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Buffered Lugol's Iodine Preserves Dna Fragment Lengths, P M Gignac, D Valdez, A C Morhardt, L M Lynch Jan 2024

Buffered Lugol's Iodine Preserves Dna Fragment Lengths, P M Gignac, D Valdez, A C Morhardt, L M Lynch

2020-Current year OA Pubs

Museum collections play a pivotal role in the advancement of biological science by preserving phenotypic and genotypic history and variation. Recently, contrast-enhanced X-ray computed tomography (CT) has aided these advances by allowing improved visualization of internal soft tissues. However, vouchered specimens could be at risk if staining techniques are destructive. For instance, the pH of unbuffered Lugol's iodine (I


Examining Heterogeneity In Dementia Using Data-Driven Unsupervised Clustering Of Cognitive Profiles, Sayantan Kumar, Inez Y. Oh, Suzanne E. Schindler, Nupur Ghoshal, Zachary Abrams, Philip R. O. Payne Jan 2024

Examining Heterogeneity In Dementia Using Data-Driven Unsupervised Clustering Of Cognitive Profiles, Sayantan Kumar, Inez Y. Oh, Suzanne E. Schindler, Nupur Ghoshal, Zachary Abrams, Philip R. O. Payne

2020-Current year OA Pubs

Dementia is characterized by a decline in memory and thinking that is significant enough to impair function in activities of daily living. Patients seen in dementia specialty clinics are highly heterogenous with a variety of different symptoms that progress at different rates. Recent research has focused on finding data-driven subtypes for revealing new insights into dementia's underlying heterogeneity, rather than assuming that the cohort is homogenous. However, current studies on dementia subtyping have the following limitations: (i) focusing on AD-related dementia only and not examining heterogeneity within dementia as a whole, (ii) using only cross-sectional baseline visit information for clustering …


Development, Usability, And Preliminary Efficacy Of A Virtual Reality Experience To Promote Healthy Lifestyle Behaviors In Children: Pilot Randomized Controlled Trial, Lauren A. Fowler, Melissa M. Vázquez, Bianca Depietro, Denise E. Wilfley, Ellen E. Fitzsimmons-Craft Jan 2024

Development, Usability, And Preliminary Efficacy Of A Virtual Reality Experience To Promote Healthy Lifestyle Behaviors In Children: Pilot Randomized Controlled Trial, Lauren A. Fowler, Melissa M. Vázquez, Bianca Depietro, Denise E. Wilfley, Ellen E. Fitzsimmons-Craft

2020-Current year OA Pubs

BACKGROUND: Virtual reality (VR) shows promise for supporting behavior change in children. This study used user-centered design to translate key tenets of behavioral health interventions into VR for children aged 6-12 years and their caregivers and examined the feasibility, acceptability, and preliminary efficacy of the VR experience in a pilot parallel, two-group randomized controlled trial (RCT).

METHODS: The VR experience incorporates psychoeducational content from evidence-based behavioral health interventions using voiceover and an interactive go-kart game related to the concepts of "food as fuel" and nutrition guidelines. Study 1 involved usability testing with n=5 child-caregiver dyads, which informed technical and content …


Factors Associated With Never Treatment And Acceptability Of Mass Drug Administration For The Elimination Of Lymphatic Filariasis In Guyana, 2021, Claudia Duguay, Reza A. Niles-Robin, Charles R. Thickstun, Horace Cox, Annastacia Sampson, Jean Seme-Fils Alexandre, Nathely Caleb-Mars, Charles W. Goss, Ana Morice, Ronaldo G. Carvalho Scholte, Alison Krentel Jan 2024

Factors Associated With Never Treatment And Acceptability Of Mass Drug Administration For The Elimination Of Lymphatic Filariasis In Guyana, 2021, Claudia Duguay, Reza A. Niles-Robin, Charles R. Thickstun, Horace Cox, Annastacia Sampson, Jean Seme-Fils Alexandre, Nathely Caleb-Mars, Charles W. Goss, Ana Morice, Ronaldo G. Carvalho Scholte, Alison Krentel

2020-Current year OA Pubs

Guyana remains one of four countries in the Americas endemic for lymphatic filariasis (LF). Elimination of LF requires repeated annual mass drug administration (MDA) with sufficient levels of coverage for success. This study assesses the acceptability and never treatment of LF MDA using data from a routine assessment survey in 2021. A subset of individuals, over 20 years of age (n = 2498), were selected to receive an expanded questionnaire to examine factors associated with acceptability and never treatment. Assessed factors include respondent demographics, knowledge, risk perceptions of LF, and opinions on the MDA programme. The majority (73%) of those …


A Multisociety Delphi Consensus Statement On New Fatty Liver Disease Nomenclature, Mary E Rinella, Samuel Klein, Et Al. Jan 2024

A Multisociety Delphi Consensus Statement On New Fatty Liver Disease Nomenclature, Mary E Rinella, Samuel Klein, Et Al.

