Health Services Research Commons^™

Metabolic Regulator Errγ Governs Gastric Stem Cell Differentiation Into Acid-Secreting Parietal Cells, Mahliyah Adkins-Threats, Sumimasa Arimura, Yang-Zhe Huang, Margarita Divenko, Sarah To, Heather Mao, Yongji Zeng, Jenie Y Hwang, Joseph R Burclaff, Shilpa Jain, Jason C Mills

Faculty, Staff and Students Publications

Parietal cells (PCs) produce gastric acid to kill pathogens and aid digestion. Dysregulated PC census is common in disease, yet how PCs differentiate is unclear. Here, we identify the PC progenitors arising from isthmal stem cells, using mouse models and human gastric cells, and show they preferentially express cell-metabolism regulator and orphan nuclear receptor Estrogen-related receptor gamma (Esrrg, encoding ERRγ). Esrrg expression facilitated the tracking of stepwise molecular, cellular, and ultrastructural stages of PC differentiation. Esrrg^P2ACreERT2 lineage tracing revealed Esrrg expression commits progenitors to differentiate into mature PCs. scRNA-seq indicated the earliest Esrrg+ PC progenitors preferentially …

Barriers To The Assessment And Recommendation Of Hpv Vaccination Among Healthcare Providers In Texas, Onyema G Chido-Amajuoyi, Ikponmwosa Osaghae, Henry K Onyeaka, Sanjay Shete

Faculty, Staff and Student Publications

BACKGROUND: Healthcare providers (HCPs) recommendations for HPV vaccination plays a critical role in increasing vaccination uptake. This study assesses the prevalence of reported barriers to HPV vaccination assessment and recommendation among HCPs in Texas.

METHODS: Study data were obtained from a population-based survey of HCPs currently practicing in Texas. Participants were asked about their HPV vaccination assessment and recommendation practices and the reasons for not assessing or recommending the vaccine. Barriers were stratified by HCP characteristics including age, sex, race/ethnicity, location of practice, provider type, and type of facility.

RESULTS: Among the 826 HCPs included in this study, 47.3 % …

Contextual Factors Influencing The Association Between The Affordable Care Act’S Medicaid Expansion And Veteran Va-Medicaid Dual Enrollment, Patrick N O'Mahen, Chase S Eck, Cheng Rebecca Jiang, Laura A Petersen

Center for Medical Ethics and Health Policy Staff Publications

Objective: To evaluate changes in dual enrollment after Affordable Care Act Medicaid expansion by VA priority group, (e.g., service connection), sex, and type of state expansion.

Study setting: Our cohort was all Veterans ages 18-64 enrolled in VA and eligible for benefits due to military service-connection or low income from 2011 to 2016; the unit of analysis was person-year.

Study design: Difference-in-difference and event-study analysis. The outcome was dual VA-Medicaid enrollment for at least 1 month annually. Medicaid expansion, VA priority status, whether a state expanded by a Section 1115 waiver, and sex were independent variables. We controlled for race, …

Anoctamin 4 Defines Glucose-Inhibited Neurons In The Ventromedial Hypothalamus, Longlong Tu, Yanlin He, Yong Xu

Faculty, Staff and Students Publications

No abstract provided.

Neighborhood-Level Disadvantage And Delayed Adjuvant Therapy In Head And Neck Cancer, Evan M Graboyes, Joshua Lee Cagle, Salma Ramadan, Kavita Prasad, Flora Yan, John Pearce, Angela L Mazul, Jean-Sebastien Anoma, Elizabeth G Hill, Bhisham S Chera, Sidharth V Puram, Ryan Jackson, Vlad C Sandulache, Samantha Tam, Michael C Topf, Russel Kahmke, Nosayaba Osazuwa-Peters, Brian Nussenbaum, Anthony J Alberg, Katherine R Sterba, Chanita Hughes Halbert

Faculty, Staff and Students Publications

Importance: For patients with head and neck squamous cell carcinoma (HNSCC), initiation of postoperative radiation therapy (PORT) within 6 weeks of surgery is recommended by the National Comprehensive Cancer Network Guidelines and the Commission on Cancer. Although individual-level measures of socioeconomic status are associated with receipt of timely, guideline-adherent PORT, the role of neighborhood-level disadvantage has not been examined.

Objective: To characterize the association of neighborhood-level disadvantage with delays in receiving PORT.

