Digital Commons Network^™

Addressing Food System Determinants Of Health Inequalities In Urban Environments:: Learnings From The Foodsequal And Foodsequal-Health Projects, Carol Wagstaff, Clare Pettinger

School of Health Professions

Diet is just one social determinant of health, with obesity and diet-related illness as leading causes of premature deaths and disability in the UK. People living in deprived areas of the UK are more likely to experience poor health outcomes, linked to many social determinants of health such as diet, housing, employment, education, power and discrimination and psycho-social factors such as isolation, quality of social network and perceived level of control. While socio-economic deprivation is a key risk for health inequalities, protected characteristics, vulnerable groups and geographical factors also indicate populations at risk of experiencing health inequalities. In this ‘opinion …

Elevated Nr2f1 Underlies The Persistence Of Invasive Disease After Treatment Of Braf-Mutant Melanoma, Manoela Tiago, Timothy J Purwin, Casey D Stefanski, Renaira Oliveira Da Silva, Mitchell E Fane, Yash Chhabra, Jelan I Haj, Jessica Lf Teh, Rama Kadamb, Weijia Cai, Sheera R Rosenbaum, Vivian Chua, Nir Hacohen, Michael A Davies, Jessie Villanueva, Inna Chervoneva, Ashani T Weeraratna, Dan A Erkes, Claudia Capparelli, Julio A Aguirre-Ghiso, Andrew E Aplin

Faculty, Staff and Student Publications

Despite the success of targeted inhibitors in cutaneous melanoma, therapeutic responses are limited by the aged tumor microenvironment and drug-tolerant residual cells. Given the similarities between drug tolerance and cellular dormancy, we studied the dormancy marker, nuclear receptor subfamily 2 group F member 1 (NR2F1), in response to BRAF-V600E inhibitors (BRAFi) plus MEK inhibitors (MEKi) in BRAF-mutant melanoma models. Transcriptomic analysis of melanoma patient samples treated with BRAFi + MEKi showed increased NR2F1. NR2F1 was highly expressed in the drug-tolerant invasive cell state of minimal residual disease in patient-derived and mouse-derived xenografts on BRAFi + MEKi. NR2F1 over-expression was sufficient …

Antiviral Use Among Children Hospitalized With Laboratory-Confirmed Influenza Illness: A Prospective, Multicenter Surveillance Study., James W. Antoon, Justin Z. Amarin, Olla Hamdan, Tess Stopczynski, Laura S. Stewart, Marian G. Michaels, John V. Williams, Eileen J. Klein, Janet A. Englund, Geoffrey A. Weinberg, Peter G. Szilagyi, Jennifer E. Schuster, Rangaraj Selvarangan, Christopher J. Harrison, Julie A. Boom, Leila C. Sahni, Flor M. Muñoz, Mary Allen Staat, Elizabeth P. Schlaudecker, James D. Chappell, Benjamin R. Clopper, Heidi L. Moline, Angela P. Campbell, Andrew J. Spieker, Samantha M. Olson, Natasha B. Halasa

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Guidelines state that all hospitalized children with suspected or confirmed influenza receive prompt treatment with influenza-specific antivirals. We sought to determine the frequency of, and factors associated with, antiviral receipt among hospitalized children.

METHODS: We conducted active surveillance of children presenting with fever or respiratory symptoms from 1 December 2016 to 31 March 2020 at 7 pediatric medical centers in the New Vaccine Surveillance Network. The cohort consisted of children hospitalized with influenza A or B confirmed by clinical or research testing. The primary outcome was frequency of antiviral receipt during hospitalization. We used logistic regression to obtain adjusted …

Trajectories Of Recovery After Intravenous Propofol Versus Inhaled Volatile Anaesthesia (Thrive) Randomised Controlled Trial In The Usa: A Protocol, Bethany R Tellor Pennington, Laura Swisher, Mara L Bollini, Michael S Avidan, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Millions of patients receive general anaesthesia every year with either propofol total intravenous anaesthesia (TIVA) or inhaled volatile anaesthesia (INVA). It is currently unknown which of these techniques is superior in relation to patient experience, safety and clinical outcomes. The primary aims of this trial are to determine (1) whether patients undergoing (a) major inpatient surgery, (b) minor inpatient surgery or (c) outpatient surgery have a superior quality of recovery after INVA or TIVA and (2) whether TIVA confers no more than a small (0.2%) increased risk of definite intraoperative awareness than INVA.

