Hemic and Immune Systems Commons^™

Identifying Modulators Of Stable Klrg1+Il7ra+ Memory Cd8+ T-Cells, Christina Ocampo Valdez

Honors Projects

Type 1 diabetes (T1D) is an autoimmune disease targeting the insulin-producing beta cells of the pancreas. The discovery of insulin revolutionized the treatment of T1D, but current research into T1D has progressed from disease management to possible prevention or delayed onset of diagnosis. One drug currently in use is teplizumab, an anti-CD3 monoclonal antibody that has been shown to delay the onset of T1D in some, but not all, at-risk individuals. High levels of a subset of peripheral blood CD8+ T cells we call SKIMs (stable KLRG1+ IL7Ra+ memory cells), which include MAIT (mucosal-associated invariant T) cells, have been associated …

Loss Of Sarm1 Affects Myelin Uptake And Clearance In Macrophages, Grace J. Bergeron

Senior Theses

Clearance of myelin debris is an essential step in nerve regeneration after injury in both the central nervous system (CNS) and peripheral nervous system (PNS), a process that is primarily carried out by macrophages. Failure to phagocytose and clear myelin can prolong inflammation and impair recovery. Sterile alpha and TIR motif-containing protein 1 (SARM1) is well researched as a regulator of axonal degeneration, yet its role in macrophages is still unclear. This study investigates how sarm1 deletion and cytokine signaling influence macrophage uptake and clearance of CNS and PNS myelin in vitro. Splenic macrophages isolated from wild-type (WT) and sarm1 …

Severe Maternal Morbidity According To Sickle Cell Disease Genotype, Tetsuya Kawakita, Natsume Furukawa, Sora A. Jones, Salimah Navaz Gangji

Department of Obstetrics & Gynecology Faculty Publications

Background

Sickle cell disease (SCD) is a genetic hemoglobinopathy that disproportionately affects individuals of African descent and is associated with elevated risks of maternal complications. However, the contribution of specific SCD genotypes to severe maternal morbidity (SMM) and postpartum readmission remains poorly characterized at the population level.

Objective

We sought to examine the association between SCD genotypes-hemoglobin SS (HbSS) disease, hemoglobin SC (HbSC) disease, sickle thalassemia, and sickle cell trait-and SMM, hospital readmission, and related adverse maternal outcomes.

Study design

This was a retrospective cohort study using the Nationwide Readmissions Database from 2016 through 2022, representing over 20 million weighted …

Chronobiology Of Meal Timing In Early-Stage Hypertension: A Controlled Feeding Pilot Study Investigating The Effects On Renal And Vascular Function, Natalie J. Bohmke, Brittany Barton, Patrice Wiecek, Paula Rodriguez-Miguelez, Dave L. Dixon, Youngdeok Kim, Salvatore Carbone, Danielle L. Kirkman

EVMS School of Health Professions Faculty Publications

Lifestyle intervention is critical for young adults with early-stage hypertension. A Western diet has negative effects on kidney function and blood pressure; however, time-of-day effects are understudied. We hypothesized that consumption of a Western-style meal that is misaligned with the endogenous circadian rhythm would have adverse effects on blood pressure, kidney function, and vascular function. Ten young adults with elevated blood pressure or stage 1 hypertension (means ± SD: 26 ± 8 yr, 50% female) underwent a randomized crossover, isocaloric controlled feeding intervention. Participants were allocated to receive a Western-style meal high in sodium, sugar, and saturated fat in the …

Successful Use Of Chimeric Antigen Receptor T-Cell (Car-T) Therapy With Lisocabtagene Maraleucel In A Renal Transplant Recipient With Refractory/Relapsed Diffuse Large B-Cell Lymphoma (Dlbcl), Waqqas Tai, Fatima Chaudhry, Nesreen Shahrour, Jessica Thomas, Afoma Anyadibe, Anuoluwa Oyetoran, Swathi Gopishetty, Precious Idogun, Dilip Samarapungavan, Jassim H. Sarmad, Ishmael Jaiyesimi

Department of Medicine Faculty Publications

This case describes a 53-year-old male with end-stage renal disease who developed monomorphic post-transplant lymphoproliferative disorder (PTLD) in the form of diffuse large B-cell lymphoma (DLBCL) after kidney transplantation. Despite initial treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP), the patient's disease progressed, and he was referred for chimeric antigen receptor (CAR) T-cell therapy with lisocabtagene maraleucel (liso-cel). Given his post-transplant status, his immunosuppressive agents (tacrolimus and mycophenolate) were held, and prednisone was tapered to 5 mg daily to maintain minimal baseline immunosuppression. After lymphodepleting chemotherapy and liso-cel infusion, the patient experienced no significant toxicities, including cytokine release syndrome (CRS) …