Design, setting, and participants: This retrospective cohort study included 681 adult patients with HNSCC undergoing curative-intent surgery and PORT from 2018 to 2020 at 4 US academic medical …

Serum Extracellular Vesicle Protein Profiling For Prediction Of Corneal Transplant Rejection, Hyun Ju Lee, Eun-Hye Bae, Jong Min Choi, Hyemee Kim, Hyeon Ji Kim, Heather Barreda, Sung Yun Jung, Joo Youn Oh, Ryang Hwa Lee

Faculty, Staff and Students Publications

Background: Corneal transplantation is the most common transplant procedure worldwide. Despite immune and angiogenic privilege of the cornea, 50% to 70% of corneal transplants fail in high-risk recipients, primarily because of immune rejection. Therefore, it is crucial to identify predictive biomarkers of rejection to improve transplant survival.

Methods: In search for predictive biomarkers, we performed proteomics analysis of serum extracellular vesicles (EVs) in a fully major histocompatibility complex-mismatched (C57BL/6-to-BALB/c) murine corneal transplantation model, wherein 50% of transplants undergo rejection by day 28 following transplantation.

Results: Our time course study revealed a decrease in the number of serum EVs on day …

Interfacility Referral Communication For Picu Transfer, Caitlin K Thirnbeck, Elizabeth T Espinoza, Elizabeth A Beaman, Alexis L Rozen, Kimberly C Dukes, Hardeep Singh, Loreen A Herwaldt, Christopher P Landrigan, Heather Schacht Reisinger, Christina L Cifra

Faculty, Staff and Students Publications

Objectives: For patients requiring transfer to a higher level of care, excellent interfacility communication is essential. Our objective was to characterize verbal handoffs for urgent interfacility transfers of children to the PICU and compare these characteristics with known elements of high-quality intrahospital shift-to-shift handoffs.

Design: Mixed methods retrospective study of audio-recorded referral calls between referring clinicians and receiving PICU physicians for urgent interfacility PICU transfers.

Setting: Academic tertiary referral PICU.

Patients: Children 0-18 years old admitted to a single PICU following interfacility transfer over a 4-month period (October 2019 to January 2020).

Interventions: None.

Measurements and main results: We reviewed …

Rural Veterans With Hiv And Alcohol Use Disorder Receive Less Video Telehealth Than Urban Veterans, Alan Z Sheinfil, Giselle Day, Annette Walder, Julianna Hogan, Thomas P Giordano, Jan Lindsay, Anthony Ecker

Faculty, Staff and Students Publications

Purpose: Alcohol use disorder (AUD) is highly prevalent among Veterans with HIV. Rural Veterans with HIV are at especially high risk for not receiving appropriate treatment. This retrospective cohort cross-sectional study aimed to investigate patterns of mental health treatment utilization across delivery modality among Veterans diagnosed with HIV and AUD. It was hypothesized that rural Veterans with HIV and AUD would receive a lower rate of mental health treatment delivered via video telehealth than urban Veterans with HIV and AUD.

Methods: A national Veterans Health Association administrative database was used to identify a cohort of Veterans diagnosed with HIV and …

Multifactoral Immune Modulation Potentiates Durable Remission In Multiple Models Of Aggressive Malignancy, Matthew M Halpert, Briana A Burns, Spencer R Rosario, Henry G Withers, Akshar J Trivedi, Colby J Hofferek, Benjamin D Gephart, Haotong Wang, Jonathan Vazquez-Perez, Sharon B Amanya, Sean T Hyslop, Jianhua Yang, Jan O Kemnade, Vlad C Sandulache, Vanaja Konduri, William K Decker

Faculty, Staff and Students Publications

Tumors typically lack canonical danger signals required to activate adaptive immunity and also frequently employ substantial immunomodulatory mechanisms that downregulate adaptive responses and contribute to escape from immune surveillance. Given the variety of mechanisms involved in shielding tumors from immune recognition, it is not surprising that single-agent immunomodulatory approaches have been largely unsuccessful in generating durable antitumor responses. Here we report a unique combination of immunomodulatory and cytostatic agents that recondition the tumor microenvironment and eliminate complex and/or poor-prognosis tumor types including the non-immunogenic 4T-1 model of TNBC, the aggressive MOC-2 model of HNSCC, and the high-risk MYCN-amplified model of …