METHODS AND ANALYSIS: This protocol was …

Association Between Climate Change Awareness And Depression & Anxiety: Findings From A U.S. Sample, Stanley Nkemjika, Colvette Brown, Henry Onyeaka, Srikanta Banerjee, Jennifer Oliphant

Department of Psychiatry and Human Behavior Faculty Papers

BACKGROUND: Exploring the connection between climate change awareness and overall well-being is crucial, particularly in how it impacts both the environment and mental health. The mental health consequences of climate change and its awareness have not been thoroughly examined, especially in the U.S. In this study, the relationship between awareness of climate change and depression or anxiety among U.S. adults was explored. Similarly, the role of climate change awareness has not been explored in relation to mental health concerns.

METHODS: Based on the HINTS-6 dataset, a nationally representative, cross-sectional survey conducted by the National Cancer Institute, a variety of statistical …

Loss Of Ptdss1 In Tumor Cells Improves Immunogenicity And Response To Anti-Pd-1 Therapy, Jielin Liu, Shelley Herbrich, Sreyashi Basu, Yulong Chen, Ashwat Nagarajan, Swetha Anandhan, Sangeeta Goswami, Liangwen Xiong, Baoxiang Guan, Padmanee Sharma

Faculty, Staff and Student Publications

PTDSS1 (phosphatidylserine synthase 1) encodes an enzyme that facilitates production of phosphatidylserine (PS), which mediates a global immunosuppressive signal. Here, based on in vivo CRISPR screen, we identified PTDSS1 as a target to improve anti-PD-1 therapy. Depletion of Ptdss1 in tumor cells increased expression of interferon-γ (IFN-γ)-regulated genes, including B2m, Cxcl9, Cxcl10, and Stat1, even in the absence of IFN-γ stimulation in vitro. Loss of Ptdss1 in tumor cells also led to increased expression of MHC-I, enhanced cytotoxicity of CD8+ T cells, and increased frequency of an iNOS+ myeloid subset. A gene signature derived from the …

A Novel Sialylation Pathway Mediated By Extracellular Vesicles In Aggressive Prostate Cancer, Camila A. Bach, Md Niamat Hossain, Ishan J. Chaudhari, Cecilia E. Verrillo, Nicole M. Naranjo, Isabella Amoroso, Anna Testa, Samuel Sey, W. Kevin Kelly, Susan L. Bellis, Aurelio Lorico, Ada G. Blidner, Gabriel A. Rabinovich, Lucia R. Languino

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Altered cell surface glycosylation is a hallmark of cancer; among aberrant glycan structures, hypersialylated proteins contribute to disease progression. The enzyme ST6 β-galactoside α2,6-sialyltransferase 1 (ST6GAL1) mediates α2,6-linked sialylation of N-glycosylated proteins and is upregulated in many cancers, including prostate cancer (PrCa). We propose that ST6GAL1 may be released by cancer cells in small extracellular vesicles (sEVs) in the PrCa tumor microenvironment to potentially modulate cell surface sialylation in recipient cells. We isolated sEVs from PrCa cells by density gradient separation and characterized them by nanoparticle tracking analysis using ZetaView and immunoblotting analysis. We identified ST6GAL1 in both its membrane-bound …

Identification And Characterization Of A Metal Binding-Independent Rift Valley Fever Virus Endonuclease Inhibitor, Cara D Kirby, Gai Liu, Farheen Fatma, Maris R Pedlow, Narendran G-Dayanandan, Nitin Sharma, Zachary D Frey, Rachael E Rush, Steven C Cardinale, Andrzej M Krezel, Amy L Hartman, Terry L Bowlin, Daisy W Leung, Gaya K Amarasinghe

2020-Current year OA Pubs

The viral cap-snatching mechanism, facilitated by the endonuclease (EndoN) domain of viral polymerases, is critical for viral gene transcription and translation and is therefore an attractive target for antiviral development. The successful development of EndoN inhibitor XOFLUZA (Baloxavir marboxil) has opened the possibility that the EndoN domain of negative-sense RNA viruses (NSVs) can be targeted in a similar fashion. Rift Valley Fever Virus (RVFV) belongs to the

