Digital Commons Network^™

Activity-Dependent Astrocytic Cholesterol Release Fine-Tunes Modes Of Synaptic Exo- And Endocytosis, Jongyun Myeong, Vitaly A Klyachko

2020-Current year OA Pubs

Cholesterol is essential for the organization of neurotransmitter release machinery, yet how it regulates the balance among different forms of synaptic exo- and endocytosis remains poorly understood. Moreover, which pre-synaptic processes rely on neuronal vs. astrocyte-derived cholesterol is unknown. Using nanoscale-precision imaging of single-vesicle release in hippocampal synapses, we demonstrate that astrocytic cholesterol is a critical determinant of both temporal and spatial aspects of presynaptic dynamics by differentially modulating the two main forms of synchronous release, univesicular (UVR) and multivesicular (MVR), effectively fine-tuning their balance. Moreover, astrocytic cholesterol determines the spatial distribution of vesicle release across the active zone and …

Emergency Medicine Updates: The Physiologically Difficult Airway, Aaron J Lacy, Brit Long, Michael Gottlieb, Jarrod M Mosier

2020-Current year OA Pubs

INTRODUCTION: Airway management is an integral skill for emergency clinicians. While most of the focus is often on anatomic challenges, clinicians must also consider the unique physiologic challenges that risk decompensation during airway management, often termed the physiologically difficult airway.

OBJECTIVE: This paper evaluates key evidence-based updates concerning management of the physiologically difficult airway for the emergency clinician.

DISCUSSION: Peri-intubation complications in the emergency department are often driven by physiologic instability rather than anatomic difficulty. Key phenotypes of the physiologically difficult airway include hypotension, hypoxemia, metabolic acidemia, and right ventricular dysfunction, and are associated with high rates of physiologic collapse …

Cannabis Retailers' Marketing Practices And Compliance With State Regulations: A 2025 Point-Of-Sale Audit In 5 U.S. Cities, Carla J Berg, Cassidy R Loparco, Matthew E Rossheim, Morgan B Speer, Elizabeth Platt, Caitlin Davie, Hermela Amdeta, Darby Mihelich, Diane M Ndisebuye, Yuxian Cui, Patricia A Cavazos-Rehg, Y Tony Yang, Scott Burris

2020-Current year OA Pubs

Cannabis retail surveillance is crucial to inform regulations and enforcement efforts. This point-of-sale audit study examined marketing practices and compliance with age verification rules, required signage, and marketing restrictions among 161 cannabis retailers in 5 US cities in states authorizing nonmedical cannabis retail (Los Angeles [LA], California; Las Vegas [LV], Nevada; Denver, Colorado; Portland, Oregon; Seattle, Washington) in summer 2025. Descriptive and bivariate analyses characterized retailers overall and across cities. Overall, 84.5 % of retailers requested age verification upon entry (range: Seattle = 43.3 % to LV = 100 %); 8.1 % never verified (range: LV/Denver = 0 % to …

Using Electronic Health Record Audit Logs To Identify Pediatric Intensive Care Unit Teams, Liem M Nguyen, Stefanie S Sebok-Syer, Dane Jacobson, Karley Mariano, John Grunyk, Shelby Burk, Yasaman Nourkhalaj, Kimberley Kirk, Jochen Profit, Christian Rose, A Jay Holmgren, Thomas Kannampallil, Daniel Tawfik

2020-Current year OA Pubs

BACKGROUND: Teamwork influences patient outcomes, but electronic health records (EHRs) do not reliably capture patient care team members, limiting its study. EHR audit logs provide insights into healthcare workers' workflows and may help identify patients' care team members.

OBJECTIVE: To develop, validate, and compare algorithms utilizing EHR audit logs to identify patient-centric primary teams (bedside nurse, frontline clinician, and attending physician) in pediatric intensive care units (ICUs).

