Medical Specialties Commons^™

Fda Approval Of Cobenfy: A New Therapeutic Option For Schizophrenia, Brenna Hissong, Penlope Mazivanhanga, Alexander Defranco, Linda Azap, Haley Brown, Megan Rizo, Joshua Honaker, Samantha Mccord, Lindsey Ferraro

Pharmacy and Wellness Review

Schizophrenia is a complex illness characterized by behavioral, emotional, and cognitive dysfunctions. Common symptoms include hallucinations, delusions, cognitive decline, and social withdrawal. The disorder is related to structural brain abnormalities, neurotransmitter imbalances, and a combination of genetic and environmental elements, and affects about 24 million individuals globally. Currently, two medication classes are most commonly used to treat schizophrenia. These medications are first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs). Due to the side effect profiles that both medication classes carry, research is being conducted for new drug classes.

Cobenfy (xanomeline/trospium chloride), also known investigationally as KarXT, is a new class of …

Social Determinants Of Health Extraction From Clinical Notes Across Institutions Using Large Language Models, Vipina K Keloth, Salih Selek, Qingyu Chen, Christopher Gilman, Sunyang Fu, Yifang Dang, Xinghan Chen, Xinyue Hu, Yujia Zhou, Huan He, Jungwei W Fan, Karen Wang, Cynthia Brandt, Cui Tao, Hongfang Liu, Hua Xu

Faculty, Staff and Student Publications

Detailed social determinants of health (SDoH) is often buried within clinical text in EHRs. Most current NLP efforts for SDoH have limitations, investigating limited factors, deriving data from a single institution, using specific patient cohorts/note types, with reduced focus on generalizability. We aim to address these issues by creating cross-institutional corpora and developing and evaluating the generalizability of classification models, including large language models (LLMs), for detecting SDoH factors using data from four institutions. Clinical notes were annotated with 21 SDoH factors at two levels: level 1 (SDoH factors only) and level 2 (SDoH factors and associated values). Compared to …

Neoadjuvant With Low-Dose Radiotherapy, Tislelizumab, Albumin-Bound Paclitaxel, And Cisplatin For Resectable Locally Advanced Head And Neck Squamous Cell Carcinoma: Phase Ii Single-Arm Trial, Zhigang Liu, Dong Wang, Guanjun Li, Muhua Yi, Zhaoyuan Zhang, Guihua Zhong, Liangfu Xu, Rong Jiang, Yannan Zheng, Linxuan Huang, Yingpeng Peng, Lizhong Liang, Jianpeng Li, Ye Liu, Jun Lai, Xianjuan Lv, Yongqiang Xu, Qiaodan Liu, Zhiqiang Wang, Zhutian Liu, Qinan Yang, Li Nie, Jiao Lei, Xiaotao Huang, Zhijie Liu, Wen Jiang

Faculty, Staff and Student Publications

Although pathological complete response (pCR) and major pathological response (MPR) rates of neoadjuvant immunotherapy combined with chemotherapy in head and neck squamous cell carcinoma (HNSCC) trials remain suboptimal, emerging evidence highlights the synergistic potential of combining low-dose radiotherapy with immunotherapy to promote the efficacy of immunotherapy. This phase II, open-label, single-arm, multicenter trial (NCT05343325) enrolled 28 patients with untreated stage III-IVB HNSCC (NeoRTPC02). Patients received neoadjuvant low-dose radiotherapy, the programmed death-1 (PD-1) inhibitor tislelizumab, albumin-bound paclitaxel, and cisplatin for two cycles, followed by radical resection ~4 weeks after treatment completion. The primary endpoint, pCR rate, was achieved in 14 of …

Detection Of Chromosomal Mosaicism- The Importance Of Karyotyping And Fish, Allison Kalinousky, Jennifer L. Roberts, Madeeha Alikhan, John Herriges, Lei Zhang, Elena Repnikova

Research Days

This project evaluates the prevalence of chromosomal mosaicism in constitutional samples using conventional cytogenetic techniques evaluated at Children's Mercy Hospital during a 20-year period.

