Digital Commons Network^™

Concordance Of Human Papillomavirus Genotypes In Mailed Home-Based Self-Collected Versus Clinician-Collected Anal Swabs Among Sexual And Gender Minority Individuals, Jenna Nitkowski, Anna R Giuliano, Tim Ridolfi, Elizabeth Chiao, Maria E Fernandez, Vanessa Schick, Michael D Swartz, Jennifer S Smith, Alan G Nyitray

Faculty, Staff and Student Publications

Background: Home-based self-sampling may be a viable option for anal cancer screening among sexual minority men (SMM). Yet limited research has compared home-based self-collected with clinician-collected anal swabs for human papillomavirus (HPV) genotyping.

Methods: The Prevent Anal Cancer Self-Swab Study recruited SMM and transgender persons 25 years and over in Milwaukee, WI to participate in an anal cancer screening study. Participants were randomized to a home or clinic arm. Home-based participants were mailed an anal self-sampling kit to complete and return via postal mail. They were also asked to attend a clinic appointment where a clinician collected an anal swab. …

Randomized Phase 2 Trial Of Tremelimumab And Durvalumab In Combination Versus Sequentially In Recurrent Platinum-Resistant Ovarian Cancer, Emily M Hinchcliff, Anne Knisely, Naomi Adjei, Bryan Fellman, Ying Yuan, Ami Patel, Cai Xu, Shannon N Westin, Anil K Sood, Pamela T Soliman, Aaron Shafer, Nicole D Fleming, David M Gershenson, Raghunandan Vikram, Tharakeswara Bathala, David Vining, Dhakshina M Ganeshan, Karen H Lu, Charlotte C Sun, Larissa A Meyer, Amir A Jazaeri

Faculty, Staff and Student Publications

BACKGROUND: Single-agent immune checkpoint inhibitors (ICIs) have demonstrated limited responses in recurrent ovarian cancer; however, 30%-40% of patients achieve stable disease. The primary objective was to estimate progression-free survival (PFS) after sequential versus combination cytotoxic T-lymphocyte antigen 4 and programmed death ligand 1 ICIs in patients with platinum-resistant high-grade serous ovarian cancer (HGSOC).

METHODS: Patients were randomized to a sequential arm (tremelimumab followed by durvalumab on progression) or a combination arm (tremelimumab plus durvalumab, followed by durvalumab) via a Bayesian adaptive design that made it more likely for patients to be randomized to the more effective arm. The primary end …

Tumor-Resident Microbes: The New Kids On The Microenvironment Block, Le Li, Vidhi Chandra, Florencia Mcallister

Faculty, Staff and Student Publications

Tumor-resident microbes (TRM) are an integral component of the tumor microenvironment (TME). TRM can influence tumor growth, distant dissemination, and response to therapies by interfering with molecular pathways in tumor cells as well as with other components of the TME. Novel technologies are improving the identification and visualization of cell type-specific microbes in the TME. The mechanisms that mediate the role of TRM at the primary tumors and metastatic sites are being elucidated. This knowledge is providing novel perspectives for targeting microbes or using microbial interventions for cancer interception or therapy.

Abatacept Pharmacokinetics And Exposure Response In Patients Hospitalized With Covid-19, Stephen J Balevic, Daniel K Benjamin, William G Powderly, P Brian Smith, Daniel Gonzalez, Matthew W Mccarthy, Linda K Shaw, Christopher J Lindsell, Sam Bozzette, Daphne Williams, Benjamin P Linas, John Blamoun, Heta Javeri, Christoph P Hornik

Faculty, Staff and Student Publications

IMPORTANCE: The pharmacokinetics of abatacept and the association between abatacept exposure and outcomes in patients with severe COVID-19 are unknown.

OBJECTIVE: To characterize abatacept pharmacokinetics, relate drug exposure with clinical outcomes, and evaluate the need for dosage adjustments.