METHODS: We observed rounds for 1931 patient days (development = 678; validation = 1253) across pediatric (PICU), neonatal (NICU) and cardiovascular (CVICU) ICUs at a quaternary children's hospital and documented each patient's daytime …

Spatial Bias In Quality Of Estimated Delivery Date Records In The Electronic Health Record, Abigail Lewis, Randi Foraker, Min Lian, Min Zhao, Inez Oh, Aditi Gupta, Antonina Frolova, Philip R O Payne

2020-Current year OA Pubs

OBJECTIVES: This study evaluates the quality of estimated delivery dates (EDD) captured in electronic health record (EHR) systems, focusing on identifying and quantifying bias in these estimates for patients seeking prenatal care.

MATERIALS AND METHODS: We measured spatial and racial biases in the completeness and concordance of EDDs recorded in the EHR for patients seeking prenatal care. Element presence and agreement were compared across the catchment area to identify spatial patterns of bias in EDD records.

RESULTS: We obtained 38 477 unique pregnancy episodes in the EHR representing 33 081 unique patients between 2018 and 2022. Clear spatial and racial …

Predictive Modeling Of Clonal Hematopoiesis Across Diverse Cohorts, Armel L Batchi-Bouyou, Duc Tran, Michael Raddatz, Teng Gao, Caitlyn Vlasschaert, Brian Sharber, Jie Liu, Giulia Petrone, Irenaeus C C Chan, J Scott Beeler, Griffen Mustion, Alexander G Bick, Sean M Devlin, Kelly L Bolton

2020-Current year OA Pubs

No abstract provided.

Proteomic Profiling Identifies Systemic Drivers Of Blood-Brain Barrier Injury In Sickle Cell Disease, Yan Wang, Serguei Astafiev, Jinsheng Yu, Slim Fellah, Martin N Reis, Vivian Chen, Amy E Mirro, Chunwei Ying, Kristin P Guilliams, Melanie E Fields, Allison A King, Yasheng Chen, Robert A Campbell, Jorge Di Paola, Carlos Cruchaga, Jin-Moo Lee, Hongyu An, Andria L Ford

2020-Current year OA Pubs

Sickle cell disease (SCD) causes brain injury and cognitive disability. Systemic inflammation and endothelial injury are central to SCD pathophysiology, yet the relationship between systemic drivers of blood-brain barrier (BBB) disruption and brain injury remains understudied. This cross-sectional study assessed whole-brain and regional BBB permeability (Ktrans) using dynamic contrast-enhanced magnetic resonance imaging for 37 adults with SCD in steady state and 37 adults without SCD. Cerebral oxygen extraction fraction (OEF) and white matter mean diffusivity (MD) measured tissue hypoxia and microstructural injury, respectively. The SCD cohort showed elevated Ktrans compared with controls (3.6 × 10-4·min-1 vs 2.58 × 10-4·min-1; 95% …

Safety And Efficacy Of Allogeneic Cd19-Directed Car-T Therapy Ctx110 In Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma, Joseph P Mcguirk, Armin Ghobadi, Et Al.

2020-Current year OA Pubs

This multicenter, single-arm, phase 1/2 study evaluated the safety and efficacy of CD19-directed allogeneic chimeric antigen receptor (CAR) immunotherapy CTX110 in adult patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL). Patients received 1 or 2 treatment courses: standard lymphodepletion, followed by 1 CTX110 infusion at dose levels (DLs) 1 to 4 (3 × 107 to 60 × 107 CAR T cells; dose escalation, N = 32), or 2 infusions at DL4 on days 1 and 35 (cohort expansion, N = 31). Primary end points in dose escalation and cohort expansion were incidence of dose-limiting toxicities and objective response rate, respectively. …

Complementary Vertebrate Wac Models Exhibit Phenotypes Relevant To Desanto-Shinawi Syndrome, Kang-Han Lee, Marwan Shinawi, Et Al.