Effects Of Genetic Polymorphisms On The Oct1 And Oct2-Mediated Uptake Of Atenolol, Mollie Margaret Walton Md, Jonathan Wagner Do, Ceclia E. Villanueva Phd, Bruno Hagenbuch Phd

Research Days

This project characterizes the role of OCT1 and OCT2 on cellular uptake of atenolol and tests the hypothesis that OCT1 and OCT2 proteins with genetic polymorphisms, when expressed in vitro, will result in altered cellular uptake of atenolol relative to the reference genotype. This approach utilizes transiently transfected OCT1 and OCT2 cell assays to perform time-dependent atenolol uptake experiments to generate kinetics information. The goal is to provide a better understanding of polymorphisms associated with OCT1 and OCT2 expression and function as a means to individualize pharmacologic therapy for atenolol.

High Kynu Expression Is Associated With Poor Prognosis, Keap1/Stk11 Mutations, And Immunosuppressive Metabolism In Patient-Derived But Not Murine Lung Adenocarcinomas, Ling Cai, Thomas J Rogers, Reza Mousavi Jafarabad, Hieu Vu, Chendong Yang, Nicole Novaresi, Ana Galán-Cobo, Luc Girard, Edwin J Ostrin, Johannes F Fahrmann, Jiyeon Kim, John V Heymach, Kathryn A O'Donnell, Guanghua Xiao, Yang Xie, Ralph J Deberardinis, John D Minna

Faculty, Staff and Student Publications

Background/Objectives: We aimed to discover genes with bimodal expression linked to patient outcomes, to reveal underlying oncogenotypes and identify new therapeutic insights in lung adenocarcinoma (LUAD).

Methods: We performed meta-analysis to screen LUAD datasets for prognostic genes with bimodal expression patterns. Kynureninase (KYNU), a key enzyme in tryptophan catabolism, emerged as a top candidate. We then examined its relationship with LUAD mutations, metabolic alterations, immune microenvironment states, and expression patterns in human and mouse models using bulk and single-cell transcriptomics, metabolomics, and preclinical model datasets. Pan-cancer prognostic associations were also assessed.

Results: Model-based clustering of KYNU expression outperformed median-based dichotomization …

Roles Of Class Iii Phosphatidylinositol 3-Kinase, Vps34, In Phagocytosis, Autophagy, And Endocytosis In Retinal Pigmented Epithelium, Feng He, Ralph M Nichols, Melina A Agosto, Theodore G Wensel

Faculty, Staff and Students Publications

Phosphatidylinositol-3-phosphate (PI(3)P) is important for multiple functions of retinal pigmented epithelial (RPE) cells, but its functions in RPE have not been studied. In RPE from mouse eyes and in cultured human RPE cells, PI(3)P-enriched membranes include endosomes, the trans-Golgi network, phagosomes, and autophagophores. Mouse RPE cells lacking activity of the PI-3 kinase, Vps34, lack detectable PI(3)P and die prematurely. Phagosomes containing rod discs accumulate, as do membrane aggregates positive for autophagosome markers. These autophagy-related membranes recruit LC3/Atg8 without Vps34, but phagosomes do not. Vps34 loss leads to accumulation of lysosomes which do not fuse with phagosomes or membranes with …

Novel Rpl30 Variant In Diamond Blackfan Anemia Demonstrates Early Impact On Erythroid Differentiation With Downregulated Gata1-Hsp70, Alexandra Prosser-Dombrowski, Irina Pushel, Jacqelyn Nemechek, Priyanka Kumar, Jay L. Vivian, Jennifer Gerton, John M. Perry

Research Days

Background: Diamond Blackfan anemia (DBA) is an inherited bone marrow failure syndrome caused by ribosomal protein gene mutations leading to apoptosis of erythroid progenitors. We identified a novel heterozygous variant (c.167+769C>T) in the noncoding region of RPL30 in a patient diagnosed with DBA.