DESIGN, SETTING, AND PARTICIPANTS: This study is a secondary analysis of data from the ACTIV-1 (Accelerating COVID-19 Therapeutic Interventions and Vaccines) Immune Modulator (IM) randomized clinical trial conducted between October 16, 2020, and December 31, 2021. The trial included hospitalized adults who received abatacept in addition to standard of care for treatment of COVID-19 pneumonia. Data analysis was performed between September 2022 …

Case Of Human Orthohantavirus Infection, Michigan, Usa, 2021, Samuel M Goodfellow, Robert A Nofchissey, Dustin Arsnoe, Chunyan Ye, Seonghyeon Lee, Jieun Park, Won-Keun Kim, Kartik Chandran, Shannon L M Whitmer, John D Klena, Jonathan W Dyal, Trevor Shoemaker, Diana Riner, Mary Grace Stobierski, Kimberly Signs, Steven B Bradfute

Faculty, Staff and Student Publications

Orthohantaviruses cause hantavirus cardiopulmonary syndrome; most cases occur in the southwest region of the United States. We discuss a clinical case of orthohantavirus infection in a 65-year-old woman in Michigan and the phylogeographic link of partial viral fragments from the patient and rodents captured near the presumed site of infection.

Clinical Epidemiological Characteristics And Risk Factors For Severity Of Sars-Cov-2 Pneumonia In Pediatric Patients: A Hospital-Based Study In Vietnam, Sang N Nguyen, Lam T Vu, Ha T Nguyen, Giang H Dao, Anh Ngoc T Nguyen

Faculty, Staff and Student Publications

Introduction Coronavirus disease (COVID-19) is an infectious disease caused by SARS-CoV-2, which can cause organ failure in several organs, cardiac problems, or acute respiratory distress syndrome (ARDS). Identifying clinical epidemiological characteristics and risk factors for complications of COVID-19 allows clinicians to diagnose and treat promptly. Objectives This study aims to describe the clinical epidemiological characteristics of COVID-19 and assess risk factors for the severity of SARS-CoV-2 pneumonia in children treated at Haiphong Children's Hospital. Methods A descriptive cross-sectional study was conducted in Haiphong Children's Hospital, Haiphong, Vietnam, for one year, from January 1, 2022, to December 31, 2022. Results In …

Rfx Transcription Factor In The Human-Associated Yeast Candida Albicans Regulates Adhesion To Oral Epithelium, Diana L Rodríguez, Elena Lindemann-Perez, J Christian Perez

Faculty, Staff and Student Publications

Adhesion to mucosal surfaces is a critical step in many bacterial and fungal infections. Here, using a mouse model of oral infection by the human fungal pathobiont Candida albicans, we report the identification of a novel regulator of C. albicans adhesion to the oral mucosa. The regulator is a member of the regulatory factor X (RFX) family of transcription factors, which control cellular processes ranging from genome integrity in model yeasts to tissue differentiation in vertebrates. Mice infected with the C. albicans rfx1 deletion mutant displayed increased fungal burden in tongues compared to animals infected with the reference strain. High-resolution …

Large-Scale Phenotyping Of Patients With Long Covid Post-Hospitalization Reveals Mechanistic Subtypes Of Disease, Felicity Liew, Claudia Efstathiou, Sara Fontanella, Matthew Richardson, Ruth Saunders, Dawid Swieboda, Jasmin K Sidhu, Stephanie Ascough, Shona C Moore, Noura Mohamed, Jose Nunag, Clara King, Olivia C Leavy, Omer Elneima, Hamish J C Mcauley, Aarti Shikotra, Amisha Singapuri, Marco Sereno, Victoria C Harris, Linzy Houchen-Wolloff, Neil J Greening, Nazir I Lone, Matthew Thorpe, A A Roger Thompson, Sarah L Rowland-Jones, Annemarie B Docherty, James D Chalmers, Ling-Pei Ho, Alexander Horsley, Betty Raman, Krisnah Poinasamy, Michael Marks, Onn Min Kon, Luke S Howard, Daniel G Wootton, Jennifer K Quint, Thushan I De Silva, Antonia Ho, Christopher Chiu, Ewen M Harrison, William Greenhalf, J Kenneth Baillie, Malcolm G Semple, Lance Turtle, Rachael A Evans, Louise V Wain, Christopher Brightling, Ryan S Thwaites, Peter J M Openshaw, Phosp-Covid Collaborative Group, Isaric Investigators