2020-Current year OA Pubs

Monogenic syndromes are associated with neurodevelopmental changes that result in cognitive impairments and neurobehavioral phenotypes, including autism and seizures. Limited studies and resources are available to make meaningful headway into the underlying molecular mechanisms that result in these symptoms. One such example is DeSanto-Shinawi Syndrome (DESSH), a rare disorder caused by pathogenic variants in the

Current State And Needs Of Clinical Laboratories In Selected Countries In Africa, Merih Tesfazghi, Anne E Tebo, Roa Harb, Anthony O Okorodudu, Lee Schroeder, Jeannette Guarner, Christine Bales, Jack Ladenson, Allison Targowski, Kerry Cosby, Olajumoke Oladipo

2020-Current year OA Pubs

The Africa Working Group, under the auspices of the Global Laboratory Quality Initiative of the Association for Diagnostics & Laboratory Medicine (ADLM), conducted several educational workshops in Africa to promote laboratory quality in the region. The challenges faced in maintaining quality in clinical laboratories in low-resource countries may differ from region to region and country to country. To better understand current gaps and inform our engagement with partners in Africa, a needs assessment survey was distributed to 1427 ADLM members in Africa and further disseminated through local partners, resulting in 121 responses from participants across 8 countries in the region. …

Benchmarking Institutional Support For Point-Of-Care Testing Programs: Scale, Staffing, And Operational Challenges, Min Yu, Nam K Tran, Julie L V Shaw, Nicholas E Larkey, Nicole V Tolan, Andrew Szczembara, Leslie J Donato, Robert D Maynard, Adil I Khan

2020-Current year OA Pubs

BACKGROUND: Point-of-care testing (POCT) has expanded rapidly across healthcare systems, increasing both program scale and operational complexity. However, quantitative benchmarking data describing how POCT programs are structured and supported across institutions remain limited.

METHODS: We conducted a cross-sectional survey to characterize POCT program support, including program scope, staffing, operational practices, governance, and challenges. The survey was distributed electronically through professional networks, and 93 institutional responses were analyzed. Descriptive analyses were performed, and derived metrics, including sites per point-of-care testing coordinator (POCC), were used to evaluate the relationship between program scale and staffing.

RESULTS: POCT programs demonstrated substantial variability in scale, …

Isolated Perianal Fistulizing Crohn's Disease In Contemporary Clinical Practice: A Multicenter Ecco-Confer Cohort Study, Kumarini Basnayake, Parakkal Deepak, Sami Samaan, Et Al.

2020-Current year OA Pubs

BACKGROUND AND AIMS: Isolated perianal fistulizing Crohn's disease (IPFCD) is an uncommon presentation of Crohn's disease with an uncertain natural history. We aimed to characterize contemporary diagnostic strategies, management approaches, and long-term outcomes, including progression to luminal Crohn's disease.

METHODS: We conducted a retrospective multicenter cohort study across 25 centers within the ECCO-CONFER network. Adult patients with IPFCD and no evidence of luminal Crohn's disease at baseline were included. The primary outcome was progression to luminal Crohn's disease. Secondary outcomes included clinical and radiological fistula response and patterns of medical and surgical management. Time-to-event analyses were performed using Kaplan-Meier methods. …

Assessment Of Timp1, Transgelin-2, And Procalcitonin As Protein Biomarkers For Diagnosis And Prognosis Of Bloodstream Infection In A Critically Ill Cohort, Sajal Tiwary, Caroline A O'Neil, Sydney Lawless, Olivia Arter, Meghan Brown, Brittany Roemmich, Carleigh Samuels, Jennie H Kwon, Christopher W Farnsworth

2020-Current year OA Pubs

BACKGROUND: Bloodstream infections (BSI) are a significant contributor to morbidity and mortality among hospitalized patients. Rapid diagnosis of BSI is critical for timely and appropriate clinical management, but current diagnostic strategies have a prolonged turnaround time or only identify select pathogens with minimal prognostic information.