Objectives/Goal: We hypothesized that this variant stunts erythroid differentiation at the proerythroblast stage and is pathogenic for DBA.

Methods/Design: We developed an induced pluripotent stem cell (iPSC) model with a wild type (WT) and three CRISPR-Cas9 edited RPL30 mutant clones. iPSCs were differentiated into hematopoietic stem cells, which were assessed by flow cytometry and single cell …

Duration Of Labor And Umbilical Artery Acidosis In Critical Congenital Heart Disease, Sarah Gwazdacz Md, Teresa Nguyen Bs, Mary Donofrio Md, Faap, Facc, Fase, Timothy Bennett Md, Amanda Mcintosh Md, Faap, Facc.

Research Days

Standard delivery protocols for most prenatally diagnosed CCHD is induction of labor at 39 weeks with aims of a vaginal delivery (VD) near a tertiary care center. There is no benefit to planned Cesarean delivery (CD) over VD for most infants with CCHD. However, longer durations of labor (DOL) in CCHD have been described as a risk factor for umbilical artery (UA) acidosis. We aim to describe the relationship between DOL and UA pH and neonatal outcomes in those with prenatally diagnosed CCHD.

Retrospective chart review of prenatally diagnosed with CCHD born at Children’s Mercy from 2012 – 2023. Inclusion …

Inpatient Thrombophilia Workup After Acute Vte: The Tests That Don’T Pay It Forward, Eliakim Munda, Bs, Ruben Rhoades, Md, Ms

Health Equity and Quality Improvement (HEQI) Summit

Background

• Venous thromboembolism is a complex multifactorial disease that is influenced by genetic, environmental and behavioral risk factors.
• Testing for inherited thrombophilia is commonly performed after a VTE event to help identify underlying genetic risk factors and assess the risk of recurrence.
• Despite clinical guidelines advising against thrombophilia testing in patients with acute VTE, these tests continue to be ordered even though lab results are unlikely to alter treatment decisions

Problem Statement

• At TJUH, activity and genetic assays are frequently ordered for patients with acute VTE during admission, increasing the likelihood of false- positive results that may lead to unnecessary …

Pcsk-9 Inhibitors Treatment: The Cardiovascular Disparity, Julia Lees, Seana-Pierre Williams, Tahir Razzaq, Michael B. Roberts

The Journal of Integrated Primary Care

Introduction: According to the Center for Disease Control and Prevention (CDC) and American Heart Association (AHA), cardiovascular disease is the leading cause of death in the United States. This phenomenon disproportionally affects the African American population, who have a 31% higher mortality rate than non-Hispanic Caucasian individuals. A retrospective review of PCSK-9 medication use, specifically in a patient population that had minimal representation in the large, landmark clinical trials, can lead to better understanding about the therapeutic potential in cardiovascular disease reduction and patient outcomes attributed to medication use. Education regarding this novel drug class, medication access and patient support, …

Literature Review Of Stiff Person Syndrome, Mustafa Ansari, Adam Davis, Donald Penney

The Journal of Integrated Primary Care

Background: Stiff Person Syndrome (SPS) is a rare, debilitating autoimmune neurological disorder characterized by progressive muscle rigidity, painful spasms, and gait disturbances. It is strongly associated with autoantibodies against glutamic acid decarboxylase (GAD), leading to impaired GABAergic neurotransmission. SPS exists on a spectrum, with both classical and paraneoplastic variants, the latter often linked to malignancies such as breast cancer.

Methods: This review synthesizes current literature on the pathophysiology, clinical presentation, diagnostic criteria, and treatment modalities of SPS. We examine emerging therapies, including immunomodulatory approaches and antibody-targeted interventions, to address the heterogeneity of disease progression and treatment response.

