Medicine and Health Sciences Commons^™

A Quick Recap: Discovering Cryptococcus Neoformans Capsule Mutants, Daphne Boodwa-Ko, Tamara L Doering

2020-Current year OA Pubs

No abstract provided.

Dorsal Hippocampus To Nucleus Accumbens Projections Drive Reinforcement Via Activation Of Accumbal Dynorphin Neurons, Khairunisa Mohamad Ibrahim, Nicolas Massaly, Hye-Jean Yoon, Rossana Sandoval, Allie J Widman, Robert J Heuermann, Sidney Williams, William Post, Sulan Pathiranage, Tania Lintz, Azra Zec, Ashley Park, Robert W Gereau 4th, Jose A Morón, Et Al.

2020-Current year OA Pubs

The hippocampus is pivotal in integrating emotional processing, learning, memory, and reward-related behaviors. The dorsal hippocampus (dHPC) is particularly crucial for episodic, spatial, and associative memory, and has been shown to be necessary for context- and cue-associated reward behaviors. The nucleus accumbens (NAc), a central structure in the mesolimbic reward pathway, integrates the salience of aversive and rewarding stimuli. Despite extensive research on dHPC→NAc direct projections, their sufficiency in driving reinforcement and reward-related behavior remains to be determined. Our study establishes that activating excitatory neurons in the dHPC is sufficient to induce reinforcing behaviors through its direct projections to the …

Mosaic Loss Of Y Chromosome Is Associated With Aging And Epithelial Injury In Chronic Kidney Disease, Parker C Wilson, Amit Verma, Yasuhiro Yoshimura, Yoshiharu Muto, Haikuo Li, Nicole P Malvin, Eryn E Dixon, Benjamin D Humphreys

2020-Current year OA Pubs

BACKGROUND: Mosaic loss of Y chromosome (LOY) is the most common chromosomal alteration in aging men. Here, we use single-cell RNA and ATAC sequencing to show that LOY is present in the kidney and increases with age and chronic kidney disease.

RESULTS: The likelihood of a cell having LOY varies depending on its location in the nephron. Cortical epithelial cell types have a greater proportion of LOY than medullary or glomerular cell types, which may reflect their proliferative history. Proximal tubule cells are the most abundant cell type in the cortex and are susceptible to hypoxic injury. A subset of …

Analysis Of Anemia And Iron Supplementation Among Glioblastoma Patients Reveals Sex-Biased Association Between Anemia And Survival, Ganesh Shenoy, Becky Slagle-Webb, Chachrit Khunsriraksakul, Bhavyata Pandya Shesh, Jingqin Luo, Vladimir Khristov, Nataliya Smith, Alireza Mansouri, Brad E Zacharia, Sheldon Holder, Justin D Lathia, Jill S Barnholtz-Sloan, James R Connor

2020-Current year OA Pubs

The association between anemia and outcomes in glioblastoma patients is unclear. We analyzed data from 1346 histologically confirmed adult glioblastoma patients in the TriNetX Research Network. Median hemoglobin and hematocrit levels were quantified for 6 months following diagnosis and used to classify patients as anemic or non-anemic. Associations of anemia and iron supplementation of anemic patients with median overall survival (median-OS) were then studied. Among 1346 glioblastoma patients, 35.9% of male and 40.5% of female patients were classified as anemic using hemoglobin-based WHO guidelines. Among males, anemia was associated with reduced median-OS compared to matched non-anemic males using hemoglobin (HR …

Clinical Situations For Which 3d Printing Is Considered An Appropriate Representation Or Extension Of Data Contained In A Medical Imaging Examination: Pediatric Congenital Heart Disease Conditions, Justin R Ryan, David Ballard, Et Al.

2020-Current year OA Pubs

BACKGROUND: The use of medical 3D printing (focusing on anatomical modeling) has continued to grow since the Radiological Society of North America's (RSNA) 3D Printing Special Interest Group (3DPSIG) released its initial guideline and appropriateness rating document in 2018. The 3DPSIG formed a focused writing group to provide updated appropriateness ratings for 3D printing anatomical models across a variety of congenital heart disease. Evidence-based- (where available) and expert-consensus-driven appropriateness ratings are provided for twenty-eight congenital heart lesion categories.

