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Pregnancy, Cancer, And Radiation-A Modern Refresher, Kelly Kisling, Sandra M Meyers, Rebecca Milman, Susan Richardson, Christina Chapman, Justine Dupere, Grace Eliason, Suzanne Evans, Titania Juang, Young Lee, Jeffrey Masten, Julia Maues, Rachel Newman, Mike Silosky, Catherine Song, Catheryn Yashar, Sara Thrower Mar 2026

Pregnancy, Cancer, And Radiation-A Modern Refresher, Kelly Kisling, Sandra M Meyers, Rebecca Milman, Susan Richardson, Christina Chapman, Justine Dupere, Grace Eliason, Suzanne Evans, Titania Juang, Young Lee, Jeffrey Masten, Julia Maues, Rachel Newman, Mike Silosky, Catherine Song, Catheryn Yashar, Sara Thrower

Faculty, Staff and Student Publications

Cancer occurs in ∼1 per 1000 pregnancies; thousands of patients may require radiation procedures for diagnosis and treatment each year in the United States alone. This rare but high-risk scenario, coupled with fear of radiation, has created ambiguity in the ideal management of pregnant patients. Without a comprehensive guide for the use of radiation in imaging and treatment for pregnant cancer patients, it is difficult for providers to offer optimal patient-centered care without introducing disparities. The goal of this paper is to provide guidance on the use of radiation for screening, diagnosis, staging, and treatment of cancer, while highlighting gaps …


Influence Of Body Composition On The Efficacy Of Nivolumab Plus Ipilimumab For Metastatic Clear Cell Renal Cell Carcinoma, Kabir Grewal, Maria Julia Moura Nascimento Santos, Pankaj Kumar Chauhan, Kai Yu, Nizar M Tannir, Sagar S Mukhida, Neha Venkatesh, Amishi Y Shah, Amado J Zurita, Andrew C Johns, Matthew T Campbell, Sangeeta Goswami, Jianjun Gao, Eric Jonasch, Jennifer L Mcquade, Omar Alhalabi, Pavlos Msaouel, Andrew W Hahn Mar 2026

Influence Of Body Composition On The Efficacy Of Nivolumab Plus Ipilimumab For Metastatic Clear Cell Renal Cell Carcinoma, Kabir Grewal, Maria Julia Moura Nascimento Santos, Pankaj Kumar Chauhan, Kai Yu, Nizar M Tannir, Sagar S Mukhida, Neha Venkatesh, Amishi Y Shah, Amado J Zurita, Andrew C Johns, Matthew T Campbell, Sangeeta Goswami, Jianjun Gao, Eric Jonasch, Jennifer L Mcquade, Omar Alhalabi, Pavlos Msaouel, Andrew W Hahn

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitor therapy (ICI) with nivolumab+ipilimumab is a first-line (1L) standard for metastatic clear cell renal cell carcinoma (ccRCC), yet outcomes remain heterogeneous. Increasing evidence suggests that host factors influence the tumor microenvironment and response to ICI. Although higher body mass index (BMI) has been associated with improved outcomes in several malignancies, BMI is an imprecise surrogate for underlying adipose and muscle compartments. We evaluated the association between body composition and outcomes with 1L nivolumab+ipilimumab in metastatic ccRCC.

Methods: We retrospectively analyzed patients with mccRCC treated with 1L nivolumab+ipilimumab at MD Anderson Cancer Center between June 2015 and …


Sex-Related Differences In Clinical Profile, Management, And Outcomes Of Patients With Type A And B Acute Aortic Dissection: Observations From Irad, Elizabeth Jackson, Andreina Carbone, Sherene Shalhub, Chih-Wen Pai, Marek Ehrlich, Toru Suzuki, G Chad Hughes, Anil Bhan, Rumi Faizer, Antonio Cittadini, Alan Braverman, Eric Isselbacher, Kim Eagle, Christoph Nienaber, Eduardo Bossone Mar 2026

Sex-Related Differences In Clinical Profile, Management, And Outcomes Of Patients With Type A And B Acute Aortic Dissection: Observations From Irad, Elizabeth Jackson, Andreina Carbone, Sherene Shalhub, Chih-Wen Pai, Marek Ehrlich, Toru Suzuki, G Chad Hughes, Anil Bhan, Rumi Faizer, Antonio Cittadini, Alan Braverman, Eric Isselbacher, Kim Eagle, Christoph Nienaber, Eduardo Bossone

2020-Current year OA Pubs

BACKGROUND: Available data about sex differences in patients with acute aortic dissection (AAD) are scant and conflicting. The aim of this study is to assess sex-related differences in clinical characteristics, presentation, diagnostic findings, management, and outcomes among patients with type A (TA-AAD) and type B AAD (TB-AAD).

METHODS: Data about 11 586 patients enrolled in the IRAD (International Registry of Acute Aortic Dissection) from 1996 to 2022, were analyzed; 7819 (67.5%) experienced TA-AAD and 3867 (33.0%) TB-AAD. Men and women were compared with regard to diagnosis, treatment, and in-hospital and long-term survival.