Results: SPS remains …

Diagnostic Considerations For Gastrointestinal Stromal Tumors With Altered Immunophenotype Following Imatinib Treatment: A Case Report And Literature Review, Jihuan Chen, Liz M. Yang, Jonathan Somma, Yujun Gan, Zengying Wu, Zhiyan Fu

School of Medicine Faculty Publications

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the gastrointestinal tract and have a high rate of recurrence and metastasis. Using an immunohistochemical (IHC) panel including KIT/CD117 and DOG1 allows for accurate diagnosis in more than 98% of cases. However, after tyrosine kinase inhibitor treatment, some cases can exhibit histologic dedifferentiation and loss of KIT/CD117 and DOG1 expression that may cause difficulty in confirming recurrent or persistent disease. We present such a case of an Imatinib treated, CD117 and DOG1 dual negative, metastatic GIST to the liver in a 55-year-old female which required molecular analysis to confirm …

Ubiquitin-Conjugating Enzyme Ube2n Modulates Proteostasis In Immunoproteasome-Positive Acute Myeloid Leukemia, Chiharu Ishikawa, Laura Barreyro, Avery M Sampson, Kathleen M Hueneman, Kwangmin Choi, Sophia Y Philbrook, Issac Choi, Lyndsey C Bolanos, Mark Wunderlich, Andrew G Volk, Stephanie S Watowich, Kenneth D Greis, Daniel T Starczynowski

Faculty, Staff and Student Publications

Altered protein homeostasis through proteasomal degradation of ubiquitinated proteins is a hallmark of many cancers. Ubiquitination, coordinated by E1, E2, and E3 enzymes, involves up to 40 E2-conjugating enzymes in humans to specify substrates and ubiquitin linkages. In a screen for E2 dependencies in acute myeloid leukemia (AML), ubiquitin conjugating enzyme E2 N (UBE2N) emerged as the top candidate. To investigate UBE2N's role in AML, we characterized an enzymatically defective mouse model of UBE2N, revealing UBE2N's requirement in AML without an impact on normal hematopoiesis. Unlike other E2s, which mediate lysine-48 (K48) polyubiquitination and degradation of proteins, UBE2N primarily synthesizes …

Development And Validation Of A Clinical Risk Model For Postoperative Outcome In Newly Diagnosed Glioblastoma: A Report Of The Rano Resect Group, Philipp Karschnia, Jacob S Young, Gilbert C Youssef, Antonio Dono, Levin Häni, Tommaso Sciortino, Francesco Bruno, Stephanie T Juenger, Nico Teske, Jorg Dietrich, Michael Weller, Michael A Vogelbaum, Martin Van Den Bent, Juergen Beck, Niklas Thon, Jasper K W Gerritsen, Shawn Hervey-Jumper, Daniel P Cahill, Susan M Chang, Roberta Rudà, Lorenzo Bello, Oliver Schnell, Yoshua Esquenazi, Maximilian I Ruge, Stefan J Grau, Raymond Y Huang, Patrick Y Wen, Mitchel S Berger, Annette M Molinaro, Joerg-Christian Tonn

Faculty, Staff and Student Publications

Background: Following surgery, patients with newly diagnosed glioblastoma frequently enter clinical trials. Nuanced risk assessment is warranted to reduce imbalances between study arms. Here, we aimed (I) to analyze the interactive effects of residual tumor with clinical and molecular factors on outcome and (II) to define a postoperative risk assessment tool.

Methods: The response assessment in neuro-oncology (RANO) resect group retrospectively compiled an international, seven-center training cohort of patients with newly diagnosed glioblastoma. The combined associations of residual tumor with molecular or clinical factors and survival were analyzed, and recursive partitioning analysis was performed for risk modeling. The resulting model …

