Digital Commons Network^™

Lipid-Laden Microglia: Characterization And Roles In Diseases, Jiani Xing, Takese Mckenzie, Jian Hu

Faculty, Staff and Student Publications

Microglia are resident phagocytes of the central nervous system that play an essential role in brain development and homeostasis. When the intracellular lipid content exceeds the metabolic capacity of microglia, lipid droplets accumulate, giving rise to a distinct population termed lipid-laden microglia (LLMs). LLMs have been implicated in various neuroinflammatory and neurodegenerative diseases, functioning as both regulators/indicators of inflammation and potential therapeutic targets. This review summarizes the current research on LLMs, focusing on disease-specific regulators and functions, protective roles, interactions with neighboring cells, and advances in diagnostic and analytical tools. We also discuss the blurred distinction between LLMs and macrophages, …

Optimizing Motion Management And Baseline Shifts In Magnetic Resonance-Guided Spine Stereotactic Body Radiation Therapy, Yao Ding, Travis C Salzillo, Debra N Yeboa, Martin C Tom, Zhiheng Wang, Parmeswaran Diagaradjane, Ergys Subashi, Jinzhong Yang, Todd Swanson, Thomas Beckham, Chenyang Wang, Amol J Ghia, Tina Briere, Jihong Wang, Fabienne Lathuilière, Sneha Cloake, Eun Young Han

Faculty, Staff and Student Publications

BACKGROUND: Stereotactic body radiation therapy (SBRT) has proven effective in controlling spinal lesions with minimal toxicity, primarily due to its ability to limit spinal cord dose. Recent advances in MR-linac (MRL) technology offer superior spinal cord visualization and real-time gating, which can facilitate dose escalation in spinal tumor treatment while maintaining safety.

PURPOSE: This study aimed to optimize motion management for spine SBRT on an MRL by analyzing patient-specific motion dynamics and evaluating the most effective registration structures. We hypothesized that baseline shifts (BLS) would improve delivery efficiency while maintaining spinal cord dose constraints. The goal was to establish displacement …

A Brief History Of Circadian Time In The Heart, Martin E Young, Vanya Khanna, Mallory Metcalfe, Niruththaan Rameshkumar, Sarah Harington, Leo H Li, Janan Shoja Doost, Heinrich Taegtmeyer, Tami A Martino

Faculty, Staff and Student Publications

This review tracks the discovery of circadian biology in cardiovascular science, starting with early clinical observations of daily changes in heart rate, blood pressure, and cardiovascular events. These patterns suggested that time of day matters, but it was not until the past two decades that the mechanisms and knowledge translation of these rhythms were uncovered. We describe the heart's intrinsic circadian properties and importantly how this leads to regulation of cardiac gene and protein expression, neuroendocrine and vascular rhythms, metabolism, cellular electrophysiology, and cell signaling pathways. Next, we explore emerging themes, including the impact of circadian timing on ischemic injury, …

Causes Of Symptoms And Symptom Persistence In Long Covid And Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, Anthony L Komaroff, Robert Dantzer

Faculty, Staff and Student Publications

Debilitating symptoms for many years can follow acute COVID-19 ("long COVID"), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and various post-acute infection syndromes (PAISs). Together, long COVID and ME/CFS affect 60-400 million individuals, globally. Many similar underlying biological abnormalities have been identified in both conditions including autoantibodies against neural targets, endothelial dysfunction, acquired mitochondrial dysfunction, and a pro-inflammatory gut microbiome. Each of these abnormalities may directly cause some of the symptoms. In addition, the symptoms also may be caused by ancient, evolutionarily conserved symptomatic and metabolic responses to vital threats-sickness behavior and torpor-responses mediated by specific, recently discovered neural circuits. These neural …

Trpc4 Regulates Limbic Behavior And Neuronal Development By Stabilizing Dendrite Branches Through Actomyosin-Driven Integrin Activation, Jaepyo Jeon, Travis I Moore, Insuk So, Marc Freichel, Veit Flockerzi, Lutz Birnbaumer, Michael X Zhu

