular domain fused to either an anti-CD19 or anti-CD20 single-chain variable fragment (scFv). These SwPs were sufficient to stimulate anti-LILRB4 CAR-T cells …


Leucine-Rich Alpha-2-Glycoprotein 1 Promotes Metastatic Colorectal Cancer Growth Through Human Epidermal Growth Factor Receptor 3 Signaling, Moeez Rathore, Kimberly Curry, Wei Huang, Michel'le Wright, Daniel Martin, Jiyeon Baek, Derek Taylor, Masaru Miyagi, Wen Tang, Hao Feng, Yamu Li, Zhenghe Wang, Hallie Graor, Joseph Willis, Elizabeth Bryson, Christina S Boutros, Omkar Desai, Bianca N Islam, Lee M Ellis, Stephen E Moss, Jordan M Winter, John Greenwood, Rui Wang Feb 2025

Leucine-Rich Alpha-2-Glycoprotein 1 Promotes Metastatic Colorectal Cancer Growth Through Human Epidermal Growth Factor Receptor 3 Signaling, Moeez Rathore, Kimberly Curry, Wei Huang, Michel'le Wright, Daniel Martin, Jiyeon Baek, Derek Taylor, Masaru Miyagi, Wen Tang, Hao Feng, Yamu Li, Zhenghe Wang, Hallie Graor, Joseph Willis, Elizabeth Bryson, Christina S Boutros, Omkar Desai, Bianca N Islam, Lee M Ellis, Stephen E Moss, Jordan M Winter, John Greenwood, Rui Wang

Faculty, Staff and Student Publications

Background & aims: Therapy failure in patients with metastatic colorectal cancer (mCRC, ∼80% occur in the liver) remains an overarching challenge. Preclinical studies demonstrated that human epidermal growth factor receptor 3 (HER3) promotes colorectal cancer (CRC) cell survival, but therapies blocking the neuregulin-induced canonical HER3 signaling have made little impact in the clinic. Recent studies suggest that the liver microenvironment promotes CRC growth by activating HER3 in a neuregulin-independent fashion, thus elucidation of these mechanisms may reveal new strategies for treating patients with mCRC.

Methods: Patient-derived primary liver endothelial cells (ECs) were used to interrogate EC-CRC crosstalk. We conducted proteomic …


In Vitro Hydrolysis Of Areca Nut Xenobiotics In Human Liver, Vincenzo Paolillo, Mahendran Jayakumar, Colton Sheperd, Andrew Tran, Stephanie Hoang, Nhu Dao, Parag Jain, Alan L Myers Feb 2025

In Vitro Hydrolysis Of Areca Nut Xenobiotics In Human Liver, Vincenzo Paolillo, Mahendran Jayakumar, Colton Sheperd, Andrew Tran, Stephanie Hoang, Nhu Dao, Parag Jain, Alan L Myers

Faculty, Staff and Student Publications

Areca nut (AN) is a substance of abuse consumed by millions worldwide, in spite of established oral and systemic toxicities associated with its use. Previous research demonstrates methyl ester alkaloids in the AN, such as arecoline and guvacoline, exhibit mood-altering and toxicological effects. Nonetheless, their metabolism has not been fully elucidated in humans. In the present study, an HPLC-UV bioanalytical method was developed to evaluate the hydrolytic kinetics and clearance rates of arecoline and guvacoline in human liver microsomes (HLM) and cytosol (HLC). The bioassay was capable of quantifying arecoline and guvacoline (and carboxylate metabolites arecaidine and guvacine, respectively) with …


Vaxbot-Hpv: A Gpt-Based Chatbot For Answering Hpv Vaccine-Related Questions, Yiming Li, Jianfu Li, Manqi Li, Evan Yu, Danniel Rhee, Muhammad Amith, Lu Tang, Lara S Savas, Licong Cui, Cui Tao Feb 2025

Vaxbot-Hpv: A Gpt-Based Chatbot For Answering Hpv Vaccine-Related Questions, Yiming Li, Jianfu Li, Manqi Li, Evan Yu, Danniel Rhee, Muhammad Amith, Lu Tang, Lara S Savas, Licong Cui, Cui Tao

Faculty, Staff and Student Publications

OBJECTIVE: Human Papillomavirus (HPV) vaccine is an effective measure to prevent and control the diseases caused by HPV. However, widespread misinformation and vaccine hesitancy remain significant barriers to its uptake. This study focuses on the development of VaxBot-HPV, a chatbot aimed at improving health literacy and promoting vaccination uptake by providing information and answering questions about the HPV vaccine.