METHODS: We examined serial serologic samples from 77 intensive care unit (ICU) patients at time points before, during, and after diagnosis of presumptive BSI to identify host-derived protein biomarkers associated with specific organisms and with clinical outcomes in BSI. ICU patients with and without BSI were included. Two candidate biomarkers, tissue metalloproteinase 1 (TIMP-1) and …

Energy Conservation In Mri: Sequence Selection And Operational Strategies, Nathan Scherer, Felicia Wang, Andrew L Chang, Mariam Malik, Anna Schroeder, Heather Craig, Benjamin E Northrup

2020-Current year OA Pubs

RATIONALE AND OBJECTIVES: The healthcare system accounts for approximately 9.8% of the United States' (U.S.) greenhouse gas emissions, much of which is due to imaging, particularly magnetic resonance imaging (MRI). This study investigates the components of MRI energy consumption and compares sequences that may be interchangeable in clinical practice. Although the greatest potential for decreasing energy expenditure lies in reduction of inappropriate imaging and optimizing energy consumption of idle MRI equipment, sequence substitution offers an underexplored solution that can potentially be implemented without changing practice patterns or capital expenditure.

MATERIALS AND METHODS: MRI energy expenditure of one machine was monitored …

Perioperative Depression And Anxiety Care In Older Patients: A Randomized Clinical Trial, Joanna Abraham, Katherine J Holzer, Simon Haroutounian, Bethany Pennington, Ana Baumann, Ryan Calfee, Theresa Cordner, Kenneth E Freedland, Thomas Kannampallil, Benjamin Kozower, Emily Lenard, J Philip Miller, Mary Politi, Michael Yingling, Michael S Avidan, Eric J Lenze

2020-Current year OA Pubs

IMPORTANCE: Depression and anxiety are common among older adults undergoing surgery and are associated with adverse postoperative outcomes. However, effective tailored perioperative mental health interventions are lacking.

OBJECTIVE: To evaluate a perioperative intervention to optimize mental health.

DESIGN, SETTING, AND PARTICIPANTS: A single-blind, hybrid, type 1, effectiveness-implementation randomized clinical trial was conducted (November 1, 2022, to March 31, 2025), with 3-month postoperative follow-up, at a US academic and community practice hospital network. Participants were 60 years or older; scheduled for cardiac, oncologic, or orthopedic surgery; and had clinically meaningful symptoms of depression and/or anxiety based on the Patient Health Questionnaire-Anxiety …

Comparison Of Safety And Efficacy Of Lower-Intensity Versus Standard Unfractionated Heparin Infusion Nomograms For Extracranial Venous Thromboembolism In The Neurological Intensive Care Unit, Abdullah M Hakoun, Megha Gupta, Rajat Dhar, Mahta Mardani, Fatih Koc, Salah G Keyrouz

2020-Current year OA Pubs

BACKGROUND: Anticoagulation for acute venous thromboembolism (VTE) in the neurological intensive care unit is challenging because patients with acute brain injury or recent neurosurgery are at high risk for hemorrhagic complications. Unfractionated heparin infusions are commonly used, sometimes with lower activated partial thromboplastin time targets, but the safety and effectiveness of lower-intensity UFH nomograms remain poorly defined.

METHODS: We performed a retrospective single-center study of patients diagnosed with acute extracranial VTE, including deep venous thrombosis and/or pulmonary embolism, between June 2018 and April 2024. Patients were grouped by treatment strategy: standard-intensity UFH targeting aPTT 60-100 s, lower-intensity UFH targeting aPTT …

Cracking The Code: Genotype-Phenotype Correlation Models In Sarcoglycanopathies, Leonela Luce, Conrad C Weihl, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Sarcoglycanopathies are among the most severe limb-girdle muscular dystrophies (LGMD), though milder presentations have been described. These diseases are primarily caused by missense variants, but the limited predictability of their effect on protein maturation, complex formation, and transport has hindered reliable genotype-phenotype correlations. This study aimed to establish accurate genotype-phenotype correlations for LGMDR3, LGMDR4, and LGMDR5.