Editor's Choice - International Expert Consensus On The Management Of Acute Aortic Type B Intramural Haematoma And Penetrating Ulcer, Francesco Squizzato, Mario D'Oria, Michele Antonello, Santi Trimarchi, Kevin Mani, Andrew Holden, Tilo Kölbel, Stephan Haulon, Eric Verhoeven, Dittmar Böckler, Tim Resch, Ali Azizzadeh, Joseph Lombardi, Michele Piazza, Aaron Thomas Fargion, Alexander Zimmerman, Ali Azizzadeh, Anders Wanhainen, Andrew Holden, Antonio Freyrie, Adam W. Beck, Adi Bachar, Barend M. E. Mees, Blandine Maurel, Cristoph A. Nienaber, Christos Karkos, Daniela Branzan, Darren Schneider, Randall Demartino, Dittmar Boeckler, Domenico Angiletta, Emanuel J. R. Tenorio, Enrico Gallitto, Eric Verhoeven, Fabio Verzini, Felice Pecoraro, Filippo Benedetto, Firas F. Mussa, Francesco Squizzato, Franco Grego, Gabriele Piffaretti, Emanuele Gatta, Giovanni Pratesi, Giovanni Tinelli, Giuseppe Asciutto, Glenn Wei Leong Tan, Hence Verhagen, Giacomo Isernia, Jean-Paul P. M. De Vries, Jacob Budtz-Lilly, Jorge Fernández-Noya, Jonathan Sobocinski, Joseph Hockley, Kak Khee Yeung, Andrea Kahlberg, Kevin Mani, Joseph V. Lombardi, Luca Bertoglio, Luca Mezzetto, Ludovic Canaud, Manar Khashram, Marcelo Ferreira, Marco Virgilio Usai, Mark G. Davies, Mark Farber, Martin Czerny, Matthew R. Smeds, Mauro Gargiulo, Germano Melissano, Michel Bosiers, Michele Antonello, Michele Piazza, Miranda Witheford, Michel M.P.J. Reijnen, Marc Schermerhorn, Nikolaos Tsilimparis, Nun Dias, Jean Panneton, Kosmas Paraskevas, Gianbattista Parlani, Patrick W.H.E. Vriens, Rafael Malgor, Raffaele Pulli, Ross Milner, Salvatore T. Scali, Sani J. Laukontaus, Santi Trimarchi, Sandro Lepidi, Konstantinos Spanos, Stefano Fazzini, Theodosios Bisdas, Thomas Maldonado, Tilo Koelbel, Tim Resch, Tomasz Jakimowicz, Nicola Troisi, Isabelle Van Herzeele, Vicente Riambau, Wassim Mansour, Wouter Van Den Eynde, Yamume Tshomba

Department Surgery Faculty Publications

Objective

The aim of this study was to achieve an international expert consensus on managing acute type B penetrating aortic ulcers (PAUs) and intramural haematomas (IMHs).

Methods

A modified Delphi consensus process was employed to develop recommendations for the management of acute type B PAU and IMH. Surveys were sent to international experts practicing in high volume aortic centres worldwide. Statements were voted on using a four point Likert scale in a three round Delphi process. Statements achieving grade A (full agreement 75%) or B (overall agreement 80%, full disagreement <  5%) were included as expert recommendations. Consistency of responses was measured using Cohen's κ and the intraclass correlation coefficient.

Results

Eighty three experts were included in the final analysis: …

Peculiarities Of Phosphatidylserine Externalization By Nano- And Microsecond Electric Pulses, Mantas Silkunas, Alayna Enos, Iurii Semenov, Giedre Silkuniene, Eleni Zivla, Olga N. Pakhomova, Andrei G. Pakhomov

Bioelectrics Publications

Phosphatidylserine (PS) externalization is a hallmark of apoptosis but can also be triggered within seconds by pulsed electric fields (PEFs). Whether PS reaches the outer leaflet by lateral migration through electropores or indirectly through Ca²⁺-dependent signaling and scramblase activation remains debated. We used total internal reflection fluorescence (TIRF) microscopy with Annexin V-Alexa Fluor 568 and/or bovine lactadherin-FITC to resolve PS externalization in HEK293 cells placed on an indium tin oxide (ITO) transparent electrode. PEF exposures produced discrete PS-positive puncta ("freckles") within ~ 10 s after a 20-µs pulse (1.2-2.5 kV/cm) or with a ~ 1-min delay after a …