Faculty, Staff and Student Publications

Transient Receptor Potential Canonical 4 (TRPC4) channels have been implicated in multiple neurological functions, including anxiety and sociability. TRPC4 variants were also found in patients with autism. However, the contributions of TRPC4 to neurodevelopment remain undefined. Here, we show that neurobehavioral deficits appear early in young TRPC4 knockout (Trpc4^−/−) mice immediately after weaning, manifesting as alterations in multiple, limbic-related behaviors, such as nesting, marble burying, burrowing, self-grooming, and social interactions. Hippocampal neurons of Trpc4−/− mice exhibit reduced dendritic arborization both in vivo and in vitro. Mechanistically, we found that TRPC4 expression in dendrites surged at the …

Dna Methylation Signatures Of Cardiovascular Health Provide Insights Into Diseases, Madeleine Carbonneau, Yi Li, Yishu Qu, Yinan Zheng, Alexis C Wood, Mengyao Wang, Chunyu Liu, Tianxiao Huan, Roby Joehanes, Xiuqing Guo, Jie Yao, Kent D Taylor, Russell P Tracy, Peter Durda, Yongmei Liu, W Craig Johnson, Wendy S Post, Tom Blackwell, Jerome I Rotter, Stephen S Rich, Susan Redline, Myriam Fornage, Jun Wang, Hongyan Ning, Lifang Hou, Donald Lloyd-Jones, Kendra Ferrier, Yuan-I Min, April P Carson, Laura M Raffield, Alexander Teumer, Hans J Grabe, Henry Völzke, Matthias Nauck, Marcus Dörr, Arce Domingo-Relloso, Amanda Fretts, Maria Tellez-Plaza, Shelley A Cole, Ana Navas-Acien, Meng Wang, Joanne M Murabito, Nancy L Heard-Costa, Brenton Prescott, Vanessa Xanthakis, Dariush Mozaffarian, Daniel Levy, Jiantao Ma

Faculty, Staff and Students Publications

Background: The association of overall cardiovascular health (CVH) with changes in DNA methylation (DNAm) has not been well characterized.

Methods: We calculated the American Heart Association's Life's Essential 8 score to reflect CVH in 5 cohorts with diverse backgrounds (mean age 54 years, 55% women, and enrollment year ranging from 1989 to 2012). Epigenome-wide association studies (EWAS) for Life's Essential 8 score were conducted, followed by bioinformatic analyses. DNAm loci significantly associated with Life's Essential 8 score were used to calculate a CVH DNAm score. We examined the association of the CVH DNAm score with incident cardiovascular disease (CVD), cardiovascular …

Changes In Self-Reported Excessive Daytime Sleepiness Are Associated With 5-Year All-Cause Mortality Risk Among Veterans, Katherine G Bay, Arash Maghsoudi, Amin Ramezani, Drew A Helmer, Amir Sharafkhaneh, Javad Razjouyan

Faculty, Staff and Students Publications

Excessive daytime sleepiness (EDS) is linked to adverse clinical outcomes. This study evaluated changes in a validated tool to assess EDS, the Epworth Sleepiness Scale (ESS) and mortality risk. This retrospective cohort study included Veterans receiving sleep-related services in the Department of Veterans Affairs (VA) from October 4, 1999 to August 18, 2018, with two qualifying ESS measures. ESS values were extracted from patient notes using a validated natural language processing (NLP) pipeline (96% accuracy). ESS scores were categorised as Normal (0-10) or Abnormal (11-24). Patients were grouped based on ESS changes: Normal-Normal, Normal-Abnormal, Abnormal-Abnormal and Abnormal-Normal. Cox proportional hazards …

Proteogenomic Characterization Unveils Biomarkers Associated With Chemoresistance In Muscle-Invasive Bladder Cancer, Matthew V Holt, Yongchao Dou, Meggie N Young, Alexander B Saltzman, Meenakshi Anurag, Jonathan T Lei, Antrix Jain, Mei Leng, Beom-Jun Kim, Lacey E Dobrolecki, Stefanie F Faucher, Sara Savage, Chenwei Wang, Zhiao Shi, Hugo Villanueva, Karoline Kremers, Kyle D Drinnon, Patricia D Castro, Michael M Ittmann, Mehak Mehboob Khatani, Sung Han Kim, Matthew J Ellis, Bing Zhang, Anna Malovannaya, Seth P Lerner