Faculty, Staff and Student Publications

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers …

Cytoplasmic Redox Imbalance In The Thioredoxin System Activates Hsf1 And Results In Hyperaccumulation Of The Sequestrase Hsp42 With Misfolded Proteins, Davi Goncalves, Duong Long Duy, Sara Peffer, Kevin A Morano

Faculty, Staff and Student Publications

Cells employ multiple systems to maintain homeostasis when experiencing environmental stress. For example, the folding of nascent polypeptides is exquisitely sensitive to proteotoxic stressors including heat, pH, and oxidative stress, and is safeguarded by a network of protein chaperones that concentrate potentially toxic misfolded proteins into transient assemblies to promote folding or degradation. The redox environment itself is buffered by both cytosolic and organellar thioredoxin and glutathione pathways. How these systems are linked is poorly understood. Here, we determine that specific disruption of the cytosolic thioredoxin system resulted in constitutive activation of the heat shock response in Saccharomyces cerevisiae and …

Association Of Nightly Fasting, Meal Frequency, And Skipping Meals With Metabolic Syndrome Among Kuwaiti Adults, Fatema Alkhulaifi, Suad Al-Hooti, Sameer Al-Zenki, Husam Alomirah, Qian Xiao, Wenyaw Chan, Fuqing Wu, Charles Darkoh

Faculty, Staff and Student Publications

Mounting evidence suggests that meal timing and frequency are associated with cardiometabolic health by influencing circadian rhythms. However, the evidence is inconsistent and limited, especially in non-Western cultures. This cross-sectional study aims to investigate the association between temporal habits of dietary intake, such as nightly fasting duration and meal frequency, and metabolic syndrome among Kuwaiti adults. A 24-hour recall was used to assess temporal habits of dietary intake. Meal frequency was defined as the number of daily eating episodes. The study included a total of 757 adults aged 20 years and older. The participants' mean age was 37.8 ± 12.3 …

Digital Twins For Health: A Scoping Review, Evangelia Katsoulakis, Qi Wang, Huanmei Wu, Leili Shahriyari, Richard Fletcher, Jinwei Liu, Luke Achenie, Hongfang Liu, Pamela Jackson, Ying Xiao, Tanveer Syeda-Mahmood, Richard Tuli, Jun Deng

Faculty, Staff and Student Publications

The use of digital twins (DTs) has proliferated across various fields and industries, with a recent surge in the healthcare sector. The concept of digital twin for health (DT4H) holds great promise to revolutionize the entire healthcare system, including management and delivery, disease treatment and prevention, and health well-being maintenance, ultimately improving human life. The rapid growth of big data and continuous advancement in data science (DS) and artificial intelligence (AI) have the potential to significantly expedite DT research and development by providing scientific expertise, essential data, and robust cybertechnology infrastructure. Although various DT initiatives have been underway in the …

Intrathecal Gene Therapy For Giant Axonal Neuropathy, Diana X Bharucha-Goebel, Joshua J Todd, Dimah Saade, Gina Norato, Minal Jain, Tanya Lehky, Rachel M Bailey, Jessica A Chichester, Roberto Calcedo, Diane Armao, A Reghan Foley, Payam Mohassel, Eshetu Tesfaye, Bradley P Carlin, Beth Seremula, Melissa Waite, Wadih M Zein, Laryssa A Huryn, Thomas O Crawford, Charlotte J Sumner, Ahmet Hoke, John D Heiss, Lawrence Charnas, Jody E Hooper, Thomas W Bouldin, Elizabeth M Kang, Denis Rybin, Steven J Gray, Carsten G Bönnemann

Faculty, Staff and Student Publications

Background: Giant axonal neuropathy is a rare, autosomal recessive, pediatric, polysymptomatic, neurodegenerative disorder caused by biallelic loss-of-function variants in GAN, the gene encoding gigaxonin.