RESULTS: One third of patients were women (TA-AAD, …


Pharmacologic And Oncohistone Inhibition Of Setd2 Converge On Genomic Instability, Alyssa T Paparella, Ashley G Boice, In Young Park, Rajkishor Nishad, Durga Tripathi, Seth A Nelson, Edward W Pietryk, H Josh Jang, Ian J Frew, W Kimryn Rathmell, Frank M Mason, Cristian Coarfa, Ruhee Dere, Cheryl Lyn Walker Mar 2026

Pharmacologic And Oncohistone Inhibition Of Setd2 Converge On Genomic Instability, Alyssa T Paparella, Ashley G Boice, In Young Park, Rajkishor Nishad, Durga Tripathi, Seth A Nelson, Edward W Pietryk, H Josh Jang, Ian J Frew, W Kimryn Rathmell, Frank M Mason, Cristian Coarfa, Ruhee Dere, Cheryl Lyn Walker

Faculty, Staff and Students Publications

Background/objectives: SETD2 is a dual-function methyltransferase important for methylation of histone H3 at lysine 36 and α-tubulin in spindle microtubules. Genetic inactivation of SETD2 during oncogenesis drives loss of H3K36me3, genomic instability, and cancer progression. This study asked if disruption of genomic stability was a canonical feature of SETD2 inactivation via different pathways.

Methods: We evaluated the impact of EPZ-719, a pharmacologic SETD2 inhibitor, and an H3.3K36M mutant histone ("oncohistone") that binds and sequesters SETD2, on methylation activity and genomic stability in human cell lines. SETD2 activity was measured using in vitro methylation assays, H3K36me3 loss confirmed by Western analysis, …


Circulating Ketone Bodies And Incident Cardiovascular Outcomes And Mortality: Insights From The Uk Biobank, Parag Anilkumar Chevli, Saeid Mirzai, Richard Kazibwe, Jeff Kingsley, Alexis C Wood, Joseph Yeboah, Leandro Slipczuk, Anurag Mehta, Harpreet S Bhatia, Ambarish Pandey, Michael D Shapiro Mar 2026

Circulating Ketone Bodies And Incident Cardiovascular Outcomes And Mortality: Insights From The Uk Biobank, Parag Anilkumar Chevli, Saeid Mirzai, Richard Kazibwe, Jeff Kingsley, Alexis C Wood, Joseph Yeboah, Leandro Slipczuk, Anurag Mehta, Harpreet S Bhatia, Ambarish Pandey, Michael D Shapiro

Children’s Nutrition Research Center Staff Publications

Background: Ketone bodies (KB) are endogenous energy sources synthesized by the liver in response to metabolic stress. Their associations with atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and mortality and their potential beneficial or harmful effects have yet to be determined. This study aimed to examine the association between KB and incident cardiovascular outcomes and mortality in a large general population cohort free from ASCVD and HF at baseline.

Methods: This analysis included 90 987 participants (mean age 56.4 ± 8.1 years; 54.7% women) from the UK Biobank without prevalent ASCVD or HF. KB were measured by nuclear magnetic resonance …


Pd-L1 Positivity Predicts A Unique Hyperaggressive Tumor Group Within Meng C Meningiomas, Vijay Nitturi, Shervin Hosseingholi Nouri, Collin English, Hsiang-Chih Lu, Elizabeth Ledbetter, Diego Rojas, Sean Lau, Malcolm Mcdonald, Jacob J Mandel, Abdul Basit Khan, Arif O Harmanci, Akdes S Harmanci, Tiemo Klisch, Akash J Patel Mar 2026

Pd-L1 Positivity Predicts A Unique Hyperaggressive Tumor Group Within Meng C Meningiomas, Vijay Nitturi, Shervin Hosseingholi Nouri, Collin English, Hsiang-Chih Lu, Elizabeth Ledbetter, Diego Rojas, Sean Lau, Malcolm Mcdonald, Jacob J Mandel, Abdul Basit Khan, Arif O Harmanci, Akdes S Harmanci, Tiemo Klisch, Akash J Patel

Duncan NRI Faculty and Staff Publications

Molecular profiling has identified 3 groups of meningiomas, with MenG C tumors exhibiting the vast majority of recurrences. Efforts to find effective treatments for recurrent meningiomas have remained elusive. Higher WHO-grade meningiomas have exhibited greater Programmed Death Ligand 1 (PD-L1) expression through various methods, but the prognostic value of PD-L1 expression has not been described in the context of molecular profiling. Additionally, trials investigating PD-1/PD-L1-targeted immunotherapies have produced disappointing results. Here, we find that PD-L1 positivity, while prevalent in MenG C tumors, does not predict recurrence in the benign MenG A and B tumors. PD-L1 positivity also occurs independently of …


Comparative Antibacterial Efficacy Of Povidone-Iodine, Citric Acid, And Starch: A Study Of Combined Activity And Interference Effects Against Clinically Relevant Bacteria, Falah Hasan Obayes Al-Khikani, Mustafa Mutar Trrad, Ali Abedulameer Alhusayni Mar 2026

Comparative Antibacterial Efficacy Of Povidone-Iodine, Citric Acid, And Starch: A Study Of Combined Activity And Interference Effects Against Clinically Relevant Bacteria, Falah Hasan Obayes Al-Khikani, Mustafa Mutar Trrad, Ali Abedulameer Alhusayni

AUIQ Complementary Biological System

Povidone-iodine and citric acid are widely used antimicrobial agents. However, data on their comparative efficacy and the functional outcomes of their combination, particularly regarding the influence of common excipients like starch, is limited. Understanding these interactions is crucial for optimizing antiseptic formulations. This study aimed to evaluate and compare the antibacterial activity of povidone-iodine, citric acid (5% and 20%), and starch (5% and 20%), both individually and in combination, against clinical isolates of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. The antibacterial activity of the agents was assessed using an agar well diffusion assay. Mean inhibition zone …