Generation Of Oviductal Glycoprotein 1 Cre Mouse Model For The Study Of Secretory Epithelial Cells Of The Oviduct, Emily A Mcglade, Jiude Mao, Kalli K Stephens, Andrew M Kelleher, Lisette A Maddison, Miranda L Bernhardt, Francesco J Demayo, John P Lydon, Wipawee Winuthayanon

Faculty, Staff and Students Publications

The epithelial cell lining of the oviduct plays an important role in oocyte pickup, sperm migration, preimplantation embryo development, and embryo transport. The oviduct epithelial cell layer comprises ciliated and nonciliated secretory cells. The ciliary function has been shown to support gamete and embryo movement in the oviduct, yet secretory cell function has not been well characterized. Therefore, our goal was to generate a secretory cell-specific Cre recombinase mouse model to study the role of the oviductal secretory cells. A knock-in mouse model, Ovgp1Cre:eGFP, was created by expressing Cre from the endogenous Ovgp1 (oviductal glycoprotein 1) locus, with enhanced green …

Optical Coherence Tomography-Guided Brillouin Microscopy Highlights Regional Tissue Stiffness Differences During Anterior Neural Tube Closure In The Mthfd1l Murine Mutant, Yogeshwari S Ambekar, Carlo Donato Caiaffa, Bogdan J Wlodarczyk, Manmohan Singh, Alexander W Schill, John W Steele, Jitao Zhang, Salavat R Aglyamov, Giuliano Scarcelli, Richard H Finnell, Kirill V Larin

Faculty, Staff and Students Publications

Neurulation is a highly synchronized biomechanical process leading to the formation of the brain and spinal cord, and its failure leads to neural tube defects (NTDs). Although we are rapidly learning the genetic mechanisms underlying NTDs, the biomechanical aspects are largely unknown. To understand the correlation between NTDs and tissue stiffness during neural tube closure (NTC), we imaged an NTD murine model using optical coherence tomography (OCT), Brillouin microscopy and confocal fluorescence microscopy. Here, we associate structural information from OCT with local stiffness from the Brillouin signal of embryos undergoing neurulation. The stiffness of neuroepithelial tissues in Mthfd1l null embryos …

Interprofessional Curriculum Delivery: Experience Of A Primary Care Education Program, Jessica A Davila, Nancy D Harada, Kathryn Wirtz Rugen, Stuart C Gilman, Shubhada Sansgiry

Faculty, Staff and Students Publications

Few post-graduate training programs offer a comprehensive curriculum that includes structured clinical experiences to teach interprofessional care. To address this need, the United States Department of Veterans Affairs, Office of Academic Affiliations funded the Centers of Excellence in Primary Care Education (CoEPCE) from 2011-2019 to provide interprofessional curricula for health profession trainees (HPTs), including physician residents, nurse practitioner residents, pharmacy residents, and psychology residents. We examined changes over time in curricular domains, system impacts, and program practices based on HPT survey data and the qualitative evaluation of narrative feedback. An annual survey was administered to participants. Indirect standardized ratios were …

Metaplastic Regeneration In The Mouse Stomach Requires A Reactive Oxygen Species Pathway, Zhi-Feng Miao, Jing-Xu Sun, Xuan-Zhang Huang, Shi Bai, Min-Jiao Pang, Jia-Yi Li, Han-Yu Chen, Qi-Yue Tong, Shi-Yu Ye, Xin-Yu Wang, Xiao-Hai Hu, Jing-Ying Li, Jin-Wei Zou, Wen Xu, Jun-Hao Yang, Xi Lu, Jason C Mills, Zhen-Ning Wang

Faculty, Staff and Students Publications

In pyloric metaplasia, mature gastric chief cells reprogram via an evolutionarily conserved process termed paligenosis to re-enter the cell cycle and become spasmolytic polypeptide-expressing metaplasia (SPEM) cells. Here, we use single-cell RNA sequencing (scRNA-seq) following injury to the murine stomach to analyze mechanisms governing paligenosis at high resolution. Injury causes induced reactive oxygen species (ROS) with coordinated changes in mitochondrial activity and cellular metabolism, requiring the transcriptional mitochondrial regulator Ppargc1a (Pgc1α) and ROS regulator Nf2el2 (Nrf2). Loss of the ROS and mitochondrial control in Ppargc1a-/- mice causes the death of paligenotic cells through ferroptosis. Blocking the cystine transporter SLC7A11(xCT), which …

Fatty Acid Concentrations In Preterm Infants Fed The Exclusive Human Milk Diet: A Prospective Cohort Study, Lindsay F Holzapfel, Jana P Unger, Pam Gordon, Heeju Yang, Joanne E Cluette-Brown, Laura A Gollins, Amy B Hair, Camilia R Martin

Faculty, Staff and Student Publications

OBJECTIVE: Quantify blood fatty acids and growth outcomes in preterm infants fed the exclusive human milk diet.