Neuroengineering Approaches Assessing Structural And Functional Changes Of Motor Descending Pathways In Stroke, Jordan N Williamson, Rita Huan-Ting Peng, Joohwan Sung, Mahmood Rajabtabar Darvish, Xiaoxi Chen, Mehreen Ali, Sheng Li, Yuan Yang

Faculty, Staff and Student Publications

Stroke is a leading cause of adult disability worldwide, with approximately 101 million survivors globally. Over 60% of these individuals live with from long-term, often lifelong, movement impairments that significantly hinder their ability to perform essential daily activities and maintain independence. Post-stroke movement disabilities are highly associated with structural and functional changes in motor descending pathways, particularly the corticospinal tract and other indirect motor pathways via the brainstem. For decades, neuroengineers have been working to quantitively evaluate the post-stroke changes of motor descending pathways, aiming to establish a precision prognosis and tailoring treatments to post-stroke motor impairment. However, a clear …

Infectious Prions In Brains And Muscles Of Domestic Pigs Experimentally Challenged With The Bse, Scrapie, And Cwd Agents, Francisca Bravo-Risi, Fraser Brydon, Angela Chong, Kane Spicker, Justin J Greenlee, Glenn Telling, Claudio Soto, Sandra Pritzkow, Marcelo A Barria, Rodrigo Morales

Faculty, Staff and Student Publications

Experimental studies suggest that animal species not previously described as naturally infected by prions are susceptible to prion diseases affecting sheep, cattle, and deer. These interspecies transmissions may generate prions with unknown host ranges. Pigs are susceptible to prions from different origins, including deer chronic wasting disease (CWD), sheep scrapie, and bovine spongiform encephalopathy (BSE). Here, we studied prions in brains and muscles from pigs previously infected with these different prion sources. Specifically, we measured the total prion protein (PrP) and PK-resistant PrP by western blot. Seeding activity in these tissues was evaluated using the protein misfolding cyclic amplification (PMCA) …

Dissecting The Effect Of Mitochondrial Bcat Inhibition In Methylmalonic Acidemia, Madeline G Hemmingsen, Guo-Fang Zhang, Yunhan Ma, Hannah Marchuk, Kalyani R Patel, Tong Chen, Xinning Li, Mark Chapman, Sabrina Collias, Dolores H Lopez-Terrada, James Beasley, Ashlee R Stiles, Randy J Chandler, Charles P Venditti, Sarah P Young, Mercedes Barzi, Beatrice Bissig-Choisat, Doug Krafte, Christopher B Newgard, Karl-Dimiter Bissig

Faculty, Staff and Students Publications

Methylmalonic acidemia (MMA) is a severe metabolic disorder affecting multiple organs because of a distal block in branched-chain amino acid (BCAA) catabolism. Standard of care is limited to protein restriction and supportive care during metabolic decompensation. Severe cases require liver/kidney transplantation, and there is a clear need for better therapy. Here, we investigated the effects of a small molecule branched-chain amino acid transaminase (BCAT) inhibitor in human MMA hepatocytes and an MMA mouse model. Mitochondrial BCAT is the first step in BCAA catabolism, and reduction of flux through an early enzymatic step is successfully used in other amino acid metabolic …

Metabolic Rewiring Of Isoniazid Sensitivity In Mycobacterium Tuberculosis, Erin R Wang, Kevin Cho, Gregory A Harrison, Asya Smirnov, Samuel R Mckee, George S Ghabrial, Kelly N Flentie, Wandy Beatty, Thomas Hurtaux, Liza Loza, Tamara L Doering, Gary J Patti, Christina L Stallings, Et Al.

2020-Current year OA Pubs

Isoniazid (INH) inhibits mycolic acid synthesis in

Fatty Acid 2-Hydroxylase Facilitates Rotavirus Uncoating And Endosomal Escape, Enkai Li, Ruochen Zang, Takahiro Kawagishi, Wei Zhang, Kruthika Iyer, Gaopeng Hou, Qiru Zeng, Rita M Meganck, Susan R Ross, Xin Wang, Xiong Su, Siyuan Ding

2020-Current year OA Pubs

Despite the clinical significance of many nonenveloped viruses, the molecular mechanisms of their internalization and membrane penetration are not well understood. Rotaviruses (RVs) are nonenveloped double-stranded RNA viruses and the leading cause of severe dehydrating diarrhea in infants and young children. We identified fatty acid 2-hydroxylase (encoded by

Identification Of Cobra And Viper Bites In Southern India Using Enzyme-Linked Immunosorbent Assay, Tejeswara Rao Asuru, Raskin Erusan Rajagopal, Albert Rajendran, Gulistan Parveen, Anushka Das, Pabitha Devi, Swapan K Dasgupta, Shantaraman Kalyanaraman, Prasenjit Guchhait, Perumal Thiagarajan

Faculty, Staff and Students Publications

Introduction: Snakebite-related deaths are major concerns in populations worldwide that lack access to medical care. Current treatment of snakebites includes administration of polyspecific and polyvalent heterologous equine antiserum. Swift diagnosis of the species of snake responsible is essential to initiate a specific treatment.