The Phoenix Trauma Response Model (Ptrm): An Integrative And Innovative Approach To Trauma Recovery And Growth, Latesha S. Holloman, Lauren B. Robins, Tammie Willis, Courtney V. Morris Mar 2026

The Phoenix Trauma Response Model (Ptrm): An Integrative And Innovative Approach To Trauma Recovery And Growth, Latesha S. Holloman, Lauren B. Robins, Tammie Willis, Courtney V. Morris

Journal of Human Services Scholarship and Interprofessional Collaboration

Trauma is increasingly understood as a developmentally consequential experience that shapes identity, regulation, and relational functioning across the lifespan. Although trauma-informed care, resilience theory, posttraumatic growth, and narrative approaches have expanded understanding of recovery, few frameworks articulate a structured developmental progression that integrates prevention, intervention, and intergenerational transformation within a unified model. The Phoenix Trauma Response Model (PTRM) addresses this gap by introducing a cyclical, phase-based framework organized around four interrelated processes: Recognition, Reframing, Reclamation, and Replication of Strength. Central to the model is the construct of conversion potential, defined as the structured capacity to translate distress into purposeful …


A Review Of Interaction Between Sleep Apnea And Apoe E4 On The Risk Of Dementia, Xiuhua Ding, Carol Watwood, Amit Patel, Krupa Hegde, Brooke Mahanna, Lindsey Escudero, Jean Neils-Strunjas Ph.D, Ccc-Slp Mar 2026

A Review Of Interaction Between Sleep Apnea And Apoe E4 On The Risk Of Dementia, Xiuhua Ding, Carol Watwood, Amit Patel, Krupa Hegde, Brooke Mahanna, Lindsey Escudero, Jean Neils-Strunjas Ph.D, Ccc-Slp

Faculty Publications

Dementia has a significant impact on individuals, families, communities, and the economy. Alzheimer’s disease (AD) accounts for 60–80% of dementia cases. The APOE e4 allele is well known as the primary genetic risk factor for AD and dementia. Studies have also shown that sleep apnea increases the risk of dementia. Some research further suggests a possible interaction between sleep apnea and the APOE in dementia development; however, this relationship remains unclear. The purpose of this study is to synthesize evidence from the existing literature and report findings on the relationship between APOE, sleep apnea, and dementia. A systematic search of …


Metabolic Responses To Freund’S Adjuvants And Oncolytic Viruses: Implications On Vaccines And Tumor Immunity, Kiruthiga Mone Mar 2026

Metabolic Responses To Freund’S Adjuvants And Oncolytic Viruses: Implications On Vaccines And Tumor Immunity, Kiruthiga Mone

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Freund’s adjuvants have been extensively used in experimental research, and they modulate immune responses through various mechanisms. While both complete Freund’s adjuvant (CFA) and incomplete Freund’s adjuvant (IFA) contain the same mineral oil base, CFA contains the killed extract of Mycobacterium tuberculosis (M. tb) as an additional ingredient. Because the CFA contains mycobacterial content similar to that of Bacillus Calmette-Guérin (BCG), which induces trained immunity (TI), we tested the hypothesis that CFA may elicit TI-like features. To test this hypothesis, we investigated the metabolic and epigenetic reprogramming induced by CFA, with IFA and BCG as controls, in inbred …


Ectopic B Lymphocyte Follicles Exacerbate Ischemic Brain Damage Via Mif-Cd74/Cxcr4 And Interferon Signaling, Sheng Yang, Hang Zhang, Lu-Lu Xu, Luo-Qi Zhou, Yun-Hui Chu, Lian Chen, Xiao-Wei Pang, Lu-Yang Zhang, Li-Fang Zhu, Ming-Hao Dong, Ke Shang, Jun Xiao, Long-Jun Wu, Wei Wang, Dai-Shi Tian, Chuan Qin Mar 2026

Ectopic B Lymphocyte Follicles Exacerbate Ischemic Brain Damage Via Mif-Cd74/Cxcr4 And Interferon Signaling, Sheng Yang, Hang Zhang, Lu-Lu Xu, Luo-Qi Zhou, Yun-Hui Chu, Lian Chen, Xiao-Wei Pang, Lu-Yang Zhang, Li-Fang Zhu, Ming-Hao Dong, Ke Shang, Jun Xiao, Long-Jun Wu, Wei Wang, Dai-Shi Tian, Chuan Qin

Faculty, Staff and Student Publications

Neuroinflammation, encompassing both innate and adaptive immune responses, plays a crucial role in ischemic stroke. Although B lymphocytes are central to adaptive immunity, their contributions to ischemic stroke remain poorly understood. Here, we demonstrated that B lymphocytes accumulate in ischemic lesions, forming germinal center-like structures at the later stage after stroke, which mainly depended on in situ proliferation. This accumulation correlated with worsened neuroinflammation and ischemic injury, whereas B cell depletion reduced chronic brain damage during stroke. Mechanistically, microglia recruited B cells into ischemic lesions through MIF-CD74/CXCR4 signaling during the early phase of stroke, while IFN-related pathways in B cells …


An Ai Approach To Differentiating Lung Squamous Cell Carcinoma From Metastases Of Other Origins, Mark G Evans, Jennifer Ribeiro, Todd Maney, Anthony Helmstetter, Jennifer Johnson, Anthony Karnezis, Casey Bales, George Sledge, David Spetzler, Ari Vanderwalde, Matthew Oberley, Balazs Halmos, Hossein Borghaei, Farah Abdulla, David Bryant, Fred Hirsch, Hassan Ghani Mar 2026