Methods: We conducted an intrathecal dose-escalation study of scAAV9/JeT-GAN (a self-complementary adeno-associated virus-based gene therapy containing the GAN transgene) in children with giant axonal neuropathy. Safety was the primary end point. The key secondary clinical end point was at least a 95% posterior probability of slowing the rate of change (i.e., slope) in the 32-item Motor Function Measure total percent score at 1 year after treatment, as compared with the pretreatment slope.

Results: One of …

Effect Of Neutralizing Monoclonal Antibody Treatment On Early Trajectories Of Virologic And Immunologic Biomarkers In Patients Hospitalized With Covid-19, Tomas O Jensen, Greg A Grandits, Mamta K Jain, Thomas A Murray, Birgit Grund, Kathryn Shaw-Saliba, Michael A Matthay, Mahsa Abassi, Magdalena Ardelt, Jason V Baker, Peter Chen, Robin L Dewar, Anna L Goodman, Timothy J Hatlen, Helene C Highbarger, Mark Holodniy, Perrine Lallemand, Sylvain Laverdure, Bradley G Leshnower, David Looney, Charalampos D Moschopoulos, Henry Mugerwa, Daniel D Murray, Eleftherios Mylonakis, Stephanie Nagy-Agren, M Tauseef Rehman, Adam Rupert, Randy A Stevens, Stuart Turville, Amy Weintrob, Katherine Wick, Jens Lundgren, Emily R Ko, Activ-3/Tico Study Group

Faculty, Staff and Student Publications

BACKGROUND: Neutralizing monoclonal antibodies (nmAbs) failed to show clear benefit for hospitalized patients with coronavirus disease 2019 (COVID-19). Dynamics of virologic and immunologic biomarkers remain poorly understood.

METHODS: Participants enrolled in the Therapeutics for Inpatients with COVID-19 trials were randomized to nmAb versus placebo. Longitudinal differences between treatment and placebo groups in levels of plasma nucleocapsid antigen (N-Ag), anti-nucleocapsid antibody, C-reactive protein, interleukin-6, and D-dimer at enrollment, day 1, 3, and 5 were estimated using linear mixed models. A 7-point pulmonary ordinal scale assessed at day 5 was compared using proportional odds models.

RESULTS: Analysis included 2149 participants enrolled between …

Btn1a1 Is A Novel Immune Checkpoint Mutually Exclusive To Pd-L1, Young-Seung Kim, Seung-Hoon Lee, Andrew H Park, Chunai Wu, Bong-Ki Hong, Hyunjin Jung, Steven H Lin, Stephen S Yoo

Faculty, Staff and Student Publications

BACKGROUND: While Programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) blockade is a potent antitumor treatment strategy, it is effective in only limited subsets of patients with cancer, emphasizing the need for the identification of additional immune checkpoints. Butyrophilin 1A1 (BTN1A1) has been reported to exhibit potential immunoregulatory activity, but its ability to function as an immune checkpoint remains to be systematically assessed, and the mechanisms underlying such activity have yet to be characterized.

METHODS: BTN1A1 expression was evaluated in primary tumor tissue samples, and its ability to suppress T-cell activation and T cell-dependent tumor clearance was examined. …

Effect Of Neutralizing Monoclonal Antibody Treatment On Early Trajectories Of Virologic And Immunologic Biomarkers In Patients Hospitalized With Covid-19, Tomas O Jensen, Greg A Grandits, Mamta K Jain, Thomas A Murray, Birgit Grund, Kathryn Shaw-Saliba, Michael A Matthay, Mahsa Abassi, Magdalena Ardelt, Jason V Baker, Peter Chen, Robin L Dewar, Anna L Goodman, Timothy J Hatlen, Helene C Highbarger, Mark Holodniy, Perrine Lallemand, Sylvain Laverdure, Bradley G Leshnower, David Looney, Charalampos D Moschopoulos, Henry Mugerwa, Daniel D Murray, Eleftherios Mylonakis, Stephanie Nagy-Agren, M Tauseef Rehman, Adam Rupert, Randy A Stevens, Stuart Turville, Amy Weintrob, Katherine Wick, Jens Lundgren, Emily R Ko

Faculty, Staff and Student Publications

BACKGROUND: Neutralizing monoclonal antibodies (nmAbs) failed to show clear benefit for hospitalized patients with coronavirus disease 2019 (COVID-19). Dynamics of virologic and immunologic biomarkers remain poorly understood.