METHODS: A structured literature search was conducted to identify all relevant articles using 3D printing technology associated with pediatric congenital heart disease …

Venovenous Extracorporeal Membrane Oxygenation After Cardiac Arrest For Acute Respiratory Distress Syndrome Caused By Legionella: A Case Report, John C Grotberg, Linda Schulte, Erin Schumer, Mary Sullivan, Kunal Kotkar, Mohammad F Masood, Amit Pawale

2020-Current year OA Pubs

BACKGROUND: Legionella remains underdiagnosed in the intensive care unit and can progress to acute respiratory distress syndrome (ARDS), multiorgan failure and death. In severe cases, venovenous extracorporeal membrane oxygenation (VV-ECMO) allows time for resolution of disease with Legionella-targeted therapy. VV-ECMO outcomes for Legionella are favorable with reported survival greater than 70%. Rapid molecular polymerase chain reaction (PCR) testing of the lower respiratory tract aids in diagnosing Legionella with high sensitivity and specificity. We present a unique case of a patient with a positive COVID-19 test and ARDS who suffered a cardiac arrest. The patient was subsequently cannulated for VV-ECMO, and …

Reviewing The Clostridioides Difficile Mouse Model: Insights Into Infection Mechanisms, José L Fachi, Marco A R Vinolo, Marco Colonna

2020-Current year OA Pubs

No abstract provided.

Association Of Genetic Variation In Col11a1 With Adolescent Idiopathic Scoliosis, Hao Yu, Lilian Antunes, Christina A Gurnett, Et Al.

2020-Current year OA Pubs

Adolescent idiopathic scoliosis (AIS) is a common and progressive spinal deformity in children that exhibits striking sexual dimorphism, with girls at more than fivefold greater risk of severe disease compared to boys. Despite its medical impact, the molecular mechanisms that drive AIS are largely unknown. We previously defined a female-specific AIS genetic risk locus in an enhancer near the

Tempo And Mode Of Gene Expression Evolution In The Brain Across Primates, Katherine Rickelton, Trisha M Zintel, Jason Pizzollo, Emily Miller, John J Ely, Mary Ann Raghanti, William D Hopkins, Patrick R Hof, Chet C Sherwood, Amy L Bauernfeind, Courtney C Babbitt

2020-Current year OA Pubs

Primate evolution has led to a remarkable diversity of behavioral specializations and pronounced brain size variation among species (Barton, 2012; DeCasien and Higham, 2019; Powell et al., 2017). Gene expression provides a promising opportunity for studying the molecular basis of brain evolution, but it has been explored in very few primate species to date (e.g. Khaitovich et al., 2005; Khrameeva et al., 2020; Ma et al., 2022; Somel et al., 2009). To understand the landscape of gene expression evolution across the primate lineage, we generated and analyzed RNA-seq data from four brain regions in an unprecedented eighteen species. Here, we …

Gliopredictor: A Deep Learning Model For Identification Of High-Risk Adult Idh-Mutant Glioma Towards Adjuvant Treatment Planning, Shuhua Zheng, Nikhil Rammohan, Timothy Sita, P Troy Teo, Yilin Wu, Maciej Lesniak, Sean Sachdev, Tarita O Thomas

2020-Current year OA Pubs

Identification of isocitrate dehydrogenase (IDH)-mutant glioma patients at high risk of early progression is critical for radiotherapy treatment planning. Currently tools to stratify risk of early progression are lacking. We sought to identify a combination of molecular markers that could be used to identify patients who may have a greater need for adjuvant radiation therapy machine learning technology. 507 WHO Grade 2 and 3 glioma cases from The Cancer Genome Atlas, and 1309 cases from AACR GENIE v13.0 datasets were studied for genetic disparities between IDH1-wildtype and IDH1-mutant cohorts, and between different age groups. Genetic features such as mutations and …

Comparative And Integrative Single Cell Analysis Reveals New Insights Into The Transcriptional Immaturity Of Stem Cell-Derived Β Cells, Mason D Schmidt, Matthew Ishahak, Punn Augsornworawat, Jeffrey R Millman

2020-Current year OA Pubs

Diabetes cell replacement therapy has the potential to be transformed by human pluripotent stem cell-derived β cells (SC-β cells). However, the precise identity of SC-β cells in relationship to primary fetal and adult β-cells remains unclear. Here, we used single-cell sequencing datasets to characterize the transcriptional identity of islets from in vitro differentiation, fetal islets, and adult islets. Our analysis revealed that SC-β cells share a core β-cell transcriptional identity with human adult and fetal β-cells, however SC-β cells possess a unique transcriptional profile characterized by the persistent expression and activation of progenitor and neural-biased gene networks. These networks are …