A Comparison Of F/Taf And F/Tdf As Hiv Pre-Exposure Prophylaxis In A Predominantly Cisgender Women Population In East And South Africa: A Randomised, Factorial, Non-Inferiority Trial, Sheena Mccormack, David Dunn, Sylvia Kusemererwa, Patricia Munseri, Nishanta Singh, Wiston William, Gertrude Mutonyi, Henry Bern, Lauriane Goldwirt, Cherry Kingsley, Arne Kkroidl, Christian Holm Hansen, Song Ding, Rachel Kawuma, Mary Amondi, Ubaldo Bahemuka, Deus Buma, Daniel Clutterbuck, Zakir Gaffoor, Angus Jennings, Agricola Joachim, Ayoub Kakande, Berna Kalanzi, Abisai Kisinda, Mabela Matsoso, Thomas Miller, Neetha Mmedsci Morar, Jacqueline Musau, Jane Nabbuto, Ayanda Nzuza, Doreen Pamba, Simona Salomone, Thandiwe Sithole, Edith Tarimo, Kubashni Woeber, Kundai Chinyenze, Glenda Gray, Eligius Lyamuya, Muhammad Bakari, Said Aboud, Lucas Maganga, Gustavo Doncel, Janet Seeley, Jonathan Weber, Pontiano Kaleebu, Julie Fox, Eugene Ruzagira, On Behalf Of The Prepvacc Study Group

CONRAD Publications

Background:

F/TAF was shown to be non-inferior to F/TDF as pre-exposure prophylaxis (PrEP) in men, but approval was not extended to cisgender women. We report the results of PrEPVacc, in which a predominantly female population was randomly allocated to receive daily oral F/TDF or F/TAF for ∼6 months within a HIV-1 prophylactic vaccine trial.

Setting:

Five study sites in three African countries (Uganda, Tanzania, South Africa).

Methods:

The two regimens were compared by the averted infections ratio (AIR) - the proportion of infections averted by F/TAF relative to F/TDF. The counterfactual HIV incidence, an essential component of this metric, was …

Stat4-Dependent Regulation Of Neuroinflammation In Atherosclerosis, Natalie Stahr, Alina K. Moriarty, Shelby D. Ma, W. Coles Keeter, Woong-Ki Kim, Larry D. Sanford, Elena V. Galkina

Department of Biomedical and Translational Sciences Faculty Publications

Atherosclerosis is linked to an increased risk of cognitive decline, with chronic inflammation being a common feature of both pathologies. IL-12 activates STAT4 to regulate myeloid cell functions, and blockade of this pathway alleviates cognitive impairment in Alzheimer's models. However, the mechanisms connecting vascular pathology to neuroinflammation remain unclear. Here, we examine whether STAT4 functions as a common mediator of neuroinflammation in atherosclerosis. We demonstrate that LysM^Cre-specific STAT4 deficiency ameliorates deficits in long-term memory in low-density lipoprotein-deficient (Ldlr^-/-) mice fed a high-fat diet (HFD-C). STAT4 deficiency moderately reduces Ser199-phosphorylated Tau burden. Atherosclerosis alters brain immune …

Cervicovaginal Lavage Fluid Iron And Manganese Levels In Women With And Without Vaginitis, Barbara Kozma, David Ratonyi, Bence Kozma, Peter Takacs, Attila G. Sipos

Department of Obstetrics & Gynecology Faculty Publications

Transition metals such as iron and manganese are critical for cellular metabolism, redox balance, and immune function, and they also influence host–pathogen interactions. Vaginitis is characterized by mucosal inflammation that may alter local trace-element homeostasis. We hypothesize that inflammatory conditions such as vaginitis may be associated with altered cervicovaginal iron and manganese levels. We performed a prospective, single-center cohort study at the University of Debrecen (Hungary) between April 2023 and April 2024, enrolling 80 women ≥ 18 years with vulvovaginal complaints. Participants were assessed at baseline and at weeks 4, 8, and 12 with clinical evaluation and cervicovaginal lavage (CVL) …

Nanofibrous Materials And Nanoparticles For Combating Antimicrobial Resistance: Synthesis, Integration, And Translational Perspectives, Rewati Raman Ujjwal, Ashish Dilip Sutar, Rahul Shukla, Gymama Slaughter

Center for Bioelectronics Publications

Antimicrobial resistance (AMR) is a major global health challenge driven by mechanisms such as biofilm formation, efflux pumps, and genetic mutations. Nanoparticulate and fibrous materials have emerged as promising strategies to overcome these limitations through multimodal antimicrobial action and controlled drug delivery. This review highlights recent advances in electrospun nanofibrous systems, including natural and synthetic polymer-based scaffolds, stimuli-responsive nanofibers, and functionalized patches. Nanoparticle-loaded nanofiber systems demonstrate enhanced performance, including bacterial eradication, sustained drug release, and significant biofilm disruption. Multifunctional systems combining antimicrobial, antioxidant, and immunomodulatory properties further show synergism. Emerging innovations, such as piezoelectric and smart sensing systems, enable self-powered …