An Ai Approach To Differentiating Lung Squamous Cell Carcinoma From Metastases Of Other Origins, Mark G Evans, Jennifer Ribeiro, Todd Maney, Anthony Helmstetter, Jennifer Johnson, Anthony Karnezis, Casey Bales, George Sledge, David Spetzler, Ari Vanderwalde, Matthew Oberley, Balazs Halmos, Hossein Borghaei, Farah Abdulla, David Bryant, Fred Hirsch, Hassan Ghani

Department of Medical Oncology Faculty Papers

IMPORTANCE: Distinguishing primary lung squamous cell carcinoma (SCC) from squamous metastases to the lung is a clinical challenge due to histopathologic similarities. Accurate diagnosis is essential to guide treatment decisions.

OBJECTIVE: To assess the utility of an artificial intelligence (AI) approach that includes evaluation of key orthogonal evidence in distinguishing primary lung SCCs from metastatic tumors of other tissue origins.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used GPSai, a tissue-of-origin AI model run automatically on each sample submitted for molecular profiling, to flag potential misdiagnoses among research-eligible cases submitted as lung SCC. Molecularly profiled cases within the Caris Life …


Surface Morphometrics Reveals Local Membrane Thickness Variation In Organellar Subcompartments, Michaela Medina, Ya-Ting Chang, Hamidreza Rahmani, Mark Frank, Zidan Khan, Daniel Fuentes, Frederick A Heberle, M Neal Waxham, Benjamin A Barad, Danielle A Grotjahn Mar 2026

Surface Morphometrics Reveals Local Membrane Thickness Variation In Organellar Subcompartments, Michaela Medina, Ya-Ting Chang, Hamidreza Rahmani, Mark Frank, Zidan Khan, Daniel Fuentes, Frederick A Heberle, M Neal Waxham, Benjamin A Barad, Danielle A Grotjahn

Faculty, Staff and Student Publications

Lipid bilayers form the basis of organellar architecture, structure, and compartmentalization in the cell. Decades of biophysical, biochemical, and imaging studies on purified or in vitro-reconstituted liposomes have shown that variations in lipid composition influence the physical properties of membranes, such as thickness and curvature. However, similar studies characterizing these membrane properties within the native cellular context have remained technically challenging. Recent advancements in cellular cryo-electron tomography (cryo-ET) imaging enable high-resolution, three-dimensional views of native organellar membrane architecture preserved in near-native conditions. We previously developed a "Surface Morphometrics" pipeline that generates surface mesh reconstructions to model and quantify cellular membrane …


Pediatric H3 G34-Mutant Diffuse Hemispheric Glioma: Clinical, Imaging And Molecular Prognostic Factors, Mgmt Expression, And Temozolomide Response., Dana Tlais, Qunyu Zhang, Jordan T. Roach, Christopher L. Tinkle, Tong Lin, Xiaoyu Li, Ayatullah Mostafa, Daniel C. Moreira, Rene Y. Mcnall-Knapp, Sarah Z. Rush, Brian H. Le, Sara Sinno, Apeksha Ramnarayan, Kevin Ginn, Sonia Partap, Arzu Onar-Thomas, Larissa V. Furtado, Asim K. Bag, Jason Chiang Mar 2026

Pediatric H3 G34-Mutant Diffuse Hemispheric Glioma: Clinical, Imaging And Molecular Prognostic Factors, Mgmt Expression, And Temozolomide Response., Dana Tlais, Qunyu Zhang, Jordan T. Roach, Christopher L. Tinkle, Tong Lin, Xiaoyu Li, Ayatullah Mostafa, Daniel C. Moreira, Rene Y. Mcnall-Knapp, Sarah Z. Rush, Brian H. Le, Sara Sinno, Apeksha Ramnarayan, Kevin Ginn, Sonia Partap, Arzu Onar-Thomas, Larissa V. Furtado, Asim K. Bag, Jason Chiang

Manuscripts, Articles, Book Chapters and Other Papers

Previous studies have demonstrated poor outcomes in pediatric patients with H3 G34-mutant diffuse hemispheric glioma (DHG). However, the biological basis for this therapeutic resistance remains poorly understood. Furthermore, the effectiveness of temozolomide (TMZ) and the role of surgery in pediatric patients remain uncertain. Therefore, we performed a multi-institutional retrospective analysis of the clinical, imaging, and molecular characteristics of 36 pediatric (≤ 18 years) patients with newly diagnosed H3 G34-mutant DHG. The median age of the cohort was 14 years (8-18 years). The median progression-free survival (PFS) was 0.7 years (95% CI 0.4-1.2 years), and the median overall survival (OS) was …


Poly(Adp-Ribose) Glycohydrolase Enforces P21 Degradation Via Deparylation To Promote Gastric Cancer Progression, Yangchan Hu, Qimei Bao, Yixing Huang, Yan Wang, Xin Zhao, Junjun Nan, Yuxin Meng, Mingcong Deng, Yuancong Li, Zirui Zhuang, Hanyi He, Dan Zu, Yuke Zhong, Chunkai Zhang, Bing Wang, Ran Li, Yanhua He, Qihan Wang, Min Liu, John A Tainer, Yin Shi, Xiangdong Cheng, Ji Jing, Zu Ye Mar 2026