Neural Mechanisms Of Face Familiarity And Learning In The Human Amygdala And Hippocampus, Runnan Cao, Jinge Wang, Peter Brunner, Jon T Willie, Xin Li, Ueli Rutishauser, Nicholas J Brandmeir, Shuo Wang

2020-Current year OA Pubs

Recognizing familiar faces and learning new faces play an important role in social cognition. However, the underlying neural computational mechanisms remain unclear. Here, we record from single neurons in the human amygdala and hippocampus and find a greater neuronal representational distance between pairs of familiar faces than unfamiliar faces, suggesting that neural representations for familiar faces are more distinct. Representational distance increases with exposures to the same identity, suggesting that neural face representations are sharpened with learning and familiarization. Furthermore, representational distance is positively correlated with visual dissimilarity between faces, and exposure to visually similar faces increases representational distance, thus …

Synergistic Protection Of Retinal Ganglion Cells (Rgcs) By Sarm1 Inactivation With Cntf In A Rodent Model Of Nonarteritic Anterior Ischemic Optic Neuropathy, Yan Guo, Zara Mehrabian, Jeffrey Milbrandt, Aaron Diantonio, Steven L Bernstein

2020-Current year OA Pubs

We evaluated whether inhibiting sterile alpha and (Toll/interleukin receptor (TIR)) motif-containing 1 (SARM1) activity protects retinal ganglion cells (RGCs) following ischemic axonopathy (rodent nonarteritic anterior ischemic optic neuropathy: rNAION) by itself and combined with ciliary neurotrophic factor (CNTF). Genetically modified SARM1(-) rats were rNAION-induced in one eye and compared against equivalently induced wild-type animals of the same background. Optic nerve (ON) diameters were quantified using optical coherence tomography (SD-OCT). RGCs were quantified 30 d post-induction using retinal stereology for Brn3a(+) nuclei. ON sections were analyzed by TEM and immunohistochemistry. SARM1(-)(-) and WT animals were then bilaterally sequentially rNAION-induced. One eye …

Human Whole-Exome Genotype Data For Alzheimer's Disease, Yuk Yee Leung, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

The heterogeneity of the whole-exome sequencing (WES) data generation methods present a challenge to a joint analysis. Here we present a bioinformatics strategy for joint-calling 20,504 WES samples collected across nine studies and sequenced using ten capture kits in fourteen sequencing centers in the Alzheimer's Disease Sequencing Project. The joint-genotype called variant-called format (VCF) file contains only positions within the union of capture kits. The VCF was then processed specifically to account for the batch effects arising from the use of different capture kits from different studies. We identified 8.2 million autosomal variants. 96.82% of the variants are high-quality, and …

Adverse Outcomes And An Immunosuppressed Endotype In Septic Patients With Reduced Ifn-Γ Elispot, Evan L. Barrios, Drew E. Del Toro, Alexandra Dram, Sandra Meszaros, Sydney Miles, Andrew H. Walton, Anne M. Drewry, Isaiah R. Turnbull, Richard S Hotchkiss, Et Al.

2020-Current year OA Pubs

BACKGROUNDSepsis remains a major clinical challenge for which successful treatment requires greater precision in identifying patients at increased risk of adverse outcomes requiring different therapeutic approaches. Predicting clinical outcomes and immunological endotyping of septic patients generally relies on using blood protein or mRNA biomarkers, or static cell phenotyping. Here, we sought to determine whether functional immune responsiveness would yield improved precision.METHODSAn ex vivo whole-blood enzyme-linked immunosorbent spot (ELISpot) assay for cellular production of interferon γ (IFN-γ) was evaluated in 107 septic and 68 nonseptic patients from 5 academic health centers using blood samples collected on days 1, 4, and 7 …

An Orally Available Compound Suppresses Glucagon Hypersecretion And Normalizes Hyperglycemia In Type 1 Diabetes, Farzad Asadi, Subhadra C. Gunawardana, Roland E. Dolle, David W. Piston