Methods: We generated murine monoclonal and rabbit polyclonal antibodies against the venom of the 3 most common venomous snakes in southern India: the Russell viper, the saw-scaled viper, and the Indian cobra. We developed an enzyme-linked immunosorbent assay to distinguish the snake by analyzing the exudates from the snakebite wound.

Results: Monoclonal antibody EC3 reacts specifically with …

Modeling The Impact Of Mmr Vaccination Strategies On Measles Outbreaks In Texas, Kaiming Bi, Thuy Nguyen, Boya Peng, Trudy Krause, Cecilia Ganduglia Cazaban, Janelle Rios, Cici Bauer, Catherine Troisi, Eric Boerwinkle, Aanand D Naik

Faculty, Staff and Student Publications

No abstract provided.

An Allele-Agnostic Mutant-Kras Inhibitor Suppresses Tumor Maintenance Signals And Reprograms Tumor Immunity In Pancreatic Cancer, Kathleen M Mcandrews, Francesca Paradiso, Clint A Stalnecker, Benson S Chellakkan, Fredrik I Thege, David H Peng, Barbara A Moreno Diaz, Hikaru Sugimoto, Sarah I Patel, Krishnan K Mahadevan, Michelle L Kirtley, Danielle Wills, Amari M Sockwell, Andre Luis F Fonseca, Yunhe Liu, Kimal I Rajapakshe, Nathaniel G Yee, Phuong Thao Tran, Huda Alchikh Omar, Antonio Tedeschi, Fiorella Schischlik-Siegl, Andrew S Boghossian, Matthew G Rees, Melissa M Ronan, Jennifer A Roth, Dorothea Rudolph, Martin Aichinger, Florian Ebner, Artem V Artemov, Jesse Lipp, Laura Pisarsky, Valerie Laura Herrmann, John Park, Jörg F Rippmann, Otmar Schaaf, Vanessa Chandler, Mariah Williams, Charles E Deckard, Linghua Wang, Channing J Der, Christopher Vellano, Paola A Guerrero, Timothy P Heffernan, Raghu Kalluri, Anirban Maitra

Faculty, Staff and Student Publications

KRAS is among the most frequently mutated oncogenes in cancer, and for decades, efforts at pharmacological blockade of its function in solid cancers have been unsuccessful. A notable advance in this endeavor is the recent development of small molecule KRAS inhibitors, which enable direct targeting of the mutant oncoprotein. Here, we comprehensively evaluate the pre-clinical efficacy of BI-2493 a panKRASi, a first-in-class allele agnostic mutant KRAS inhibitor, in pancreatic ductal adenocarcinoma (PDAC). We report effective tumor growth suppression across a broad range of models, including cell lines, patient-derived xenografts (PDXs), syngeneic orthotopic models, and prolonged survival in genetically engineered mouse …

Handling Hemolytic Blood Samples From High-Risk Clinical Areas: A Call To Action, Alan H B Wu, Jerrold H Levy, W Franklin Peacock, Ramzy Rimawi, Manuel Sanchez Luna, Christopher Farnsworth, Hugo Stiegler, Robert H Christenson

2020-Current year OA Pubs

BACKGROUND: Spectrophotometric testing to detect sample hemolysis is available from central laboratory chemistry analyzers. While the cause and preventative measures are known, hemolysis continues to be a common preanalytical error, especially for specimens collected from the emergency department (ED) and intensive care units (ICUs) where point-of-care analyzers are commonly used for whole blood electrolyte testing. Recently, these analyzers have employed technology to detect hemolysis directly on whole blood samples.