2020-Current year OA Pubs

The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favor of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panelists from 56 countries participated in 4 …


The Ithildin Library For Efficient Numerical Solution Of Anisotropic Reaction-Diffusion Problems In Excitable Media, Desmond Kabus, Marie Cloet, Christian Zemlin, Olivier Bernus, Hans Dierckx Jan 2024

The Ithildin Library For Efficient Numerical Solution Of Anisotropic Reaction-Diffusion Problems In Excitable Media, Desmond Kabus, Marie Cloet, Christian Zemlin, Olivier Bernus, Hans Dierckx

2020-Current year OA Pubs

Ithildin is an open-source library and framework for efficient parallelized simulations of excitable media, written in the C++ programming language. It uses parallelization on multiple CPU processors via the message passing interface (MPI). We demonstrate the library's versatility through a series of simulations in the context of the monodomain description of cardiac electrophysiology, including the S1S2 protocol, spiral break-up, and spiral waves in ventricular geometry. Our work demonstrates the power of Ithildin as a tool for studying complex wave patterns in cardiac tissue and its potential to inform future experimental and theoretical studies. We publish our full code with this …


Tract-Based Analyses Of White Matter In Schizophrenia, Bipolar Disorder, Aging, And Dementia Using High Spatial And Directional Resolution Diffusion Imaging: A Pilot Study, Daniel Mamah, Shingshiun Chen, Joshua S Shimony, Michael P Harms Jan 2024

Tract-Based Analyses Of White Matter In Schizophrenia, Bipolar Disorder, Aging, And Dementia Using High Spatial And Directional Resolution Diffusion Imaging: A Pilot Study, Daniel Mamah, Shingshiun Chen, Joshua S Shimony, Michael P Harms

2020-Current year OA Pubs

INTRODUCTION: Structural brain connectivity abnormalities have been associated with several psychiatric disorders. Schizophrenia (SCZ) is a chronic disabling disorder associated with accelerated aging and increased risk of dementia, though brain findings in the disorder have rarely been directly compared to those that occur with aging.

METHODS: We used an automated approach to reconstruct key white matter tracts and assessed tract integrity in five participant groups. We acquired one-hour-long high-directional diffusion MRI data from young control (CON, n =28), bipolar disorder (BPD, n =21), and SCZ (n =22) participants aged 18-30, and healthy elderly (ELD, n =15) and dementia (DEM, n …


Janus Kinase Inhibition In The Treatment And Prevention Of Graft-Versus-Host Disease, Elisa De Togni, Oladipo Cole, Ramzi Abboud Jan 2024

Janus Kinase Inhibition In The Treatment And Prevention Of Graft-Versus-Host Disease, Elisa De Togni, Oladipo Cole, Ramzi Abboud

2020-Current year OA Pubs

Graft-versus-host disease (GVHD) is a significant cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). For many years, corticosteroids have been the mainstay treatment for GVHD, but cases of steroid-refractory GVHD and the severe adverse effects of high-dose corticosteroids have increased the need for preventative and therapeutic strategies for GVHD. Due to the nature of alloreactive T cells, GVHD is inherently linked to the graft-versus-leukemia (GVL) effect, the therapeutic driving force behind stem cell transplantation. A considerable clinical challenge is to preserve GVL while suppressing GVHD. The field of GVHD research has greatly expanded over the past …


Analyses Of Patients Who Self-Administered Diazepam Nasal Spray For Acute Treatment Of Seizure Clusters, Sunita N Misra, Michael R Sperling, Vikram R Rao, Jurriaan M Peters, Patricia Penovich, James Wheless, R Edward Hogan, Charles S Davis, Enrique Carrazana, Adrian L Rabinowicz Jan 2024