2020-Current year OA Pubs

Suppression of glucagon hypersecretion can normalize hyperglycemia during type 1 diabetes (T1D). Activating erythropoietin-producing human hepatocellular receptor type-A4 (EphA4) on α cells reduced glucagon hypersecretion from dispersed α cells and T1D islets from both human donor and mouse models. We synthesized a high-affinity small molecule agonist for the EphA4 receptor, WCDD301, which showed robust plasma and liver microsome metabolic stability in both mouse and human preparations. In islets and dispersed islet cells from nondiabetic and T1D human donors, WCDD301 reduced glucagon secretion comparable to the natural EphA4 ligand, Ephrin-A5. In diabetic NOD and streptozotocin-treated mice, once-daily oral administration of WCDD301 …

Neuronal Deletion Of The Circadian Clock Gene Bmal1 Induces Cell-Autonomous Dopaminergic Neurodegeneration, Michael K. Kanan, Patrick W. Sheehan, Jessica N. Haines, Pedro G. Gomez, Adya Dhuler, Collin J. Nadarajah, Zachary M. Wargel, Brittany M. Freeberg, Hemanth R. Nelvagal, Mariko Izumo, Joseph S. Takahashi, Jonathan D. Cooper, Albert A. Davis, Erik S. Musiek

2020-Current year OA Pubs

Circadian rhythm dysfunction is a hallmark of Parkinson disease (PD), and diminished expression of the core clock gene Bmal1 has been described in patients with PD. BMAL1 is required for core circadian clock function but also serves nonrhythmic functions. Germline Bmal1 deletion can cause brain oxidative stress and synapse loss in mice, and it can exacerbate dopaminergic neurodegeneration in response to the toxin MPTP. Here we examined the effect of cell type-specific Bmal1 deletion on dopaminergic neuron viability in vivo. We observed that global, postnatal deletion of Bmal1 caused spontaneous loss of tyrosine hydroxylase+ (TH+) dopaminergic neurons in the substantia …

B Cells Mediate Lung Ischemia/Reperfusion Injury By Recruiting Classical Monocytes Via Synergistic B Cell Receptor/Tlr4 Signaling, Khashayar Farahnak, Yun Zhu Bai, Yuhei Yokoyama, Deniz B. Morkan, Zhiyi Liu, Junedh M. Amrute, Alejandro De Filippis Falcon, Yuriko Terada, Fuyi Liao, Wenjun Li, Hailey M. Shepherd, Ramsey R. Hachem, Varun Puri, Kory J. Lavine, Andrew E. Gelman, Ankit Bharat, Daniel Kreisel, Ruben G. Nava

2020-Current year OA Pubs

Ischemia/reperfusion injury-mediated (IRI-mediated) primary graft dysfunction (PGD) adversely affects both short- and long-term outcomes after lung transplantation, a procedure that remains the only treatment option for patients suffering from end-stage respiratory failure. While B cells are known to regulate adaptive immune responses, their role in lung IRI is not well understood. Here, we demonstrated by intravital imaging that B cells are rapidly recruited to injured lungs, where they extravasate into the parenchyma. Using hilar clamping and transplant models, we observed that lung-infiltrating B cells produce the monocyte chemokine CCL7 in a TLR4-TRIF-dependent fashion, a critical step contributing to classical monocyte …

Targeting Efferocytosis In Inflammaging, Ivan K H Poon, Kodi S Ravichandran

2020-Current year OA Pubs

Rapid removal of apoptotic cells by phagocytes, a process known as efferocytosis, is key for the maintenance of tissue homeostasis, the resolution of inflammation, and tissue repair. However, impaired efferocytosis can result in the accumulation of apoptotic cells, subsequently triggering sterile inflammation through the release of endogenous factors such as DNA and nuclear proteins from membrane permeabilized dying cells. Here, we review the molecular basis of the three key phases of efferocytosis, that is, the detection, uptake, and degradation of apoptotic materials by phagocytes. We also discuss how defects in efferocytosis due to the alteration of phagocytes and dying cells …

Cpsa Mediates Infection Of Recruited Lung Myeloid Cells By Mycobacterium Tuberculosis, Steven J Grigsby, G V R Krishna Prasad, Joshua B Wallach, Ekansh Mittal, Fong-Fu Hsu, Dirk Schnappinger, Jennifer A Philips