Faculty, Staff and Students Publications

To explore potential chemoresistance mechanisms and identify therapeutic opportunities in muscle-invasive bladder cancer (MIBC), we conduct comprehensive proteogenomic characterization of 46 pre- and 14 post-treatment MIBC tumors incorporating genomics, transcriptomics, proteomics, and phosphoproteomics. Multi-omics clustering not only recapitulated established molecular subtypes but also revealed subtypes associated with chemotherapy sensitivity. Protein isoform level analysis identifies protein abundance of a short isoform of ATAD1 and RAF family proteins as biomarkers of chemosensitivity. Integration of proteomic and phosphoproteomic data reveals Wnt signaling via GSK3B-S9 phosphorylation and the JAK/STAT pathway as potential targets to overcome chemoresistance. Correlations between PD-L1 and TROP-2/NECTIN-4 indicate an additive …

Anti-Tumor Activity Of Camptothecin Analog Conjugate Of An Rspo4-Based Peptibody Targeting Lgr4/5/6 In Preclinical Models Of Colorectal Cancer, Yukimatsu Toh, Ling Wu, Jianghua Tu, Zhengdong Liang, Adela M Aldana, Jake J Wen, Li Li, Sheng Pan, Julie H Rowe, Martha E Hensel, Carolyn L Hodo, Rick A Finch, Kendra S Carmon, Qingyun J Liu

The Brown Foundation: Institute of Molecular Medicine

Background: Antibody-drug conjugates (ADCs) are a significant advancement in targeted cancer therapy, but none are approved for colorectal cancer (CRC). LGR4/5/6, highly expressed in most CRCs, are promising targets. While LGR5-targeting ADCs show strong anti-tumor effects, their efficacy is limited by LGR5 loss in some CRC cells. RSPO4, a natural ligand for LGR4/5/6, binds all three receptors with high affinity. This research develops RSPO4-based peptibody drug-conjugates (PDCs) to simultaneously target LGR4/5/6, offering a novel therapeutic approach for CRC.

Methods: LGR4/5/6 expression in CRCs was analysed using RNA-seq datasets and Western blot. Peptibody binding affinities were measured, conjugated to camptothecin analog, …

Anti-Inflammatory Diet And Probiotic Supplementation As Strategies To Modulate Immune Dysregulation In Autism Spectrum Disorder, Carlos Andrés Naranjo-Galvis, Diana María Trejos-Gallego, Cristina Correa-Salazar, Jessica Triviño-Valencia, Marysol Valencia-Buitrago, Andrés Felipe Ruiz-Pulecio, Luisa Fernanda Méndez-Ramírez, Jovanny Zabaleta, Miguel Andres Meñaca-Puentes, Carlos Alberto Ruiz-Villa, Marcela Orjuela-Rodriguez, Juan Carlos Carmona-Hernández, Luisa Matilde Salamanca-Duque

School of Medicine Faculty Publications

Background/Objectives: Autism spectrum disorder (ASD) is a neurodevelopmental condition associated with behavioral and cognitive impairments. Increasing evidence also links ASD with systemic immune dysregulation, including abnormal cytokine profiles and chronic low-grade inflammation. Emerging evidence suggests that targeted dietary strategies and probiotic supplementation may modulate immune responses and gut–brain interactions in patients with ASD. This study aimed to evaluate the immunomodulatory effects of a structured anti-inflammatory diet (NeuroGutPlus) compared to multi-strain probiotics in children with ASD. NeuroGutPlus is a nutritionally complete anti-inflammatory dietary protocol that targets gut integrity, inflammation, and mitochondrial function. It includes a diet low in gluten, FODMAPs, casein, …

Improving Automated Deep Phenotyping Through Large Language Models Using Retrieval-Augmented Generation, Brandon T Garcia, Lauren Westerfield, Priya Yelemali, Nikhita Gogate, E Andres Rivera-Munoz, Haowei Du, Moez Dawood, Angad Jolly, James R Lupski, Jennifer E Posey

