Medicine and Health Sciences Commons^™

Longitudinal Natural History Studies Based On Real-World Data In Rare Diseases: Opportunity And A Novel Approach, Laura Ann Adang, Anjana Sevagamoorthy, Omar Sherbini, Jamie L Fraser, Joshua L Bonkowsky, Francesco Gavazzi, Russel D'Aiello, Nicholson B Modesti, Emily Yu, Sylvia Mutua, Emma Kotes, Justine Shults, Ariel Vincent, Lisa T Emrick, Stephanie Keller, Keith P Van Haren, Sarah Woidill, Isabella Barcelos, Amy Pizzino, Johanna L Schmidt, Florian Eichler, Ali Fatemi, Adeline Vanderver

Faculty, Staff and Students Publications

Growing interest in therapeutic development for rare diseases necessitate a systematic approach to the collection and curation of natural history data that can be applied consistently across this group of heterogenous rare diseases. In this study, we discuss the challenges facing natural history studies for leukodystrophies and detail a novel standardized approach to creating a longitudinal natural history study using existing medical records.

Prospective studies are uniquely challenging for rare diseases. Delays in diagnosis and overall rarity limit the timely collection of natural history data. When feasible, prospective studies are often cross-sectional rather than longitudinal and are unlikely to capture …

Cardiac Conduction Diseases: Understanding The Molecular Mechanisms To Uncover Targets For Future Treatments, Tingting Li, Qussay Marashly, Jitae A Kim, Na Li, Mihail G Chelu

Faculty, Staff and Students Publications

Introduction: The cardiac conduction system (CCS) is crucial for maintaining adequate cardiac frequency at rest and modulation during exercise. Furthermore, the atrioventricular node and His-Purkinje system are essential for maintaining atrioventricular and interventricular synchrony and consequently maintaining an adequate cardiac output.

Areas covered: In this review article, we examine the anatomy, physiology, and pathophysiology of the CCS. We then discuss in detail the most common genetic mutations and the molecular mechanisms of cardiac conduction disease (CCD) and provide our perspectives on future research and therapeutic opportunities in this field.

Expert opinion: Significant advancement has been made in understanding the molecular …

Piezo1 Regulates Meningeal Lymphatic Vessel Drainage And Alleviates Excessive Csf Accumulation, Dongwon Choi, Eunkyung Park, Joshua Choi, Renhao Lu, Jin Suh Yu, Chiyoon Kim, Luping Zhao, James Yu, Brandon Nakashima, Sunju Lee, Dhruv Singhal, Joshua P Scallan, Bin Zhou, Chester J Koh, Esak Lee, Young-Kwon Hong

Faculty, Staff and Students Publications

Piezo1 regulates multiple aspects of the vascular system by converting mechanical signals generated by fluid flow into biological processes. Here, we find that Piezo1 is necessary for the proper development and function of meningeal lymphatic vessels and that activating Piezo1 through transgenic overexpression or treatment with the chemical agonist Yoda1 is sufficient to increase cerebrospinal fluid (CSF) outflow by improving lymphatic absorption and transport. The abnormal accumulation of CSF, which often leads to hydrocephalus and ventriculomegaly, currently lacks effective treatments. We discovered that meningeal lymphatics in mouse models of Down syndrome were incompletely developed and abnormally formed. Selective overexpression of …

Robotic-Assisted Single-Site Abdominal Cerclage In The Bicornuate Uterus Patient With Cervical Insufficiency, Nurul Farhanah Binte Abdul Latif, Zhenkun Guan, Sylvia Asare, Xiaoming Guan

Faculty, Staff and Students Publications

Objective: To demonstrate the surgical techniques for improving safety in robotic-assisted abdominal cerclage in patients with bicornuate uteri complicated by recurrent pregnancy loss and cervical insufficiency.

Design: Stepwise demonstration with narrated video footage.

Setting: An academic tertiary care hospital.