The Lung Cancer Autochthonous Model Gene Expression Database Enables Cross-Study Comparisons Of The Transcriptomic Landscapes Across Mouse Models, Ling Cai, Fangjiang Wu, Qinbo Zhou, Ying Gao, Bo Yao, Ralph J Deberardinis, George K Acquaah-Mensah, Vassilis Aidinis, Jennifer E Beane, Shyam Biswal, Ting Chen, Carla P Concepcion-Crisol, Barbara M Grüner, Deshui Jia, Robert A Jones, Jonathan M Kurie, Min Gyu Lee, Per Lindahl, Yonathan Lissanu, Corina Lorz, David Macpherson, Rosanna Martinelli, Pawel K Mazur, Sarah A Mazzilli, Shinji Mii, Herwig P Moll, Roger A Moorehead, Edward E Morrisey, Sheng Rong Ng, Matthew G Oser, Arun R Pandiri, Charles A Powell, Giorgio Ramadori, Mirentxu Santos, Eric L Snyder, Rocio Sotillo, Kang-Yi Su, Tetsuro Taki, Kekoa Taparra, Phuoc T Tran, Yifeng Xia, J Edward Van Veen, Monte M Winslow, Guanghua Xiao, Charles M Rudin, Trudy G Oliver, Yang Xie, John D Minna

Faculty, Staff and Student Publications

Lung cancer, the leading cause of cancer mortality, exhibits diverse histological subtypes and genetic complexities. Numerous preclinical mouse models have been developed to study lung cancer, but data from these models are disparate, siloed, and difficult to compare in a centralized fashion. In this study, we established the Lung Cancer Autochthonous Model Gene Expression Database (LCAMGDB), an extensive repository of 1,354 samples from 77 transcriptomic datasets covering 974 samples from genetically engineered mouse models (GEMMs), 368 samples from carcinogen-induced models, and 12 samples from a spontaneous model. Meticulous curation and collaboration with data depositors produced a robust and comprehensive database, …

G-Quadruplex Stabilizer Cx-5461 Effectively Combines With Radiotherapy To Target Α-Thalassemia/Mental Retardation X-Linked-Deficient Malignant Glioma, Sharvari Dharmaiah, Prit Benny Malgulwar, William E Johnson, Brandon A Chen, Vladislav Sharin, Benjamin T Whitfield, Christian Alvarez, Vasudev Tadimeti, Ahsan S Farooqi, Jason T Huse

Faculty, Staff and Student Publications

Background: Inactivation of α-thalassemia/mental retardation X-linked (ATRX) represents a defining molecular feature in large subsets of malignant glioma. ATRX deficiency gives rise to abnormal G-quadruplex (G4) DNA secondary structures, enhancing replication stress and genomic instability. Building on earlier work, we evaluated the extent to which pharmacological G4 stabilization selectively enhances DNA damage and cell death in ATRX-deficient preclinical glioma models.

Methods: Using the G4 stabilizer CX-5461, we treated patient-derived glioma stem cells (GSCs) in vitro and GSC flank and intracranial murine xenografts in vivo to evaluate efficacy as both a single agent and in combination with ionizing radiation (IR), the …

Long-Term Efficacy Of Pembrolizumab And The Clinical Utility Of Ctdna In Locally Advanced Dmmr/Msi-H Solid Tumors, Michael Lapelusa, Wei Qiao, Bryan Iorgulescu, Francis San Lucas, Keyur Patel, Deepak Bhamidipati, Jane Varkey Thomas, Nancy You, Wai Chin Foo, Dipen Maru, Selvi Thirumurthi, Van Morris, Scott Kopetz, Michael Overman, Kaysia Ludford

Faculty, Staff and Student Publications

Neoadjuvant immunotherapy can induce pathologic complete response (pCR) in patients with localized deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H) tumors. The long-term outcomes of these patients are unknown, as is the clinical utility of measuring circulating tumor DNA (ctDNA). Follow-up was evaluated in patients enrolled in a phase II trial (NCT04082572) that evaluated the efficacy and safety of pembrolizumab in patients with localized dMMR/MSI-H tumors. The primary outcomes of this trial have previously been reported. 3-year EFS and OS rates were 80% (95% CI: 66% - 93%) and 94% (95% CI: 86% - 100%). Patients without detectable ctDNA after pembrolizumab had …

Movement Disorders In Relapsing And Progressive Ms: A Comprehensive Prospective Evaluation Of A Large Real-Life Cohort, Hannah Kelly, Rongyi Sun, Mohamed Elkasaby, Alexander Wang, Hesham Abboud

