Digital Commons Network^™

Tuberculosis In Adult Migrants In Europe: A Tbnet Consensus Statement, Heinke Kunst, Berit Lange, Olga Hovardovska, Annabelle Bockey, Dominik Zenner, Aase B Andersen, Sally Hargreaves, Manish Pareek, Jon S Friedland, Christian Wejse, Graham Bothamley, Lorenzo Guglielmetti, Dumitru Chesov, Simon Tiberi, Alberto Matteelli, Anna M Mandalakas, Jan Heyckendorf, Johannes Eimer, Akanksha Malhotra, Javier Zamora, Anca Vasiliu, Christoph Lange, Tbnet

Faculty, Staff and Students Publications

INTRODUCTION: Global migration has increased in recent decades owing to war, conflict, persecution and natural disasters, but also secondary to increased opportunities related to work or study. Migrants' risk of tuberculosis (TB) differs depending on migration, socioeconomic status, mode of travel and TB risk in transit, TB incidence and healthcare provision in country of origin. Despite advances in TB care for migrants and new treatment strategies, decisions for managing migrants at risk of TB often rely on expert opinions, rather than clinical evidence.

METHODS: A systematic literature search was conducted, studies were mapped to different recommendation groups and included studies …

Fructose Induces Inflammatory Activation In Macrophages And Microglia Through The Nutrient-Sensing Ghrelin Receptor, Zheng Shen, Zeyu Liu, Hongying Wang, Danilo Landrock, Ji Yeon Noh, Qun Sophia Zang, Chih-Hao Lee, Yuhua Z Farnell, Zheng Chen, Yuxiang Sun

Faculty, Staff and Student Publications

High fructose corn syrup (HFCS) is a commonly used sweetener in soft drinks and processed foods, and HFCS exacerbates inflammation when consumed in excess. Fructose, a primary component of HFCS; however, it is unclear whether fructose directly activates inflammatory signaling. Growth hormone secretagogue receptor (GHSR) is a receptor of the nutrient‐sensing hormone ghrelin. We previously reported that GHSR ablation mitigates HFCS‐induced inflammation in adipose tissue and liver, shifting macrophages toward an anti‐inflammatory spectrum. Since inflammation is primarily governed by innate immune cells, such as macrophages in the peripheral tissues and microglia in the brain, this study aims to investigate whether …

Invasive Haemophilus Influenzae Disease At A Us Children's Hospital In The Sars-Cov-2 Era, J Chase Mcneil, David R Mcdonald, James J Dunn, Sheldon L Kaplan, Kristina G Hulten, Jesus G Vallejo

Faculty, Staff and Students Publications

Background: National data previously demonstrated an increase in invasive disease due to non-type b Haemophilus influenzae from the 2000s to the 2010s. Significant shifts in the epidemiology of respiratory pathogens in children have occurred in the post-SARS-CoV-2 era. We examined pediatric invasive H. influenzae disease in the pre- and post-SARS-CoV-2 years.

Methods: Invasive H. influenzae infections were identified from culture records of the Texas Children's Hospital microbiology laboratory from January 2011 to December 2023. Invasive cases were considered those with isolation of H. influenzae from a sterile site. The annual number of cases/1000 admissions was used as a surrogate for …

Complement Activity And Autophagy Are Dysregulated In The Lungs Of Patients With Nonresolvable Covid-19 Requiring Lung Transplantation, Pooja Shivshankar, Stacey L Mueller-Ortiz, Aleksey Y Domozhirov, Weizhen Bi, Scott D Collum, Marie-Francoise Doursout, Manish Patel, Isabella N Lefebvre, Bindu Akkanti, Simon Yau, Howard J Huang, Rahat Hussain, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced coronavirus disease 2019 (COVID-19) pandemic has challenged the current understanding of the complement cascade mechanisms of host immune responses during infection-induced nonresolvable lung disease. While the complement system is involved in opsonization and phagocytosis of the invading pathogens, uncontrolled complement activation also leads to aberrant autophagic response and tissue damage. Our recent study revealed unique pathologic and fibrotic signature genes associated with epithelial bronchiolization in the lung tissues of patients with nonresolvable COVID-19 (NR-COVID-19) requiring lung transplantation. However, there is a knowledge gap if complement components are modulated to contribute to tissue …