Faculty, Staff and Students Publications

Background: Diagnosing rare genetic disorders relies on precise phenotypic and genotypic analysis, with the Human Phenotype Ontology (HPO) providing a standardized language for capturing clinical phenotypes. Rule-based HPO extraction tools use concept recognition to automatically identify phenotypes, but they often struggle with incomplete phenotype assignment, requiring significant manual review. While large language models (LLMs) hold promise for more context-driven phenotype extraction, they are prone to errors and "hallucinations," making them less reliable without further refinement. We present RAG-HPO, a Python-based tool that leverages retrieval-augmented generation (RAG) to elevate accuracy of HPO term assignment by LLM. This approach bypasses the limitations …

Extended Survival With Pancreatic Carcinosarcoma: A Case Report And Literature Review, Tian Xiao, Claire Browne, Morgan Black, Celia Marginean, Elena Tsvetkova

Faculty, Staff and Students Publications

Pancreatic carcinosarcoma is a rare and aggressive malignancy that can mimic pancreatic adenocarcinomas in presentation but often has different disease biology and different responses to conventional treatment for pancreatic adenocarcinoma. Case reports have documented a 5-year overall survival of approximately 13% only if the disease is caught at an earlier stage and is amenable to multi-modality treatment, including surgery, chemotherapy, and radiation. In the advanced stage, treatments do not often provide benefit, and patients may decline rapidly. There are currently no studies demonstrating survival benefits with chemotherapy in patients with metastatic carcinosarcoma, owing to both the rarity and the often …

Newly Diagnosed Acute Myeloid Leukemia In Unfit Patients: 2026 Treatment Algorithms, Naseema Gangat, Courtney D Dinardo

Faculty, Staff and Student Publications

Management paradigms for newly-diagnosed acute myeloid leukemia (ND-AML) in patients considered unfit to receive intensive chemotherapy have evolved with improved understanding of disease biology. In this setting, management requires clear delineation of goals of therapy that should include preservation of quality-of-life (QoL). Combination of venetoclax (Ven) and a hypomethylating agent (HMA) is the current standard-of-care in most circumstances with flexible options in regard to drug dose and duration of treatment as well as the addition (triplet combinations) or alternative use of targeted therapies, such as inhibitors of FLT3, IDH1, IDH2, or menin for patients with NPM1MUT …

Kdm2b Variants In The Cxxc Domain Impair Its Dna-Binding Ability And Cause A Distinct Neurodevelopmental Syndrome, Amber S E Van Oirsouw, Michael A Hadders, Martijn Koetsier, Edith D J Peters, Nurit Assia Batzir, Tahsin Stefan Barakat, Diana Baralle, Adelyn Beil, Marie-Noëlle Bonnet-Dupeyron, Philip M Boone, Arjan Bouman, Deanna Alexis Carere, Benjamin Cogne, Leslie Dunnington, Laura S Farach, Casie A Genetti, Bertrand Isidor, Louis Januel, Aakash Joshi, Nayana Lahiri, Kristen N Lee, Idit Maya, Meriel Mcentagart, Hope Northrup, Mathilde Pujalte, Kate Richardson, Susan Walker, Bobby P C Koeleman, Mariëlle Alders, Richard H Van Jaarsveld, Renske Oegema

Faculty, Staff and Student Publications

Rare variants affecting the epigenetic regulator KDM2B cause a recently delineated neurodevelopmental disorder. Interestingly, we previously identified both a general KDM2B-associated episignature and a subsignature specific to variants in the DNA-binding CxxC domain. In light of the existence of a distinct subsignature, we set out to determine if KDM2B CxxC variants are associated with a unique phenotype and disease mechanism. We recruited individuals with heterozygous CxxC variants and assessed the variants' effect on protein expression and DNA-binding ability. We analyzed clinical data from 19 individuals, including ten previously undescribed individuals with seven novel CxxC variants. The core phenotype of the …

Evaluation Of Rheumatic Etiologies Underlying Childhood-Onset Arthritis, Seher Şener, Erdal Atalay, Ezgi̇ Deni̇z Batu, Cansu Ayten Tatar, Özge Başaran, Yelda Bi̇lgi̇ner, Seza Özen

Turkish Journal of Medical Sciences

Background/aim: Childhood-onset arthritis may result from various rheumatic diseases. This study aimed to systematically evaluate their distribution and characteristics in a large pediatric cohort.