Patients: Our patient is a 22-year-old G2P0020 with a history of recurrent pregnancy loss. During her first pregnancy, she was asymptomatic until 19 weeks and delivered because of a preterm premature rupture of membranes. A transvaginal cerclage was performed for her second pregnancy at 14 weeks, which ended at 16 weeks because of preterm premature rupture of membranes. The final magnetic …

Engineering Small-Molecule And Protein Drugs For Targeting Bone Tumors, Yixian Wang, Chenhang Wang, Meng Xia, Zeru Tian, Joseph Zhou, Julian Meyer Berger, Xiang H-F Zhang, Han Xiao

Faculty, Staff and Students Publications

Bone cancer is common and severe. Both primary (e.g., osteosarcoma, Ewing sarcoma) and secondary (e.g., metastatic) bone cancers lead to significant health problems and death. Currently, treatments such as chemotherapy, hormone therapy, and radiation therapy are used to treat bone cancer, but they often only shrink or slow tumor growth and do not eliminate cancer completely. The bone microenvironment contributes unique signals that influence cancer growth, immunogenicity, and metastasis. Traditional cancer therapies have limited effectiveness due to off-target effects and poor distribution on bones. As a result, therapies with improved specificity and efficacy for treating bone tumors are highly needed. …

Clinical Outcomes, Return To Sport, And Complications After Isolated Primary Latarjet Versus Latarjet As A Revision Procedure: A Systematic Review And Meta-Analysis, Garrett R Jackson, Trevor Tuthill, Shaan Asif, Daniel Dewald, Morgan Wessels, Johnathon R Mccormick, Enzo S Mameri, Derrick M Knapik, Filippo Familiari, Mario Hevesi, Anjay K Batra, Jorge Chahla, Nikhil N Verma

2020-Current year OA Pubs

BACKGROUND: The purpose of this review was to compare clinical outcomes, return to sport (RTS), and complications in comparative studies examining patients undergoing primary Latarjet procedure versus Latarjet in the revision setting following soft tissue stabilization.

METHODS: A literature search was conducted using PubMed and Scopus databases using Preferred Reporting Items for Systematic Meta-Analyses guidelines. Inclusion criteria consisted of level I to III human clinical studies reporting clinical outcomes (Visual Analogue Pain Scale [VAS]), RTS metrics, and complications in patients following primary versus revision Latarjet procedures. Study quality was assessed using the Methodological Index for Non-Randomized Studies (MINORS) criteria.

RESULTS: …

Contemporary Management Of Aneurysmal Subarachnoid Haemorrhage. An Update For The Intensivist, Chiara Robba, Katharina M Busl, Jan Claassen, Michael N Diringer, Raimund Helbok, Soojin Park, Alejandro Rabinstein, Miriam Treggiari, Mervyn D I Vergouwen, Giuseppe Citerio

2020-Current year OA Pubs

Aneurysmal subarachnoid haemorrhage (aSAH) is a rare yet profoundly debilitating condition associated with high global case fatality and morbidity rates. The key determinants of functional outcome include early brain injury, rebleeding of the ruptured aneurysm and delayed cerebral ischaemia. The only effective way to reduce the risk of rebleeding is to secure the ruptured aneurysm quickly. Prompt diagnosis, transfer to specialized centers, and meticulous management in the intensive care unit (ICU) significantly improved the prognosis of aSAH. Recently, multimodality monitoring with specific interventions to correct pathophysiological imbalances has been proposed. Vigilance extends beyond intracranial concerns to encompass systemic respiratory and …

Plecanatide Improves Abdominal Bloating And Bowel Symptoms Of Irritable Bowel Syndrome With Constipation, Darren M Brenner, Amol Sharma, Satish S C Rao, Adam P Laitman, Zeev Heimanson, Christopher Allen, Gregory S Sayuk

2020-Current year OA Pubs

BACKGROUND: Bloating is a bothersome symptom in irritable bowel syndrome with constipation (IBS-C).

AIM: To evaluate plecanatide efficacy in patients with IBS-C stratified by bloating intensity.