Interim Estimates Of 2024-2025 Seasonal Influenza Vaccine Effectiveness - Four Vaccine Effectiveness Networks, United States, October 2024-February 2025, Aaron M Frutos, Seana Cleary, Emily L Reeves, Haris M Ahmad, Ashley M Price, Wesley H Self, Yuwei Zhu, Basmah Safdar, Ithan D Peltan, Kevin W Gibbs, Matthew C Exline, Adam S Lauring, Sarah W Ball, Malini Desilva, Sara Y Tartof, Kristin Dascomb, Stephanie A Irving, Nicola P Klein, Brian E Dixon, Toan C Ong, Ivana A Vaughn, Stacey L House, Kiran A Faryar, Mary Patricia Nowalk, Manjusha Gaglani, Karen J Wernli, Vel Murugan, Olivia L Williams, Rangaraj Selvarangan, Geoffrey A Weinberg, Mary A Staat, Natasha B Halasa, Leila C Sahni, Marian G Michaels, Janet A Englund, Marie K Kirby, Diya Surie, Fatimah S Dawood, Benjamin R Clopper, Heidi L Moline, Ruth Link-Gelles, Amanda B Payne, Elizabeth Harker, Kristina Wielgosz, Zachary A Weber, Duck-Hye Yang, Nathaniel M Lewis, Jennifer Decuir, Samantha M Olson, Jessie R Chung, Brendan Flannery, Lisa A Grohskopf, Carrie Reed, Shikha Garg, Sascha Ellington, Cdc Influenza Vaccine Effectiveness Collaborators

Faculty, Staff and Students Publications

Annual influenza vaccination is recommended for all persons aged ≥6 months in the United States. Interim influenza vaccine effectiveness (VE) was calculated among patients with acute respiratory illness–associated outpatient visits and hospitalizations from four VE networks during the 2024–25 influenza season (October 2024–February 2025). Among children and adolescents aged <18 years, VE against any influenza was 32%, 59%, and 60% in the outpatient setting in three networks, and against influenza-associated hospitalization was 63% and 78% in two networks. Among adults aged ≥18 years, VE in the outpatient setting was 36% and 54% in two networks and was 41% and 55% against hospitalization in two networks. Preliminary estimates indicate that receipt of the 2024–2025 influenza vaccine reduced the likelihood of medically attended influenza and influenza-associated hospitalization. CDC recommends annual receipt of an age-appropriate influenza vaccine by all eligible persons aged ≥6 months as long as influenza viruses continue to circulate locally.

Immunological Biomarkers Of Response And Resistance To Treatment With Cabozantinib And Nivolumab In Recurrent Endometrial Cancer, Vladimir Roudko, Diane Marie Del Valle, Emir Radkevich, Geoffrey Kelly, Xie Hui, Manishkumar Patel, Edgar Gonzalez-Kozlova, Kevin Tuballes, Howard Streicher, Swati Atale, Lisa Wang, Benito Czinczin, Seunghee Kim-Schulze, Ignacio I Wistuba, Cara L Haymaker, Gheath Al-Atrash, Ganiraju Manyam, Jianjun Zhang, Ryan Thompson, Mayte Suarez-Farinas, Stephanie Lheureux, Sacha Gnjatic

Faculty, Staff and Student Publications

Background: Antiangiogenics combined with immune checkpoint blockade have become standard of care for recurrent endometrial cancer after standard platinum-based chemotherapy. To dissect mechanisms and define biomarkers associated with clinical outcomes to these combinations, we applied multidimensional immune monitoring to peripheral blood specimens collected from a randomized phase 2 trial of nivolumab with or without cabozantinib in 75 evaluable patients with recurrent endometrial cancer (NCI ETCTN 10104, NCT03367741). This trial demonstrated superiority of the combination to nivolumab alone.

Methods and results: Using Olink proteomics, mass cytometry, tumor antigen-specific ELISA, and whole exome tumor sequencing, we identified longitudinal immune signatures specific …

Loss Of Mucin 2 And Mhc Ii Molecules Causes Rare Resistance To Murine Rv Infection, Carolyn Bomidi, Faith M Sawyer, Noah Shroyer, Margaret Conner, Mary K Estes, Sarah E Blutt

Faculty, Staff and Students Publications

Enteric pathogen rotavirus (RV) primarily infects mature enterocytes at the tips of the intestinal villi; however, the role of secretory Paneth and goblet cells in RV pathogenesis remains unappreciated. Atoh1 knockout mice (Atoh1cKO) were used to conditionally delete Paneth, goblet, and enteroendocrine cells in the epithelium to investigate the role of secretory cells in RV infection. Unexpectedly, the number of infected enterocytes and the amount of RV shedding in the stool were greatly decreased following secretory cell deletion. Resistance to RV infection persisted for 7 days after virus inoculation, and Atoh1 knockout mice co-housed with infected wild-type mice were uninfected, …