Materials and methods: We retrospectively analyzed all pediatric patients who presented with arthritis to the pediatric rheumatology clinic between January 2000 and January 2023.

Results: A total of 1713 pediatric patients who presented with arthritis were included in this study (median age at diagnosis: 6.8 years; F/M = 1.2). Most of the patients (n = 859, 50.1%) had juvenile idiopathic arthritis (JIA) (especially oligoarticular JIA). Patients with familial Mediterranean fever, comprising 277 individuals (16.2%) presented with …

Evaluation Of Metabolic Uptake In Gynecological Organs Using Fdg-Pet In Women Diagnosed With Non-Gynecological Malignancies, Funda Atalay, Uğurcan Zorlu, Koray Aslan, Fatma Batak, Tuba Zengi̇n Aksel, Güli̇n Uçmak

Turkish Journal of Medical Sciences

Background/aim: Gynecological malignancies, including those affecting the uterus, cervix, vagina, vulva, and adnexa, pose significant physical and psychosocial burdens. Early detection and effective management of these malignancies are critical for improving outcomes. This study aims to evaluate metabolic uptake patterns in gynecological organs using fluorodeoxyglucose positron emission tomography (FDG-PET) and to analyze their malignancy potential in women with nongynecological cancers.

Materials and methods: A retrospective analysis was conducted on 221 women with nongynecological malignancies who exhibited pathological FDG uptake in gynecological organs on FDG-PET/CT imaging. Lesions were evaluated based on the standardized uptake value maximum (SUVmax), morphological characteristics on contrast-enhanced …

Ultrasonographic And Elastographic Evaluation Of Plantar Fascia And Achilles Tendon Alterations In Type 2 Diabetes Mellitus, Rifat Bozkuş, İhsani̇ye Süer Doğan, Berna Turhan, Sümeyya Duran Kaymak, Mustafa Hulusi̇ Kurt, Rasi̇me Peli̇n Kavak

Turkish Journal of Medical Sciences

Background/aim: The primary aim of this study is to compare the thickness and stiffness of the PF and AT between healthy volunteers and patients with type 2 diabetes mellitus (T2DM). A secondary objective is to explore the correlations between the thickness and stiffness of the PF and AT with diabetes duration (in months) and hemoglobin A1c (HbA1c) levels in T2DM patients without peripheral neuropathy or foot ulcers, with peripheral neuropathy or with foot ulcers.Material and Methods: A total of 289 participants, including 117 healthy volunteers (Group A) and 172 T2DM patients (59.5%), matched for age, sex, and body mass index, …

Detection And Quantification Of Microplastics In Cerumen, Bengi̇ Arslan, Yüce İslamoğlu, Ali̇ Sami̇ Berçi̇n, Selen Akbulut, Mehmet Meli̇koğlu

Turkish Journal of Medical Sciences

Background/aim: Microplastics (MPs) are a growing concern due to their pervasive environmental presence and potential environmental and human exposure impacts. Given evidence of systemic MP presence in human tissues and fluids, and the ear canal's environmental exposure, this novel study aimed to identify these particles in human cerumen. Cerumen was collected from the proximal ear canal to minimize potential airborne contamination.

Materials and methods: Cerumen samples were prospectively collected from 12 adult patients (23 patient-derived specimens) and 3 control water samples, following ethical approval and consent. Samples were extracted using sterile instruments, stored in glass, diluted, and filtered through 0.22 …

Are Paraplegic Wheelchair Users Vulnerable To Overuse Syndromes?, Kutay Tezel, Esra Ülgen Kiratlioğlu, Hüseyi̇n Kayadi̇bi̇, İlkay Karabay, Mi̇tat Cebeci̇, Eda Gürçay

Turkish Journal of Medical Sciences

Background and Aims: The purposes of this study are to determine the frequency of upper extremity overuse syndromes in patients with spinal cord injury (SCI) using manual wheelchairs, to evaluate them clinically and sonographically, and to reveal possible factors that predispose to overuse syndromes.