METHODS: Participants enrolled in the Therapeutics for Inpatients with COVID-19 trials were randomized to nmAb versus placebo. Longitudinal differences between treatment and placebo groups in levels of plasma nucleocapsid antigen (N-Ag), anti-nucleocapsid antibody, C-reactive protein, interleukin-6, and D-dimer at enrollment, day 1, 3, and 5 were estimated using linear mixed models. A 7-point pulmonary ordinal scale assessed at day 5 was compared using proportional odds models.

RESULTS: Analysis included 2149 participants enrolled between …

Unraveling Trends In Schistosomiasis: Deep Learning Insights Into National Control Programs In China, Qing Su, Cici Xi Chen Bauer, Robert Bergquist, Zhiguo Cao, Fenghua Gao, Yi Hu, Zhijie Zhang

Faculty, Staff and Student Publications

OBJECTIVES: to achieve the ambitious goal of eliminating schistosome infections, the Chinese government has implemented diverse control strategies. This study explored the progress of the 2 most recent national schistosomiasis control programs in an endemic area along the Yangtze River in China.

METHODS: We obtained village-level parasitological data from cross-sectional surveys combined with environmental data in Anhui Province, China from 1997 to 2015. A convolutional neural network (CNN) based on a hierarchical integro-difference equation (IDE) framework (i.e., CNN-IDE) was used to model spatio-temporal variations in schistosomiasis. Two traditional models were also constructed for comparison with 2 evaluation indicators: the mean-squared …

Draft Genome Sequences Of Pseudomonas Strains Zfem001–005 Isolated From The Intestine Of Larval Zebrafish Danio Rerio, Sabona B Simbassa, Justin Clark, Keiko Salazar, Anthony Maresso, Anne-Marie Krachler

Faculty, Staff and Student Publications

Here, we report the draft genome sequences of Pseudomonas strains zfem001–005, five isolates from the intestinal microbiota of healthy larval zebrafish Danio rerio at a developmental age of 7 days post fertilization. The isolates have been identified as Pseudomonas sediminis, Pseudomonas japonica, Pseudomonas otitidis, Pseudomonas sichuanensis, and Pseudomonas tohonis, respectively.

Deep Learning Model For Personalized Prediction Of Positive Mrsa Culture Using Time-Series Electronic Health Records, Masayuki Nigo, Laila Rasmy, Bingyu Mao, Bijun Sai Kannadath, Ziqian Xie, Degui Zhi

Faculty, Staff and Student Publications

Methicillin-resistant Staphylococcus aureus (MRSA) poses significant morbidity and mortality in hospitals. Rapid, accurate risk stratification of MRSA is crucial for optimizing antibiotic therapy. Our study introduced a deep learning model, PyTorch_EHR, which leverages electronic health record (EHR) time-series data, including wide-variety patient specific data, to predict MRSA culture positivity within two weeks. 8,164 MRSA and 22,393 non-MRSA patient events from Memorial Hermann Hospital System, Houston, Texas are used for model development. PyTorch_EHR outperforms logistic regression (LR) and light gradient boost machine (LGBM) models in accuracy (AUROC

Liax Is A Surrogate Marker For Cell Envelope Stress And Daptomycin Non-Susceptibility In Enterococcus Faecium, Dierdre B Axell-House, Shelby R Simar, Diana Panesso, Sandra Rincon, William R Miller, Ayesha Khan, Orville A Pemberton, Lizbet Valdez, April H Nguyen, Kara S Hood, Kirsten Rydell, Andrea M Detranaltes, Mary N Jones, Rachel Atterstrom, Jinnethe Reyes, Pranoti V Sahasrabhojane, Geehan Suleyman, Marcus Zervos, Samuel A Shelburne, Kavindra V Singh, Yousif Shamoo, Blake M Hanson, Truc T Tran, Cesar A Arias

Faculty, Staff and Student Publications

Daptomycin (DAP) is often used as a first-line therapy to treat vancomycin-resistant