METHODS: A prospective cohort study of 30 infants 24-34 weeks gestation and ≤1250 g fed the exclusive human milk diet. Blood fatty acids were quantified at two time points. Comparisons were made using two-sample t-tests and Wilcoxon rank sum.

RESULTS: Donor human milk-fed (n = 12) compared to mother's own milk-fed infants (n = 18) from birth to after 28 days of life, had an increased interval change of linoleic to docosahexaenoic acid ratio (5.5 vs. -1.1 mole percent ratio, p = 0.034). …

Trends And Updates On The Epidemiology Of Cancer Associated Thrombosis: A Systematic Review, Ang Li, Emily Zhou

Faculty, Staff and Students Publications

Introduction: Cancer associated thrombosis (CAT) is a significant complication for patients with cancer. This review summarizes an updated epidemiology of CAT in the past decade.

Methods: A systematic review was conducted on relevant population cohort studies published 2011-2024.

Results: The 12-month incidence of CAT among patients with unselected cancers is approximately 3-5% (9-fold increase vs. matched non-cancer population); although the risk increases to 6-8% in patients with advanced cancers requiring systemic therapy (20-fold increase vs. matched non-cancer population). Despite improvement in anticoagulation usage and adherence, recurrence risk remains high at 5-8% at 6 months and 7-15% at 12 months. Important …

Risk Evaluation In Occupational Safety And Health Research: Results From A Benchmarking Exercise Of Federal And Academic Irbs, Sarah A Felknor, Jessica M K Streit, Angela M Morley, John D Piacentino

Faculty, Staff and Student Publications

OBJECTIVE: Research involving working populations can pose unique ethical and risk evaluation challenges. The purpose of this benchmarking project was to assess how federal agencies and academic institutions approach the interpretation and application of key risk evaluation concepts in research involving workers in their places of employment.

METHODS: Key informant interviews were conducted to ascertain current practices related to assessing soundness of research design, determining risk reasonableness and research relatedness of risks, and evaluating the risk of noninvasive clinical tests in occupational settings.

RESULTS: There were noteworthy commonalities among the approaches described to review and address critical aspects of risk …

Natural History Of Cancer-Associated Splanchnic Vein Thrombosis, Hanqing Shang, Jun Y Jiang, Danielle Guffey, Francisco Novoa, Raka Bandyo, Shengling Ma, Ang Li

Faculty, Staff and Students Publications

Background: There is uncertainty in the management of cancer-associated isolated splanchnic vein thrombosis (SpVT).

Objectives: To describe the natural history of SpVT by cancer type and thrombus composition and to review anticoagulation (AC) practices and associated rates of usual-site venous thromboembolism (VTE), major and clinically relevant nonmajor bleeding (MB/CRNMB), recanalization/progression, and mortality.

Methods: We performed a retrospective cohort study in patients with SpVT at 2 cancer care centers in Houston, Texas. We estimated the incidence of usual-site VTE and MB/CRNMB at 6 months using competing risk methods and examined venous patency in a subset of patients with repeat imaging. We …

Proteomic Biomarkers Of Quantitative Interstitial Abnormalities In Copdgene And Cardia Lung Study, Bina Choi, Gabrielle Y Liu, Quanhu Sheng, Kaushik Amancherla, Andrew Perry, Xiaoning Huang, Ruben San José Estépar, Samuel Y Ash, Weihua Guan, David R Jacobs, Fernando J Martinez, Ivan O Rosas, Russell P Bowler, Jonathan A Kropski, Nicholas E Banovich, Sadiya S Khan, Raúl San José Estépar, Ravi Shah, Bharat Thyagarajan, Ravi Kalhan, George R Washko

Faculty, Staff and Students Publications

Rationale: Quantitative interstitial abnormalities (QIAs) are early measures of lung injury automatically detected on chest computed tomography scans. QIAs are associated with impaired respiratory health and share features with advanced lung diseases, but their biological underpinnings are not well understood. Objectives: To identify novel protein biomarkers of QIAs using high-throughput plasma proteomic panels within two multicenter cohorts.