Poly(Adp-Ribose) Glycohydrolase Enforces P21 Degradation Via Deparylation To Promote Gastric Cancer Progression, Yangchan Hu, Qimei Bao, Yixing Huang, Yan Wang, Xin Zhao, Junjun Nan, Yuxin Meng, Mingcong Deng, Yuancong Li, Zirui Zhuang, Hanyi He, Dan Zu, Yuke Zhong, Chunkai Zhang, Bing Wang, Ran Li, Yanhua He, Qihan Wang, Min Liu, John A Tainer, Yin Shi, Xiangdong Cheng, Ji Jing, Zu Ye

Faculty, Staff and Student Publications

Dysregulation of cell cycle checkpoints is a cancer hallmark, with ubiquitination-controlled protein stability playing a pivotal role. Although p21, a key cyclin-dependent kinase inhibitor, is tightly regulated by ubiquitin-mediated degradation, the key upstream modulators of its ubiquitination remain incompletely defined. Here, we identify poly(ADP-ribose) glycohydrolase (PARG) as a regulator of p21 stability in gastric cancer (GC) cells. We show that PARG expression is markedly upregulated in GC tissues and correlates with poor patient prognosis. Functional assays revealed that genetic depletion of PARG triggers G2/M phase arrest and impairs GC cell proliferation. Mechanistically, we demonstrate that PARG loss enhances p21 PARylation, …


Mechanometabolism Instructs Hematopoietic Stem Cell Specification, Paulina D Horton, Alina Syed, Michelle Winkler, Abishek B Vaidya, Michael Rariden, Neha Arora, Yong Zhou, Michihiro Kobayashi, Momoko Yoshimoto, Hyun Jung Lee, Hyun-Eui Kim, John P Hagan, Catherine Denicourt, Travis I Moore, Pamela L Wenzel Mar 2026

Mechanometabolism Instructs Hematopoietic Stem Cell Specification, Paulina D Horton, Alina Syed, Michelle Winkler, Abishek B Vaidya, Michael Rariden, Neha Arora, Yong Zhou, Michihiro Kobayashi, Momoko Yoshimoto, Hyun Jung Lee, Hyun-Eui Kim, John P Hagan, Catherine Denicourt, Travis I Moore, Pamela L Wenzel

Faculty, Staff and Student Publications

Mechanical force generated by blood flow stimulates emergence of the first hematopoietic stem cells (HSCs) that populate the blood system. Force drives the transition of HSC precursors from an endothelial to hematopoietic identity, yet the molecular regulation of this fate switch remains poorly understood. We report that shear stress triggers adaptation in mitochondrial composition, ultrastructure, and function, which are essential for hematopoietic fate and engraftment potential. Shear stress remodels mitochondria in hemogenic endothelium by promoting mitochondrial gene transcription and protein synthesis. Laminar flow selectively initiates translation of 5' terminal polypyrimidine (5'TOP) motif-containing transcripts, which commonly encode ribosome and translation machinery. …


The Relationship Between Apparent Potentiation And The Magnitude Of The Control Response, Joe Henry Steinbach, Gustav Akk Mar 2026

The Relationship Between Apparent Potentiation And The Magnitude Of The Control Response, Joe Henry Steinbach, Gustav Akk

2020-Current year OA Pubs

The effect of a potentiating drug on ion channel function is typically evaluated by comparing current responses to the control agonist in the presence and absence of the potentiator. Differences in ratios of responses are then taken as proof of distinct potentiation properties when comparing modulation by different compounds. In these experiments, the concentration of the agonist is typically kept low to generate a small fractional control response. The precise relative magnitude of the control response is, however, not standardized among labs and can range from a concentration producing a response equal to just 2% of maximal (EC2) to over …


Activin A Secretion By Muscle-Repairing Macrophages Induces Heterotopic Ossification In Mice, Wenqiang Yin, Kazuo Okamoto, Asuka Terashima, Warunee Pluemsakunthai, Takehito Ono, Taku Ito-Kureha, Shizuo Akira, Yoshinobu Hashizume, Roland Baron, Satoshi Ueha, Kouji Matsushima, Martin M Matzuk, Yuji Mishina, Hiroshi Takayanagi Mar 2026

Activin A Secretion By Muscle-Repairing Macrophages Induces Heterotopic Ossification In Mice, Wenqiang Yin, Kazuo Okamoto, Asuka Terashima, Warunee Pluemsakunthai, Takehito Ono, Taku Ito-Kureha, Shizuo Akira, Yoshinobu Hashizume, Roland Baron, Satoshi Ueha, Kouji Matsushima, Martin M Matzuk, Yuji Mishina, Hiroshi Takayanagi

Faculty, Staff and Students Publications

The immune system is not only essential for host defense, but it is also involved in tissue maintenance and disease pathogenesis. Macrophages play a key role in tissue repair, fibrosis, and tumorigenesis, but the mechanisms underlying their multifunctionality have not been fully explored. Here, we identified Mrep (Ly6ChiCX3CR1loPDPN+CD9+) as a crucial subset of macrophages for muscle regeneration after muscle injury. Muscle regeneration required Mrep-derived activin A, which was produced via the TLR4/TIR domain-containing adapter-inducing interferon-β/TANK-binding kinase 1/interferon regulatory factor 3/7 signaling pathway in response to muscle injury. Mrep exerted pathological effects by secreting activin A in a model of genetically …