Analyses Of Patients Who Self-Administered Diazepam Nasal Spray For Acute Treatment Of Seizure Clusters, Sunita N Misra, Michael R Sperling, Vikram R Rao, Jurriaan M Peters, Patricia Penovich, James Wheless, R Edward Hogan, Charles S Davis, Enrique Carrazana, Adrian L Rabinowicz

2020-Current year OA Pubs

For acute treatment of seizure clusters in patients with epilepsy, intranasal administration of acute seizure therapies has been shown to provide accessibility and ease of use to care partners as well as the potential for self-administration by patients. Diazepam nasal spray (Valtoco®) was approved by the US Food and Drug Administration for acute treatment of intermittent, stereotypic episodes of frequent seizure activity (ie, seizure clusters, acute repetitive seizures) in patients with epilepsy aged ≥6 years. Self-administration consistent with the prescribing information is feasible and was reported by a subgroup of patients (n = 27 of 163) in a long-term phase …


Early-Phase Insulin Secretion During Mixed-Meal Tolerance Testing Predicts Β-Cell Function And Secretory Capacity In Cystic Fibrosis, Saba Sheikh, Darko Stefanovski, Marissa J Kilberg, Denis Hadjiliadis, Ronald C Rubenstein, Michael R Rickels, Andrea Kelly Jan 2024

Early-Phase Insulin Secretion During Mixed-Meal Tolerance Testing Predicts Β-Cell Function And Secretory Capacity In Cystic Fibrosis, Saba Sheikh, Darko Stefanovski, Marissa J Kilberg, Denis Hadjiliadis, Ronald C Rubenstein, Michael R Rickels, Andrea Kelly

2020-Current year OA Pubs

UNLABELLED: Insulin secretion within 30 minutes of nutrient ingestion is reduced in people with cystic fibrosis (PwCF) and pancreatic insufficiency and declines with worsening glucose tolerance. The glucose potentiated arginine (GPA) test is validated for quantifying β-cell secretory capacity as an estimate of functional β-cell mass but requires technical expertise and is burdensome. This study sought to compare insulin secretion during mixed-meal tolerance testing (MMTT) to GPA-derived parameters in PwCF.

METHODS: Secondary data analysis of CF-focused prospective studies was performed in PwCF categorized as 1) pancreatic insufficient [PI-CF] or 2) pancreatic sufficient [PS-CF] and in 3) non-CF controls. MMTT: insulin …


Mapping Of A Hybrid Insulin Peptide In The Inflamed Islet Β-Cells From Nod Mice, Janet M Wenzlau, Orion J Peterson, Anthony N Vomund, James E Dilisio, Anita Hohenstein, Kathryn Haskins, Xiaoxiao Wan Jan 2024

Mapping Of A Hybrid Insulin Peptide In The Inflamed Islet Β-Cells From Nod Mice, Janet M Wenzlau, Orion J Peterson, Anthony N Vomund, James E Dilisio, Anita Hohenstein, Kathryn Haskins, Xiaoxiao Wan

2020-Current year OA Pubs

There is accumulating evidence that pathogenic T cells in T1D recognize epitopes formed by post-translational modifications of β-cell antigens, including hybrid insulin peptides (HIPs). The ligands for several CD4 T-cell clones derived from the NOD mouse are HIPs composed of a fragment of proinsulin joined to peptides from endogenous β-cell granule proteins. The diabetogenic T-cell clone BDC-6.9 reacts to a fragment of C-peptide fused to a cleavage product of pro-islet amyloid polypeptide (6.9HIP). In this study, we used a monoclonal antibody (MAb) to the 6.9HIP to determine when and where HIP antigens are present in NOD islets during disease progression …


Referent Data For Investigations Of Upper Limb Accelerometry: Harmonized Data From Three Cohorts Of Typically-Developing Children, Catherine E Lang, Catherine R Hoyt, Jeffrey D Konrad, Kayla R Bell, Natasha Marrus, Marghuretta D Bland, Keith R Lohse, Allison E Miller Jan 2024

Referent Data For Investigations Of Upper Limb Accelerometry: Harmonized Data From Three Cohorts Of Typically-Developing Children, Catherine E Lang, Catherine R Hoyt, Jeffrey D Konrad, Kayla R Bell, Natasha Marrus, Marghuretta D Bland, Keith R Lohse, Allison E Miller

2020-Current year OA Pubs

AIM: The rise of wearable sensing technology shows promise for addressing the challenges of measuring motor behavior in pediatric populations. The current pediatric wearable sensing literature is highly variable with respect to the number of sensors used, sensor placement, wearing time, and how data extracted from the sensors are analyzed. Many studies derive conceptually similar variables via different calculation methods, making it hard to compare across studies and clinical populations. In hopes of moving the field forward, this report provides referent upper limb wearable sensor data from accelerometers on 25 variables in typically-developing children, ages 3-17 years.