Methods: We measured the plasma proteomics of 4,383 participants in an older, ever-smoker cohort (COPDGene [Genetic Epidemiology of Chronic Obstructive Pulmonary Disease]) and 2,925 participants in a younger population cohort (CARDIA [Coronary Artery Disease Risk in Young Adults]) using the SomaLogic SomaScan assays. …

Emerging Evidence For Glucagon-Like Peptide-1 Agonists In Slowing Chronic Kidney Disease Progression, Michael W Holliday, Livia Frost, Sankar D Navaneethan

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: Diabetic kidney disease continues to increase, and several novel therapeutic agents have been shown to slow the progression of chronic kidney disease in those with diabetes. This review summarizes more recent data on the role of glucagon-like peptide-1 (GLP-1) receptor agonists and kidney outcomes.

RECENT FINDINGS: Posthoc analysis of cardiovascular outcome trials, as well as several retrospective studies, demonstrate benefits of GLP-1 receptor agonist therapy for chronic kidney disease progression in diabetics. Although limited randomized clinical trials evidence assessing the effects of GLP-1 receptor agonists on kidney outcomes in diabetic chronic kidney disease patients have been published, …

Caenorhabditis Elegans Endorse Bacterial Nanocellulose Fibers As Functional Dietary Fiber Reducing Lipid Markers, Amanda Muñoz-Juan, Adrien Assié, Anna Esteve-Codina, Marta Gut, Núria Benseny-Cases, Buck S Samuel, Esther Dalfó, Anna Laromaine

Faculty, Staff and Students Publications

Bacterial nanocellulose (BNC) is a promising dietary fiber with potential as a functional food additive. We evaluated BNC fibers (BNCf) in the Caenorhabditis elegans model to obtain insight into the BNCf's biointeraction with its gastrointestinal tract while reducing the variables of higher complex animals. BNCf were uptaken and excreted by worms without crossing the intestinal barrier, confirming its biosafety regarding survival rate, reproduction, and aging for concentrations up to 34 μg/ml BNCf. However, a slight decrease in the worms' length was detected. A possible nutrient shortage or stress produced by BNCf was discarded by measuring stress and chemotactic response pathways. …

Engineering Small-Molecule And Protein Drugs For Targeting Bone Tumors, Yixian Wang, Chenhang Wang, Meng Xia, Zeru Tian, Joseph Zhou, Julian Meyer Berger, Xiang H-F Zhang, Han Xiao

Faculty, Staff and Students Publications

Bone cancer is common and severe. Both primary (e.g., osteosarcoma, Ewing sarcoma) and secondary (e.g., metastatic) bone cancers lead to significant health problems and death. Currently, treatments such as chemotherapy, hormone therapy, and radiation therapy are used to treat bone cancer, but they often only shrink or slow tumor growth and do not eliminate cancer completely. The bone microenvironment contributes unique signals that influence cancer growth, immunogenicity, and metastasis. Traditional cancer therapies have limited effectiveness due to off-target effects and poor distribution on bones. As a result, therapies with improved specificity and efficacy for treating bone tumors are highly needed. …

Angiogenic Gene Therapy For Refractory Angina: Results Of The Exact Phase 2 Trial, Kenta Nakamura, Timothy D Henry, Jay H Traverse, David A Latter, Nahush A Mokadam, Geoffrey A Answini, Adam R Williams, Benjamin C Sun, Christopher R Burke, Faisal G Bakaeen, Marcelo F Dicarli, Bernard R Chaitman, Mark W Peterson, Dawn G Byrnes, E Magnus Ohman, Carl J Pepine, Ronald G Crystal, Todd K Rosengart, Elaine Kowalewski, Gary G Koch, Howard C Dittrich, Thomas J Povsic, Exact Trial Investigators

Faculty, Staff and Students Publications

Background: XC001 is a novel adenoviral-5 vector designed to express multiple isoforms of VEGF (vascular endothelial growth factor) and more safely and potently induce angiogenesis. The EXACT trial (Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment) assessed the safety and preliminary efficacy of XC001 in patients with no option refractory angina.