Clostridioides Difficile Colonization Is Not Mediated By Bile Salts And Utilizes Stickland Fermentation Of Proline In An In Vitro Model, Xiaoyun Huang, April E Johnson, Joshua N Brehm, Thi Van Thanh Do, Thomas A Auchtung, Hugh C Mccullough, Armando I Lerma, Sigmund J Haidacher, Kathleen M Hoch, Thomas D Horvath, Joseph A Sorg, Anthony M Haag, Jennifer M Auchtung

Faculty, Staff and Students Publications

Treatment with antibiotics is a major risk factor for Clostridioides difficile infection, likely due to depletion of the gastrointestinal microbiota. Two microbiota-mediated mechanisms thought to limit C. difficile colonization include the conversion of conjugated primary bile salts into secondary bile salts toxic to C. difficile growth and competition between the microbiota and C. difficile for limiting nutrients. Using a continuous flow model that simulates the nutrient conditions of the distal colon, we investigated how treatment with 6 clinically used antibiotics influenced susceptibility to C. difficile infection in 12 different microbial communities cultivated from healthy individuals. Antibiotic treatment reduced microbial richness; …

Conformational Flexibility Is A Critical Factor In Designing Broad-Spectrum Human Norovirus Protease Inhibitors, Son Pham, Boyang Zhao, Neetu Neetu, Banumathi Sankaran, Ketki Patil, Sasirekha Ramani, Yongcheng Song, Mary K Estes, Timothy Palzkill, B V Venkataram Prasad

Faculty, Staff and Students Publications

UNLABELLED: Human norovirus (HuNoV) is a leading cause of gastroenteritis worldwide and is associated with significant morbidity, mortality, and economic impact. There are currently no licensed antiviral drugs for the treatment of HuNoV-associated gastroenteritis. The HuNoV protease plays a critical role in the initiation of virus replication by cleaving the polyprotein. Thus, it is an ideal target for developing antiviral small-molecule inhibitors. While rupintrivir, a potent small-molecule inhibitor of several picornavirus proteases, effectively inhibits GI.1 protease, it is an order of magnitude less effective against GII protease. Other GI.1 protease inhibitors also tend to be less effective against GII proteases. …

Pitavastatin Is Well-Tolerated With No Detrimental Effects On Physical Function, Kristine M Erlandson, Triin Umbleja, Heather J Ribaudo, Jennifer A Schrack, Edgar T Overton, Carl J Fichtenbaum, Kathleen V Fitch, Jhoanna C Roa, Marissa R Diggs, Kenneth Wood, Markella V Zanni, Gerald S Bloomfield, Carlos Malvestutto, Judith A Aberg, Maria C Rodriguez-Barradas, Rosalba Gomez Morones, Katherine Breaux, Pamela S Douglas, Steven K Grinspoon, Todd T Brown

Faculty, Staff and Students Publications

Background: Little is known about the potential benefits or harms of statins on physical function among people with human immunodeficiency virus (PWH).

Methods: REPRIEVE was a double-blind randomized controlled trial evaluating pitavastatin for primary prevention of major adverse cardiovascular events in PWH. Time to complete 10 chair rises, 4-m gait speed, grip strength, and a modified short physical performance test were assessed annually for up to 5 years in the ancillary study PREPARE and analyzed using linear mixed models.

Findings: Of 602 PWH, 52% were randomized to pitavastatin and 48% to placebo. Median age was 51 years; 18% were female …

Membrane Lipids Augment Cell Envelope Stress Signaling Via The Madrs System To Defend Against Antimicrobial Peptides And Antibiotics In Enterococcus Faecalis, William R Miller, April Nguyen, Kavindra V Singh, Samie Rizvi, Ayesha Khan, Sam G Erickson, Stephanie L Egge, Melissa Cruz, An Q Dinh, Lorena Diaz, Philip C Thornton, Rutan Zhang, Libin Xu, Danielle A Garsin, Yousif Shamoo, Cesar A Arias