METHODS: We analyzed the largest sarcoglycanopathy cohort to date (n = 541). Clinical data, including age at symptom onset and loss of ambulation, were collected and used to define phenotype severity. Predictive models were developed considering the impact of non-truncating variants on secondary …

Opioid Dispensing Volume And Per-Patient Intensity In Sickle Cell Disease, Kevin Y Xu, Brandon K Attell, Joanna L Buss, Tashalee R Brown, Charles R Jonassaint, Richard A Grucza, Allison A King, Max Jordan Nguemeni Tiako

2020-Current year OA Pubs

IMPORTANCE: Opioids remain central to management of acute and chronic pain in sickle cell disease (SCD). Opioid dispensing declined over the 2010s amid opioid stewardship efforts, but patterns since 2020 are less clear. Analyses aggregating opioids into morphine milligram equivalents (MME) may obscure agent-specific patterns.

OBJECTIVE: To characterize opioid dispensing volume and per-recipient frequency, duration, and dose among individuals with SCD.

DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study of commercially insured and Medicaid-enrolled patients with SCD using the Merative MarketScan databases across 3 periods from January 2011 to February 2016, March 2016 to December 2020, and January 2021 to …

Parent-Child Neural Dynamics During A Stressful Task: Probing Associations With Temperament And Anxiety, Joscelin Rocha-Hidalgo, Harmony Nguyen, Dakota Reis, Denny Schaedig, Kahlil I Thompson, Susan B Perlman, Koraly E Pérez-Edgar

2020-Current year OA Pubs

Dynamic social interactions between parents and children can contribute to anxiety risk, amplifying shared genetic risk. Research has focused on observed behaviors to explain intergenerational transmission. Neural synchrony may contribute as a biological conduit for behavioral transmission of risk. We examined 109 parent-child dyads (

Spinal Cord Imaging For Multiple Sclerosis: Advances, Priorities, And Opportunities, Cornelia Laule, Matthew R Brier, Et Al.

2020-Current year OA Pubs

The spinal cord plays a central role in the pathophysiology and clinical manifestations of multiple sclerosis (MS), yet remains under-studied compared with the brain. This review summarizes key insights from the 2025 North American Imaging in MS Spinal Cord Imaging Workshop, highlighting recent advances, ongoing challenges, and future opportunities in MS spinal cord imaging. We review pathological studies and outline the clinical relevance of spinal cord lesions and atrophy for diagnosis, prognosis, and disease monitoring, highlighting emerging biomarkers of progression independent of relapse activity. Correlations between magnetic resonance imaging, histopathology, and clinical outcomes support the validation and translational potential of …

Pediatric Hypertension Prevalence With 1 Vs. 2 Vs. 3 Within-Visit Blood Pressure Readings (Nhanes 2013-2020), Sandeep K Riar, Donald L Batisky, Scott Gillespie, Andrew M South

2020-Current year OA Pubs

To compare hypertension prevalence using 'initial' blood pressure (BP), 'subsequent' BP (averaged second and third readings) and 'total' BP (averaged three readings), we included 8-17-year-old youth with three BP readings from NHANES 2013-2020. From 2013-2016, BP was obtained using auscultation (manual protocol, MP) and subsequently, using oscillometry (automated protocol, AP). We excluded subjects with 'zero' diastolic blood pressure (DBP). In 5656 subjects, clinical hypertension (high systolic blood pressure [SBP] and/or DBP) prevalence was highest with 'initial' BP (350/5 642, 6.2% [95% CI 5.6-6.9%]), lower with 'subsequent' BP (289/5 642, 5.1% [4.6-5.7%], p <  0.001), and lowest with 'total' BP (251/5 642, 4.4% [3.9-5.0%], p <  0.001). Both MP and AP groups maintained this trend with a significantly lower hypertension prevalence with 'total' vs. 'subsequent' BP. An exception to the trend occurred in the AP group for three conditions: diastolic hypertension, hypertension in high BMI and Hispanic subjects. Diastolic hypertension prevalence with 'subsequent' DBP (86/2 285, 3.8% [3.1-4.6%]) exceeded that with 'initial' DBP (83/2 285, 3.6% [2.9-4.5%]) and was lowest with 'total' DBP (59/2 285, 2.6% [2.0-3.3%]). Diastolic hypertension prevalence was higher (126/5 642, 2.2% [1.9 - 2.7%]) with the 2016 European guidelines (same as 'subsequent' DBP) than with 'total' DBP (94/5 642, 1.7% [1.4 - 2.0%]). Our findings support the inclusion of the first BP reading in BP categorization, as 'total BP' leads to lower hypertension classification than 'subsequent' BP.