METHODS: This is …


Transcriptional Precision In Photoreceptor Development And Diseases - Lessons From 25 Years Of Crx Research, Yiqiao Zheng, Shiming Chen Jan 2024

Transcriptional Precision In Photoreceptor Development And Diseases - Lessons From 25 Years Of Crx Research, Yiqiao Zheng, Shiming Chen

2020-Current year OA Pubs

The vertebrate retina is made up of six specialized neuronal cell types and one glia that are generated from a common retinal progenitor. The development of these distinct cell types is programmed by transcription factors that regulate the expression of specific genes essential for cell fate specification and differentiation. Because of the complex nature of transcriptional regulation, understanding transcription factor functions in development and disease is challenging. Research on the


Negligence In Biomedical Research: An Anti-Racist Approach For Substance Use Researchers, Jonathan Lehman, Danniella Balangoy, Angie P Mejia, Carlos Cardenas-Iniguez, Scott Marek, Anita C Randolph Jan 2024

Negligence In Biomedical Research: An Anti-Racist Approach For Substance Use Researchers, Jonathan Lehman, Danniella Balangoy, Angie P Mejia, Carlos Cardenas-Iniguez, Scott Marek, Anita C Randolph

2020-Current year OA Pubs

Racism is embedded in the fabric of society at structural, disciplinary, hegemonic, and interpersonal levels, working as a mechanism that drives health disparities. In particular, stigmatized views of substance use get entangled with racialization, serving as a tool to uphold oppressive systems. While national health institutions have made commitments to dismantle these systems in the United States, anti-racism has not been integrated into biomedical research practice. The ways in which substance use researchers use and interpret race data-without engaging in structural racism as a mechanism of health inequity-can only be described as inadequate. Drawing upon concepts from the Public Health …


Arid1a Loss Is Associated With Increased Nrf2 Signaling In Human Head And Neck Squamous Cell Carcinomas, Vinh Nguyen, Travis P. Schrank, Michael B. Major, Bernard E. Weissman Jan 2024

Arid1a Loss Is Associated With Increased Nrf2 Signaling In Human Head And Neck Squamous Cell Carcinomas, Vinh Nguyen, Travis P. Schrank, Michael B. Major, Bernard E. Weissman

2020-Current year OA Pubs

Prior to the next generation sequencing and characterization of the tumor genome landscape, mutations in the SWI/SNF chromatin remodeling complex and the KEAP1-NRF2 signaling pathway were underappreciated. While these two classes of mutations appeared to independently contribute to tumor development, recent reports have demonstrated a mechanistic link between these two regulatory mechanisms in specific cancer types and cell models. In this work, we expand upon these data by exploring the relationship between mutations in BAF and PBAF subunits of the SWI/SNF complex and activation of NRF2 signal transduction across many cancer types. ARID1A/B mutations were strongly associated with NRF2 transcriptional …


Reference Ranges For Left Modified Myocardial Performance Index: Systematic Review And Meta-Analysis, Katherine H Bligard, Michelle Doering, Shay Porat, Joshua I Rosenbloom Jan 2024

Reference Ranges For Left Modified Myocardial Performance Index: Systematic Review And Meta-Analysis, Katherine H Bligard, Michelle Doering, Shay Porat, Joshua I Rosenbloom

2020-Current year OA Pubs

INTRODUCTION: The modified myocardial performance index (mod-MPI) is a noninvasive Doppler-derived metric used to evaluate fetal cardiac function. However, the reference ranges for mod-MPI in normal fetuses are not clearly defined, which limits the use of this technology in fetuses with potential cardiac compromise. Thus, we aimed to perform a systematic review and meta-analysis of published mod-MPI reference ranges across gestation.