Faculty, Staff and Student Publications

Enterococci have evolved resistance mechanisms to protect their cell envelopes against bacteriocins and host cationic antimicrobial peptides (CAMPs) produced in the gastrointestinal environment. Activation of the membrane stress response has also been tied to resistance to the lipopeptide antibiotic daptomycin. However, the actual effectors mediating resistance have not been elucidated. Here, we show that the MadRS (formerly YxdJK) membrane antimicrobial peptide defense system controls a network of genes, including a previously uncharacterized 3-gene operon (madEFG) that protects the Enterococcus faecalis cell envelope from antimicrobial peptides. Constitutive activation of the system confers protection against CAMPs and daptomycin in the absence of …

Zika Virus Ns1 Drives Tunneling Nanotube Formation For Mitochondrial Transfer And Stealth Transmission In Trophoblasts, Rafael T Michita, Long B Tran, Steven J Bark, Deepak Kumar, Shay A Toner, Joyce Jose, Indira U Mysorekar, Anoop Narayanan

Faculty, Staff and Students Publications

Zika virus (ZIKV) is unique among orthoflaviviruses in its vertical transmission capacity in humans, yet the underlying mechanisms remain incompletely understood. Here, we show that ZIKV induces tunneling nanotubes (TNTs) in placental trophoblasts which facilitate transfer of viral particles, proteins, mitochondria, and RNA to neighboring uninfected cells. TNT formation is driven exclusively via ZIKV non-structural protein 1 (NS1). Specifically, the N-terminal 1-50 amino acids of membrane-bound ZIKV NS1 are necessary for triggering TNT formation in host cells. Trophoblasts infected with TNT-deficient ZIKV

Silencing Faf2 Mitigates Alcohol-Induced Hepatic Steatosis By Modulating Lipolysis And Pcsk9 Pathway, Nazmul Huda, Praveen Kusumanchi, Yanchao Jiang, Hui Gao, Themis Thoudam, Ge Zeng, Nicholas J. Skill, Zhaoli Sun, Suthat Liangpunsakul, Jing Ma, Zhihong Yang

School of Medicine Faculty Publications

BACKGROUND: Chronic alcohol consumption leads to lipid accumulation, oxidative stress, cellular damage, and inflammation in the liver, collectively referred to as alcohol-associated liver disease (ALD). FAF2/UBXD8/ETEA (Fas-associated factor 2) is a ubiquitin ligase adaptor protein that plays a crucial role in the ubiquitin-mediated degradation of misfolded proteins in the endoplasmic reticulum. A recent genome-wide association study indicated an association between FAF2 and ALD; however, the exact contribution of FAF2 to ALD pathogenesis remains unclear. METHODS: FAF2 was knocked down using AAV-delivered shRNA in C57/BL6 mice. Mice were subjected to a chronic-plus-single binge ethanol feeding (NIAAA) model. Nine hours after gavage, …

Antifungal Prophylaxis In High-Risk Patients With Hematologic Malignancy:A Comparison Of Practice With Guidelines In Türkiye, Özlem Güzel Tunçcan, Seçki̇n Çağirgan, Hakan Özdoğu, Si̇nem Ci̇vri̇z Bozdağ, Fi̇li̇z Vural, Mustafa Pehli̇van, Hüseyi̇n Saffet Beköz, Yasemi̇n Esen, Tuba Koç, Petek Gi̇li̇k, Esi̇n Şenol

Turkish Journal of Medical Sciences

Background/aim: Primary antifungal prophylaxis (AFP) is recommended by guidelines as the gold standard for patients with hematologic malignancies. This study aimed to investigate the level of knowledge and translation of guideline recommendations into real-life setting among physicians in Türkiye.Materials and methods: In this prospective, observational study, the physicians’ knowledge of ΑFP guideline recommendations in patients with acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) undergoing first remission-induction (Group I), and graft-versus-host-disease (GvHD) after allogeneic stem cell transplant (Group II), was compared with clinical practice via 11-item multiple-choice questionnaire evaluating the timing and patients in whom AFP was initiated, with AFP …

Outbreak Of Bacteremia Caused By Ralstonia Insidiosa Isolated From Contaminated Blood Gas Syringe, Eli̇f Ayça Şahi̇n, Özge Özgen Top, Pınar Aysert Yildiz, Eli̇f Seren Tanriverdi̇, Hasan Selçuk Özger, Bariş Otlu, Özlem Güzel Tunçcan, Murat Di̇zbay, Ayşe Kalkanci, Kayhan Çağlar