METHODS: We constructed the knowledge base (KB) for VaxBot-HPV, which consists of 451 documents from biomedical literature and web sources on the HPV vaccine. We extracted 202 question-answer pairs from the KB and 39 questions generated by GPT-4 for training and …


Plasma Proteomic Characterization Of Motoric Cognitive Risk And Mild Cognitive Impairment, Gabriela T Gomez, Sanish Sathyan, Jingsha Chen, Myriam Fornage, Pascal Schlosser, Zhongsheng Peng, Jenifer Cordon, Priya Palta, Kevin J Sullivan, Adrienne Tin, B Gwen Windham, Rebecca F Gottesman, Nir Barzilai, Sofiya Milman, Joe Verghese, Josef Coresh, Keenan A Walker Feb 2025

Plasma Proteomic Characterization Of Motoric Cognitive Risk And Mild Cognitive Impairment, Gabriela T Gomez, Sanish Sathyan, Jingsha Chen, Myriam Fornage, Pascal Schlosser, Zhongsheng Peng, Jenifer Cordon, Priya Palta, Kevin J Sullivan, Adrienne Tin, B Gwen Windham, Rebecca F Gottesman, Nir Barzilai, Sofiya Milman, Joe Verghese, Josef Coresh, Keenan A Walker

Faculty, Staff and Student Publications

INTRODUCTION: Motoric cognitive risk (MCR) is a pre-dementia syndrome characterized by mobility and cognitive dysfunction. This study conducted a proteome-wide study of MCR and compared the proteomic signatures of MCR to that of mild cognitive impairment (MCI).

METHODS: Participants were classified as MCR using a memory questionnaire and 4-meter walk. We measured 4877 plasma proteins collected during late-life and midlife. Multivariable logistic regression related each protein to late-life MCR/MCI. MCR-associated proteins were replicated internally at midlife and in an external cohort.

RESULTS: Proteome-wide analysis (n = 4076) identified 25 MCR-associated proteins. Eight of these proteins remained associated with late-life MCR …


High Shear Stress Reduces Erg Causing Endothelial-Mesenchymal Transition And Pulmonary Arterial Hypertension, Tsutomu Shinohara, Jan-Renier Moonen, Yoon Hong Chun, Yannick C. Lee-Yow, Kenichi Okamura, Jason M. Szafron, Jordan Kaplan, Aiqin Cao, Lingli Wang, Weiguang Yang Feb 2025

High Shear Stress Reduces Erg Causing Endothelial-Mesenchymal Transition And Pulmonary Arterial Hypertension, Tsutomu Shinohara, Jan-Renier Moonen, Yoon Hong Chun, Yannick C. Lee-Yow, Kenichi Okamura, Jason M. Szafron, Jordan Kaplan, Aiqin Cao, Lingli Wang, Weiguang Yang

Mechanical Engineering Faculty Publications

Background: Computational modeling indicated that pathological high shear stress (HSS; 100 dyn/cm2) is generated in pulmonary arteries (PAs; 100-500 µm) in congenital heart defects causing PA hypertension (PAH) and in idiopathic PAH with occlusive vascular remodeling. Endothelial-to-mesenchymal transition (EndMT) is a feature of PAH. We hypothesize that HSS induces EndMT, contributing to the initiation and progression of PAH.

Methods: We used the Ibidi perfusion system to determine whether HSS applied to human PA endothelial cells (ECs) induces EndMT when compared with physiological laminar shear stress (15 dyn/cm2). The mechanism was investigated and targeted to prevent PAH in a mouse with …


Introduction To The Special Issue On Verification And Validation Of Source And Propagation Models For Underwater Sounda), Kathleen J. Vigness-Raposa, Klaus Lucke, Michael A. Ainslie, Michele B. Halvorsen, Christ A. F. De Jong, Stanley J. Labak, Martin Siderius Feb 2025

Introduction To The Special Issue On Verification And Validation Of Source And Propagation Models For Underwater Sounda), Kathleen J. Vigness-Raposa, Klaus Lucke, Michael A. Ainslie, Michele B. Halvorsen, Christ A. F. De Jong, Stanley J. Labak, Martin Siderius