METHODS: The published literature was systematically searched, and all published articles in any language that provided values for the left ventricular mod-MPI obtained in low-risk, singleton fetuses were considered eligible for further review. All retrieved titles and abstracts were …


Efficacy And Safety Of Bempedoic Acid In Patients With Heterozygous Familial Hypercholesterolemia: Analysis Of Pooled Patient-Level Data From Phase 3 Clinical Trials, P Barton Duell, Maciej Banach, Alberico L Catapano, Ulrich Laufs, G B John Mancini, Kausik K Ray, Christine Broestl, Yang Zhang, Lei Lei, Anne C Goldberg Jan 2024

Efficacy And Safety Of Bempedoic Acid In Patients With Heterozygous Familial Hypercholesterolemia: Analysis Of Pooled Patient-Level Data From Phase 3 Clinical Trials, P Barton Duell, Maciej Banach, Alberico L Catapano, Ulrich Laufs, G B John Mancini, Kausik K Ray, Christine Broestl, Yang Zhang, Lei Lei, Anne C Goldberg

2020-Current year OA Pubs

BACKGROUND: Patients with heterozygous familial hypercholesterolemia (HeFH) often cannot reach guideline-recommended low-density lipoprotein cholesterol (LDL-C) goals despite multidrug therapy.

OBJECTIVE: To evaluate the efficacy and safety of bempedoic acid as an add-on therapy for lowering LDL-C in patients with HeFH.

METHODS: Pooled data from two 52-week phase 3 clinical trials of patients with atherosclerotic cardiovascular disease and/or HeFH receiving maximally tolerated statin therapy (randomized 2:1 to bempedoic acid or placebo) were analyzed by HeFH status. Endpoints included changes from baseline to week 12 (and up to week 52) in LDL-C and other lipid parameters, achievement of LDL-C goals, and safety. …


Lung Infection With Classical Klebsiella Pneumoniae Strains Establishes Robust Macrophage-Dependent Protection Against Heterologous Reinfection, Joseph J Mackel, Casey L G Mick, Emily Guo, David A Rosen Jan 2024

Lung Infection With Classical Klebsiella Pneumoniae Strains Establishes Robust Macrophage-Dependent Protection Against Heterologous Reinfection, Joseph J Mackel, Casey L G Mick, Emily Guo, David A Rosen

2020-Current year OA Pubs

At present, there is no approved vaccine for prevention of infection by the opportunistic bacterium Klebsiella pneumoniae (Kp); success in treating these infections is increasingly challenged by the spread of antibiotic resistance. Preclinical investigation of adaptive immunity elicited by lung infection with live classical Kp may reveal host mechanisms of protection against this pathogen. Here, we utilize multiple virulent classical Kp strains to demonstrate that following lung infection, surviving wild-type mice develop protective immunity against both homologous and heterologous (heterotypic) reinfection. For Kp strains with low capacity to disseminate from the lung, this immunity is B-cell-independent. We further demonstrate that …


A Novel Crispr/Cas9-Mediated Mouse Model Of Colon Carcinogenesis, Hajime Kashima, Anthony Fischer, Daniel A Veronese-Paniagua, Vered A Gazit, Changqing Ma, Yan Yan, Marc S Levin, Blair B Madison, Deborah C Rubin Jan 2024

A Novel Crispr/Cas9-Mediated Mouse Model Of Colon Carcinogenesis, Hajime Kashima, Anthony Fischer, Daniel A Veronese-Paniagua, Vered A Gazit, Changqing Ma, Yan Yan, Marc S Levin, Blair B Madison, Deborah C Rubin

2020-Current year OA Pubs

BACKGROUND & AIMS: Human sporadic colorectal cancer (CRC) results from a multistep pathway with sequential acquisition of specific genetic mutations in the colorectal epithelium. Modeling CRC in vivo is critical for understanding the tumor microenvironment. To accurately recapitulate human CRC pathogenesis, mouse models must include these multi-step genetic abnormalities. The aim of this study was to generate a sporadic CRC model that more closely mimics this multi-step process and to use this model to study the role of a novel Let7 target PLAGL2 in CRC pathogenesis.

METHODS: We generated a CRISPR/Cas9 somatic mutagenesis mouse model that is inducible and multiplexed …


Evolution Of Proton Radiation Therapy Brainstem Constraints On The Pediatric Proton/Photon Consortium Registry, Dora Correia, Stephanie M Perkins, Et Al. Jan 2024

Evolution Of Proton Radiation Therapy Brainstem Constraints On The Pediatric Proton/Photon Consortium Registry, Dora Correia, Stephanie M Perkins, Et Al.