2020-Current year OA Pubs

Mycobacterium tuberculosis (Mtb) possesses an arsenal of virulence factors to evade host immunity. Previously, we showed that the Mtb protein CpsA, which protects Mtb against the host NADPH oxidase, is required in mice during the first 3 weeks of infection but is thereafter dispensable for full virulence. Using flow cytometry, we find that ΔcpsA Mtb is retained in alveolar macrophages, impaired in recruiting and disseminating into monocyte-derived cells, and more likely to be localized in airway cells than wild-type Mtb. The lungs of ΔcpsA-infected mice also have markedly fewer antigen-specific T cells, indicating a delay in adaptive immunity. Thus, we …

Self-Renewing Human Naïve Pluripotent Stem Cells Dedifferentiate In 3d Culture And Form Blastoids Spontaneously, Mingyue Guo, Jinyi Wu, Chuanxin Chen, Xinggu Wang, An Gong, Wei Guan, Rowan M Karvas, Kexin Wang, Mingwei Min, Yixuan Wang, Thorold W Theunissen, Shaorong Gao, José C R Silva

2020-Current year OA Pubs

Human naïve pluripotent stem cells (hnPSCs) can generate integrated models of blastocysts termed blastoids upon switch to inductive medium. However, the underlying mechanisms remain obscure. Here we report that self-renewing hnPSCs spontaneously and efficiently give rise to blastoids upon three dimensional (3D) suspension culture. The spontaneous blastoids mimic early stage human blastocysts in terms of structure, size, and transcriptome characteristics and are capable of progressing to post-implantation stages. This property is conferred by the glycogen synthase kinase-3 (GSK3) signalling inhibitor IM-12 present in 5iLAF self-renewing medium. IM-12 upregulates oxidative phosphorylation-associated genes that underly the capacity of hnPSCs to generate blastoids …

Mypathway Human Epidermal Growth Factor Receptor 2 Basket Study: Pertuzumab + Trastuzumab Treatment Of A Tissue-Agnostic Cohort Of Patients With Human Epidermal Growth Factor Receptor 2-Altered Advanced Solid Tumors, Christopher J Sweeney, Ron Bose, Et Al.

2020-Current year OA Pubs

No abstract provided.

Drug Preparation, Injection-Related Infections, And Harm Reduction Practices Among A National Sample Of Individuals Entering Treatment For Opioid Use Disorder, Laura R Marks, Michael J Durkin, Kelly Ayres, Matthew Ellis

2020-Current year OA Pubs

BACKGROUND: The rise in injection drug use in the USA has led to an increase in injection site infections. We performed a national survey of people who use drugs to evaluate common drug use preparation, harm reduction practices, and experiences with injection site infections.

METHODS: A survey was disseminated to members of the Survey of Key Informants' Patients Program from 2021 to 2022 and distributed to patients 18 years or older newly entering one of 68 substance use disorder treatment programs across the USA with a primary diagnosis of an opioid use disorder. Participants were surveyed about practices when preparing …

Comprehensive Workflow And Its Validation For Simulating Diffuse Speckle Statistics For Optical Blood Flow Measurements, Lisa Kobayashi Frisk, Manish Verma, Faruk Bešlija, Chen-Hao P Lin, Nishighanda Patil, Sumana Chetia, Jason W Trobaugh, Joseph P Culver, Turgut Durduran

2020-Current year OA Pubs

Diffuse optical methods including speckle contrast optical spectroscopy and tomography (SCOS and SCOT), use speckle contrast (

Factors Affecting The Ability Of Patients With Complex Vascular Anomalies To Navigate The Healthcare System, Bryan Sisk, Sunny Lin, Anna M Kerr

2020-Current year OA Pubs

BACKGROUND: Vascular anomalies (VAs) are rare congenital disorders that can cause pain, disfigurement, coagulopathy, asymmetric growth, and disability. Patients with complex VAs experience multiple barriers to accessing expert care. It is imperative to understand which factors support these patients' ability to navigate the healthcare system.