METHODS: Experienced laboratorians and physicians from the clinical laboratory, ED, adult and neonatal ICUs provide a summary of the medical importance of in vitro hemolysis. Causes for in vivo hemolysis are …

Efficacy Of Atr Kinase Inhibitor Elimusertib Monotherapy Or Combination In Tumors With Dna Damage Response Pathway And Other Genomic Alterations, Kaushik Varadarajan, Christian X Cruz Pico, Kurt W Evans, Maria Gabriela Raso, Yasmeen Qamar Rizvi, Xiaofeng Zheng, Dhruv Chachad, Timothy P Diperi, Bailiang Wang, Stephen M Scott, Ming Zhao, Argun Akcakanat, Antje M Wengner, Timothy A Yap, Funda Meric-Bernstam

Faculty, Staff and Student Publications

The ataxia telangiectasia and RAD3-related (ATR) kinase functions with ataxia telangiectasia-mutated (ATM) kinase as a modulator of DNA damage response (DDR). We assessed the antitumor effects of the ATR inhibitor elimusertib (BAY-1895344) in patient-derived xenograft (PDX) models with DDR alterations. Antitumor activity was assessed by change in tumor volume (TV) from baseline. Responses were categorized as follows: partial response (PR), ≥30% decrease in TV; ≥20% increase in TV, progressive disease; and non-PR/progressive disease, stable disease (SD). Event-free survival was defined as time for tumor doubling (EFS-2). Of 21 PDX models tested, 11 had significant prolongation of EFS-2 with elimusertib monotherapy. …

Risk Of Cardiovascular Events During Delivery Hospitalization Among Pregnant Patients With Mental Health Conditions, Kavya Parekh, R J Waken, Khavya Avula, Katelin B Nickel, Kathryn J Lindley, Cynthia Rogers, Karen E Joynt Maddox

2020-Current year OA Pubs

BACKGROUND: Cardiovascular disease remains the leading cause of maternal mortality. Mental health disorders are risk factors for cardiovascular disease in nonpregnant populations, but their association with delivery outcomes is unknown.

METHODS: This cross-sectional study used delivery hospitalizations from the 2021 National Inpatient Sample. We used generalized estimating equations to fit quasi-Poisson regression models for cardiovascular severe maternal morbidity and mortality (SMM) events as defined by the Centers for Disease Control and Prevention, and non-SMM cardiovascular conditions or complications as defined by the Alliance for Innovation on Maternal Health. Incidence rate ratios were calculated for depression, anxiety, psychosis, bipolar, obsessive-compulsive disorder, …

Targeting The Il-36 Receptor With Spesolimab Mitigates Residual Inflammation And Prevents Generalized Pustular Psoriasis Flares, James G. Krueger, Milan J. Anadkat, Et Al.

2020-Current year OA Pubs

People with generalized pustular psoriasis experience underlying skin inflammation, even in the absence of flares. Spesolimab treatment helps control the inflammation and prevent future flares.

Looking Beyond Hospital Discharge: One-Year Mortality Following Tracheostomy Creation In Traumatically Injured Older Adults, Heather R Kregel, Jan-Michael Van Gent, Fatimah Sunez, Michael W Wandling, Krislynn M Mueck, Bryan A Cotton, David E Meyer, Laura J Moore, Lillian S Kao, Thaddeus J Puzio

Faculty, Staff and Student Publications

Introduction: We aimed to evaluate long-term outcomes following tracheostomy in older trauma patients and hypothesized that 1-year survival decreases with older age.

Methods: This was a descriptive analysis of intensive care unit patients ≥65 y old who underwent tracheostomy from 2015 to 2020. The National Death Index was accessed to determine time from tracheostomy creation to death. Groups were categorized by age. The primary outcome was 1-year mortality. Survival by age strata was analyzed using the Kaplan-Meier method.

Results: Of 205 eligible patients, 125 (61%) were 65-74, 68 (33%) were 75-84, and 12 (6%) were >85 y old. Median injury …

The Role Of Liver Macrophages In Viral Liver Pathogenesis, Alexis Brantly, Kyle Yeakle, Michael J. Bouchard, Peter J. Gaskill, Michael R. Nonnemacher

Kimmel Cancer Center Faculty Papers

Liver macrophages play important roles in the pathophysiology of liver fibrosis and hepatocellular carcinoma. However, liver macrophages are a heterogenous population and have differing roles in maintenance of liver function and response in disease. In a healthy liver, macrophages play a critical role in antigen processing, maintaining tolerance to the high levels of gut-derived bacterial products, and regulating inflammation through cytokine response. However, macrophages also play a critical role in liver pathology, specifically in the context of viral infection. The liver is targeted by multiple viruses, including human immunodeficiency virus, hepatitis B virus, and hepatitis C virus, which dysregulate macrophage …

