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Il-17 Producing Lymphocytes Cause Dry Eye And Corneal Disease With Aging In Rxrα Mutant Mouse, Jehan Alam, Ghasem Yazdanpanah, Rinki Ratnapriya, Nicholas Borcherding, Cintia S De Paiva, Dequan Li, Rodrigo Guimaraes De Souza, Zhiyuan Yu, Stephen C Pflugfelder Jan 2022

Il-17 Producing Lymphocytes Cause Dry Eye And Corneal Disease With Aging In Rxrα Mutant Mouse, Jehan Alam, Ghasem Yazdanpanah, Rinki Ratnapriya, Nicholas Borcherding, Cintia S De Paiva, Dequan Li, Rodrigo Guimaraes De Souza, Zhiyuan Yu, Stephen C Pflugfelder

2020-Current year OA Pubs

PURPOSE: To investigate IL-17 related mechanisms for developing dry eye disease in the Pinkie mouse strain with a loss of function RXRα mutation.

METHODS: Measures of dry eye disease were assessed in the cornea and conjunctiva. Expression profiling was performed by single-cell RNA sequencing (scRNA-seq) to compare gene expression in conjunctival immune cells. Conjunctival immune cells were immunophenotyped by flow cytometry and confocal microscopy. The activity of RXRα ligand 9-cis retinoic acid (RA) was evaluated in cultured monocytes and γδ T cells.

RESULTS: Compared to wild type (WT) C57BL/6, Pinkie has increased signs of dry eye disease, including decreased tear …


Gardnerella Exposures Alter Bladder Gene Expression And Augment Uropathogenic Escherichia Coli Urinary Tract Infection In Mice, Nicole M Gilbert, Valerie P O'Brien, Chevaughn Waller, Ekatherina Batourina, Cathy Lee Mendelsohn, Amanda L Lewis Jan 2022

Gardnerella Exposures Alter Bladder Gene Expression And Augment Uropathogenic Escherichia Coli Urinary Tract Infection In Mice, Nicole M Gilbert, Valerie P O'Brien, Chevaughn Waller, Ekatherina Batourina, Cathy Lee Mendelsohn, Amanda L Lewis

2020-Current year OA Pubs

The anaerobic actinobacterium


The Chasm In Percutaneous Coronary Intervention And In-Hospital Mortality Rates Among Acute Myocardial Infarction Patients In Rural And Urban Hospitals In China: A Mediation Analysis, Miao Cai, Echu Liu, Peng Bai, Nan Zhang, Siyu Wang, Wei Li, Hualiang Lin, Xiaojun Lin Jan 2022

The Chasm In Percutaneous Coronary Intervention And In-Hospital Mortality Rates Among Acute Myocardial Infarction Patients In Rural And Urban Hospitals In China: A Mediation Analysis, Miao Cai, Echu Liu, Peng Bai, Nan Zhang, Siyu Wang, Wei Li, Hualiang Lin, Xiaojun Lin

2020-Current year OA Pubs

No abstract provided.


Elevated Axonal Protein Markers Following Repetitive Blast Exposure In Military Personnel, Rany Vorn, Rosanne Naunheim, Chen Lai, Chelsea Wagner, Jessica M Gill Jan 2022

Elevated Axonal Protein Markers Following Repetitive Blast Exposure In Military Personnel, Rany Vorn, Rosanne Naunheim, Chen Lai, Chelsea Wagner, Jessica M Gill

2020-Current year OA Pubs

Blast exposures that occur during training are common in military personnel; however, the biomarkers that relate to these subtle injuries is not well understood. Therefore, the purpose of this study is to identify the acute biomarkers related to blast injury in a cohort of military personnel exposure to blast-related training. Thirty-four military personnel who participated in the training program were included in this study. Blood samples were collected before and after repetitive blast-related training on days 2 (


Glial Dysfunction And Its Contribution To The Pathogenesis Of The Neuronal Ceroid Lipofuscinoses, Keigo Takahashi, Hemanth R Nelvagal, Jenny Lange, Jonathan D Cooper Jan 2022