RESULTS: We surveyed adult patients with VAs using previously validated measures, recruiting participants from five patient advocacy groups and multidisciplinary VA clinics. The primary outcome was self-reported ability to access needed medical care, using the "Navigating the Healthcare System" subscale of the Health Literacy Questionnaire. We evaluated factors associated with the ability to navigate the …

Identification Of Molecular Subphenotypes In Two Cohorts Of Paediatric Ards, Nadir Yehya, Matt S Zinter, Jill M Thompson, Michelle J Lim, Mark R Hanudel, Mustafa F Alkhouli, Hector Wong, Matthew N Alder, Daniel J Mckeone, E Scott Halstead, Pratik Sinha, Anil Sapru

2020-Current year OA Pubs

BACKGROUND: Two subphenotypes of acute respiratory distress syndrome (ARDS), hypoinflammatory and hyperinflammatory, have been reported in adults and in a single paediatric cohort. The relevance of these subphenotypes in paediatrics requires further investigation. We aimed to identify subphenotypes in two large observational cohorts of paediatric ARDS and assess their congruence with prior descriptions.

METHODS: We performed latent class analysis (LCA) separately on two cohorts using biomarkers as inputs. Subphenotypes were compared on clinical characteristics and outcomes. Finally, we assessed overlap with adult cohorts using parsimonious classifiers.

FINDINGS: In two cohorts from the Children's Hospital of Philadelphia (n=333) and from a …

Post-Exposure Intranasal Ifnα Suppresses Replication And Neuroinvasion Of Venezuelan Equine Encephalitis Virus Within Olfactory Sensory Neurons, Matthew D Cain, N Rubin Klein, Xiaoping Jiang, Hamid Salimi, Qingping Wu, Mark J Miller, William B Klimstra, Robyn S Klein

2020-Current year OA Pubs

BACKGROUND: Venezuelan Equine Encephalitis virus (VEEV) may enter the central nervous system (CNS) within olfactory sensory neurons (OSN) that originate in the nasal cavity after intranasal exposure. While it is known that VEEV has evolved several mechanisms to inhibit type I interferon (IFN) signaling within infected cells, whether this inhibits virologic control during neuroinvasion along OSN has not been studied.

METHODS: We utilized an established murine model of intranasal infection with VEEV and a repository of scRNAseq data from IFN-treated OSN to assess the cellular targets and IFN signaling responses after VEEV exposure.

RESULTS: We found that immature OSN, which …

Draft Genomes Of 12 Bifidobacterium Isolates From Human Ibd Fecal Samples, Cole E Souza, Nicole E Jacobson, Michelle A An, Lindsay Droit, Alejandro A Vega, Mariel Rosales, Kathie A Mihindukulasuriya, Karina Pastrana, Scott A Handley, Miles Parkes, Joanna Rimmer, David Wang, Elizabeth A Dinsdale, Robert A Edwards, Anca M Segall

2020-Current year OA Pubs

Twelve

Very-Low-Density Lipoprotein Triglyceride And Free Fatty Acid Plasma Kinetics In Women With High Or Low Brown Adipose Tissue Volume And Overweight/Obesity, Maria Chondronikola, Jun Yoshino, Raja Ramaswamy, Joseph Daniel Giardina, Richard Laforest, Richard L Wahl, Bruce W Patterson, Bettina Mittendorfer, Samuel Klein

2020-Current year OA Pubs

Although a high amount of brown adipose tissue (BAT) is associated with low plasma triglyceride concentration, the mechanism responsible for this relationship in people is not clear. Here, we evaluate the interrelationships among BAT, very-low-density lipoprotein triglyceride (VLDL-TG), and free fatty acid (FFA) plasma kinetics during thermoneutrality in women with overweight/obesity who had a low (< 20 mL) or high (≥20 mL) volume of cold-activated BAT (assessed by using positron emission tomography in conjunction with 2-deoxy-2-[

Targeting Cell-Type-Specific, Choroid-Peripheral Immune Signaling To Treat Age-Related Macular Degeneration, Joseph B Lin, Andrea Santeford, Jason J Colasanti, Yoon Lee, Aaditya V Shah, Tzu Jui Wang, Philip A Ruzycki, Rajendra S Apte

2020-Current year OA Pubs

Age-related macular degeneration (AMD) is a leading cause of blindness featuring pathogenic neovascularization of the choroidal vasculature (CNV). Although systemic immunity plays a role in AMD, the ocular signals that recruit and activate immune cells remain poorly defined. Using single-cell RNA sequencing, we prospectively profile peripheral blood mononuclear cells from 65 individuals including AMD and controls, which we integrate with existing choroid data. We generate a network of choroid-peripheral immune interactions dysregulated in AMD, including known AMD-relevant gene vascular endothelial growth factor (VEGF) receptor 2. Additionally, we find CYR61 is upregulated in choroidal veins and may signal to circulating monocytes. …