Methods: In this single-arm, multicenter, open-label trial, 32 patients with no option refractory angina received a single treatment of XC001 (1×1011 viral particles) via transepicardial delivery.

Results: There were no severe adverse events attributed to the study drug. Twenty expected severe adverse events in 13 patients …

Mechanisms Driving Fasting-Induced Protection From Genotoxic Injury In The Small Intestine, Kali Deans-Fielder, Timothy Wu, Thanh Nguyen, Sarah To, Yang-Zhe Huang, Steven J Bark, Jason C Mills, Noah F Shroyer

Faculty, Staff and Students Publications

Genotoxic agents such as doxorubicin (DXR) can cause damage to the intestines that can be ameliorated by fasting. How fasting is protective and the optimal timing of fasting and refeeding remain unclear. Here, our analysis of fasting/refeeding-induced global intestinal transcriptional changes revealed metabolic shifts and implicated the cellular energetic hub mechanistic target of rapamycin complex 1 (mTORC1) in protecting from DXR-induced DNA damage. Our analysis of specific transcripts and proteins in intestinal tissue and tissue extracts showed that fasting followed by refeeding at the time of DXR administration reduced damage and caused a spike in mTORC1 activity. However, continued fasting …

Targeting Idh2r140q And Other Neoantigens In Acute Myeloid Leukemia, Wingchi K Leung, Alejandro G Torres Chavez, Matthew French-Kim, Paul Shafer, Maksim Mamonkin, Laquisa C Hill, Manik Kuvalekar, Yovana Velazquez, Ayumi Watanabe, Norihiro Watanabe, Valentina Hoyos, Premal Lulla, Ann M Leen

Faculty, Staff and Students Publications

For patients with high-risk or relapsed/refractory acute myeloid leukemia (AML), allogeneic stem cell transplantation (allo-HSCT) and the graft-versus-leukemia effect mediated by donor T cells, offer the best chance of long-term remission. However, the concurrent transfer of alloreactive T cells can lead to graft-versus-host disease that is associated with transplant-related morbidity and mortality. Furthermore, ∼60% of patients will ultimately relapse after allo-HSCT, thus, underscoring the need for novel therapeutic strategies that are safe and effective. In this study, we explored the feasibility of immunotherapeutically targeting neoantigens, which arise from recurrent nonsynonymous mutations in AML and thus represent attractive targets because they …

Centralized Interactive Phenomics Resource: An Integrated Online Phenomics Knowledgebase For Health Data Users, Jacqueline Honerlaw, Yuk-Lam Ho, Francesca Fontin, Michael Murray, Ashley Galloway, David Heise, Keith Connatser, Laura Davies, Jeffrey Gosian, Monika Maripuri, John Russo, Rahul Sangar, Vidisha Tanukonda, Edward Zielinski, Maureen Dubreuil, Andrew J Zimolzak, Vidul A Panickan, Su-Chun Cheng, Stacey B Whitbourne, David R Gagnon, Tianxi Cai, Katherine P Liao, Rachel B Ramoni, J Michael Gaziano, Sumitra Muralidhar, Kelly Cho

Faculty, Staff and Students Publications

Objective: Development of clinical phenotypes from electronic health records (EHRs) can be resource intensive. Several phenotype libraries have been created to facilitate reuse of definitions. However, these platforms vary in target audience and utility. We describe the development of the Centralized Interactive Phenomics Resource (CIPHER) knowledgebase, a comprehensive public-facing phenotype library, which aims to facilitate clinical and health services research.

Materials and methods: The platform was designed to collect and catalog EHR-based computable phenotype algorithms from any healthcare system, scale metadata management, facilitate phenotype discovery, and allow for integration of tools and user workflows. Phenomics experts were engaged in the …