Pda (Privacy-Preserving Distributed Algorithms) In Action: Ten Principles For High-Quality Multi-Site Clinical Evidence Generation, Yong Chen, Chongliang Luo, Et Al.

2020-Current year OA Pubs

BACKGROUND: Distributed Research Networks (DRNs) offer significant opportunities for collaborative multi-site research and have significantly advanced healthcare research based on clinical observational data. However, generating high-quality real-world evidence using fit-for-use data from multi-site studies faces important challenges, including biases associated with various types of heterogeneity within and across sites and data sharing difficulties. Over the last 10 years, Privacy-Preserving Distributed Algorithms (PDA) have been developed and utilized in numerous national and international real-world studies spanning diverse domains, from comparative effectiveness research, target trial emulation, to healthcare delivery, policy evaluation, and system performance assessment. Despite these advances, there remains a lack …

Irs: Iterative Reference Selection Improves Normalization Of Microbiome Sequencing Data, Yiming Shi, Lili Liu, Jun Chen, Kristine M Wylie, Todd N Wylie, Sung Hee Park, Ruiwen Zhou, Yin Cao, Stephanie A Fritz, Molly J Stout, Maria Cristina Vazquez Guillamet, Lei Liu

2020-Current year OA Pubs

Microbiome studies often seek to determine how the absolute abundances of individual taxa change across biological conditions, yet sequencing read counts are sample-specific scaled representations of those abundances. Because sampling depth can differ across samples, fold changes calculated directly from sequencing read counts do not generally represent absolute-abundance fold changes. Normalization methods attempt to account for these between-sample differences in sampling depth, but their accuracy depends on the reference used. In particular, total-sum scaling uses all taxa as the reference and can introduce compositional bias. Reference-based methods instead rely on taxa that are stable across conditions, but contamination of the …

Implementation Of A New Mri Contrast Policy At A Large Hospital System: Access To Contrast-Enhanced Mri And Development Of Nsf In Patients With Renal Insufficiency, Daniel R Ludwig, Fan Zhang, Brittany Minor, Tammie L S Benzinger, Anup S Shetty

2020-Current year OA Pubs

RATIONALE AND OBJECTIVES: To evaluate access to contrast-enhanced MRI among patients with acute or chronic renal failure after implementation of a more permissive contrast policy and determine whether any patients developed nephrogenic systemic fibrosis (NSF).

MATERIALS AND METHODS: This retrospective study included all patients who had an order for contrast-enhanced MRI in our healthcare system between July 1st, 2023 and June 30th, 2025. Each exam was categorized as completed or cancelled, and multivariable analysis was performed to identify factors associated with exam cancellation. Potential diagnoses of NSF were identified by searching the problem list and encounter diagnoses using ICD-10 codes. …

Unlocking Cis-Regulatory Landscapes Across 500 Million Years Of Evolution And Disease Mechanisms, Tássia Mangetti Gonçalves, Casey L Stewart, Samantha D Baxley, Jason Xu, Kevin Boyer, Bijesh George, Daofeng Li, Chengran Yang, Harrison W Gabel, Xianhua Piao, Carlos Cruchaga, Yang E Li, Ting Wang, Oshri Avraham, Guoyan Zhao

2020-Current year OA Pubs

Genomic DNA encodes regulatory information that determines where, when, and to what extent genes are expressed. Theoretically, we should be able to identify these transcriptional "instructions" by examining genomic DNA sequence alone, yet this has remained challenging. Here we present the Vertebrate Regulatory MOdule Detector (VRMOD), a method that accurately predicts gene regulatory sequences using only the query genomic sequences. We applied VRMOD to 309 Ensembl genomes, generating a compendium of high-resolution, genome-position-fixed

Gamclust: Identification Of Regulated Metabolic Modules In Bulk, Single Cell And Spatial Gene Expression Data, Anastasiia Gainullina, Evgeniia Chikina, Maxim N Artyomov, Alexey Sergushichev

2020-Current year OA Pubs

MOTIVATION: Metabolism operates as a highly interconnected biochemical network, and its regulation emerges from coordinated changes across many reactions and metabolites. The integration of gene expression profiling data with organism-scale metabolic networks has proven to be a valuable tool for understanding cellular metabolic regulation. However, the increasing complexity of profiling technologies and experimental designs requires the development of specialized tools.