Circulating Biomarker Results From A Phase 2 Study Of Seralutinib In Pulmonary Arterial Hypertension, Robin Osterhout, Athénaïs Boucly, Raymond L. Benza, Richard N. Channick, Kelly M. Chin, Robert P. Frantz, Anna R. Hemnes, Luke S. Howard, Vallerie V. Mclaughlin, Olivier Sitbon, Jean-Luc Vachiéry, Rotham T. Zamanian, Richard Aranda, Matt Cravets, Zhaoqing Ding, Thao Duong-Verlé, David Mattola, Robert F. Roscigno, Ravikumar Sitapara, Lawrence S. Zisman, Jean-Marie Bruey, Hossein-Ardeschir Ghofrani

Department of Medicine Faculty Publications

[Introduction] To the Editor: Pulmonary arterial hypertension (PAH) is a progressive disease characterized by obstructive pulmonary arterial remodeling (1). Seralutinib, an investigational inhaled tyrosine kinase inhibitor, potently and selectively targets kinases relevant to PAH pathobiology including platelet-derived growth factor receptors (PDGFR) α and β, colony stimulating factor 1 receptor (CSF1R), and mast/stem cell growth factor receptor kit (c-KIT) (2). In preclinical models, seralutinib improved cardiopulmonary hemodynamics, reversed pulmonary vascular pathology and decreased right ventricular hypertrophy (3). In TORREY, a phase 2, multicenter, double-blind, randomized, placebo-controlled trial in PAH, seralutinib significantly reduced pulmonary vascular resistance (PVR) after 24 weeks with good …

Baseline Lymphopenia Predicts Survival In Ici-Naïve Solid Tumor Patients Receiving Immune Checkpoint Inhibitors: A Propensity-Matched Real-World Pan-Cancer Analysis, Ahmed Ismail, Nina Balanchivadze, George R. Simon, Yanis Boumber

Department of Medicine Faculty Publications

Background: Baseline lymphopenia is common among advanced solid tumors and may influence the efficacy/safety of immune checkpoint inhibitors (ICIs), but large real-world evidence is limited. We evaluated the association between baseline absolute lymphocyte count (ALC) and clinical outcomes in adults with solid tumors treated with ICIs in routine practice. Methods: We performed a retrospective cohort study using TriNetX. Adults with solid tumors who received pembrolizumab, nivolumab, or atezolizumab (ICI-Naïve) between January 2015 and June 2026 were included. Baseline ALC was measured within 30 days before first treatment and was classified as lymphopenic (ALC < 1.5 × 10⁹/L) or non-lymphopenic (ALC ≥ 1.5 × 10⁹/L). Propensity score matching (1:1) yielded 5249 patients per group. The index date was the first immunotherapy date, and outcomes were assessed at 6, 12, 24, 36 months, and 5 years. The primary outcome was 24-month overall survival (OS); secondary outcomes were OS at 6 and 12 months and 6-month risks of healthcare utilization, immune-related adverse events (irAEs), and serious infections; and exploratory outcomes included OS at 36 months and 5 years. All outcomes were analyzed using Kaplan–Meier analysis, Cox proportional hazards models, and risk ratios. Subgroup analysis included OS stratified by solid tumor subtypes and prior lines of therapy. Results: After matching, patients with baseline lymphopenia …

Microarray Analysis Of Human Abdominal Aortic Aneurysm With Emphasis On Cardiovascular Genes Revealed Differentially Expressed Genes, Song Lu, Li Ping Li, John V. White, Xiaoying Zhang, Ifeyinwa Nwaneshiudu, Adaobi Nwaneshiudu, Nectaria Ntaoula, John Gaughan, Dimitri S. Monos, Wan-Lu Lin, Charalambos C. Solomides, Emilia L. Oleszak, Chris D. Platsoucas

Biological Sciences Faculty Publications

Background/Aim: We examined gene expression profiles in abdominal aortic aneurysm (AAA) lesions vs. normal aortas by cDNA microarray and real-time quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR).

Materials and Methods: Phosphorus (32P)-labeled cDNA from AAA specimens (mean AAA size 6.65 cm) and normal aortas were hybridized with a 588-gene microarray primarily of the cardiovascular system. The results were validated by qRT-PCR.

Results: A total of 35 out of the 588 genes were differentially expressed, with either log2 ratio of AAAs/controls ≥1 (upregulated; 20 genes) or ≤−1 (downregulated; 15 genes) in AAA lesions vs. normal aorta, and 25 of these were significantly …