Glial Dysfunction And Its Contribution To The Pathogenesis Of The Neuronal Ceroid Lipofuscinoses, Keigo Takahashi, Hemanth R Nelvagal, Jenny Lange, Jonathan D Cooper

2020-Current year OA Pubs

While significant efforts have been made in developing pre-clinical treatments for the neuronal ceroid lipofuscinoses (NCLs), many challenges still remain to bring children with NCLs a cure. Devising effective therapeutic strategies for the NCLs will require a better understanding of pathophysiology, but little is known about the mechanisms by which loss of lysosomal proteins causes such devastating neurodegeneration. Research into glial cells including astrocytes, microglia, and oligodendrocytes have revealed many of their critical functions in brain homeostasis and potential contributions to neurodegenerative diseases. Genetically modified mouse models have served as a useful platform to define the disease progression in the …


Prospective Biomarker Study In Newly Diagnosed Glioblastoma: Cyto-C Clinical Trial, Corinne E Griguer, Milan G Chheda, Et Al. Jan 2022

Prospective Biomarker Study In Newly Diagnosed Glioblastoma: Cyto-C Clinical Trial, Corinne E Griguer, Milan G Chheda, Et Al.

2020-Current year OA Pubs

BACKGROUND: Glioblastoma (GBM) has a 5-year survival rate of 3%-5%. GBM treatment includes maximal resection followed by radiotherapy with concomitant and adjuvant temozolomide (TMZ). Cytochrome C oxidase (CcO) is a mitochondrial enzyme involved in the mechanism of resistance to TMZ. In a prior retrospective trial, CcO activity in GBMs inversely correlated with clinical outcome. The current Cyto-C study was designed to prospectively evaluate and validate the prognostic value of tumor CcO activity in patients with newly diagnosed primary GBM, and compared to the known prognostic value of

METHODS: This multi-institutional, blinded, prospective biomarker study enrolled 152 patients with newly diagnosed …


Multivariate Analysis Of Associations Between Clinical Sequencing And Outcome In Glioblastoma, Peter H Yang, Yu Tao, Jingqin Luo, Mounica Paturu, Hsiang-Chih Lu, Shakti Ramkissoon, Jonathan W Heusel, Eric C Leuthardt, Michael R Chicoine, Joshua L Dowling, Gavin P Dunn, Eric Duncavage, Sonika Dahiya, Arindam R Chattherjee, Albert H Kim Jan 2022

Multivariate Analysis Of Associations Between Clinical Sequencing And Outcome In Glioblastoma, Peter H Yang, Yu Tao, Jingqin Luo, Mounica Paturu, Hsiang-Chih Lu, Shakti Ramkissoon, Jonathan W Heusel, Eric C Leuthardt, Michael R Chicoine, Joshua L Dowling, Gavin P Dunn, Eric Duncavage, Sonika Dahiya, Arindam R Chattherjee, Albert H Kim

2020-Current year OA Pubs

BACKGROUND: Many factors impact survival in patients with glioblastoma, including age, Karnofsky Performance Status, postoperative chemoradiation,

METHODS: We utilized a widely available diagnostic platform (FoundationOne CDx) to perform high-throughput next-generation sequencing on 185 patients with newly diagnosed glioblastoma in our tertiary care center. We performed multivariate analysis to control for clinical parameters with known impact on survival to elucidate the independent prognostic value of prevalent mutant genes and the independent impact of gross total resection.