RESULTS: Here, we present GAMclust, an R package implementing and extending the previously published GAM-clustering pipeline for identifying transcriptionally regulated metabolic modules in complex gene expression datasets. GAMclust supports bulk, single-cell, and spatial gene expression profiling. It includes built-in KEGG …

Searching The Druggable Genome Using Large Language Models, Lars Schimmelpfennig, Matthew Cannon, Quentin Cody, Joshua Mcmichael, Adam C Coffman, Susanna Kiwala, Kilannin Krysiak, Alex H Wagner, Malachi Griffith, Obi L Griffith

2020-Current year OA Pubs

SUMMARY: The druggable genome encompasses the genes that are known or predicted to interact with drugs. The Drug-Gene Interaction Database (DGIdb) provides an integrated resource for discovering and contextualizing these interactions, supporting a broad range of research and clinical applications. DGIdb is currently accessed through structured web interfaces and API calls, requiring users to translate natural-language questions into database-specific query patterns. To allow for the use of DGIdb through natural language, we developed the DGIdb Model Context Protocol (MCP) server, which allows large language models (LLMs) access to up-to-date information through the DGIdb API. We demonstrate that the MCP server …

Altered Postnatal Chromatin Development In The Nucleus Accumbens Primes Enduring Stress Sensitivity, Rebekah L Rashford, Lisa Z Fang, Michael Deberardine, Hye Ji J Kim, Laura W Hirschfield, Ella Cervi, Mason R Barrett, Jeremy M Thompson, Meaghan C Creed, Catherine Jensen Peña

2020-Current year OA Pubs

Early life stress (ELS) sensitizes individuals to subsequent stressors to increase lifetime risk for psychiatric disorders. Within the nucleus accumbens (NAc)-a key limbic and reward-associated brain region-ELS sensitizes both cellular and transcriptional response to later stress, which are programmed by enduring epigenetic changes. Among the histone modifications persistently enriched by ELS in NAc is H3K4me1, which is associated with open chromatin and epigenetic priming of genomic enhancers. Here, we sought to determine whether H3K4me1 enrichment in NAc was sufficient to prime cellular and behavioral responses to adult stress. Viral-mediated overexpression of the histone H3 monomethyltransferase

Heritable Transgenic Schistosomes As A Living Platform For Sars-Cov-2 Neutralizing Antibody Secretion, Wannaporn Ittiprasert, Bruce A Rosa, Sergej Djuranovic, Makedonka Mitreva, Et Al.

2020-Current year OA Pubs

We report the generation and propagation of not only the first heritable transgenic schistosome line but also a line that secretes a functional therapeutic protein in vivo. Using multiplexed CRISPR/Cas-mediated homology-directed knock-in targeted to a predicted genomic safe-harbor, we inserted a VHH-IgG1 Fc (termed C5-Fc) transgene into Schistosoma mansoni eggs. Single-miracidium infections of Biomphalaria glabrata yielded parental P0 lines; serial passage through snail and mouse hosts produced an F2 cohort in which all parasites carried the C5-Fc transgene and secreted C5-Fc into the murine venous circulation. Molecular assays confirmed chromosomal insertion, germline transmission and systemic secretion. Sera from mice harboring …

Long-Term Follow-Up Of A Pediatric Regimen For Aya With Ph-Negative All: 10-Year Survival Of Calgb 10403 (Alliance), Wellington F Silva, Geoffrey L Uy, Et Al.

2020-Current year OA Pubs

No abstract provided.