Faculty Scholarship

Background: Recent studies suggest that movement disorders are common in early MS. However, the frequency and clinical characteristics of movement disorders at all stages of MS remain unknown. Objectives: To evaluate the frequency, clinical characteristics, and anatomical generators of movement disorders in relapsing and progressive MS. Methods: We conducted a prospective study of adult MS patients from 2016 to 2022 at a neuroimmunology clinic. Patients were evaluated for demyelination-related movement disorders via a survey and focused examination. We classified movement disorders based on phenomenology and identified anatomic correlates according to lesion locations and relation to relapses. Findings were compared between …

The Identification Of Xpr1 As A Voltage- And Phosphate-Activated Phosphate-Permeable Ion Channel, Hongjiang Wu, Liang Sun, Tong Huo, Theodore G Wensel, Frank T Horrigan, Zhao Wang

Faculty, Staff and Students Publications

Maintaining a balance of inorganic phosphate (Pi) is vital for cellular functionality. Proper phosphate levels are managed through Pi import and export; and the processes governing Pi export remain the least understood. Xenotropic and Polytropic retrovirus Receptor 1 (XPR1) has been identified as the only known Pi export protein in mammals. In this study, we introduce the cryogenic electron microscopy structure of human XPR1 (hXPR1), unveiling a structural arrangement distinct from that of any known ion transporter. Our structural results suggest that hXPR1 may operate as an ion channel, a hypothesis supported by patch clamp recordings revealing hXPR1's voltage- and …

Safety And Efficacy Of A Mesenchymal Stem Cell Secretome Therapy (Kpi-012) For Persistent Corneal Epithelial Defects: A Phase 1b Trial, Valeria Sánchez Huerta, Hugo Quiroz-Mercado, Enrique O Graue-Hernández, Alejandro Navas, Spencer Alford, Darius Kharabi, Stephen Pflugfelder

Faculty, Staff and Students Publications

Background: Persistent corneal epithelial defect (PCED) is a condition often refractory to conventional treatments. KPI-012 is a topical mesenchymal stem cell secretome therapy under investigation for PCED management.

Objective: To assess the safety, tolerability, and corneal wound healing efficacy of KPI-012 in a phase 1b, proof-of-concept, open-label, single-arm clinical trial.

Methods: The safety profile and tolerability of topical self-administered KPI-012 therapy (twice daily, 1-week duration) were first evaluated in an initial safety cohort of participants with pre-existing permanent vision loss and no active corneal disease (n = 3). The safety profile and efficacy of KPI-012 were then assessed in participants …

Discrepancy Between Hyaluronic Acid Levels And Mri-Based Measurements Of Hepatic Fat And Fibrosis, Daniel Aaron Borman, Rachel L. Chevalier, Jonathan Body Ingestion Clinical Wagner, Michele T. Pritchard, Sherwin S. Chan, Nathan S. Artz, Johnston K. Fite, Yoon Y. Cho, Valentina Shakhnovich, Veronica Williams, Voytek Slowik

Research Days

Introduction

Metabolic-dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease in children in the United States and, when left untreated, can progress to liver fibrosis. Clinicians currently utilize imaging and biopsy to assess fibrosis in this patient population as there is no validated serum biomarker available for detecting fibrosis. Previous research suggests that serum hyaluronic acid levels are predictive of hepatic fibrosis in children with MASLD.

Methods

Retrospective data were obtained from the Children’s Mercy Hospital Liver Lab study. Pediatric subjects with both hyaluronic acid (HA) samples and MRI evaluation within a month were identified and included for …

Assessing The Relationship Between Planter Fascia And Planter Calcaneonavicular Ligament Thickness In Individuals Suffering From Planter Fasciitis Using Musculoskeletal Ultrasonography, Wessam Eissa Hamed Attia