RESULTS: When controlling for factors with known prognostic significance including

CONCLUSIONS: This study verifies the independent prognostic value of several mutant genes in glioblastoma. Six …


Characterization Of The Genomic And Immunologic Diversity Of Malignant Brain Tumors Through Multisector Analysis, Maximilian O Schaettler, Megan M Richters, Anthony Z Wang, Zachary L Skidmore, Bryan Fisk, Albert H Kim, Michael R Chicoine, Joshua W Osbun, Eric C Leuthardt, Joshua L Dowling, Gregory J Zipfel, Ralph G Dacey, Hsiang-Chih Lu, Tanner M Johanns, Obi L Griffith, Malachi Griffith, Gavin P Dunn, Et Al. Jan 2022

Characterization Of The Genomic And Immunologic Diversity Of Malignant Brain Tumors Through Multisector Analysis, Maximilian O Schaettler, Megan M Richters, Anthony Z Wang, Zachary L Skidmore, Bryan Fisk, Albert H Kim, Michael R Chicoine, Joshua W Osbun, Eric C Leuthardt, Joshua L Dowling, Gregory J Zipfel, Ralph G Dacey, Hsiang-Chih Lu, Tanner M Johanns, Obi L Griffith, Malachi Griffith, Gavin P Dunn, Et Al.

2020-Current year OA Pubs

Despite some success in secondary brain metastases, targeted or immune-based therapies have shown limited efficacy against primary brain malignancies such as glioblastoma (GBM). Although the intratumoral heterogeneity of GBM is implicated in treatment resistance, it remains unclear whether this diversity is observed within brain metastases and to what extent cancer cell-intrinsic heterogeneity sculpts the local immune microenvironment. Here, we profiled the immunogenomic state of 93 spatially distinct regions from 30 malignant brain tumors through whole-exome, RNA, and T-cell receptor sequencing. Our analyses identified differences between primary and secondary malignancies, with gliomas displaying more spatial heterogeneity at the genomic and neoantigen …


Genetic And Transcriptional Contributions To Relapse In Normal Karyotype Acute Myeloid Leukemia, Allegra A Petti, Saad M Khan, Ziheng Xu, Nichole Helton, Catrina C Fronick, Robert Fulton, Sai M Ramakrishnan, Sridhar Nonavinkere Srivatsan, Sharon E Heath, Peter Westervelt, Jacqueline E Payton, Matthew J Walter, Daniel C Link, John Dipersio, Christopher Miller, Timothy J Ley Jan 2022

Genetic And Transcriptional Contributions To Relapse In Normal Karyotype Acute Myeloid Leukemia, Allegra A Petti, Saad M Khan, Ziheng Xu, Nichole Helton, Catrina C Fronick, Robert Fulton, Sai M Ramakrishnan, Sridhar Nonavinkere Srivatsan, Sharon E Heath, Peter Westervelt, Jacqueline E Payton, Matthew J Walter, Daniel C Link, John Dipersio, Christopher Miller, Timothy J Ley

2020-Current year OA Pubs

To better understand clonal and transcriptional adaptations after relapse in patients with acute myeloid leukemia (AML), we collected presentation and relapse samples from six normal karyotype AML cases. We performed enhanced whole-genome sequencing to characterize clonal evolution, and deep-coverage single-cell RNA sequencing on the same samples, which yielded 142,642 high-quality cells for analysis. Identifying expressed mutations in individual cells enabled us to discriminate between normal and AML cells, to identify coordinated changes in the genome and transcriptome, and to identify subclone-specific cell states. We quantified the coevolution of genetic and transcriptional heterogeneity during AML progression, and found that transcriptional changes …


Combination Tigit/Pd-1 Blockade Enhances The Efficacy Of Neoantigen Vaccines In A Model Of Pancreatic Cancer, Hui Peng, Lijin Li, Chong Zuo, Michael Y Chen, Xiuli Zhang, Nancy B Myers, Graham D Hogg, David G Denardo, S Peter Goedegebuure, William G Hawkins, William E Gillanders Jan 2022

Combination Tigit/Pd-1 Blockade Enhances The Efficacy Of Neoantigen Vaccines In A Model Of Pancreatic Cancer, Hui Peng, Lijin Li, Chong Zuo, Michael Y Chen, Xiuli Zhang, Nancy B Myers, Graham D Hogg, David G Denardo, S Peter Goedegebuure, William G Hawkins, William E Gillanders

2020-Current year OA Pubs

BACKGROUND: Cancer neoantigens are important targets of cancer immunotherapy and neoantigen vaccines are currently in development in pancreatic ductal adenocarcinoma (PDAC) and other cancer types. Immune regulatory mechanisms in pancreatic cancer may limit the efficacy of neoantigen vaccines. Targeting immune checkpoint signaling pathways in PDAC may improve the efficacy of neoantigen vaccines.