METHODS: Pooled phase 3 data (2 randomized, controlled IBS-C trials) from adults treated with plecanatide 3 mg or placebo for 12 weeks were analyzed. Patients were stratified post-hoc by baseline bloating severity (11-point scale: mild [≤ 5] and moderate-to-severe [> 5]). Assessments included change from baseline in bloating, abdominal pain, and complete spontaneous bowel movement (CSBM) frequency. Abdominal pain and bloating composite responders were defined as patients with ≥ 30% improvement from baseline in …

Guardians Of Precision: Advancing Radiation Protection, Safety, And Quality Systems In Nuclear Medicine, Francesco Giammarile, Peter Knoll, Jolanta Kunikowska, Diana Paez, Enrique Estrada Lobato, Miriam Mikhail-Lette, Richard Wahl, Ola Holmberg, May Abdel-Wahab, Andrew M Scott, Roberto C Delgado Bolton

2020-Current year OA Pubs

BACKGROUND: In the rapidly evolving field of nuclear medicine, the paramount importance of radiation protection, safety, and quality systems cannot be overstated. This document provides a comprehensive analysis of the intricate regulatory frameworks and guidelines, meticulously crafted and updated by national and international regulatory bodies to ensure the utmost safety and efficiency in the practice of nuclear medicine.

METHODS: We explore the dynamic nature of these regulations, emphasizing their adaptability in accommodating technological advancements and the integration of nuclear medicine with other medical and scientific disciplines.

RESULTS: Audits, both internal and external, are spotlighted for their pivotal role in assessing …

Coenzyme Q4 Is A Functional Substitute For Coenzyme Q10 And Can Be Targeted To The Mitochondria, Laura H Steenberge, Sean Rogers, Andrew Y Sung, Jing Fan, David J Pagliarini

2020-Current year OA Pubs

Coenzyme Q10 (CoQ

Validation Of A Stenotrophomonas Maltophilia Bloodstream Infection Prediction Score In The Hematologic Malignancy Population, Emily L Gill, Christian M Gill, Colleen Mcevoy

2020-Current year OA Pubs

Stenotrophomonas maltophilia (SM) bloodstream infections (BSIs) contribute to significant mortality in hematologic malignancy (HM) and hematopoietic stem cell transplantation (HSCT) patients. A risk score to predict SM BSI could reduce time to appropriate antimicrobial therapy (TTAT) and improve patient outcomes. A single center cohort study of hospitalized adults with HM/HSCT was conducted. Patients had ≥ 1 blood culture with a Gram-negative (GN) organism. A StenoSCORE was calculated for each patient. The StenoSCORE2 was developed using risk factors for SM BSI identified via logistic regression. Receiver operating characteristic (ROC) curves were plotted. Sensitivity and specificity for the StenoSCORE and StenoSCORE2 were …

Explainable Ai-Based Deep-Shap For Mapping The Multivariate Relationships Between Regional Neuroimaging Biomarkers And Cognition, Puskar Bhattarai, Deepa Singh Thakuri, Yuzheng Nie, Ganesh B Chand

2020-Current year OA Pubs

BACKGROUND: Mild cognitive impairment (MCI)/Alzheimer's disease (AD) is associated with cognitive decline beyond normal aging and linked to the alterations of brain volume quantified by magnetic resonance imaging (MRI) and amyloid-beta (Aβ) quantified by positron emission tomography (PET). Yet, the complex relationships between these regional imaging measures and cognition in MCI/AD remain unclear. Explainable artificial intelligence (AI) may uncover such relationships.

METHOD: We integrate the AI-based deep learning neural network and Shapley additive explanations (SHAP) approaches and introduce the Deep-SHAP method to investigate the multivariate relationships between regional imaging measures and cognition. After validating this approach on simulated data, we …

Post-Covid Small Fiber Neuropathy, Implications Of Innate Immunity, And Challenges On Ivig Therapy, Marinos Dalakas

Department of Neurology Faculty Papers

No abstract provided.