Electrical and Computer Engineering Faculty Publications and Presentations

This joint Special Issue of JASA and JASA Express Letters focuses on underwater sound source and propagation modelling, both of ambient sound as well as sources of relevance to possible effects of sound on aquatic life, and corresponding acoustical metrics. Combining information on the sound field with information on a dose-effect relationship enables estimation of the potential effects. The Special Issue presents a collection of eighteen articles on the following topics: (1) verification of source and propagation models, (2) validation of source and propagation models, and (3) bioacoustical metrics for assessment of the risk of environmental effects. This special issue …


Higher Amounts Of Habitual Physical Activity Changes The Relationship Between Hot Flashes And Subclinical Cardiovascular Disease Risk, Sarah Witkowski, Tint Tha Ra Wun, Jo Sophia Brunzelle, Sara Buszkiewicz, Lorna Murphy, Randi L. Garcia, Lynnette Leidy Sievert Feb 2025

Higher Amounts Of Habitual Physical Activity Changes The Relationship Between Hot Flashes And Subclinical Cardiovascular Disease Risk, Sarah Witkowski, Tint Tha Ra Wun, Jo Sophia Brunzelle, Sara Buszkiewicz, Lorna Murphy, Randi L. Garcia, Lynnette Leidy Sievert

Exercise and Sport Studies: Faculty Publications

The menopausal transition is associated with increased risk for cardiovascular disease (CVD). Hot flashes (HF), a cardinal symptom of menopause, have been associated with increased CVD risk, particularly in perimenopausal women. Flow-mediated dilation (FMD) is an indicator of endothelial function and a subclinical CVD risk factor. Lower FMD has been associated with more HF. As moderate to vigorous physical activity (MVPA) is recognized to reduce CVD risk, our goal was to determine whether higher levels of MVPA change the relationship between HF and FMD in perimenopausal women. Healthy perimenopausal women had HF measured objectively using sternal skin conductance for 24 …


Decolonizing Psychology As A Scientific And Ethical Necessity, Heidi Keller Feb 2025

Decolonizing Psychology As A Scientific And Ethical Necessity, Heidi Keller

Online Readings in Psychology and Culture

The starting point of this paper is the colonial heritage of mainstream psychology, and particularly of developmental psychology. The dominant paradigm is still the assumption of universality of theories and findings that originate in research from and with a tiny part of the world’s population. Associated is the neglect, even ignorance, concerning existing anthropological, cultural, and psychological ethnographic research from different communities across the globe, which demonstrate that the so-called WEIRD science (Western, Educated, Industrialized, Rich, Democratic) is different in many respects from the multitude of existing cultural patterns, representing an outlier in a statistical sense. The paper presents a …


Characterizing The Nutrition-Gut Microbiome-Host Physiology Axis To Examine Flexibility In A Fruit-Specialist Primate, Nina Beeby Feb 2025

Characterizing The Nutrition-Gut Microbiome-Host Physiology Axis To Examine Flexibility In A Fruit-Specialist Primate, Nina Beeby

Dissertations, Theses, and Capstone Projects

Nutrition and, increasingly, microbiota are recognized in shaping all aspects of animal behavioral ecology and physiology. Since diet and nutrition shape not only animal physiology but also gut microbiota, and these microbiota serve as suppliers of and competitors to host nutrition, this raises questions of how these complex nutritional and microbial environments synergistically affect animal physiology. Examining this nutrition-gut microbiome-host physiology axis has immense potential to unveil how these intricate relationships contribute to animals’ responses to environmental change at multiple scales. Most of what we know about primate responses to environmental change is based upon studies examining one or few …


Quantified Lives: Data, Bias, And The Cost Of Categorization, Colin F. Geraghty Feb 2025

Quantified Lives: Data, Bias, And The Cost Of Categorization, Colin F. Geraghty

Dissertations, Theses, and Capstone Projects

This project critically examines how statistical methods and data visualization have historically been used to categorize, rank, and control human populations. By exploring the works of key figures like Francis Galton, Karl Pearson, and R.A. Fisher, it traces the evolution of categorization frameworks from their eugenic roots to modern applications in artificial intelligence and global metrics like the World Happiness Report. Through interactive visualizations and historical analysis, the project invites users to question the legitimacy of these frameworks and reflect on their impact on society. At its core, this work emphasizes the need to move beyond rigid classification systems, challenging …


Institutionalized Ostracism, Danieli Evans Feb 2025

Institutionalized Ostracism, Danieli Evans

Articles

Belonging is a fundamental need, like food or water. Hundreds of social psychology studies find that people who are ostracized (excluded, rejected, or ignored) experience severe pain and suffering. Ostracism threatens basic needs, triggers the same neurocognitive processing system as physical pain, and impairs functioning. Furthermore, ostracized people may cope in ways that beget “deviant” labeling and further ostracism.