Outcomes In Biomarker-Selected Subgroups From The Kestrel Study Of Durvalumab And Tremelimumab In Recurrent Or Metastatic Head And Neck Squamous Cell Carcinoma, Tanguy Y Seiwert, Sophie Wildsmith, Jérôme Fayette, Kevin Harrington, Maura Gillison, Myung-Ju Ahn, Shunji Takahashi, Jared Weiss, Jean-Pascal Machiels, Shrujal Baxi, Valerie Baker, Brent Evans, Nassim Morsli, Jill Walker, Katia Real, Anne L'Hernault, Amanda Psyrri

Faculty, Staff and Student Publications

BACKGROUND: Selective biomarkers may improve outcomes in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) treated with immune checkpoint inhibitor therapy. We investigated three independent biomarkers for association with efficacy in the randomized, phase III KESTREL study (NCT02551159) of first-line durvalumab monotherapy or durvalumab plus tremelimumab versus the EXTREME regimen: programmed cell death ligand-1 (PD-L1) immunohistochemistry, blood tumor mutational burden (bTMB) via circulating tumor DNA, and neutrophil-to-lymphocyte ratio (NLR).

METHODS: Tumor or blood samples from patients enrolled in the KESTREL study were analyzed for PD-L1, bTMB, and NLR. Associations with overall survival (OS) or objective …

Global Trend In Exosome Isolation And Application: An Update Concept In Management Of Diseases, Mohammadhassan Omrani, Hanieh Beyrampour-Basmenj, Rana Jahanban-Esfahlan, Mahnaz Talebi, Mortaza Raeisi, Zeinab Aliyari Serej, Naeimeh Akbar-Gharalari, Sina Khodakarimi, Jiaqian Wu, Abbas Ebrahimi-Kalan

Faculty, Staff and Student Publications

Extracellular vesicles (EVs) secreted by various cells offer great potential for use in the diagnosis and treatment of disease. EVs are heterogeneous membranous vesicles. Exosomes are a subtype of EVs, 40-150 nm spherical vesicles with a lipid layer derived from endosomes. Exosomes, which are involved in signal transduction and maintain homeostasis, are released from almost all cells, tissues, and body fluids. Although several methods exist to isolate and characterize EVs and exosomes, each technique has significant drawbacks and limitations that prevent progress in the field. New approaches in the biology of EVs show great potential for isolating and characterizing EVs, …

Genome-Wide Gene-Environment Interaction Analyses To Understand The Relationship Between Red Meat And Processed Meat Intake And Colorectal Cancer Risk, Mariana C Stern, Joel Sanchez Mendez, Andre E Kim, Mireia Obón-Santacana, Ferran Moratalla-Navarro, Vicente Martín, Victor Moreno, Yi Lin, Stephanie A Bien, Conghui Qu, Yu-Ru Su, Emily White, Tabitha A Harrison, Jeroen R Huyghe, Catherine M Tangen, Polly A Newcomb, Amanda I Phipps, Claire E Thomas, Eric S Kawaguchi, Juan Pablo Lewinger, John L Morrison, David V Conti, Jun Wang, Duncan C Thomas, Elizabeth A Platz, Kala Visvanathan, Temitope O Keku, Christina C Newton, Caroline Y Um, Anshul Kundaje, Anna Shcherbina, Neil Murphy, Marc J Gunter, Niki Dimou, Nikos Papadimitriou, Stéphane Bézieau, Franzel J B Van Duijnhoven, Satu Männistö, Gad Rennert, Alicja Wolk, Michael Hoffmeister, Hermann Brenner, Jenny Chang-Claude, Yu Tian, Loïc Le Marchand, Michelle Cotterchio, Konstantinos K Tsilidis, D Timothy Bishop, Yohannes Adama Melaku, Brigid M Lynch, Daniel D Buchanan, Cornelia M Ulrich, Jennifer Ose, Anita R Peoples, Andrew J Pellatt, Li Li, Matthew A M Devall, Peter T Campbell, Demetrius Albanes, Stephanie J Weinstein, Sonja I Berndt, Stephen B Gruber, Edward Ruiz-Narvaez, Mingyang Song, Amit D Joshi, David A Drew, Jessica L Petrick, Andrew T Chan, Marios Giannakis, Ulrike Peters, Li Hsu, W James Gauderman

Faculty, Staff and Student Publications

Background: High red meat and/or processed meat consumption are established colorectal cancer risk factors. We conducted a genome-wide gene-environment (GxE) interaction analysis to identify genetic variants that may modify these associations.