Journal of Medicine in Scientific Research

Abstract Objective: There is uncertainty regarding how thick spring ligament is in persons with plantar fasciitis complaints, despite the fact that they exhibit laxity of this ligament. The purpose of this study was to use an ultrasonic imaging system (US) to clarify the anatomical features of spring ligament in individuals who suffer from plantar fasciitis. Methods: The study was conducted on 30 feet of thirty patients suffering from plantar fasciitis representing the painful group and 30 feet of thirty healthy individuals that have no planter pain representing the healthy group that were chosen from Mataria Teaching Hospital's rheumatology and rehabilitation …

Molecular Characterization And Predictors Of Relapse In Patients With Ph + All After Frontline Ponatinib And Blinatumomab, Nicholas J Short, Hagop Kantarjian, Ken Furudate, Nitin Jain, Farhad Ravandi, Omer Karrar, Sanam Loghavi, Lewis Nasr, Fadi G Haddad, Jayastu Senapati, Rebecca Garris, Koichi Takahashi, Elias Jabbour

Faculty, Staff and Student Publications

Background: Several studies have suggested that chemotherapy-free regimens consisting of blinatumomab and a BCR::ABL1 tyrosine kinase inhibitor are highly effective in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). However, the clinical and molecular characteristics that predict for relapse with these chemotherapy-free regimens are largely unknown.

Methods: We conducted a prospective phase II clinical trial of the combination of blinatumomab and ponatinib in 76 patients with newly diagnosed Ph + ALL. Patients received 12-15 doses of intrathecal chemotherapy as central nervous systemic (CNS) prophylaxis. The patterns of relapse and the clinical and molecular predictors of relapse were analyzed.

Results: With …

Immunotherapy With Nebulized Pattern Recognition Receptor Agonists Restores Severe Immune Paralysis And Improves Outcomes In Mice With Influenza-Associated Pulmonary Aspergillosis, Jezreel Pantaleón García, Sebastian Wurster, Nathaniel D Albert, Uddalak Bharadwaj, Keerthi Bhoda, Vikram K Kulkarni, Mbaya Ntita, Paris Rodríguez Carstens, Madeleine Burch-Eapen, Daniela Covarrubias López, Jania Foncerrada Lizaola, Katherine E Larsen, Lauren M Matula, Seyed J Moghaddam, Yongxing Wang, Dimitrios P Kontoyiannis, Scott E Evans

Faculty, Staff and Student Publications

Influenza-associated pulmonary aspergillosis (IAPA) is a potentially deadly superinfection in patients with influenza pneumonia, especially those with severe disease, underlying immunosuppression, corticosteroid therapy, or requiring intensive care support. Given the high mortality of IAPA, adjunct immunomodulatory strategies remain a critical unmet need. Previously, the desensitization of pattern recognition pathways has been described as a hallmark of IAPA pathogenesis and a predictor of mortality in IAPA patients. Therefore, we studied the impact of nebulized Toll-like receptor 2/6/9 agonists Pam2 CSK4 (Pam2) and CpG oligodeoxynucleotides (ODNs) on infection outcomes and pulmonary immunopathology in a corticosteroid-immunosuppressed murine IAPA model. Mice with IAPA receiving …

Forward Genetic Screen In Zebrafish Identifies New Fungal Regulators That Limit Host-Protective Candida-Innate Immune Interaction, Bailey A Blair, Emma Bragdon, Gursimran Dhillon, Nnamdi Baker, Lena Stasiak, Mya Muthig, Pedro Miramon, Michael C Lorenz, Robert T Wheeler

Faculty, Staff and Student Publications

Candida is one of the most frequent causes of bloodstream infections, and our first line of defense against these invasive infections is the innate immune system. The early immune response is critical in controlling Candida albicans infection, but C. albicans has several strategies to evade host immune attack. Phagocytosis of C. albicans blocks hyphal growth, limiting host damage and virulence, but how C. albicans limits early recruitment and phagocytosis in vertebrate infection is poorly understood. To study innate immune evasion by intravital imaging, we utilized the transparent larval zebrafish infection model to screen 131 C. albicans mutants for altered …