METHODS: We used KPC4580P, an established model of PDAC, to test whether neoantigen vaccines can generate therapeutic efficacy against PDAC. We focused on two immunogenic neoantigens associated with genetic alterations in the CAR12 and CDK12 genes. We tested a neoantigen vaccine comprised of two 20-mer synthetic long peptides …


Socioecological Model-Based Design And Implementation Principles Of Lower Limb Preservation Programs As Partners For Limb-Loss Rehabilitation Programs- A Mini-Review, Vipul Khetarpaul, John P Kirby, Patrick Geraghty, John Felder, Prateek Grover Jan 2022

Socioecological Model-Based Design And Implementation Principles Of Lower Limb Preservation Programs As Partners For Limb-Loss Rehabilitation Programs- A Mini-Review, Vipul Khetarpaul, John P Kirby, Patrick Geraghty, John Felder, Prateek Grover

2020-Current year OA Pubs

People with lower limb loss, especially of dysvascular etiology, are at substantial risk for both ipsilateral and contralateral reamputation. Additionally, while not as well documented for reamputation, there is recognition that amputation incidence is influenced by not only sociodemographic factors such as sex, race, socioeconomic status, but also by system factors such as service access. A systems strategy to address this disparity within the field of limb-loss rehabilitation is for Limb-loss Rehabilitation Programs (LRP) to partner with medical specialists, mental health professionals, and Limb Preservation Programs (LPP) to provide comprehensive limb care. While LPPs exist around the nation, design principles …


Mechanisms Of Persistent Atrial Fibrillation And Recurrences Within 12 Months Post-Ablation: Non-Invasive Mapping With Electrocardiographic Imaging, Ramya Vijayakumar, Mitchell N Faddis, Phillip S Cuculich, Yoram Rudy Jan 2022

Mechanisms Of Persistent Atrial Fibrillation And Recurrences Within 12 Months Post-Ablation: Non-Invasive Mapping With Electrocardiographic Imaging, Ramya Vijayakumar, Mitchell N Faddis, Phillip S Cuculich, Yoram Rudy

2020-Current year OA Pubs

INTRODUCTION: Catheter ablation of persistent AF has not been consistently successful in terminating AF or preventing arrhythmia recurrences. Non-invasive Electrocardiographic Imaging (ECGI) can help to understand recurrences by mapping the mechanisms of pre-ablation AF and comparing them with the patterns of recurrent arrhythmias in the same patient.

METHODS: Seventeen persistent AF patients underwent ECGI before their first catheter ablation. Time-domain activation maps and phase progression maps were obtained on the bi-atrial epicardium. Location of arrhythmogenic drivers were annotated on the bi-atrial anatomy. Activation and phase movies were examined to understand the wavefront dynamics during AF. Eight patients recurred within 12 …


Use Of Leishmania Major Parasites Expressing A Recombinant Trypanosoma Cruzi Antigen As Live Vaccines Against Chagas Disease, Catherine W Cai, Anne O'Shea, Christopher S Eickhoff, Hongjie Guo, Warren G Lewis, Stephen M Beverley, Daniel F Hoft Jan 2022

Use Of Leishmania Major Parasites Expressing A Recombinant Trypanosoma Cruzi Antigen As Live Vaccines Against Chagas Disease, Catherine W Cai, Anne O'Shea, Christopher S Eickhoff, Hongjie Guo, Warren G Lewis, Stephen M Beverley, Daniel F Hoft

2020-Current year OA Pubs

INTRODUCTION:

METHODS: We generated recombinant

RESULTS: We demonstrate that mice inoculated with these recombinant TS-expressing