Belonging and ostracism are prevalent themes in social psychology research, but these constructs have received relatively little attention in law. This Article begins to explore the implications of this research for law. I make three contributions: First, I name and describe …


Secondary Stage Students' Perceptions Regarding (Myschool) Learning Management System's Role In Learning English, Huda Ali Sallam Feb 2025

Secondary Stage Students' Perceptions Regarding (Myschool) Learning Management System's Role In Learning English, Huda Ali Sallam

Journal of Human Services: Training, Research, and Practice

This study set out to explore students' opinions and self-efficacy level in relation to the use of MySchool learning management system. The study has added focus on its usefulness in facilitating English language learning. The study sample involved 420 female secondary stage students within one educational district in Riyadh. The study instrument is a 24-item closed-ended questionnaire which was distributed using a Microsoft Forms link. The items of the questionnaire were divided into four main elements: perceived practicality, perceived usefulness, general satisfaction, and sense of self-efficacy. The obtained data was subsequently analyzed using Statistical Packages for Social Sciences (SPSS) 24 …


Speech And Language Assessment Practices For Bilingual Children In The School Setting: Where Do We Go From Here?, Seijra Toogood, Raul Prezas Feb 2025

Speech And Language Assessment Practices For Bilingual Children In The School Setting: Where Do We Go From Here?, Seijra Toogood, Raul Prezas

Journal of Human Services: Training, Research, and Practice

Abstract

The field of speech-language pathology has demonstrated growth in bilingual assessment and evaluations. However, many questions remain regarding formal and informal assessment practices, intervention recommendations, and cultural competency or responsiveness. Sixty-one SLPs in Virginia completed a survey on demographics, bilingual assessment practices, cultural competence, and language development of ELL students. Seven SLPs who work with bilingual and/or ELL students were also interviewed to ascertain bilingual assessment practices, cultural competence, and language development knowledge. Areas of concern included assessment of bilingual students, lack of developmental norms and standardized assessment tools in languages other than English, and lack of knowledge of …


Improving The Measurement Of Gender In Surveys: Effects Of Categorical Versus Open-Ended Response Formats On Measurement And Data Quality Among College Students, Dana Garbarski, Jennifer Dykema, James A. Yonker, Rosie Eungyuhl Bae, Rachel A. Rosenfeld Feb 2025

Improving The Measurement Of Gender In Surveys: Effects Of Categorical Versus Open-Ended Response Formats On Measurement And Data Quality Among College Students, Dana Garbarski, Jennifer Dykema, James A. Yonker, Rosie Eungyuhl Bae, Rachel A. Rosenfeld

Sociology: Faculty Publications and Other Works

While researchers have some recommendations for measuring gender identity in surveys based on research and other sources that are summarized in a series of working group and panel reports, we continue to refine our understanding and practices. Gender identity is usually measured in surveys using a categorical selection response format with a small number of response options (e.g., "female,""male,""nonbinary") and an open text response field to capture additional responses ("not listed, please tell us"). There is limited research guiding researchers on the use of other response formats. This study reports results from a between-subjects experiment embedded in a campus climate …


Kras Mutations In Cancer: Understanding Signaling Pathways To Immune Regulation And The Potential Of Immunotherapy, Priyanka Uniyal, Vivek Kumar Kashyap, Tapan Behl, Deepak Parashar, Ravi Rawat Feb 2025

Kras Mutations In Cancer: Understanding Signaling Pathways To Immune Regulation And The Potential Of Immunotherapy, Priyanka Uniyal, Vivek Kumar Kashyap, Tapan Behl, Deepak Parashar, Ravi Rawat

School of Medicine Publications

The Kirsten rat sarcoma viral oncogene homologue (KRAS) mutation is one of the most prevailing mutations in various tumors and is difficult to cure. Long-term proliferation in carcinogenesis is primarily initiated by oncogenic KRAS-downstream signaling. Recent research suggests that it also activates the autocrine effect and interplays the tumor microenvironment (TME). Here, we discuss the emerging research, including KRAS mutations to immune evasion in TME, which induce immunological modulation that promotes tumor development. This review gives an overview of the existing knowledge of the underlying connection between KRAS mutations and tumor immune modulation. It also addresses the mechanisms to reduce …