Direct Parieto-Occipital Connectivity Of The Amygdala Via The Parahippocampal Segment Of The Cingulum Bundle, Arash Kamali, Kamand Khalaj, Atif Ali, Farbod Khalaj, Diana Kokash, Andres R Gonzalez, Michael A Jacobs, Alireza Akhbardeh, Paul E Schulz, Khader M Hasan

Faculty, Staff and Student Publications

Background

The amygdala is a key structure involved in memory, emotional processing, and sensory integration. While the cortical connectivity of the amygdala with the frontal and temporal lobes has been extensively studied, its direct connections with the parieto-occipital cortices remain underexplored. This study aims to delineate the direct connectivity between the amygdala and the parietal and occipital cortices via the parahippocampal segment of the cingulum bundle.

Methods

High-resolution diffusion-weighted imaging (DWI) tractography was performed on 30 healthy adult brains. Fiber tracking was conducted using three regions of interest (ROIs) placed in the parietal, occipital, and medial temporal lobes. A fractional …

Clinical And Fundamental Research Progressions On Tumor-Infiltrating Lymphocytes Therapy In Cancer, Jiandong Hu, Mengli Jin, Weihong Feng, Barbara Nassif-Rausseo, Alexandre Reuben, Chunhua Ma, Gregory Lizee, Fenge Li

Faculty, Staff and Student Publications

Malignant tumors represent a significant threat to human health. Among the various therapeutic strategies available, cancer immunotherapy-encompassing adoptive cell transfer (ACT) and immune checkpoint blockade therapy-has emerged as a particularly promising approach following surgical resection, radiotherapy, chemotherapy, and molecular targeted therapies. This form of treatment elicits substantial antigen-specific immune responses, enhances or restores anti-tumor immunity, thereby facilitating the control and destruction of tumor cells, and yielding durable responses across a range of cancers, which can lead to the eradication of tumor lesions and the prevention of recurrence. Tumor-infiltrating lymphocytes (TILs), a subset of ACT, are characterized by their heterogeneity and …

Theta Oscillons In Behaving Rats, M S Zobaer, Nastaran Lotfi, Carli M Domenico, Clarissa Hoffman, Luca Perotti, Daoyun Ji, Yuri Dabaghian

Faculty, Staff and Students Publications

Recently discovered constituents of the brain waves—the oscillons—provide a high-resolution representation of the extracellular field dynamics. Here, we study the most robust, highest-amplitude oscillons recorded in actively behaving male rats, which underlie the traditional θ-waves. The resemblances between θ-oscillons and the conventional θ-waves are manifested primarily at the ballpark level—mean frequencies, mean amplitudes, and bandwidths. In addition, both hippocampal and cortical oscillons exhibit a number of intricate, behavior-attuned, transient properties that suggest a new vantage point for understanding the θ-rhythms’ structure, origins and functions. In particular, we demonstrate that oscillons are frequency-modulated waves, with speed-controlled …

The Genestar Manual For Biospecimen Collection Biobanking And Omics Data Generation From Commercial Space Missions, Aparna Krishnavajhala, Marie-Claude Gingras, Emmanuel Urquieta, Hsu Chao, Dilrukshi Bandaranaike, Yi Chen, Sravya Bhamidipati, Viktoriya Korchina, S Michelle Griffin, Michal M Masternak, Hannah Moreno, Javid Mohammed, Mullai Murugan, Jennifer E Posey, Jimmy H Wu, Donna Muzny, Richard A Gibbs, Harsha Doddapaneni

Faculty, Staff and Students Publications

The surge in commercial and civilian spaceflight enables the systematic and longitudinal, large-scale biospecimen collection to understand the prospective effects of space travel on human health. The Genomics and Space Medicine (Space Omics) project at BCM-HGSC involves a comprehensive biospecimen collection plan from commercial/private space flight participants. The manuscript addresses the critical gaps in the biospecimen collection process including details of the informed consent process, a provision for subjects to obtain custom CLIA-WGS reports, a data dictionary and a LIMS enabled biobank. The manuscript also discusses the biospecimens collection, processing methodologies and nucleic acid suitability for Omics data generation. Results …