DISCUSSION: Altogether, these data indicate that


Multi-Omics Insights Into The Biological Mechanisms Underlying Statistical Gene-By-Lifestyle Interactions With Smoking And Alcohol Consumption, Timothy D Majarian, Mary F Feitosa, Michael Province, Dabeeru C Rao, Karen Schwander, Yun Ju Sung, C Charles Gu, Et Al. Jan 2022

Multi-Omics Insights Into The Biological Mechanisms Underlying Statistical Gene-By-Lifestyle Interactions With Smoking And Alcohol Consumption, Timothy D Majarian, Mary F Feitosa, Michael Province, Dabeeru C Rao, Karen Schwander, Yun Ju Sung, C Charles Gu, Et Al.

2020-Current year OA Pubs

Though both genetic and lifestyle factors are known to influence cardiometabolic outcomes, less attention has been given to whether lifestyle exposures can alter the association between a genetic variant and these outcomes. The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium's Gene-Lifestyle Interactions Working Group has recently published investigations of genome-wide gene-environment interactions in large multi-ancestry meta-analyses with a focus on cigarette smoking and alcohol consumption as lifestyle factors and blood pressure and serum lipids as outcomes. Further description of the biological mechanisms underlying these statistical interactions would represent a significant advance in our understanding of gene-environment …


Implicating Genes, Pleiotropy, And Sexual Dimorphism At Blood Lipid Loci Through Multi-Ancestry Meta-Analysis, Stavroula Kanoni, Adam E. Locke, E Warwick Daw, Mary F. Feitosa, Mary K. Wojczynski, Bernhard Banas, Carsten A. Boger, Bettina Jung, D C. Rao, Michael A. Province, Et Al. Jan 2022

Implicating Genes, Pleiotropy, And Sexual Dimorphism At Blood Lipid Loci Through Multi-Ancestry Meta-Analysis, Stavroula Kanoni, Adam E. Locke, E Warwick Daw, Mary F. Feitosa, Mary K. Wojczynski, Bernhard Banas, Carsten A. Boger, Bettina Jung, D C. Rao, Michael A. Province, Et Al.

2020-Current year OA Pubs

No abstract provided.


Evaluation Of Dose-Dependent Treatment Effects After Mid-Trial Dose Escalation In Biomarker, Clinical, And Cognitive Outcomes For Gantenerumab Or Solanezumab In Dominantly Inherited Alzheimer's Disease, Guoqiao Wang, Yan Li, Chengjie Xiong, Eric Mcdade, David B Clifford, Susan L Mills, Anna M Santacruz, Andrew J Aschenbrenner, Jason Hassenstab, Tammie L S Benzinger, Brian A Gordon, Anne M Fagan, Kelley A Coalier, Jorge J Libre-Guerra, Austin Mccullough, Nelly Joseph-Mathurin, Charles D Chen, Randall J Bateman, Et Al. Jan 2022

Evaluation Of Dose-Dependent Treatment Effects After Mid-Trial Dose Escalation In Biomarker, Clinical, And Cognitive Outcomes For Gantenerumab Or Solanezumab In Dominantly Inherited Alzheimer's Disease, Guoqiao Wang, Yan Li, Chengjie Xiong, Eric Mcdade, David B Clifford, Susan L Mills, Anna M Santacruz, Andrew J Aschenbrenner, Jason Hassenstab, Tammie L S Benzinger, Brian A Gordon, Anne M Fagan, Kelley A Coalier, Jorge J Libre-Guerra, Austin Mccullough, Nelly Joseph-Mathurin, Charles D Chen, Randall J Bateman, Et Al.

2020-Current year OA Pubs

INTRODUCTION: While the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) was ongoing, external data suggested higher doses were needed to achieve targeted effects; therefore, doses of gantenerumab were increased 5-fold, and solanezumab was increased 4-fold. We evaluated to what extent mid-trial dose increases produced a dose-dependent treatment effect.

METHODS: Using generalized linear mixed effects (LME) models, we estimated the annual low- and high-dose treatment effects in clinical, cognitive, and biomarker outcomes.