Association Of Systemic Inflammation And Long-Term Dysfunction In Covid-19 Patients: A Prospective Cohort, Felipe Dal-Pizzol, Bruno Kluwe-Schiavon, Henrique Ritter Dal-Pizzol, Gabriele Da Silveira Prestes, Diogo Dominguini, Carolina Saibro Girardi, Lucas Santos, José Cláudio Fonseca Moreira, Daniel Pens Gelain, Roger Walz, Tatiana Barichello, Cristiane Ritter Feb 2025

Association Of Systemic Inflammation And Long-Term Dysfunction In Covid-19 Patients: A Prospective Cohort, Felipe Dal-Pizzol, Bruno Kluwe-Schiavon, Henrique Ritter Dal-Pizzol, Gabriele Da Silveira Prestes, Diogo Dominguini, Carolina Saibro Girardi, Lucas Santos, José Cláudio Fonseca Moreira, Daniel Pens Gelain, Roger Walz, Tatiana Barichello, Cristiane Ritter

Faculty, Staff and Student Publications

COVID-19 has significant long-term impacts, including a chronic syndrome known as long-COVID, characterized by persistent symptoms post-recovery. The inflammatory response during acute infection is hypothesized to influence long-term outcomes. This study aimed to identify inflammatory biomarkers predictive of functional outcomes one year after hospital discharge. A prospective cohort study was conducted with 213 COVID-19 patients admitted to ICUs in Southern Brazil between June and November 2020. After exclusions and follow-ups, 109 patients were evaluated for one-year post-discharge. Plasma levels of Th1 (TNF-α, INF-γ, IL-12), Th2 (IL-4, IL-5, IL-6, IL-10, IL-13), and Th17 (IL-17, IL-22) cytokines were measured. Functional outcomes in …


Transcriptome Size Matters For Single-Cell Rna-Seq Normalization And Bulk Deconvolution, Songjian Lu, Jiyuan Yang, Lei Yan, Jingjing Liu, Judy Jiaru Wang, Rhea Jain, Jiyang Yu Feb 2025

Transcriptome Size Matters For Single-Cell Rna-Seq Normalization And Bulk Deconvolution, Songjian Lu, Jiyuan Yang, Lei Yan, Jingjing Liu, Judy Jiaru Wang, Rhea Jain, Jiyang Yu

Faculty, Staff and Student Publications

The variation of transcriptome size across cell types significantly impacts single-cell RNA sequencing (scRNA-seq) data normalization and bulk RNA-seq cellular deconvolution, yet this intrinsic feature is often overlooked. Here we introduce ReDeconv, a computational algorithm that incorporates transcriptome size into scRNA-seq normalization and bulk deconvolution. ReDeconv introduces a scRNA-seq normalization approach, Count based on Linearized Transcriptome Size (CLTS), which corrects differential expressed genes typically misidentified by standard count per 10 K normalization, as confirmed by orthogonal validations. By maintaining transcriptome size variation, CLTS-normalized scRNA-seq enhances the accuracy of bulk deconvolution. Additionally, ReDeconv mitigates gene length effects and models expression variances, …


Pharmacologic Management Of Heart Failure With Preserved Ejection Fraction (Hfpef) In Older Adults, Ashkan Hashemi, Min Ji Kwak, Parag Goyal Feb 2025

Pharmacologic Management Of Heart Failure With Preserved Ejection Fraction (Hfpef) In Older Adults, Ashkan Hashemi, Min Ji Kwak, Parag Goyal

Faculty, Staff and Student Publications

There are several pharmacologic agents that have been touted as guideline-directed medical therapy for heart failure with preserved ejection fraction (HFpEF). However, it is important to recognize that older adults with HFpEF also contend with an increased risk for adverse effects from medications due to age-related changes in pharmacokinetics and pharmacodynamics of medications, as well as the concurrence of geriatric conditions such as polypharmacy and frailty. With this review, we discuss the underlying evidence for the benefits of various treatments in HFpEF and incorporate key considerations for older adults, a subpopulation that may be at higher risk for adverse drug …


Exploring Unintended Consequences From The Prospective Payment System Transitional Drug Add-On Payment Adjustment To Refine Program Enhancement Strategies, Donald Andrew Molony, Dia Rose Waguespack Feb 2025

Exploring Unintended Consequences From The Prospective Payment System Transitional Drug Add-On Payment Adjustment To Refine Program Enhancement Strategies, Donald Andrew Molony, Dia Rose Waguespack

Faculty, Staff and Student Publications

No abstract provided.