Spatial Mapping Of Hematopoietic Clones In Human Bone Marrow, Andrew L Young, Hannah C Davis, Maggie J Cox, Tyler M Parsons, Samantha C Burkart, Diane E Bender, Lulu Sun, Stephen T Oh, Grant A Challen

2020-Current year OA Pubs

UNLABELLED: Clonal hematopoiesis (CH) is the expansion of somatically mutated cells in the hematopoietic compartment of individuals without hematopoietic dysfunction. Large CH clones (i.e., >2% variant allele fraction) predispose to hematologic malignancy, but CH is detected at lower levels in nearly all middle-aged individuals. Prior work has extensively characterized CH in peripheral blood, but the spatial distribution of hematopoietic clones in human bone marrow is largely undescribed. To understand CH at this level, we developed a method for spatially aware somatic mutation profiling and characterized the bone marrow of a patient with polycythemia vera. We identified the complex clonal distribution …

Patient Engagement In Designing, Conducting, And Disseminating Clinical Pain Research: Immpact Recommended Considerations, Simon Haroutounian, Katherine J. Holzer, Et Al.

2020-Current year OA Pubs

In the traditional clinical research model, patients are typically involved only as participants. However, there has been a shift in recent years highlighting the value and contributions that patients bring as members of the research team, across the clinical research lifecycle. It is becoming increasingly evident that to develop research that is both meaningful to people who have the targeted condition and is feasible, there are important benefits of involving patients in the planning, conduct, and dissemination of research from its earliest stages. In fact, research funders and regulatory agencies are now explicitly encouraging, and sometimes requiring, that patients are …

Person-Centred Interventions To Improve Patient-Provider Relationships For Hiv Services In Low- And Middle-Income Countries: A Systematic Review, Laura K Beres, Ashley Underwood, Noelle Le Tourneau, Christopher Galloway Kemp, Gauri Kore, Lauren Yaeger, Jingjia Li, Alec Aaron, Claire Keene, Deepthi Priyanka Mallela, Banda A A Khalifa, Aaloke Mody, Sheree Renae Schwartz, Stefan Baral, Chanda Mwamba, Kombatende Sikombe, Ingrid Eshun-Wilson, Elvin H Geng, Marie-Claude C Lavoie

2020-Current year OA Pubs

INTRODUCTION: Person-centred care (PCC) has been recognized as a critical element in delivering quality and responsive health services. The patient-provider relationship, conceptualized at the core of PCC in multiple models, remains largely unexamined in HIV care. We conducted a systematic review to better understand the types of PCC interventions implemented to improve patient-provider interactions and how these interventions have improved HIV care continuum outcomes and person-reported outcomes (PROs) among people living with HIV in low- and middle-income countries.

METHODS: We searched databases, conference proceedings and conducted manual targeted searches to identify randomized trials and observational studies published up to January …

Deconstructing Pathological Tau By Biological Process In Early Stages Of Alzheimer Disease: A Method For Quantifying Tau Spatial Spread In Neuroimaging, Stephanie Doering, Austin Mccullough, Brian A Gordon, Charles D Chen, Nicole Mckay, Diana Hobbs, Sarah Keefe, Shaney Flores, Jalen Scott, Hunter Smith, Stephen Jarman, Kelley Jackson, Russ C Hornbeck, Beau M Ances, Chengjie Xiong, Andrew J Aschenbrenner, Jason Hassenstab, Carlos Cruchaga, Alisha Daniels, Randall J Bateman, John C Morris, Tammie L S Benzinger, Et Al.

2020-Current year OA Pubs

BACKGROUND: Neuroimaging studies often quantify tau burden in standardized brain regions to assess Alzheimer disease (AD) progression. However, this method ignores another key biological process in which tau spreads to additional brain regions. We have developed a metric for calculating the extent tau pathology has spread throughout the brain and evaluate the relationship between this metric and tau burden across early stages of AD.

METHODS: 445 cross-sectional participants (aged ≥ 50) who had MRI, amyloid PET, tau PET, and clinical testing were separated into disease-stage groups based on amyloid positivity and cognitive status (older cognitively normal control, preclinical AD, and …

Asct2-Targeting Antibody-Drug Conjugate Medi7247 In Adult Patients With Relapsed/Refractory Hematological Malignancies: A First-In-Human, Phase 1 Study, Michael Maris, Camille N Abboud, Et Al.