Turkish Journal of Medical Sciences

Background/aim: Ralstonia species are opportunistic, waterborne microorganisms known for their ability to survive and proliferate in a wide range of water-based environments. They can contaminate solutions used for patient care and cause hospital outbreaks due to contaminated solutions. The aim of this study was to investigate the source and clonal relationship of Ralstonia insidiosa bacteremia detected in 28 patients between August and December 2021, as part of an unusual outbreak.Materials and methods: Active prospective surveillance studies were conducted, and environmental samples, including saline, antiseptic, and antibiotic solutions, injectors, arterial blood gas syringes, tap water, and hand soap, were collected from …

Single-Cell Rna Sequencing Identifies Molecular Biomarkers Predicting Late Progression To Cdk4/6 Inhibition In Patients With Hr+/Her2- Metastatic Breast Cancer, Linjie Luo, Peng Yang, Sofia Mastoraki, Xiayu Rao, Yan Wang, Nicole M Kettner, Akshara Singareeka Raghavendra, Debasish Tripathy, Senthil Damodaran, Kelly K Hunt, Jing Wang, Ziyi Li, Khandan Keyomarsi

Faculty, Staff and Student Publications

Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) in combination with endocrine therapy are the standard treatment for patients with hormone receptor-positive, HER2-negative metastatic breast cancer (mBC). Despite the efficacy of CDK4/6is, intrinsic resistance occurs in approximately one-third of patients, highlighting the need for reliable predictive biomarkers.

Methods: Single-cell RNA sequencing analyzed metastatic tumors from HR+/HER2- mBC patients pre-CDK4/6i treatment at baseline (BL) and/or at disease progression. BL samples were from CDK4/6i responders (median progression-free survival [mPFS] = 25.5 months), while progressors were categorized as early-progressors (EP, mPFS = 3 months) and late-progressors (LP, mPFS = 11 months). Metastatic sites included liver, …

Mage-A4 Induces Non-Small Cell Lung Cancer And Tumor-Promoting Plasma Cell Accumulation, Dominique Armstrong, Cheng-Yen Chang, Monica J Hong, Linda Green, Yichao Shen, William Hudson, Kelsey E Mauk, Li-Zhen Song, Sheetal Jammi, Benjamin Casal, Brianna Burns, Chad J Creighton, Alexandre Carisey, Xiang H-F Zhang, Neil J Mckenna, Sung Wook Kang, Hyun-Sung Lee, William Decker, David B Corry, Farrah Kheradmand

Faculty, Staff and Students Publications

Adaptive immunity is critical in eliminating tumors, but cancer-intrinsic factors can subvert this function. Melanoma antigen-A4 (MAGE-A4), a cancer-testis antigen, is expressed in solid tumors and correlates with poor survival, but its role in tumorigenesis and antitumor immunity remains unclear. We found that expression of MAGE-A4 was highly associated with the loss of PTEN, a tumor suppressor, in human non–small cell lung cancers (NSCLC). Here, we show that constitutive expression of human MAGE-A4 with Pten loss in mouse airway epithelia results in metastatic adenocarcinoma. Tumors showed distinct enrichment in IgA+ CD138+ CXCR4+ plasma cells (PCs) and increased expression of …

Plasma Micrornas To Select Optimal Patients For Antibody Production From Anti-Addiction Vaccines, Thomas R Kosten, Amrit Koirala, David A Nielsen, Coreen B Domingo, Ynhi T Thomas, Preethi H Gunaratne, Cristian Coarfa

Faculty, Staff and Students Publications

Background: Cocaine and illicit amphetamines (disguised as “Adderall”) are being laced with fentanyl and producing accidental and intentional fatal overdoses. Vaccines can prevent these overdoses, but 33% of humans generate insufficient anti-drug antibody (AB) levels. Plasma microRNAs (miRs) can be used to predict non-responders. We have plasma stored from 152 cocaine vaccine trial participants following three vaccinations over 9 weeks and examined miRs as potential response biomarkers. Methods: We compared 2517 miRs before anti-cocaine vaccination in participants with the highest (n = 25) to the lowest (n = 23) antibody levels. False Discovery Rates (FDRs) were applied to identify differentially …

Inhibition Of Histone Methyltransferase Ezh2 For Immune Interception Of Colorectal Cancer In Lynch Syndrome, Charles M Bowen, Fahriye Duzagac, Abel Martel-Martel, Laura Reyes-Uribe, Mahira Zaheer, Jacklyn Thompson, Nan Deng, Ria Sinha, Soham Mazumdar, Melissa W Taggart, Abhinav K Jain, Elena Tosti, Winfried Edelmann, Krishna M Sinha, Eduardo Vilar