Immunogenomic Determinants Of Exceptional Response To Immune Checkpoint Inhibition In Renal Cell Carcinoma, Tejas Jammihal, Renee Maria Saliby, Chris Labaki, Hanna Soulati, Juan Gallegos, Arnau Peris, Dustin Mccurry, Chunlei Yu, Valisha Shah, Deepak Poduval, Talal El Zarif, Nourhan El Ahmar, Yasmin Nabil Laimon, Marc Eid, Aseman Bagheri Sheshdeh, Katherine M Krajewski, Florian A Büttner, Matthias Schwab, Daniel Heng, Rafael C Casellas, Kunal Rai, Niki M Zacharias Millward, Pavlos Msaouel, Jose Karam, Sabina Signoretti, Eliezer Van Allen, Toni K Choueiri, David A Braun, Sachet A Shukla Feb 2025

Immunogenomic Determinants Of Exceptional Response To Immune Checkpoint Inhibition In Renal Cell Carcinoma, Tejas Jammihal, Renee Maria Saliby, Chris Labaki, Hanna Soulati, Juan Gallegos, Arnau Peris, Dustin Mccurry, Chunlei Yu, Valisha Shah, Deepak Poduval, Talal El Zarif, Nourhan El Ahmar, Yasmin Nabil Laimon, Marc Eid, Aseman Bagheri Sheshdeh, Katherine M Krajewski, Florian A Büttner, Matthias Schwab, Daniel Heng, Rafael C Casellas, Kunal Rai, Niki M Zacharias Millward, Pavlos Msaouel, Jose Karam, Sabina Signoretti, Eliezer Van Allen, Toni K Choueiri, David A Braun, Sachet A Shukla

Faculty, Staff and Student Publications

Immune checkpoint inhibitors can lead to 'exceptional', durable responses in a subset of persons. However, the molecular basis of exceptional response (ER) to immunotherapy in metastatic clear cell renal cell carcinoma (mccRCC) has not been well characterized. Here we analyzed pretherapy genomic and transcriptomic data in treatment-naive persons with mccRCC treated with standard-of-care immunotherapies: (1) combination of programmed cell death protein and ligand 1 (PD1/PDL1) and cytotoxic T lymphocyte-associated protein 4 inhibitors (IO/IO) or (2) combination of PD1/PDL1 and vascular endothelial growth factor (VEGF) receptor inhibitors (IO/VEGF). In the IO/IO cohort, clonal neoantigen load was significantly higher in persons with …


Molecular Profiling Of Bladder Cancer Xenografts Defines Relevant Molecular Subtypes And Provides A Resource For Biomarker Discovery, Sharada Mokkapati, Ganiraju Manyam, Alexis R Steinmetz, Côme Tholomier, Alberto Martini, Woonyoung Choi, Bogdon Czerniak, Byron H Lee, Colin P Dinney, David J Mcconkey Feb 2025

Molecular Profiling Of Bladder Cancer Xenografts Defines Relevant Molecular Subtypes And Provides A Resource For Biomarker Discovery, Sharada Mokkapati, Ganiraju Manyam, Alexis R Steinmetz, Côme Tholomier, Alberto Martini, Woonyoung Choi, Bogdon Czerniak, Byron H Lee, Colin P Dinney, David J Mcconkey

Faculty, Staff and Student Publications

Bladder cancer (BLCA) genomic profiling has identified molecular subtypes with distinct clinical characteristics and variable sensitivities to frontline therapy. BLCAs can be categorized into luminal or basal subtypes based on their gene expression. We comprehensively characterized nine human BLCA cell lines (UC3, UC6, UC9, UC13, UC14, T24, SCaBER, RT4V6 and RT112) into molecular subtypes using orthotopic xenograft models. Patient-derived, luciferase-tagged BLCA cell lines were cultured in vitro and engrafted into bladders of NSG mice. Tumor growth was monitored using bioluminescence imaging and mRNA-based molecular classification was used to characterize xenografts into molecular subtypes. RNAseq analysis and basal, luminal, and epithelial-mesenchymal …