Communicating Wastewater-Based Surveillance Data To Drive Action, Kata Farkas, Devrim Kaya, Rasha Maal-Bared, Ahmad I. Al-Mustapha, Sarmila Tandukar, Ishi Keenum, Teemu Gunnar, Aaron Bivins, Matthew J Wade, Kyle Bibby, Tarja M. Pitkänen, Ananda Tiwari

Michigan Tech Publications

As exemplified during the COVID-19 pandemic, wastewater-based surveillance (WBS) can deliver near real-time, population-level pathogen data to guide public health action. Its impact, however, hinges on timely, transparent, and context-specific communication to stakeholders, including health authorities, policymakers, scientists, clinicians, and the public. This review examines current WBS communication practices, identifies persistent challenges, and proposes strategies to enhance relevance. Key challenges include data complexity, lack of standardised communication frameworks, ethical and privacy concerns, and variable stakeholder capabilities. The strategic use of digital platforms, such as dashboards, reports, press releases, and social media, alongside traditional media, can broaden reach and aid interpretation. …

Integrating Environmental Risk Factors Into Pediatric Cancer Care: Laying The Groundwork For Improved Outcomes And Primary Prevention., Nicole Wood, Omar Shakeel, Juan A. Ortega-Garcia, Mark D. Miller

Manuscripts, Articles, Book Chapters and Other Papers

Childhood cancer incidence has steadily risen both in the United States and worldwide, yet its environmental contributors remain underrecognized in clinical care. Children and cancer survivors are particularly susceptible to environmental exposures due to their unique physiology and the long-term health vulnerabilities that follow cancer treatment. Although exposures to substances such as pesticides, air pollution, and household chemicals are linked to increased cancer risk, limited clinical frameworks and clinician training leave oncologists underprepared to address growing environmental health concerns from families. A holistic pediatric oncology environmental health program in Murcia, Spain offers a scalable vision for embedding the environment into …

The Late Positive Potential Predicts Contingency Management Outcomes For Cocaine Use Disorder, Heather E Webber, Douglas J Calvillo, Francesco Versace, Constanza De Dios, Robert Suchting, Charles E Green, Scott D Lane, Joy M Schmitz

Faculty, Staff and Student Publications

Contingency management (CM) relies on motivation and reward processing and is among the most effective treatments available for cocaine use disorder (CUD), yet success rates do not meet desired clinical efficacy. To improve treatment-individual fit, we investigated the late positive potential (LPP), a measure of incentive salience to cues, as a predictor of treatment response. Treatment-seeking adults with CUD (N = 58) completed an EEG task where they viewed pleasant, unpleasant, cocaine, and neutral images. Participants received CM and counseling for four weeks. Urine was collected thrice weekly. We defined incentive salience to cues by A) cluster analyses on LPP …

Isatuximab Plus Bortezomib, Lenalidomide, And Dexamethasone For Transplant-Ineligible Newly Diagnosed Multiple Myeloma Patients: A Frailty Subgroup Analysis Of The Imroz Trial, Salomon Manier, Meletios-Athanasios Dimopoulos, Xavier P Leleu, Philippe Moreau, Michele Cavo, Hartmut Goldschmidt, Robert Z Orlowski, Muriel Tron, Christina Tekle, Marie-France Brégeault, Andrea T Shafer, Meral Beksac, Thierry Facon

Faculty, Staff and Student Publications

Patients with multiple myeloma (MM) meeting frailty criteria have worse outcomes than those identified as non-frail. Here, we present a post hoc subgroup analysis of IMROZ, a global, phase III, open-label study investigating isatuximab (Isa) with bortezomib, lenalidomide, and dexamethasone (VRd) followed by Isa-Rd (N=265) versus VRd followed by Rd (N=181) in newly diagnosed transplant-ineligible MM (Ti NDMM) patients using the simplified International Myeloma Working Group (sIMWG) frailty score. Although patients aged >80 years were excluded, there was no exclusion for patients meeting frailty criteria. All patients received standard VRd/Rd dosing; Isa-VRd patients received intravenous Isa (cycle 1, 10 mg/kg …