2020-Current year OA Pubs

BACKGROUND: MEDI7247 is a first-in-class antibody-drug conjugate (ADC) consisting of an anti-sodium-dependent alanine-serine-cysteine transporter 2 antibody-conjugated to a pyrrolobenzodiazepine dimer.

OBJECTIVE: This first-in-human phase 1 trial evaluated MEDI7247 in patients with hematological malignancies.

PATIENTS AND METHODS: Adults with acute myeloid leukemia (AML), multiple myeloma (MM), or diffuse large B-cell lymphoma (DLBCL) relapsed or refractory (R/R) to standard therapies, or for whom no standard therapy exists, were eligible. Primary endpoints were safety and determination of the maximum tolerated dose (MTD). Secondary endpoints included assessments of antitumor activity, pharmacokinetics (PK), and immunogenicity.

RESULTS: As of 26 March 2020, 67 patients were treated …

Mapping Brain Function In Adults And Young Children During Naturalistic Viewing With High-Density Diffuse Optical Tomography, Kalyan Tripathy, Morgan Fogarty, Alexandra M Svoboda, Mariel L Schroeder, Sean M Rafferty, Edward J Richter, Christopher Tracy, Patricia K Mansfield, Madison Booth, Andrew K Fishell, Arefeh Sherafati, Zachary E Markow, Muriah D Wheelock, Ana María Arbeláez, Bradley L Schlaggar, Christopher D Smyser, Adam T Eggebrecht, Joseph P Culver

2020-Current year OA Pubs

Human studies of early brain development have been limited by extant neuroimaging methods. MRI scanners present logistical challenges for imaging young children, while alternative modalities like functional near-infrared spectroscopy have traditionally been limited by image quality due to sparse sampling. In addition, conventional tasks for brain mapping elicit low task engagement, high head motion, and considerable participant attrition in pediatric populations. As a result, typical and atypical developmental trajectories of processes such as language acquisition remain understudied during sensitive periods over the first years of life. We evaluate high-density diffuse optical tomography (HD-DOT) imaging combined with movie stimuli for high …

Decade-Long Trends In Incidence Of Slipped Capital Femoral Epiphysis In The United States: A Nationwide Database Analysis Of Over 33 Million Patients, Aaron Singh, Travis Kotzur, Beltran Torres-Izquierdo, David Momtaz, Rishi Gonuguntla, Amir Human Hoveidaei, Ali Seifi, María Galán-Olleros, Pooya Hosseinzadeh

2020-Current year OA Pubs

PURPOSE: Slipped capital femoral epiphysis (SCFE) is a prevalent pediatric hip disorder linked to severe complications, with childhood obesity as a crucial risk factor. Despite the rising obesity rates, contemporary data on SCFE's epidemiology remain scarce in the United States. This study examined SCFE incidence trends and demographic risk factors in the United States over a decade.

METHODS: A decade-long (2011 to 2020) retrospective cohort study was undertaken using the Healthcare Cost and Utilization Project National Inpatient Sample. Patients aged younger than 18 years were identified and further analyzed if diagnosed with SCFE through ICD-9 or ICD-10 codes. Key metrics …

Is Crystalloid Co-Loading Necessary To Prevent Spinal Hypotension During Elective Cesarean Delivery? A Randomized Double-Blind Trial, B S Buddeberg, E Seeberger, C Bläsi, G Dutilh, L A Steiner, O Bandschapp, A Palanisamy, T Girard

2020-Current year OA Pubs

BACKGROUND: Hypotension is common during spinal anesthesia for cesarean delivery. Preventive strategies include fluid loading and phenylephrine. We hypothesized that if prophylactic phenylephrine infusion is used, omission of fluid loading would be non-inferior to fluid co-loading in maintaining cardiac output. We assumed that if there was a difference, the increase in cardiac output would be greater in the no-loading than in the co-loading group.