Emapalumab Treatment In Patients With Rheumatologic Disease-Associated Hemophagocytic Lymphohistiocytosis In The United States: A Retrospective Medical Chart Review Study., Shanmuganathan Chandrakasan, Carl E. Allen, Deepika Bhatla, John Carter, May Chien, Robert Cooper, Lauren Draper, Olive S. Eckstein, Rabi Hanna, J Allyson Hays, Michelle L. Hermiston, Ashley P. Hinson, Patricia M. Hobday, Michael S. Isakoff, Michael B. Jordan, Jennifer W. Leiding, Renee Modica, Taizo A. Nakano, Abiola Oladapo, Sachit A. Patel, Priti Pednekar, Mona Riskalla, Susmita N. Sarangi, Prakash Satwani, Anand Tandra, Kelly J. Walkovich, John D. Yee, Adi Zoref-Lorenz, Edward M. Behrens, Real‐Hlh Investigators Feb 2025

Emapalumab Treatment In Patients With Rheumatologic Disease-Associated Hemophagocytic Lymphohistiocytosis In The United States: A Retrospective Medical Chart Review Study., Shanmuganathan Chandrakasan, Carl E. Allen, Deepika Bhatla, John Carter, May Chien, Robert Cooper, Lauren Draper, Olive S. Eckstein, Rabi Hanna, J Allyson Hays, Michelle L. Hermiston, Ashley P. Hinson, Patricia M. Hobday, Michael S. Isakoff, Michael B. Jordan, Jennifer W. Leiding, Renee Modica, Taizo A. Nakano, Abiola Oladapo, Sachit A. Patel, Priti Pednekar, Mona Riskalla, Susmita N. Sarangi, Prakash Satwani, Anand Tandra, Kelly J. Walkovich, John D. Yee, Adi Zoref-Lorenz, Edward M. Behrens, Real‐Hlh Investigators

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Rheumatologic disease-associated hemophagocytic lymphohistiocytosis (HLH), a rare, life-threatening, systemic hyperinflammatory syndrome, occurs as a complication of underlying rheumatologic disease. Real-world evidence is lacking on emapalumab, a fully human monoclonal antibody that neutralizes the proinflammatory cytokine interferon-γ, approved for treating patients with primary HLH.

METHODS: REAL-HLH, a retrospective medical chart review study conducted across 33 US hospitals, assessed real-world treatment patterns and outcomes in patients with HLH treated with one or more dose of emapalumab between November 20, 2018, and October 31, 2021. Data are presented for the subset of patients with rheumatologic disease-associated HLH.

RESULTS: Fifteen of 105 patients …


The Metabolic Basis Of Cancer-Related Fatigue, Robert Dantzer, Brandon Chelette, Elisabeth G Vichaya, A Phillip West, Aaron Grossberg Feb 2025

The Metabolic Basis Of Cancer-Related Fatigue, Robert Dantzer, Brandon Chelette, Elisabeth G Vichaya, A Phillip West, Aaron Grossberg

Faculty, Staff and Student Publications

Although we are all familiar with the sensation of fatigue, there are still profound divergences on what it represents and its mechanisms. Fatigue can take various forms depending on the condition in which it develops. Cancer-related fatigue is considered a symptom of exhaustion that is often present at the time of diagnosis, increases in intensity during cancer therapy, and does not always recede after completion of treatment. It is usually attributed to the inflammation induced by damage-associated molecular patterns released by tumor cells during cancer progression and in response to its treatment. In this review, we argue that it is …


Rapid And Scalable Personalized Aso Screening In Patient-Derived Organoids., John C. Means, Anabel L. Martinez-Bengochea, Daniel A. Louiselle, Jacqelyn Nemechek, John M. Perry, Emily G. Farrow, Tomi Pastinen, Scott T. Younger Feb 2025

Rapid And Scalable Personalized Aso Screening In Patient-Derived Organoids., John C. Means, Anabel L. Martinez-Bengochea, Daniel A. Louiselle, Jacqelyn Nemechek, John M. Perry, Emily G. Farrow, Tomi Pastinen, Scott T. Younger

Manuscripts, Articles, Book Chapters and Other Papers

Personalized antisense oligonucleotides (ASOs) have achieved positive results in the treatment of rare genetic disease. As clinical sequencing technologies continue to advance, the ability to identify patients with rare disease harbouring pathogenic genetic variants amenable to this therapeutic strategy will probably improve. Here we describe a scalable platform for generating patient-derived cellular models and demonstrate that these personalized models can be used for preclinical evaluation of patient-specific ASOs. We describe protocols for delivery of ASOs to patient-derived organoid models and confirm reversal of disease-associated phenotypes in cardiac organoids derived from a patient with Duchenne muscular dystrophy (DMD) with a structural …