Materials and methods: A total of 38 traumatic SCI patients who were over 18 years of age and manual wheelchair users were enrolled in this cross-sectional study. The patients were evaluated with clinical and sonographic findings of the wrist, elbow and shoulder joints. Functional capacity, physical ability and symptoms of upper extremity, and quality of …

Prognostic Role Of Systemic Immune-Inflammation Index And Pan-Immune-Inflammation Value In Acute Methanol Poisoning, Hati̇ce Şahi̇n, Gülay Ulusal Okyay, Fatma Ayerden Ebi̇nç, Fevzi̇ Coşkun Sökmen, Emre Yaşar, Gülşen Akçay, Mehmet Deni̇z Ayli

Turkish Journal of Medical Sciences

Background/aim: Acute methanol poisoning (MP) poses a significant public health challenge, with inflammation increasingly recognized as a key factor in its pathophysiology. Identifying accessible and reliable prognostic biomarkers could help enhance clinical outcomes. This study aimed to assess the prognostic value of the Systemic Immune-Inflammation Index (SII) and the Pan-Immune-Inflammation Value (PIV), measured upon emergency department admission, in predicting in-hospital mortality in patients with acute MP.Material and methods: This retrospective study included patients diagnosed with acute MP at two tertiary care centers in Ankara, Türkiye [University of Health Sciences Dışkapı Yıldırım Beyazıt Education and Research Hospital (January 1, 2015–October 1, …

Mirna-Target Gene Network Analysis In Siblings With Cystic Fibrosis And Phenotypic Variability, Ayberk Mustafaoğlu, Senem Noyan, Yeli̇z Z. Akkaya Ulum, Bala Gür Dedeoğlu, Nagehan Emi̇rali̇oğlu, Uğur Özçeli̇k, Ebru Yalçin, Deni̇z Doğru, Nural Ki̇per, Di̇dem Dayangaç Erden

Turkish Journal of Medical Sciences

Background/aim: Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CF is characterized by respiratory tract infections, pancreatic insufficiency, meconium ileus, intestinal obstruction, and male infertility. A genotype to phenotype correlation is difficult to establish because of the heterogeneity of disease severity. Even patients with the same CFTR mutation can have varying clinical severities. In recent years, studies have explored the role of microRNA (miRNA) expression in the regulation of respiratory diseases. However, no research has been conducted to date on miRNAs in siblings with the same CFTR mutation. …

Metabolic And Genotypic Characterization Of Meropenem Susceptible And Resistant Serratia Marcescens Isolates, Şeyma Ni̇gi̇z, Gülşen Hazirolan, Gülşen Altinkanat Gelmez, Ceren Özkul Koçak, Engi̇n Koçak, Sevi̇lay Erdoğan Kablan, Emi̇rhan Nemutlu, Aycan Gündoğdu, Fatma Bayrakdar, Ufuk Hasdemi̇r, Deni̇z Gür

Turkish Journal of Medical Sciences

Background/aim: Serratia marcescens which is a nosocomial pathogen, is naturally resistant to a wide spectrum of antibiotics, which makes the management of infections difficult. The aim of this study was to determine the in vitro susceptibilities of S. marcescens to ceftriaxone, ceftazidime, meropenem, amikacin, gentamicin, ciprofloxacin, and to compare the metabolic profiles of meropenemresistant isolates under basal conditions and after exposure to sublethal concentrations of meropenem.

Materials and methods: A total of 84 S. marcescens isolates were included from various samples. Genes for meropenem resistance were determined by polymerase chain reaction (PCR). Genetic similarities among isolates of S. marcescens were …

Letter To The Editor Regarding “Kılıçarslan A, Kurt Çevik G, Doğan M, Aksoy Altınboğa A, Ceran F, Et Al. Does Cd47 Expression Have Prognostic Significance In Classical Hodgkin Lymphoma? Turkish Journal Of Medical Sciences: 2025; 55 (1): 22”, Burcu Baba, Ayşegül Akbay

Turkish Journal of Medical Sciences

No abstract provided.