Cell Type-Specific Gene Regulatory Atlas Prioritizes Drug Targets And Repurposable Medicines In Alzheimer's Disease, Yunxiao Ren, Ming Hu, Yang E Li, Andrew A Pieper, Jeffrey Cummings, Feixiong Cheng Mar 2026

Cell Type-Specific Gene Regulatory Atlas Prioritizes Drug Targets And Repurposable Medicines In Alzheimer's Disease, Yunxiao Ren, Ming Hu, Yang E Li, Andrew A Pieper, Jeffrey Cummings, Feixiong Cheng

2020-Current year OA Pubs

Alzheimer's disease (AD) is a complex and poorly understood neurodegenerative disorder that lacks sufficiently effective treatments. Computational and integrative analyses that leverage multiomic data provide a promising strategy to uncover disease mechanisms and identify therapeutic opportunities. Here, we develop a cell type-specific regulatory atlas of the human middle temporal gyrus via leveraging single-nucleus RNA-seq (1,197,032 nuclei) and ATAC-seq (740,875 nuclei) data sets from 84 donors across four stages of AD neuropathological change (ADNC). We observe differential gene expression for six major cell types intensified at severe ADNC. Integrating peak-to-gene linkages and motif enrichment analyses, we reconstruct transcription factor (TF)-target gene …


The Impact Of Human Myoblasts On Macrophage Polarization In A Coculture Model, Elisabeth Ann Stodola Mar 2026

The Impact Of Human Myoblasts On Macrophage Polarization In A Coculture Model, Elisabeth Ann Stodola

Biomedical Engineering

Peripheral Artery Disease (PAD) is characterized by the buildup of atherosclerotic plaque in the lower extremities that occludes blood flow, and affects over 200 million people worldwide. Without effective treatment, PAD can lead to claudication, ischemia, ulcers, and gangrene. PAD causes more amputations in the United States than any other condition, and for severe cases that require revascularization, procedures benefit fewer than 50% of patients. This demonstrates a clear need for alternative therapies. Potential therapies for PAD target expansion of collateral blood vessels around the area of occlusion – a process called arteriogenesis to compensate for loss of blood flow …


Differential Effects Of Neighborhood Ambient Pm2.5 Exposure And Social Vulnerability On Cancer-Related Systemic Inflammation By Race In A Large Health Care System Population From 2000 To 2020, Benjamin A. Rybicki, Zihan Lin, Amber L. Pearson Mar 2026

Differential Effects Of Neighborhood Ambient Pm2.5 Exposure And Social Vulnerability On Cancer-Related Systemic Inflammation By Race In A Large Health Care System Population From 2000 To 2020, Benjamin A. Rybicki, Zihan Lin, Amber L. Pearson

Biological, Geological, and Environmental Faculty Publications

BackgroundThe environment can impact cancer risk both directly, such as through the air we breathe, and indirectly, through the neighborhoods we live in. These risk factors often work in concert but can have disparate effects.MethodsTo understand how air pollution, as measured by ambient particulate matter 2.5 (PM2.5) levels and neighborhood disadvantage based on a geographically assigned social vulnerability index (SVI), may act together to impact cancer risk, we used 2000-2020 statewide cohort data from a large health system based in metropolitan Detroit, MI, USA (n = 245,438). Systemic inflammation was used as a surrogate indicator of cancer risk among study …


Pharmacokinetic Profiles Of Sertraline In Pregnancy As A Predictor Of Postpartum Depressive Symptoms, Sílvia M. Illamola, Zachary N. Stowe, Marc L. Kalin, Michael D. Evans, Catherine M.T. Sherwin, Maged M. Costantine, D. Jeffrey Newport, James C. Ritchie, Angela K. Birnbaum Mar 2026

Pharmacokinetic Profiles Of Sertraline In Pregnancy As A Predictor Of Postpartum Depressive Symptoms, Sílvia M. Illamola, Zachary N. Stowe, Marc L. Kalin, Michael D. Evans, Catherine M.T. Sherwin, Maged M. Costantine, D. Jeffrey Newport, James C. Ritchie, Angela K. Birnbaum

Pediatrics Faculty Publications

Aim: To characterize pharmacokinetic changes of sertraline and its metabolite during pregnancy and postpartum, and their relationship to maternal postpartum depressive symptoms. Methods: This was a prospective observational, longitudinal study of pregnant women with a major depressive disorder treated with sertraline (N = 185 women, 205 pregnancies). Women were enrolled at <16 weeks' gestation and followed at 4-8 week intervals throughout pregnancy and the first postpartum year. Baseline measures included structured clinical interviews and demographic information. Drug and metabolite concentrations and psychometric measures (study outcomes) (ie, Hamilton Rating Scale for depression - 17 item, Beck Depression Inventory, Edinburgh Postnatal Depression Scale [EPDS], Clinical Global Impression [CGI]) were measured at follow-up visits. Serum sertraline and N-desmethylsertraline exposure were reported asstandardized 24-h concentration-to-dose (C/D) and parent to metabolite (P/M) ratios. Linear mixed-effects and latent trajectory models were used to characterize longitudinal patterns in concentration measures across pregnancy and postpartum, and their association with study outcomes. Results: Mean 24-h C/D ratios showed high variability throughout pregnancy and postpartuM.T.hat were characterized by three trajectories for sertraline and five for N-desmethylsertraline and P/M ratio corresponding to different sertraline pharmacokinetic profiles. At postpartum, sertraline drug exposure was inversely associated with higher EPDS score (P < .05), while N-desmethylsertraline exposure was associated with higher scores for all measured depression scales (P < .001). Higher P/M ratios had higher CGI scores (P < .05) postpartum. Conclusion: Sertraline pharmacokinetic profiles varied across pregnant women and were associated with postpartum depressive symptoms. The use of therapeutic monitoring may provide clinical insight that can be useful for identifying patients with a potential toward depressive symptoms.