RESULTS: Both gantenerumab and solanezumab demonstrated dose-dependent treatment effects (significant for gantenerumab, non-significant for solanezumab) in their respective target amyloid biomarkers (Pittsburgh compound B positron emission tomography standardized uptake …


Age Differences In The Association Between Sleep And Alzheimer's Disease Biomarkers In The Epad Cohort, Sharon L Naismith, Yue Leng, Jake R Palmer, Brendan P Lucey Jan 2022

Age Differences In The Association Between Sleep And Alzheimer's Disease Biomarkers In The Epad Cohort, Sharon L Naismith, Yue Leng, Jake R Palmer, Brendan P Lucey

2020-Current year OA Pubs

INTRODUCTION: We aimed to determine the independent association between sleep quality and Alzheimer's disease (AD) biomarkers, and whether the associations differ with age.

METHODS: We included 1240 individuals aged ≥50, without dementia from the

RESULTS: For the youngest age tertile, shorter sleep duration and higher sleep efficiency were associated with greater p-tau/Aβ42 ratio. For the oldest tertile, longer sleep latency was associated with greater p-tau/Aβ42.

DISCUSSION: Differential relationships between sleep and AD pathology depend on age. Short sleep duration and sleep efficiency are relevant in middle age whereas time taken to fall asleep is more closely linked to AD biomarkers …


Clinical And Molecular Characteristics Of A Novel Rare De Novo Variant In Ppp2ca In A Patient With A Developmental Disorder, Autism, And Epilepsy, Iris Verbinnen, Sara S Procknow, Lisa Lenaerts, Sara Reynhout, Aujan Mehregan, Chris Ulens, Veerle Janssens, Katherine A King Jan 2022

Clinical And Molecular Characteristics Of A Novel Rare De Novo Variant In Ppp2ca In A Patient With A Developmental Disorder, Autism, And Epilepsy, Iris Verbinnen, Sara S Procknow, Lisa Lenaerts, Sara Reynhout, Aujan Mehregan, Chris Ulens, Veerle Janssens, Katherine A King

2020-Current year OA Pubs

PP2A-related (neuro) developmental disorders are a family of genetic diseases caused by a heterozygous alteration in one of several genes encoding a subunit of type 2A protein phosphatases. Reported affected genes, so far, are


Donor Chimerism And Immune Reconstitution Following Haploidentical Transplantation In Sickle Cell Disease, Yaya Chu, Brenda Grossman, Shalini Shenoy, Et Al Jan 2022

Donor Chimerism And Immune Reconstitution Following Haploidentical Transplantation In Sickle Cell Disease, Yaya Chu, Brenda Grossman, Shalini Shenoy, Et Al

2020-Current year OA Pubs

INTRODUCTION: We previously reported the initial results of a phase II multicenter transplant trial using haploidentical parental donors for children and aolescents with high-risk sickle cell disease achieving excellent survival with exceptionally low rates of graft-versus-host disease and resolution of sickle cell disease symptoms. To investigate human leukocyte antigen (HLA) sensitization, graft characteristics, donor chimerism, and immune reconstitution in these recipients.

METHODS: CD34 cells were enriched using the CliniMACS

RESULTS: HLA antibodies were detected in 7 of 11 (64%) evaluable patients but rarely were against donor antigens. Myeloid engraftment was rapid (100%) at a median of 9 days. At 30 …


Primates Chunk Simultaneously-Presented Memoranda, Charles D Holmes, Shinung Ching, Lawrence H Snyder Jan 2022

Primates Chunk Simultaneously-Presented Memoranda, Charles D Holmes, Shinung Ching, Lawrence H Snyder

2020-Current year OA Pubs

Though much research has characterized both the behavior and electrophysiology of spatial memory for single targets in non-human primates, we know much less about how multiple memoranda are handled. Multiple memoranda may interact in the brain, affecting the underlying representations. Mnemonic resources are famously limited, so items may compete for "space" in memory or may be encoded cooperatively or in a combined fashion. Understanding the mode of interaction will inform future neural studies. As a first step, we quantified interactions during a multi-item spatial memory task. Two monkeys were shown 1-4 target locations. After a delay, the targets reappeared with …