Faculty, Staff and Student Publications

Colorectal precancers in Lynch syndrome (LS) exhibit a distinct immune profile, presenting unique opportunities for developing immune-interception strategies to prevent carcinogenesis. Epigenetic modulation by EZH2 of immune-related genes is implicated in the carcinogenesis of different cancer types, including colorectal cancer. This study utilizes a mouse model of LS and ex vivo colonic organoids to assess the effects of the EZH2 inhibitor GSK503 on immune regulatory pathways, tumorigenesis, and epigenetic reprogramming. Our findings revealed that GSK503 significantly increased CD4+ and CD8+ T cells in both splenocytes and colonic mucosa of treated mice compared with controls. Additionally, a preventive dose of GSK503 …

Navigating Epstein-Barr Virus (Ebv) And Post-Transplant Lymphoproliferative Disorder (Ptld) In Pediatric Liver Transplantation: Current Knowledge And Strategies For Treatment And Surveillance, Erin Y Chen, Natasha Dilwali, Krupa R Mysore, Sara Hassan, Sara Kathryn Smith, Wikrom Karnsakul

Faculty, Staff and Students Publications

Epstein-Barr virus (EBV) is strongly associated with the development of post-transplant lymphoproliferative disorder (PTLD) in pediatric liver transplant recipients. PTLD is one of the most common malignancies following liver transplantation and is associated with significant morbidity and mortality. Factors such as EBV-serostatus mismatch and prolonged or high levels of immunosuppression impact a patient's risk of developing PTLD. While pre-transplant EBV serological screening and post-transplant monitoring of EBV-DNA levels are strongly recommended, universal guidelines for its prevention and management are lacking. Due to a lack of robust prospective studies, current clinical practices vary widely. The treatment of PTLD typically involves reducing …

Thrombocytopenia In Sepsis, Alireza Setarehaseman, Robert W. Maitta

Faculty Scholarship

Platelets, traditionally known for their role in hemostasis, have emerged as key players in immune response and inflammation. Sepsis, a life-threatening condition characterized by systemic inflammation, often presents with thrombocytopenia, which at times, can be significant. Platelets contribute to the inflammatory response by interacting with leukocytes, endothelial cells, and the innate immune system. However, excessive platelet activation and consumption can lead to thrombocytopenia and exacerbate the severity of sepsis. Understanding the multifaceted roles of platelets in sepsis is crucial for developing effective therapeutic strategies. Targeting platelet-mediated inflammatory responses and promoting platelet production may offer potential avenues for improving outcomes in …

Axl Signaling In Cancer: From Molecular Insights To Targeted Therapies, Monika Yadav, Akansha Sharma, Ketki Patne, Saba Tabasum, Jyoti Suryavanshi, Laxminarayan Rawat, Marc Machaalani, Marc Eid, Rana Singh, Toni Choueiri, Soumitro Pal, Akash Sabarwal

Department of Microbiology and Immunology Faculty Papers

AXL, a member of the TAM receptor family, has emerged as a potential target for advanced-stage human malignancies. It is frequently overexpressed in different cancers and plays a significant role in various tumor-promoting pathways, including cancer cell proliferation, invasion, metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, stemness, DNA damage response, acquired therapeutic resistance, immunosuppression, and inflammatory responses. Beyond oncology, AXL also facilitates viral infections, including SARS-CoV-2 and Zika highlighting its importance in both cancer and virology. In preclinical models, small-molecule kinase inhibitors targeting AXL have shown promising anti-tumorigenic potential. This review primarily focuses on the induction, regulation and biological functions of AXL …

Neutralizing Antibody Immune Correlates For A Recombinant Protein Vaccine In The Covail Trial, Youyi Fong, Lauren Dang, Bo Zhang, Jonathan Fintzi, Shiyu Chen, Jing Wang, Nadine G Rouphael, Angela R Branche, David J Diemert, Ann R Falsey, Cecilia Losada, Lindsey R Baden, Sharon E Frey, Jennifer A Whitaker, Susan J Little, Satoshi Kamidani, Emmanuel B Walter, Richard M Novak, Richard Rupp, Lisa A Jackson, Chenchen Yu, Craig A Magaret, Cindy Molitor, Bhavesh Borate, Tara M Babu, Angelica C Kottkamp, Anne F Luetkemeyer, Lilly C Immergluck, Rachel M Presti, Martín Bäcker, Patricia L Winokur, Siham M Mahgoub, Paul A Goepfert, Dahlene N Fusco, Robert L Atmar, Christine M Posavad, Jinjian Mu, Mat Makowski, Mamodikoe K Makhene, Seema U Nayak, Paul C Roberts, Dean Follmann, Peter B Gilbert