METHODS: Term pregnant women scheduled for elective cesarean delivery were randomized to receive 1 L crystalloid co-loading or maintenance fluids only. Phenylephrine was titrated to maintain blood pressure. Changes in cardiac output following spinal anesthesia were …

Disruption Of Polyunsaturated Fatty Acid Biosynthesis Drives Sting-Dependent Acute Myeloid Leukemia Cell Maturation And Death, Joice Kanefsky, Mary Basse, Judith Sokei, Orsola Di Martino, Liana Valin, Jeffrey A Magee, Francesca Ferraro, Stephen M Sykes, Et Al.

2020-Current year OA Pubs

The role of polyunsaturated fatty acid (PUFA) biosynthesis in acute myeloid leukemia (AML) remains largely undefined. A comparative expression analysis of 35 genes encoding fatty acid biosynthesis enzymes showed that fatty acid desaturase 1 (FADS1) was highly expressed across multiple AML subtypes relative to healthy controls and that elevated FADS1 expression correlates with worse overall AML patient survival. Functionally, shRNA-mediated inhibition of FADS1 reduced AML cell growth in vitro and significantly delayed leukemia onset in an AML mouse model. AML cell lines depleted of FADS1 arrested in the G1/S-phase of the cell cycle, acquired characteristics of myeloid maturation and subsequently …

Alport Syndrome And Alport Kidney Diseases - Elucidating The Disease Spectrum, Pongpratch Puapatanakul, Jeffrey H. Miner

2020-Current year OA Pubs

PURPOSE OF REVIEW: With the latest classification, variants in three collagen IV genes, COL4A3 , COL4A4 , and COL4A5 , represent the most prevalent genetic kidney disease in humans, exhibiting diverse, complex, and inconsistent clinical manifestations. This review breaks down the disease spectrum and genotype-phenotype correlations of kidney diseases linked to genetic variants in these genes and distinguishes "classic" Alport syndrome (AS) from the less severe nonsyndromic genetically related nephropathies that we suggest be called "Alport kidney diseases".

RECENT FINDINGS: Several research studies have focused on the genotype-phenotype correlation under the latest classification scheme of AS. The historic diagnoses of …

Complement Regulation In The Eye: Implications For Age-Related Macular Degeneration, Georgia A. Wilke, Rajendra S. Apte

2020-Current year OA Pubs

Careful regulation of the complement system is critical for enabling complement proteins to titrate immune defense while also preventing collateral tissue damage from poorly controlled inflammation. In the eye, this balance between complement activity and inhibition is crucial, as a low level of basal complement activity is necessary to support ocular immune privilege, a prerequisite for maintaining vision. Dysregulated complement activation contributes to parainflammation, a low level of inflammation triggered by cellular damage that functions to reestablish homeostasis, or outright inflammation that disrupts the visual axis. Complement dysregulation has been implicated in many ocular diseases, including glaucoma, diabetic retinopathy, and …

Image Quality Characterization Of An Ultra-High-Speed Kilovoltage Cone-Beam Computed Tomography Imaging System On An O-Ring Linear Accelerator, Euidam Kim, Yang Kyun Park, Tianyu Zhao, Eric Laugeman, Xiaodong Neo Zhao, Yao Hao, Yoonsun Chung, Hugh Lee

2020-Current year OA Pubs

PURPOSE: The quality of on-board imaging systems, including cone-beam computed tomography (CBCT), plays a vital role in image-guided radiation therapy (IGRT) and adaptive radiotherapy. Recently, there has been an upgrade of the CBCT systems fused in the O-ring linear accelerators called HyperSight, featuring a high imaging performance. As the characterization of a new imaging system is essential, we evaluated the image quality of the HyperSight system by comparing it with Halcyon 3.0 CBCT and providing benchmark data for routine imaging quality assurance.

METHODS: The HyperSight features ultra-fast scan time, a larger kilovoltage (kV) detector, a more substantial kV tube, and …

Epidemiology Of Dsm-5 Psychiatric Disorders In Kenyan Youth With Low And High Psychosis Risk, Rebekka H Sæle, David M Ndetei, Victoria N Mutiso, Daniel Mamah

2020-Current year OA Pubs

INTRODUCTION: There are few psychiatric epidemiology studies among Kenyan youth and fewer among those at high psychosis risk (HR).