Structural Polymorphism And Diversity Of Human Segmental Duplications., Hyeonsoo Jeong, Philip C. Dishuck, Dongahn Yoo, William T. Harvey, Katherine M. Munson, Alexandra P. Lewis, Jennifer Kordosky, Gage H. Garcia, Human Genome Structural Variation Consortium (Hgsvc), Feyza Yilmaz, Pille Hallast, Charles Lee, Tomi Pastinen, Evan E. Eichler Feb 2025

Structural Polymorphism And Diversity Of Human Segmental Duplications., Hyeonsoo Jeong, Philip C. Dishuck, Dongahn Yoo, William T. Harvey, Katherine M. Munson, Alexandra P. Lewis, Jennifer Kordosky, Gage H. Garcia, Human Genome Structural Variation Consortium (Hgsvc), Feyza Yilmaz, Pille Hallast, Charles Lee, Tomi Pastinen, Evan E. Eichler

Manuscripts, Articles, Book Chapters and Other Papers

Segmental duplications (SDs) contribute significantly to human disease, evolution and diversity but have been difficult to resolve at the sequence level. We present a population genetics survey of SDs by analyzing 170 human genome assemblies (from 85 samples representing 38 Africans and 47 non-Africans) in which the majority of autosomal SDs are fully resolved using long-read sequence assembly. Excluding the acrocentric short arms and sex chromosomes, we identify 173.2 Mb of duplicated sequence (47.4 Mb not present in the telomere-to-telomere reference) distinguishing fixed from structurally polymorphic events. We find that intrachromosomal SDs are among the most variable, with rare events …


Management Of Isolated Partial Acl Tears: A Survey Of International Acl Surgeons, Christopher S Frey, Kinsley J Pierre, Nicole S Pham, Geoffrey D Abrams, Seth L Sherman, Tim Spalding, Marc R Safran Feb 2025

Management Of Isolated Partial Acl Tears: A Survey Of International Acl Surgeons, Christopher S Frey, Kinsley J Pierre, Nicole S Pham, Geoffrey D Abrams, Seth L Sherman, Tim Spalding, Marc R Safran

Faculty, Staff and Student Publications

Background: Partial anterior cruciate ligament (ACL) tears, particularly injuries detected with magnetic resonance imaging (MRI) but stable on ligamentous examination, appear to be recognized more frequently; however, there remains no consensus management for this complex pathology.

Purpose: To present the results of a survey of a group of international ACL experts on the management of partial ACL injuries.

Study design: Survey study; Level of evidence, 5.

Methods: The ACL Study Group is an international group of orthopaedic surgeons with a special interest in the ACL. There are 169 members overall, with 135 clinically active surgeons. A branching logic survey was …


Adipose Tissue Deficiency Impairs Transient Lipid Accumulation And Delays Liver Regeneration Following Partial Hepatectomy In Male Seipin Knockout Mice, Qianqian Dong, Ziwei Liu, Yidan Ma, Xin Chen, Xiaowei Wang, Jinye Tang, Kexin Ma, Chenxi Liang, Mengyu Wang, Xiaoqin Wu, Yang Liu, Yaru Zhou, Hongyuan Yang, Mingming Gao Feb 2025

Adipose Tissue Deficiency Impairs Transient Lipid Accumulation And Delays Liver Regeneration Following Partial Hepatectomy In Male Seipin Knockout Mice, Qianqian Dong, Ziwei Liu, Yidan Ma, Xin Chen, Xiaowei Wang, Jinye Tang, Kexin Ma, Chenxi Liang, Mengyu Wang, Xiaoqin Wu, Yang Liu, Yaru Zhou, Hongyuan Yang, Mingming Gao

Faculty, Staff and Student Publications

Background: Liver diseases pose significant health challenges, underscoring the importance of understanding liver regeneration mechanisms. Systemic adipose tissue is thought to be a primary source of lipids and energy during this process; however, empirical data on the effects of adipose tissue deficiency are limited. This study investigates the role of adipose tissue in liver regeneration, focusing on transient regeneration-associated steatosis (TRAS) and hepatocyte proliferation using a Seipin knockout mouse model that mimics severe human lipodystrophy. Additionally, the study explores therapeutic strategies through adipose tissue transplantation.

Methods: Male Seipin knockout (Seipin-/-) and wild-type (WT) mice underwent 2/3 partial hepatectomy (PHx). Liver …