2020-Current year OA Pubs

PURPOSE: Increasing concern that brainstem toxicity incidence after proton radiation therapy might be higher than with photons led to a 2014 University of Florida (UF) landmark paper identifying its risk factors and proposing more conservative dose constraints. We evaluated how practice patterns changed among the Pediatric Proton/Photon Consortium Registry (PPCR).

MATERIAL AND METHODS: This prospective multicenter cohort study gathered data from patients under the age of 22 years enrolled on the PPCR, treated between 2002 and 2019 for primary posterior fossa brain tumors. After standardizing brainstem contours, we garnered dosimetry data and correlated those meeting the 2014 proton-specific brainstem constraint …


Ct-Based Online Adaptive Radiotherapy Improves Target Coverage And Organ At Risk (Oar) Avoidance In Stereotactic Body Radiation Therapy (Sbrt) For Prostate Cancer, Michael Waters, Alex Price, Eric Laugeman, Lauren Henke, Geoff Hugo, Hayley Stowe, Neal Andruska, Randall Brenneman, Yao Hao, Olga Green, Clifford Robinson, Hiram Gay, Jeff Michalski, Brian C Baumann Jan 2024

Ct-Based Online Adaptive Radiotherapy Improves Target Coverage And Organ At Risk (Oar) Avoidance In Stereotactic Body Radiation Therapy (Sbrt) For Prostate Cancer, Michael Waters, Alex Price, Eric Laugeman, Lauren Henke, Geoff Hugo, Hayley Stowe, Neal Andruska, Randall Brenneman, Yao Hao, Olga Green, Clifford Robinson, Hiram Gay, Jeff Michalski, Brian C Baumann

2020-Current year OA Pubs

INTRODUCTION: Stereotactic body radiation therapy (SBRT) is an emerging treatment modality for clinically localized prostate cancer (PCa). Online daily adaptive radiotherapy (ART) could potentially improve the therapeutic ratio of prostate SBRT by accounting for inter-fraction variation in target and OAR volumes. To our knowledge, no group has evaluated the clinical utility of a novel AI-augmented CT-based ART system for prostate SBRT. In this study we hypothesized that adaptive prostate SBRT plans would result in improved target coverage and lower dose to OARs in comparison to unadapted treatment plans.

METHODS: Seven patients with favorable intermediate to oligometastatic PCa treated with 5-fx …


Intratumoral T-Cell Receptor Repertoire Composition Predicts Overall Survival In Patients With Pancreatic Ductal Adenocarcinoma, Vikram S Pothuri, Graham D Hogg, Leah Conant, Nicholas Borcherding, C Alston James, Jacqueline Mudd, Greg Williams, Yongwoo David Seo, William G Hawkins, Venu G Pillarisetty, David G Denardo, Ryan C Fields Jan 2024

Intratumoral T-Cell Receptor Repertoire Composition Predicts Overall Survival In Patients With Pancreatic Ductal Adenocarcinoma, Vikram S Pothuri, Graham D Hogg, Leah Conant, Nicholas Borcherding, C Alston James, Jacqueline Mudd, Greg Williams, Yongwoo David Seo, William G Hawkins, Venu G Pillarisetty, David G Denardo, Ryan C Fields

2020-Current year OA Pubs

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy that is refractory to immune checkpoint inhibitor therapy. However, intratumoral T-cell infiltration correlates with improved overall survival (OS). Herein, we characterized the diversity and antigen specificity of the PDAC T-cell receptor (TCR) repertoire to identify novel immune-relevant biomarkers. Demographic, clinical, and TCR-beta sequencing data were collated from 353 patients across three cohorts that underwent surgical resection for PDAC. TCR diversity was calculated using Shannon Wiener index, Inverse Simpson index, and "True entropy." Patients were clustered by shared repertoire specificity. TCRs predictive of OS were identified and their associated transcriptional states were characterized …


Delayed Macrophage Targeting By Clodronate Liposomes Worsens The Progression Of Cytokine Storm Syndrome, Kunjan Khanna, Emily Eul, Hui Yan, Roberta Faccio Jan 2024

Delayed Macrophage Targeting By Clodronate Liposomes Worsens The Progression Of Cytokine Storm Syndrome, Kunjan Khanna, Emily Eul, Hui Yan, Roberta Faccio

2020-Current year OA Pubs

Excessive macrophage activation and production of pro-inflammatory cytokines are hallmarks of the Cytokine Storm Syndrome (CSS), a lethal condition triggered by sepsis, autoimmune disorders, and cancer immunotherapies. While depletion of macrophages at disease onset protects from lethality in an infection-induced CSS murine model, patients are rarely diagnosed early, hence the need to characterize macrophage populations during CSS progression and assess the therapeutic implications of macrophage targeting after disease onset. In this study, we identified MHCII