Transcriptomic And Epigenomic Profiling Of Immune Cells Responses To Simian Immunodeficiency Virus Infection In The Brain, Xiaoke Xu

Theses & Dissertations

Human immunodeficiency virus type 1 (HIV-1) is an enveloped retrovirus that significantly impairs the human immune system. A common complication of HIV-1 infection is HIV-associated neurocognitive disorder (HAND), which, prior to the introduction of antiretroviral therapy (ART), led to considerable morbidity and mortality due to untreated neuropsychiatric manifestations. Although ART has substantially reduced the incidence of HIV-associated dementia (HAD), approximately 50% of people living with HIV (PLWH) continue to experience milder forms of HAND. The CNS is seeded by HIV during the acute phase of infection. Once in the brain, HIV targets and activates resident immune cells, primarily microglia and …

Sinapic Acid Alleviates Renal Ischemia-Reperfusion Injury By Regulating Oxidative Stress, Apoptosis, And Inflammation, Mustafa Can Güler, Fazi̇le Nur Eki̇nci̇ Akdemi̇r, Ersen Eraslan, Ayhan Tanyeli̇, Derya Güzel Erdoğan, Behzat Tebri̇zi̇

Turkish Journal of Medical Sciences

Background/aim: Acute kidney injury (AKI) is a major clinical issue, frequently resulting from ischemia-reperfusion (I/R) injury. Sinapic acid (SA), a natural phenolic molecule included in numerous plant-based foods, exhibits antiapoptotic, antioxidant, and antiinflammatory properties. This study aimed to investigate the renoprotective effects of SA in an I/R-induced acute kidney injury (AKI) model.

Materials and methods: Sprague–Dawley male rats (n = 32) were randomly assigned to four groups: sham, I/R, SA 20 mg/kg, and SA 40 mg/kg. SA was administered intraperitoneally before reperfusion. Renal tissues were examined using biochemical, histopathological, and immunohistochemical methods, focusing on oxidative stress, cytokine expression, and apoptosis …

Outcomes Of Patients With Newly Diagnosed Acute Myeloid Leukemia With Flt3-Tyrosine Kinase Domain Mutations: Prognostic Implications Of Npm1 Co-Mutation, Sankalp Arora, Wei-Ying Jen, Musa Yilmaz, Indraneel Deshmukh, Jayastu Senapati, Sanam Loghavi, Ghayas C Issa, Nicholas J Short, Tapan M Kadia, Courtney D Dinardo, Gautam Borthakur, Joseph Jabbour, Naveen Pemmaraju, Michael Andreeff, Koichi Takahashi, Kapil Bhalla, Uday Popat, Elizabeth J Shpall, Betul Oran, Hussein A Abbas, Guillermo Garcia-Manero, Farhad Ravandi, Hagop Kantarjian, Naval Daver

Faculty, Staff and Student Publications

Background: The prognostic impact of Fms-like tyrosine kinase 3 (FLT3)-tyrosine kinase domain (TKD) mutation in patients with acute myeloid leukemia (AML) is not well defined. The authors described outcomes of one of the largest cohorts of patients with FLT3-TKD mutated (FLT3-TKDmut) AML to date.

Methods: This retrospective study included patients with newly diagnosed AML who received frontline treatment at The University of Texas MD Anderson Cancer Center from January 2012 to March 2024 divided into two cohorts: FLT3-TKDmut AML and nucleophosmin-mutated (NPM1mut)/FLT3-TKD wild-type (FLT3-TKDwt) AML. Patients with FLT3 internal tandem duplication mutations were excluded.

Results: In total, 2922 patients were …

Lipidomic And Proteomic Insights From Extracellular Vesicles In The Postmortem Dorsolateral Prefrontal Cortex Reveal Substance Use Disorder-Induced Brain Changes, Chioma M Okeoma, Wasifa Naushad, Bryson C Okeoma, Carlos Gartner, Yulica Santos-Ortega, Calvin Vary, Savio Lima-Bastos, Victor Corasolla Carregari, Martin R Larsen, Alessio Noghero, Consuelo Walss-Bass, Rodrigo Grassi-Oliveira