Multi-Omics Analysis Reveals Immune Features Associated With Immunotherapy Benefit In Patients With Squamous Cell Lung Cancer From Phase Iii Lung-Map S1400i Trial, Edwin Roger Parra, Jiexin Zhang, Dzifa Yawa Duose, Edgar Gonzalez-Kozlova, Mary W Redman, Hong Chen, Ganiraju C Manyam, Gayatri Kumar, Jianhua Zhang, Xingzhi Song, Rossana Lazcano, Mario L Marques-Piubelli, Caddie Laberiano-Fernandez, Frank Rojas, Baili Zhang, Len Taing, Aashna Jhaveri, Jacob Geisberg, Jennifer Altreuter, Franziska Michor, James Provencher, Joyce Yu, Ethan Cerami, Radim Moravec, Kasthuri Kannan, Rajyalakshmi Luthra, Gheath Alatrash, Hsin-Hui Huang, Hui Xie, Manishkumar Patel, Kai Nie, Jocelyn Harris, Kimberly Argueta, James Lindsay, Roshni Biswas, Stephen Van Nostrand, Seunghee Kim-Schulze, Jhanelle E Gray, Roy S Herbst, Ignacio I Wistuba, Scott Gettinger, Karen Kelly, Lyudmila Bazhenova, Sacha Gnjatic, J Jack Lee, Jianjun Zhang, Cara Haymaker

Faculty, Staff and Student Publications

PURPOSE: Identifying molecular and immune features to guide immune checkpoint inhibitor (ICI)-based regimens remains an unmet clinical need.

EXPERIMENTAL DESIGN: Tissue and longitudinal blood specimens from phase III trial S1400I in patients with metastatic squamous non-small cell carcinoma (SqNSCLC) treated with nivolumab monotherapy (nivo) or nivolumab plus ipilimumab (nivo+ipi) were subjected to multi-omics analyses including multiplex immunofluorescence (mIF), nCounter PanCancer Immune Profiling Panel, whole-exome sequencing, and Olink.

RESULTS: Higher immune scores from immune gene expression profiling or immune cell infiltration by mIF were associated with response to ICIs and improved survival, except regulatory T cells, which were associated with worse …

Clearing The Air: Innovations In Imaging For Early Detection And Management Of Chronic Obstructive Pulmonary Disease, Francesca Polverino

Faculty, Staff and Students Publications

No abstract provided.

Evaluation Of Four Computed Tomography Reconstruction Algorithms Using A Coronary Artery Phantom, Shungo Sawamura, Shingo Kato, Yoshinori Funama, Seitaro Oda, Harumi Mochizuki, Sayuri Inagaki, Yuka Takeuchi, Tsubasa Morioka, Toshiharu Izumi, Yoichiro Ota, Hironori Kawagoe, Shihyao Cheng, Naoki Nakayama, Kazuki Fukui, Takashi Tsutsumi, Tae Iwasawa, Daisuke Utsunomiya

Faculty, Staff and Student Publications

BACKGROUND: Despite advancements in coronary computed tomography angiography (CTA), challenges in positive predictive value and specificity remain due to limited spatial resolution. The purpose of this experimental study was to investigate the effect of 2nd generation deep learning-based reconstruction (DLR) on the quantitative and qualitative image quality in coronary CTA.

METHODS: A vessel model with stepwise non-calcified plaque was scanned using 320-detector CT. Image reconstruction was performed using four techniques: hybrid iterative reconstruction (HIR), model-based iterative reconstruction (MBIR), DLR, and 2nd generation DLR. The luminal peak CT number, contrast-to-noise ratio (CNR), and edge rise slope (ERS) were quantitatively evaluated via …

An Oocyte-Specific Cas9-Expressing Mouse For Germline Crispr/Cas9-Mediated Genome Editing, Denise G Lanza, Jianqiang Mao, Isabel Lorenzo, Lan Liao, John R Seavitt, M Cecilia Ljungberg, Elizabeth M Simpson, Francesco J Demayo, Jason D Heaney

Faculty, Staff and Students Publications

Cas9 transgenes can be employed for genome editing in mouse zygotes. However, using transgenic instead of exogenous Cas9 to produce gene-edited animals creates unique issues including ill-defined transgene integration sites, the potential for prolonged Cas9 expression in transgenic embryos, and increased genotyping burden. To overcome these issues, we generated mice harboring an oocyte-specific, Gdf9 promoter driven, Cas9 transgene (Gdf9-Cas9) targeted as a single copy into the Hprt1 locus. The X-linked Hprt1 locus was selected because it is a defined integration site that does not influence transgene expression, and breeding of transgenic males generates obligate transgenic females to serve as embryo …

Alveolar Epithelial Cell Dysfunction In Idiopathic Pulmonary Fibrosis Linked To Lipid Alterations: Therapeutic Implications, Francesca Polverino, Ana Mora

Faculty, Staff and Students Publications

No abstract provided.