Translatability Of Findings From Cynomolgus Monkey To Human Suggests A Mechanistic Role For Il-21 In Promoting Immunogenicity To An Anti-Pd-1/Il-21 Mutein Fusion Protein, Mark A Kroenke, Ramaswamy Govindan, Et Al. Jan 2024

Translatability Of Findings From Cynomolgus Monkey To Human Suggests A Mechanistic Role For Il-21 In Promoting Immunogenicity To An Anti-Pd-1/Il-21 Mutein Fusion Protein, Mark A Kroenke, Ramaswamy Govindan, Et Al.

2020-Current year OA Pubs

AMG 256 is a bi-specific, heteroimmunoglobulin molecule with an anti-PD-1 antibody domain and a single IL-21 mutein domain on the C-terminus. Nonclinical studies in cynomolgus monkeys revealed that AMG 256 administration led to the development of immunogenicity-mediated responses and indicated that the IL-21 mutein domain of AMG 256 could enhance the anti-drug antibody response directed toward the monoclonal antibody domain. Anti-AMG 256 IgE were also observed in cynomolgus monkeys. A first-in-human (FIH) study in patients with advanced solid tumors was designed with these risks in mind. AMG 256 elicited ADA in 28 of 33 subjects (84.8%). However, ADA responses were …


Phosphorylation Regulates Viral Biomolecular Condensates To Promote Infectious Progeny Production, Nicholas Grams, Matthew Charman, Edwin Halko, Richard Lauman, Benjamin A Garcia, Matthew D Weitzman Jan 2024

Phosphorylation Regulates Viral Biomolecular Condensates To Promote Infectious Progeny Production, Nicholas Grams, Matthew Charman, Edwin Halko, Richard Lauman, Benjamin A Garcia, Matthew D Weitzman

2020-Current year OA Pubs

Biomolecular condensates (BMCs) play important roles in diverse biological processes. Many viruses form BMCs which have been implicated in various functions critical for the productive infection of host cells. The adenovirus L1-52/55 kilodalton protein (52K) was recently shown to form viral BMCs that coordinate viral genome packaging and capsid assembly. Although critical for packaging, we do not know how viral condensates are regulated during adenovirus infection. Here we show that phosphorylation of serine residues 28 and 75 within the N-terminal intrinsically disordered region of 52K modulates viral condensates in vitro and in cells, promoting liquid-like properties. Furthermore, we demonstrate that …


Neurosteroids: Mechanistic Considerations And Clinical Prospects, Jamie L Maguire, Steven Mennerick Jan 2024

Neurosteroids: Mechanistic Considerations And Clinical Prospects, Jamie L Maguire, Steven Mennerick

2020-Current year OA Pubs

Like other classes of treatments described in this issue's section, neuroactive steroids have been studied for decades but have risen as a new class of rapid-acting, durable antidepressants with a distinct mechanism of action from previous antidepressant treatments and from other compounds covered in this issue. Neuroactive steroids are natural derivatives of progesterone but are proving effective as exogenous treatments. The best understood mechanism is that of positive allosteric modulation of GABA


Surviving Septic Patients Endotyped With A Functional Assay Demonstrate Active Immune Responses, Adam D Price, Andrew H Walton, Sydney Miles, Richard S Hotchkiss, Et Al. Jan 2024

Surviving Septic Patients Endotyped With A Functional Assay Demonstrate Active Immune Responses, Adam D Price, Andrew H Walton, Sydney Miles, Richard S Hotchkiss, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Sepsis is a complex clinical syndrome characterized by a heterogenous host immune response. Historically, static protein and transcriptomic metrics have been employed to describe the underlying biology. Here, we tested the hypothesis that

METHODS: This prospective, observational study of patient samples collected from the SPIES consortium included patients at five health systems enrolled over 17 months, with 46 healthy control patients, 68 ICU patients without sepsis, and 107 ICU patients with sepsis. Whole blood was collected on day 1, 4, and 7 of ICU admission. Outcomes included in-hospital and 180-day mortality and non-favorable discharge disposition defined by skilled nursing …