Methods: A pooled sample of 29,842 colorectal cancer cases and 39,635 controls of European ancestry from 27 studies were included. Quantiles for red meat and processed meat intake were constructed from harmonized questionnaire data. Genotyping arrays were imputed to the Haplotype Reference Consortium. Two-step EDGE and joint tests of GxE interaction were utilized in our genome-wide scan.

Results: Meta-analyses confirmed positive associations between increased consumption of red meat and …

Rehabilitation Outcomes In Multiple Sclerosis Patients On Ocrelizumab Diagnosed With West Nile Virus Encephalitis, Taylor R Johnson, Stephanie Gandelman, Lauren R Serafin, Jeremy Y Charles, Dina Jacobs

Faculty, Staff and Student Publications

Multiple sclerosis (MS) has a global prevalence exceeding two million people and is a leading cause of non-traumatic physical disability. MS can be treated with ocrelizumab, an anti-CD20 monoclonal antibody. West Nile virus (WNV) is the most common cause of mosquito-borne viral encephalitis in North America. It can lead to neuroinvasive WNV disease (WNND) affecting the brain and peripheral nervous system, especially in immunocompromised patients, such as those being treated with ocrelizumab for MS. WNND is exceedingly rare and reported in less than 1% of cases of WNV. It has been established that inpatient rehabilitation improves functional outcomes in patients …

Omics-Based Profiles And Biomarkers Of Respiratory Infections: Are We There Yet?, Jezreel Pantaleon Garcia, Scott E Evans

Faculty, Staff and Student Publications

Descriptive omics-based clinical research provides valuable early steps in understanding host immune responses to respiratory pathogens in our global efforts to mitigate the impacts of severe respiratory infections with rapidly evolving technologies https://bit.ly/4bjJsvL

Peroxisome Proliferator-Activated Receptors As Therapeutic Target For Cancer, Yuqing Wang, Feifei Lei, Yiyun Lin, Yuru Han, Lei Yang, Huabing Tan

Faculty, Staff and Student Publications

Peroxisome proliferator-activated receptors (PPARs) are transcription factors belonging to the nuclear receptor family. There are three subtypes of PPARs, including PPAR-α, PPAR-β/δ and PPAR-γ. They are expressed in different tissues and act by regulating the expression of target genes in the form of binding to ligands. Various subtypes of PPAR have been shown to have significant roles in a wide range of biological processes including lipid metabolism, body energy homeostasis, cell proliferation and differentiation, bone formation, tissue repair and remodelling. Recent studies have found that PPARs are closely related to tumours. They are involved in cancer cell growth, angiogenesis and …

Safety, Efficacy And Determinants Of Response Of Allogeneic Cd19-Specific Car-Nk Cells In Cd19+ B Cell Tumors: A Phase 1/2 Trial, David Marin, Ye Li, Rafet Basar, Hind Rafei, May Daher, Jinzhuang Dou, Vakul Mohanty, Merve Dede, Yago Nieto, Nadima Uprety, Sunil Acharya, Enli Liu, Jeffrey Wilson, Pinaki Banerjee, Homer A Macapinlac, Christina Ganesh, Peter F Thall, Roland Bassett, Mariam Ammari, Sheetal Rao, Kai Cao, Mayra Shanley, Mecit Kaplan, Chitra Hosing, Partow Kebriaei, Loretta J Nastoupil, Christopher R Flowers, Sadie Mae Moseley, Paul Lin, Sonny Ang, Uday R Popat, Muzaffar H Qazilbash, Richard E Champlin, Ken Chen, Elizabeth J Shpall, Katayoun Rezvani