An Odd Protocol For An Agent-Based Model Of Hepatitis C Virus Transmission In A Homogeneous Syringe-Sharing Network, Seun Ale, Que Thi Nguyet Nguyen Dr., John D. Kelleher Prof., Elizabeth Hunter Dr. Mar 2026

An Odd Protocol For An Agent-Based Model Of Hepatitis C Virus Transmission In A Homogeneous Syringe-Sharing Network, Seun Ale, Que Thi Nguyet Nguyen Dr., John D. Kelleher Prof., Elizabeth Hunter Dr.

Reports

The model described in this ODD is an agent-based model of hepatitis C virus (HCV) transmission among people who inject drugs (PWID). The model assumes homogeneous mixing among syringe-sharing agents, without any form of heterogeneity in the agents interactions or syringe-sharing attitude. All syringe-sharing PWID are treated as identical in terms of their interaction frequency and syringe-sharing probability. Interactions are generated dynamically using proximity-based sampling at each timestep (one day), allowing agents to form syringe-sharing interactions based on spatial closeness. The number of daily interaction events is fixed at the population level, and each syringe-sharing agent has the same probability …


An Odd Protocol For An Agent-Based Model Of Hepatitis C Virus Transmission With Inter- And Intra-Group Structural And Behavioural Heterogeneous Syringe-Sharing Networks (5), Seun Ale, Que Nguyen Dr., John D. Kelleher Prof., Elizabeth Hunter Dr. Mar 2026

An Odd Protocol For An Agent-Based Model Of Hepatitis C Virus Transmission With Inter- And Intra-Group Structural And Behavioural Heterogeneous Syringe-Sharing Networks (5), Seun Ale, Que Nguyen Dr., John D. Kelleher Prof., Elizabeth Hunter Dr.

Reports

The model described in this ODD is an agent-based model of hepatitis C virus (HCV) transmission among people who inject drugs (PWID). The model incorporates structural heterogeneity through a three-group interaction framework and behavioural heterogeneity through group-specific syringe-sharing rates with additional intra-group variability. The syringe-sharing population in the model is divided into core, inner, and outer circle groups representing individuals with high, moderate, and low levels of syringe-sharing interaction intensity, respectively. In addition to differences in the number of daily interaction opportunities across groups, agents in each group are assigned syringe-sharing probabilities that vary at the individual level around their …


Issue 17: Pulmonary & Critical Care Insider, Bharat Bajantri Md, Sarah Ellsworth Mls, Stephanie Subart Pharmd Mar 2026

Issue 17: Pulmonary & Critical Care Insider, Bharat Bajantri Md, Sarah Ellsworth Mls, Stephanie Subart Pharmd

Critical Care & Pulmonary

Pulmonary & Critical Care Insider Issue 17

Compiled by Bharat Bajantri, MD, and librarian Sarah Ellsworth, MLS for the clinicians of the Pulmonary and Critical Care team of Parkview.

The Pulmonary & Critical Care Insider newsletter was created by Dr. Bharat Bajantri, MD and Sarah Ellsworth, MLS in 2023 as a form of current awareness for current practice at our hospital, Parkview Health.

Topics: 

  • Management of Uncomplicated Gram-Negative Bacteremia
  • Complicated Urinary Tract Infection Guidelines Update
  • Ketamine vs Etomidate for RSI
  • STORM-PE 
  • Lung Ultrasound–Guided Weaning
  •  D-Dimer for Pulmonary Embolism
  • Extubation Failure
  •  A Multimodal, physiology-Driven approach to pleural effusions
  • Dexmedetomidine for Hyperactive …


Association Of Human Papillomavirus On Risk Of Hiv Acquisition In African Women: Analyses From Mtn-020/Aspire, Christine L. Hathaway, Elizabeth R. Brown, Stephen Cherne, Alyssa L. Sepulveda, Zvavahera M. Chirenje, Nitesha Jeenarain, Logashvari Naidoo, Samantha Siva, Nishanta Singh, Kubashni Woeber Mar 2026

Association Of Human Papillomavirus On Risk Of Hiv Acquisition In African Women: Analyses From Mtn-020/Aspire, Christine L. Hathaway, Elizabeth R. Brown, Stephen Cherne, Alyssa L. Sepulveda, Zvavahera M. Chirenje, Nitesha Jeenarain, Logashvari Naidoo, Samantha Siva, Nishanta Singh, Kubashni Woeber

School of Medicine Publications

Background: Observational data on the synergy between human papillomavirus (HPV) infection and risk for HIV acquisition are needed. HPV clearance, associated with an influx of cells targeted by HIV, may increase HIV risk. This study examined the association between HPV and HIV acquisition using endocervical swabs collected in MTN-020/ASPIRE.