The Potential Impact Of Exercise On Affect And Neuroinflammation In Older Adults Living With Fibromyalgia: A Scoping Review, Taylor L Taylor, Fitzgerald Dodds, Mckenna Tharpe, Emily L Zumbro, Michael Hankes, Raymond Jones, Deanna Rumble, Lisa Antoine, Kristen Allen-Watts, Andrew Sims, Reshu Chandra, Burel R Goodin, Jarred Younger, Thomas W Buford Jan 2024

The Potential Impact Of Exercise On Affect And Neuroinflammation In Older Adults Living With Fibromyalgia: A Scoping Review, Taylor L Taylor, Fitzgerald Dodds, Mckenna Tharpe, Emily L Zumbro, Michael Hankes, Raymond Jones, Deanna Rumble, Lisa Antoine, Kristen Allen-Watts, Andrew Sims, Reshu Chandra, Burel R Goodin, Jarred Younger, Thomas W Buford

2020-Current year OA Pubs

INTRODUCTION: Fibromyalgia (FM) is a widespread chronic pain condition with prevalence increasing in older adults. Older adults living with FM experience longer pain symptom durations that can negatively impact their quality of life. Affect and neuroinflammation are potential factors that can exacerbate pain symptoms. Exercise is a recommended intervention to manage pain symptoms; however, adherence limitations persist. Drawing on the Biopsychosocial Framework of Chronic Pain, this scoping review explores how exercise impacts factors related to neuroinflammation and affect, and how these factors contribute to exercise adherence in older adults living with FM.

METHODS: We conducted a scoping search of articles …


Non-Invasive Auricular Vagus Nerve Stimulation For Subarachnoid Hemorrhage (Navsah): Protocol For A Prospective, Triple-Blinded, Randomized Controlled Trial, Anna Huguenard, Gansheng Tan, Gabrielle Johnson, Markus Adamek, Andrew Coxon, Terrance Kummer, Joshua Osbun, Ananth Vellimana, David Limbrick, Gregory Zipfel, Peter Brunner, Eric Leuthardt Jan 2024

Non-Invasive Auricular Vagus Nerve Stimulation For Subarachnoid Hemorrhage (Navsah): Protocol For A Prospective, Triple-Blinded, Randomized Controlled Trial, Anna Huguenard, Gansheng Tan, Gabrielle Johnson, Markus Adamek, Andrew Coxon, Terrance Kummer, Joshua Osbun, Ananth Vellimana, David Limbrick, Gregory Zipfel, Peter Brunner, Eric Leuthardt

2020-Current year OA Pubs

BACKGROUND: Inflammation has been implicated in driving the morbidity associated with subarachnoid hemorrhage (SAH). Despite understanding the important role of inflammation in morbidity following SAH, there is no current effective way to modulate this deleterious response. There is a critical need for a novel approach to immunomodulation that can be safely, rapidly, and effectively deployed in SAH patients. Vagus nerve stimulation (VNS) provides a non-pharmacologic approach to immunomodulation, with prior studies demonstrating VNS can reduce systemic inflammatory markers, and VNS has had early success treating inflammatory conditions such as arthritis, sepsis, and inflammatory bowel diseases. The aim of the Non-invasive …


Chemotherapy-Induced Neutropenia Management In A Patient With Metastatic Breast Cancer And Shwachman-Diamond Syndrome (Sds): A Case Report, Renee Morecroft, Constantine N. Logothetics, Stefan P. Tarnawsky, Andrew A. Davis Jan 2024

Chemotherapy-Induced Neutropenia Management In A Patient With Metastatic Breast Cancer And Shwachman-Diamond Syndrome (Sds): A Case Report, Renee Morecroft, Constantine N. Logothetics, Stefan P. Tarnawsky, Andrew A. Davis

2020-Current year OA Pubs

BACKGROUND: Shwachman-Diamond syndrome (SDS) is a rare inherited bone marrow failure syndrome associated with cytopenia and the development of hematologic malignancies. Solid tumor occurrence is rare and, historically, these patients have had poor outcomes due to chemotherapy-induced myelosuppression and increased susceptibility to infections. We report the administration of cytotoxic systemic therapy with granulocyte colony-stimulating factor (G-CSF) in a patient with SDS and metastatic breast cancer. We describe the risk-benefit profile of utilizing G-CSF in managing this patient to improve her therapeutic outcome and review the prior literature.

CASE DESCRIPTION: A 41-year-old Caucasian female with SDS developed stage IV triple-positive [estrogen …