Faculty, Staff and Students Publications

For COVAIL recipients of a coronavirus disease 2019 (COVID-19) Sanofi booster vaccine, neutralizing antibody titers were assessed as a correlate of risk (CoR) of COVID-19. Peak and exposure-proximal titers were inverse CoRs with covariate-adjusted hazard ratios (95% confidence intervals) 0.30 (0.11, 0.78) and 0.25 (0.07, 0.85) per 10-fold increase in weighted average titer.

A Randomized, Double-Blind, Placebo-Controlled Trial Of Il-7 In Critically Ill Patients With Covid-19, Manu Shankar-Hari, Bruno Francois, Kenneth E Remy, Cristina Gutierrez, Stephen Pastores, Thomas Daix, Robin Jeannet, Jane Blood, Andrew H Walton, Reinaldo Salomao, Georg Auzinger, David Striker, Robert S Martin, Nitin J Anand, James Bosanquet, Teresa Blood, Scott Brakenridge, Lyle L Moldawer, Vidula Vachharajani, Cassian Yee, Felipe Dal-Pizzol, Michel Morre, Frederique Berbille, Marcel Van Den Brink, Richard Hotchkiss

Faculty, Staff and Student Publications

Background: Lymphopenia and failure of lymphocytes to mount an early IFN-γ response correlate with increased mortality in COVID-19. Given the essential role of CD4 helper and CD8 cytotoxic cells in eliminating viral pathogens, this profound loss in lymphocytes may impair patients' ability to eliminate the virus. IL-7 is a pleiotropic cytokine that is obligatory for lymphocyte survival and optimal function.

Methods: We conducted a prospective, double-blind, randomized, placebo-controlled trial of CYT107, recombinant human IL-7, in 109 critically ill, patients with lymphopenia who have COVID-19. The primary endpoint was to assess CYT107's effect on lymphocyte recovery with secondary clinical endpoints including …

Investigating The In Vivo Effects Of Anti-Prion Protein Nanobodies On Prion Disease With Aav Vector, Jingjing Zhang, Mengfei Wang, Dan Wang, Xiangyi Zhang, Yue Ma, Els Pardon, Jan Steyaert, Romany Abskharon, Fei Wang, Jiyan Ma

Faculty, Staff and Student Publications

Prion diseases are fatal neurodegenerative disorders affecting humans and animals, and the central pathogenic event is the conversion of normal prion protein (PrPC) into the pathogenic PrPSc isoform. Previous studies have identified nanobodies that specifically recognize PrPC and inhibit the PrPC to PrPSc conversion in vitro. In this study, we investigated the potential for in vivo expression of anti-PrPC nanobodies and evaluated their impact on prion disease. The coding sequences of three nanobodies were packaged into recombinant adeno-associated virus (rAAV) and were administered via intracerebroventricular (ICV) injection in newborn mice. We found that the expression of these nanobodies remained robust …

Sustainable Solutions To The Continuous Threat Of Antimicrobial Resistance, Brad Spellberg, David N Gilbert, Michael Baym, Gonzalo Bearman, Tom Boyles, Arturo Casadevall, Graeme N Forrest, Sarah Freling, Bassam Ghanem, Fergus Hamilton, Brian Luna, Jessica Moore, Daniel M Musher, Travis B Nielsen, Priya Nori, Matthew C Phillips, Liise-Anne Pirofski, Andrew F Shorr, Steven Y C Tong, Todd C Lee, Emily G Mcdonald

Faculty, Staff and Students Publications

To combat antimicrobial resistance (AMR), advocates have called for passage of the Pioneering Antimicrobial Subscriptions To End Upsurging Resistance (PASTEUR) Act in the United States, which would appropriate $6 billion in new taxpayer-funded subsidies for antibiotic development. However, the number of antibiotics in clinical development, and US Food and Drug Administration approvals of new antibiotics, have already markedly increased in the last 15 years. Thus, instead of focusing on more economic subsidies, we recommend reducing selective pressure driving AMR by (1) establishing pay-for-performance mechanisms that disincentivize overprescribing of antibiotics, (2) focusing existing research and development funding on strategies that decrease …