Faculty, Staff and Student Publications

There is a pressing need for allogeneic chimeric antigen receptor (CAR)-immune cell therapies that are safe, effective and affordable. We conducted a phase 1/2 trial of cord blood-derived natural killer (NK) cells expressing anti-CD19 chimeric antigen receptor and interleukin-15 (CAR19/IL-15) in 37 patients with CD19+ B cell malignancies. The primary objectives were safety and efficacy, defined as day 30 overall response (OR). Secondary objectives included day 100 response, progression-free survival, overall survival and CAR19/IL-15 NK cell persistence. No notable toxicities such as cytokine release syndrome, neurotoxicity or graft-versus-host disease were observed. The day 30 and day 100 OR rates were …

Oxidation Of Hydrogen Sulfide To Polysulfide And Thiosulfate By A Carbon Nanozyme: Therapeutic Implications With An Emphasis On Down Syndrome, Paul J Derry, Anton V Liopo, Karthik Mouli, Emily A Mchugh, Anh T T Vo, Ann Mckelvey, Larry J Suva, Gang Wu, Yan Gao, Kenneth R Olson, James M Tour, Thomas A Kent

Faculty, Staff and Student Publications

Hydrogen sulfide (H2S) is a noxious, potentially poisonous, but necessary gas produced from sulfur metabolism in humans. In Down Syndrome (DS), the production of H2S is elevated and associated with degraded mitochondrial function. Therefore, removing H2S from the body as a stable oxide could be an approach to reducing the deleterious effects of H2S in DS. In this report we describe the catalytic oxidation of hydrogen sulfide (H2S) to polysulfides (HS2+n−) and thiosulfate (S2O32−) by poly(ethylene glycol) hydrophilic carbon clusters (PEG-HCCs) and poly(ethylene glycol) oxidized activated charcoal (PEG-OACs), examples of oxidized carbon nanozymes (OCNs). We show that OCNs oxidize H2S …

Reply To Williams Et Al., M Hong Nguyen, Luis Ostrosky-Zeichner, Peter G Pappas, Thomas J Walsh, Joseph Bubalo, Barbara D Alexander, Marisa H Miceli, Jeanette Jiang, Yi Song, George R Thompson

Faculty, Staff and Student Publications

No abstract provided.

Treatment Outcomes With Standard Of Care In Relapsed/Refractory Diffuse Large B-Cell Lymphoma: Real-World Data Analysis, Andrew Ip, Alex Mutebi, Tongsheng Wang, Monika Jun, Anupama Kalsekar, Fernando Rivas Navarro, Anthony Wang, Rajesh Kamalakar, Mariana Sacchi, Brian Elliott

Faculty, Staff and Student Publications

INTRODUCTION: Despite new therapies for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), treatments with chemotherapy, single-agent rituximab/obinutuzumab, single-agent lenalidomide, or combinations of these agents continue to be commonly used.

METHODS: This retrospective study utilized longitudinal data from 4226 real-world electronic health records to characterize outcomes in patients with R/R DLBCL. Eligible patients were diagnosed with DLBCL between January 2010 and March 2022 and had R/R disease treated with ≥ 1 prior systemic line of therapy (LOT), including ≥ 1 anti-CD20-containing regimen.

RESULTS: A total of 573 patients treated with ≥ 1 prior LOT were included (31.2% and 13.4% …

Cost Analysis For Robotic And Open Gastrectomy, Yuki Hirata, Heather G Lyu, Ahad M Azimuddin, Pamela Lu, Jeeva Ajith, Jason A Schmeisser, Elizabeth P Ninan, Kyung Hyun Lee, Brian D Badgwell, Paul Mansfield, Naruhiko Ikoma

Faculty, Staff and Student Publications

Objective: To determine the magnitude of the perioperative costs associated with robotic gastrectomy (RG).

Background: A robotic surgery platform has a high implementation cost and requires maintenance costs; however, whether the overall cost of RG, including all perioperative costs, is higher than conventional open gastrectomy (OG) remains unknown.

Methods: Patients who underwent a major gastrectomy during February 2018 through December 2021 were retrospectively identified. We calculated the perioperative costs of RG and OG and compared them overall as well as in different phases, including intraoperative costs and 30-day postsurgery inpatient and outpatient costs. We investigated factors potentially associated with high …