Immune Impacts Of Fire Smoke Exposure, Mary M Johnson, Abhinav Kaushik, Olivia A Kline, Eric M Smith, Xiaoying Zhou, Yagiz Pat, Laura Buergi, Juan Aguilera, Shifaa Alkotob, Elisabeth M Simonin, Alberto Favaro, Miguel Couto, Oscar Bennett, R Sharon Chinthrajah, Ella Parsons, Mohamed Shamji, Marshall Burke, Melissa Bondy, Mubeccel Akdis, Cezmi A Akdis, Kari C Nadeau

Faculty, Staff and Student Publications

Fire smoke exposure has become a global health concern and is associated with increased morbidity and mortality. There is a lack of understanding of the specific immune mechanisms involved in smoke exposure with preventative and targeted interventions needed. After exposure to fire smoke, which includes PM2.5, toxic metals and per- and polyfluoroalkyl substances (PFAS), epidemiology-based studies demonstrate increases in respiratory (e.g. asthma exacerbations), cardiac (e.g. myocardial infarctions, arrhythmias), neurologic (e.g. stroke) and pregnancy-related (e.g. low birthweight, premature births) outcomes. However, mechanistic studies exploring how smoke exposure disrupts cellular homeostasis are lacking. Therefore, we collected blood from smoke-exposed individuals (n …

Clinical Uptake Of An Antigen-Based Approach To Membranous Nephropathy: A Survey Of General Nephrologists And Glomerular Disease Experts., Eibhlin Goggins, Andrew Delaat, Bryce Barr, Jonathan Taliercio, Ali Mehdi, Georges Nakhoul, Brendan Bowman, Corey Cavanaugh

Ambulatory and Primary Care Articles

BACKGROUND: In recent years, there has been an emergence of new antigens discovered in membranous nephropathy (MN). Whether these antigens have impacted the approach to, and management of, MN patients undertaken by nephrologists is still unclear.

METHODS: We conducted a cross-sectional international survey pertaining to 13 antigens recently discovered in MN. The survey was distributed by the National Kidney Foundation, direct emails, and social media.

RESULT: PLA2R, THSD7A, NELL1, and EXT1/2 testing were readily available while the most common response for other antigen testing was 'Not Performed' or 'Unknown'. All respondents had tested for or treated PLA2R-positive MN. Of 79 …

Using Extension-Based Mrna Display To Design Antibody-Like Proteinogenic Peptides For Human Pd-L1, Justin N Ong, Brian J Grindel, Scott A Rankin, Sarah H Naylon, Anupallavi Srinivasamani, Guillaume J Trusz, Xiaowen Liang, Md Nasir Uddin, Lauren Fuller, Michael Curran, Stephane P Roche, Terry T Takahashi, Richard W Roberts, Steven W Millward

Faculty, Staff and Student Publications

Many peptide drugs rely on nonproteinogenic amino acids and chemical modifications for improved activity and proteolytic stability. However, these features also make drug production expensive and challenging to scale. Here, we engineered small, linear, proteinogenic peptides that bind human programmed death-ligand 1 (hPD-L1) with high affinity and stability using mRNA display affinity maturation. The resulting peptides, SPAM2 and SPAM3, have antibody-like affinities for hPD-L1 (dissociation constants between ~250 and 300 pM) and are selective for hPD-L1. Both SPAM2 and SPAM3 compete with hPD-L1 ligands known to interact with the programmed cell death protein 1 site and are stable in human …

Eugenics And Polygenic Embryo Screening: Public, Clinician, And Patient Perceptions Of Conditions Versus Traits, Dorit Barlevy, Rémy A Furrer, Asha Kalapatapu, Abigail Martinez, Todd Lencz, Shai Carmi, Gabriel Lázaro-Muñoz, Stacey Pereira

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Polygenic embryo screening (PES) estimates an embryo's genetic chances of developing complex conditions (eg, cancer) and traits (eg, height). Stakeholders have raised concerns that PES promotes eugenic practices and ideology.

Methods: We surveyed a nationally representative sample of the US public on approval of screening embryos for 12 conditions and 12 traits and examined the association between disapproval and concern about eugenics. We also conducted semistructured interviews with US-based reproductive endocrinology and infertility specialists and patients undergoing in vitro fertilization on their perspectives toward PES.

Results: Among the US public (n = 1423), disapproval of screening embryos for traits …