Faculty, Staff and Student Publications

Substance use disorder (SUD) significantly increases the risk of neurotoxicity, inflammation, oxidative stress, and impaired neuroplasticity. The activation of inflammatory pathways by substances may lead to reactive astrogliosis and chronic neuroinflammation, potentially mediated by the release of extracellular particles (EPs), such as extracellular condensates (ECs) and extracellular vesicles (EVs). These particles, which reflect the physiological, pathophysiological, and metabolic states of their cells of origin, might carry molecular signatures indicative of SUD. In particular, our study investigated neuroinflammatory signatures in SUD patients by isolating EVs from the dorsolateral prefrontal cortex (dlPFC) Brodmann's area 9 (BA9) from postmortem subjects. We isolated BA9-derived …

Randomised, Placebo-Controlled Trial Of Oral Hymecromone In Adults With Pulmonary Hypertension, Kathryn Czepiel, Nadine Nagy, Tamera Panjalingam, Anissa Kalinowski, Adam R Frymoyer, Harry Karmouty-Quintana, Bo Gu, Haley Hedlin, Gernot Kaber, Sylvie Dobrota Lai, Joelle I Rosser, Paul L Bollyky, Vinicio De Jesus Perez, Roham T Zamanian

Faculty, Staff and Student Publications

Background: Pulmonary hypertension (PH) is a progressive cardiopulmonary condition associated with increased morbidity and mortality. The extracellular matrix component hyaluronan (HA) is linked to vascular remodelling and interstitial fibrosis in PH. We hypothesised that inhibition of HA synthesis with hymecromone could serve as a reverse-remodelling therapy in PH.

Methods: We performed a proof-of-concept phase IIa randomised, double-blind, placebo-controlled study in adults with pulmonary arterial hypertension and PH associated with interstitial lung disease (PH-ILD). Patients were randomised to a 5:3 ratio and stratified by PH group to receive oral hymecromone or placebo two times per day over 24 weeks. The primary …

Mathematical Modeling And Association Analysis Decipher The Impact Of The Gut Microbiome On Cancer Immunotherapy, Andreas G Hadjigeorgiou, Constantinos Harkos, Aditya K Mishra, Golnaz Morad, Sarah B Johnson, Nadim J Ajami, Jennifer A Wargo, Lance L Munn, Triantafyllos Stylianopoulos, Rakesh K Jain

Faculty, Staff and Student Publications

The gut microbiome has emerged as a key regulator of response to cancer immunotherapy. However, a better understanding of the underlying mechanisms by which the microbiome influences immunotherapy is needed to identify strategies to optimize outcomes. To this end, we developed a mathematical model to obtain insights into the effect of the microbiome on the immune system and immunotherapy response. This model was based on (i) gut microbiome data derived from preclinical studies, (ii) mathematical modeling of the antitumor immune response, (iii) association analysis of microbiome profiles with model-predicted immune profiles, and (iv) statistical models that correlate model parameters with …

Clinical, Tumor, And Product Features Associated With Outcomes After Axicabtagene Ciloleucel Therapy In Follicular Lymphoma, Soumya Poddar, Jiali Yan, Gayatri Tiwari, Darawan Rinchai, Justin Budka, Wangshu Zhang, Weixin Peng, Shruti Salunkhe, Madison Davis, Qinghua Song, Sara Beygi, Harry Miao, Mike Mattie, Rhine S Shen, Caron A Jacobson, Davide Bedognetti, Simone Filosto, Sattva S Neelapu

Faculty, Staff and Student Publications

Background: Axicabtagene ciloleucel (axi-cel), anti-CD19 chimeric antigen receptor (CAR) T cell therapy, demonstrated remarkable efficacy with manageable toxicity in relapsed/refractory indolent B cell lymphomas in the ZUMA-5 trial.

Methods:Here, we report associations of product attributes, serum biomarkers, clinical features, and tumor characteristics with outcome in 124 patients with follicular lymphoma (FL).

Results: In univariate and multivariate analyses, pretreatment inflammatory markers, including TNF-α and IL-12p40, as well as total metabolic tumor volume (TMTV), associated with disease progression. Conversely, T-naive–like product phenotype associated with improved outcome, particularly in patients with high TMTV. These covariates improved risk stratification when combined with the …