METHODS: This study assessed the epidemiology of DSM-5 psychiatric disorders in HR and low-risk (LR) individuals to inform research and mental health services. 567 participants (aged 15-25) in HR (n = 246) and LR (n = 260) groups based on Washington Early Recognition Center Affectivity and Psychosis (WERCAP) Screen scores. Diagnostic Interview Schedule, version 5 (DIS-5) assessed DSM-5 psychiatric disorder prevalence. Diagnostic comorbidity and demographic relationships were investigated.

RESULTS: A higher prevalence was observed for all DSM-5 disorders in the HR …

Preexisting Diabetes And Breast Cancer Treatment Among Low-Income Women, Bayu Begashaw Bekele, Min Lian, Chester Schmaltz, Tracy Greever-Rice, Pratibha Shrestha, Ying Liu

2020-Current year OA Pubs

IMPORTANCE: Diabetes is associated with poorer prognosis of patients with breast cancer. The association between diabetes and adjuvant therapies for breast cancer remains uncertain.

OBJECTIVE: To comprehensively examine the associations of preexisting diabetes with radiotherapy, chemotherapy, and endocrine therapy in low-income women with breast cancer.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study included women younger than 65 years diagnosed with nonmetastatic breast cancer from 2007 through 2015, followed up through 2016, continuously enrolled in Medicaid, and identified from the linked Missouri Cancer Registry and Medicaid claims data set. Data were analyzed from January 2022 to October 2023.

EXPOSURE: Preexisting …

Targeting Dendritic Cell Dysfunction To Circumvent Anti-Pd1 Resistance In Head And Neck Cancer, Shin Saito, Michihisa Kono, Hoang C B Nguyen, Ann Marie Egloff, Cameron Messier, Patrick Lizotte, Cloud Paweletz, Douglas Adkins, Ravindra Uppaluri

2020-Current year OA Pubs

PURPOSE: Neoadjuvant anti-PD1 (aPD1) therapies are being explored in surgically resectable head and neck squamous cell carcinoma (HNSCC). Encouraging responses have been observed, but further insights into the mechanisms underlying resistance and approaches to improve responses are needed.

EXPERIMENTAL DESIGN: We integrated data from syngeneic mouse oral carcinoma (MOC) models and neoadjuvant pembrolizumab HNSCC patient tumor RNA-sequencing data to explore the mechanism of aPD1 resistance. Tumors and tumor-draining lymph nodes (DLN) from MOC models were analyzed for antigen-specific priming. CCL5 expression was enforced in an aPD1-resistant model.

RESULTS: An aPD1-resistant mouse model showed poor priming in the tumor DLN due …

Targeting Hematologic Malignancies By Inhibiting E-Selectin: A Sweet Spot For Aml Therapy?, Geoffrey L Uy, Daniel J Deangelo, Jay N Lozier, Dennis M Fisher, Brian A Jonas, John L Magnani, Pamela S Becker, Hillard M Lazarus, Ingrid G Winkler

2020-Current year OA Pubs

E-selectin, a cytoadhesive glycoprotein, is expressed on venular endothelial cells and mediates leukocyte localization to inflamed endothelium, the first step in inflammatory cell extravasation into tissue. Constitutive marrow endothelial E-selectin expression also supports bone marrow hematopoiesis via NF-κB-mediated signaling. Correspondingly, E-selectin interaction with E-selectin ligand (sialyl Lewis

Modulation Of Host Immunity By Sensory Neurons, Telma Saraiva-Santos, Tiago H Zaninelli, Felipe A Pinho-Ribeiro

2020-Current year OA Pubs

Recent studies have uncovered a new role for sensory neurons in influencing mammalian host immunity, challenging conventional notions of the nervous and immune systems as separate entities. In this review we delve into this groundbreaking paradigm of neuroimmunology and discuss recent scientific evidence for the impact of sensory neurons on host responses against a wide range of pathogens and diseases, encompassing microbial infections and cancers. These valuable insights enhance our understanding of the interactions between the nervous and immune systems, and also pave the way for developing candidate innovative therapeutic interventions in immune-mediated diseases highlighting the importance of this interdisciplinary …