Methods: Healthy, sexually active women without HIV participating in the ASPIRE dapivirine ring study in Malawi, South Africa, Uganda, and Zimbabwe provided endocervical swabs monthly, which were tested for HPV-DNA. HPV status was classified into prevalent, persistent (HPV+ for at least 4 months), HPV clearance (HPV+ followed by HPV-), HPV acquisition …


An Odd Protocol For An Agent-Based Model Of Hepatitis C Virus Transmission In A Two-Group Structural Heterogeneous Syringe-Sharing Network (M2), Seun Ale, Que Nguyen Dr., John D. Kelleher Prof., Elizabeth Hunter Dr. Mar 2026

An Odd Protocol For An Agent-Based Model Of Hepatitis C Virus Transmission In A Two-Group Structural Heterogeneous Syringe-Sharing Network (M2), Seun Ale, Que Nguyen Dr., John D. Kelleher Prof., Elizabeth Hunter Dr.

Reports

The model described in this ODD is an agent-based model of hepatitis C virus (HCV) transmission among people who inject drugs (PWID). The model extended a baseline homogeneous model by incorporating structural heterogeneity via a two-group interaction framework. The syringe-sharing population in the model is divided into inner and outer circle groups representing individuals with differing levels of syringe-sharing interaction intensity. While all agents share the same syringe-sharing probability and epidemiological processes remain identical across agents, the number of daily interaction opportunities differs between the two groups. Interactions in the model are generated dynamically using proximity-based sampling at each timestep …


An Odd Protocol For An Agent-Based Model Of Hepatitis C Virus Transmission In A Three-Group Structural Heterogeneous Syringe-Sharing Network (M3), Seun Ale, Que Nguyen Dr., John D. Kelleher Prof., Elizabeth Hunter Dr. Mar 2026

An Odd Protocol For An Agent-Based Model Of Hepatitis C Virus Transmission In A Three-Group Structural Heterogeneous Syringe-Sharing Network (M3), Seun Ale, Que Nguyen Dr., John D. Kelleher Prof., Elizabeth Hunter Dr.

Reports

The model described in this ODD is an agent-based model of hepatitis C virus (HCV) transmission among people who inject drugs (PWID). The model incorporates structural heterogeneity through a three-group interaction framework. The syringe-sharing population in the model is divided into core, inner, and outer circle groups representing individuals with high, moderate, and low levels of syringe-sharing interaction intensity, respectively. While the syringe-sharing rate and all epidemiological processes remain identical across agents, the number of daily interaction opportunities differs by agent grouping, capturing variation in structural position within the syringe-sharing network. Interactions are generated dynamically using proximity-based sampling at each …


An Odd Protocol For An Agent-Based Model Of Hepatitis C Virus Transmission With Inter-Group Structural And Behavioural Heterogeneous Syringe-Sharing Networks (M4), Seun Ale, Que Nguyen Dr., John D. Kelleher Prof., Elizabeth Hunter Dr. Mar 2026

An Odd Protocol For An Agent-Based Model Of Hepatitis C Virus Transmission With Inter-Group Structural And Behavioural Heterogeneous Syringe-Sharing Networks (M4), Seun Ale, Que Nguyen Dr., John D. Kelleher Prof., Elizabeth Hunter Dr.

Reports

The model described in this ODD is an agent-based model of hepatitis C virus (HCV) transmission among people who inject drugs (PWID). The model incorporates structural heterogeneity through a three-group interaction framework and behavioural heterogeneity through group-specific syringe-sharing rates. The syringe-sharing population in the model is divided into core, inner, and outer circle groups representing individuals with high, moderate, and low levels of syringe-sharing interaction intensity, respectively. In addition to differences in the number of daily interaction opportunities across groups, agents in each group are assigned distinct syringe-sharing probabilities, reflecting variation in risk-taking behaviour across structural groups within the syringe-sharing …


Neutrophil-To-Lymphocyte Ratio As A Prognostic Factor Of Survival Outcomes In Head And Neck Squamous Cell Carcinoma Receiving Neoadjuvant Immunotherapy, Pablo Llerena, Praneet C. Kaki, Kathryn Nunes, Eric Mastrolonardo, Kelly Bridgham, Annie Moroco, Hani Samarah, Mouadh Barbirou, David Baek, Chun Wang, Voichita Bar-Ad, David Cognetti, Joseph Curry, Jennifer M. Johnson, Hushan Yang, Larry A. Harshyne, Adam J. Luginbuhl Mar 2026

Neutrophil-To-Lymphocyte Ratio As A Prognostic Factor Of Survival Outcomes In Head And Neck Squamous Cell Carcinoma Receiving Neoadjuvant Immunotherapy, Pablo Llerena, Praneet C. Kaki, Kathryn Nunes, Eric Mastrolonardo, Kelly Bridgham, Annie Moroco, Hani Samarah, Mouadh Barbirou, David Baek, Chun Wang, Voichita Bar-Ad, David Cognetti, Joseph Curry, Jennifer M. Johnson, Hushan Yang, Larry A. Harshyne, Adam J. Luginbuhl

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

PURPOSE: The neutrophil-to-lymphocyte ratio (NLR) is a prognostic marker in cancers treated with immune checkpoint inhibitors (ICI), reflecting the link between inflammation and cancer immune response. This study examines NLR's prognostic value in head and neck squamous cell carcinoma (HNSCC) patients receiving neoadjuvant ICI therapy, focusing on its potential as an independent predictor of overall survival (OS) and disease-free survival (DFS).

METHODS: We conducted a retrospective cohort study including three neoadjuvant trials: durvalumab ± metformin, nivolumab ± tadalafil, or nivolumab ± BMS-986205 from 2017 to 2022. Pre-treatment NLR was calculated using absolute neutrophil and absolute lymphocyte counts obtained before neoadjuvant …