Respiratory Syncytial Virus Disease Burden And Nirsevimab Effectiveness In Young Children From 2023-2024, Heidi L Moline, Ariana P Toepfer, Ayzsa Tannis, Geoffrey A Weinberg, Mary A Staat, Natasha B Halasa, Julie A Boom, Eileen J Klein, John V Williams, Jennifer E Schuster, Leah Goldstein, Erin R Mckeever, Casey Kalman, Clinton Paden, Lydia Atherton, Megha Aggarwal, Pavitra Roychoudhury, Pedro A Piedra, Leila C Sahni, Laura S Stewart, Rangaraj Selvarangan, Marian G Michaels, Elizabeth P Schlaudecker, Peter G Szilagyi, Janet A Englund, Benjamin R Clopper, Natalie J Thornburg, Gordana Derado, Meredith L Mcmorrow, Fatimah S Dawood, New Vaccine Surveillance Network Collaborators

Faculty, Staff and Students Publications

Importance: During the 2023-2024 respiratory syncytial virus (RSV) season in the United States, 2 new RSV prevention products were recommended to protect infants in their first RSV season: nirsevimab and Pfizer's maternal RSV vaccine. Postlicensure studies are needed to assess prevention product impact and effectiveness.

Objective: To compare the epidemiology and disease burden of medically attended RSV-associated acute respiratory illness (ARI) among children younger than 5 years during the 2023-2024 RSV season with 3 prepandemic RSV seasons (2017-2020), estimate nirsevimab effectiveness against medically attended RSV-associated ARI, and compare nirsevimab binding site mutations among circulating RSV in infants with and without …

Mirnaome-Metabolome Wide Association Study Reveals Effects Of Mirna Regulation In Eosinophilia And Airflow Obstruction In Childhood Asthma, Rinku Sharma, Kevin Mendez, Sofina Begum, Su Chu, Nicole Prince, Julian Hecker, Rachel S. Kelly, Qingwen Chen, Craig E. Wheelock, Juan C. Celedón, Clary Clish, Robert Gertszen, Kelan G. Tantisira, Scott T. Weiss, Jessica Lasky-Su, Michael Mcgeachie

Research outputs 2022 to 2026

Background: There are important inter-relationships between miRNAs and metabolites: alterations in miRNA expression can be induced by various metabolic stimuli, and miRNAs play a regulatory role in numerous cellular processes, impacting metabolism. While both specific miRNAs and metabolites have been identified for their role in childhood asthma, there has been no global assessment of the combined effect of miRNAs and the metabolome in childhood asthma. Methods: We performed miRNAome-metabolome-wide association studies (‘miR-metabo-WAS’) in two childhood cohorts of asthma to evaluate the contemporaneous and persistent miRNA-metabolite associations: 1) Genetic Epidemiology of Asthma in Costa Rica Study (GACRS) (N = 1121); 2) …

Establishment Of The Nichols Strain As The Type Strain Of Treponema Pallidum, Steven J Norris

Faculty, Staff and Student Publications

In this article, it is proposed that the Nichols strain of Treponema pallidum be established as the type strain. T. pallidum was first identified as the causative agent of syphilis in 1905, and the Nichols strain was isolated in 1912 by inoculation of a rabbit with cerebrospinal fluid from a patient with neurosyphilis. The Nichols strain has been maintained by serial passage in rabbits for over a century, and historically most studies of T. pallidum have been conducted using this strain. In recent years, a procedure for continuous in vitro culture of T. pallidum in a tissue culture system has …

Developing A High-Performing Network Computation Of Big Bipartite Network Data Toward Alcohol Use Disorder Treatment Referrals, Muhammad Tuan Amith, Sharon Andrews, Angela Heads, Bruno Kluwe-Schiavon, Atchyutha Choday, Ramya Poonam, Sai Venkat Ballem, Cui Tao, Jane Hamilton

Faculty, Staff and Student Publications

Electronic health care records offer big data to mine and analyze towards improving public health outcomes. The information extracted, specifically social network data, could help us understand the primary care referrals for patients experiencing alcohol use disorder and wield that knowledge to better inform the engagement of this patient population. Network exposure and affiliation exposure models are two metrics that can be utilized to analyze the influence of social networks. We developed a core software library that address the scalability issue of our previous work. Our library computed high volume, randomly generated network graphs that range from 500–10,000 nodes (~126,000–40 …