Expert Guidance On Prophylaxis And Treatment Of Dermatologic Adverse Events With Tumor Treating Fields (Ttfields) Therapy In The Thoracic Region, Milan J Anadkat, Mario Lacouture, Adam Friedman, Zachary D Horne, Jae Jung, Benjamin Kaffenberger, Sujith Kalmadi, Liza Ovington, Rupesh Kotecha, Huda Ismail Abdullah, Federica Grosso Jan 2022

Expert Guidance On Prophylaxis And Treatment Of Dermatologic Adverse Events With Tumor Treating Fields (Ttfields) Therapy In The Thoracic Region, Milan J Anadkat, Mario Lacouture, Adam Friedman, Zachary D Horne, Jae Jung, Benjamin Kaffenberger, Sujith Kalmadi, Liza Ovington, Rupesh Kotecha, Huda Ismail Abdullah, Federica Grosso

2020-Current year OA Pubs

Tumor Treating Fields (TTFields) are electric fields, delivered via wearable arrays placed on or near the tumor site, that exert physical forces to disrupt cellular processes critical for cancer cell viability and tumor progression. As a first-in-class treatment, TTFields therapy is approved for use in newly diagnosed glioblastoma, recurrent glioblastoma, and pleural mesothelioma. Additionally, TTFields therapy is being investigated in non-small cell lung cancer (NSCLC), brain metastases from NSCLC, pancreatic cancer, ovarian cancer, hepatocellular carcinoma, and gastric adenocarcinoma. Because TTFields therapy is well tolerated and delivery is locoregional, there is low risk of additive systemic adverse events (AEs) when used …


Sars-Cov-2 Booster Vaccination Rescues Attenuated Igg1 Memory B Cell Response In Primary Antibody Deficiency Patients, Frank J Lin, Alexa Michelle Altman Doss, Hannah G Davis-Adams, Lucas J Adams, Christopher H Hanson, Laura A Vanblargan, Chieh-Yu Liang, Rita E Chen, Jennifer Marie Monroy, H James Wedner, Anthony Kulczycki, Tarisa L Mantia, Caitlin C O'Shaughnessy, Saravanan Raju, Fang R Zhao, Elise Rizzi, Christopher J Rigell, Tiffany Biason Dy, Andrew L Kau, Zhen Ren, Jackson S Turner, Jane A O'Halloran, Rachel M Presti, Daved H Fremont, Peggy L Kendall, Ali H Ellebedy, Philip A Mudd, Michael S Diamond, Ofer Zimmerman, Brian J Laidlaw Jan 2022

Sars-Cov-2 Booster Vaccination Rescues Attenuated Igg1 Memory B Cell Response In Primary Antibody Deficiency Patients, Frank J Lin, Alexa Michelle Altman Doss, Hannah G Davis-Adams, Lucas J Adams, Christopher H Hanson, Laura A Vanblargan, Chieh-Yu Liang, Rita E Chen, Jennifer Marie Monroy, H James Wedner, Anthony Kulczycki, Tarisa L Mantia, Caitlin C O'Shaughnessy, Saravanan Raju, Fang R Zhao, Elise Rizzi, Christopher J Rigell, Tiffany Biason Dy, Andrew L Kau, Zhen Ren, Jackson S Turner, Jane A O'Halloran, Rachel M Presti, Daved H Fremont, Peggy L Kendall, Ali H Ellebedy, Philip A Mudd, Michael S Diamond, Ofer Zimmerman, Brian J Laidlaw

2020-Current year OA Pubs

BACKGROUND: Although SARS-CoV-2 vaccines have proven effective in eliciting a protective immune response in healthy individuals, their ability to induce a durable immune response in immunocompromised individuals remains poorly understood. Primary antibody deficiency (PAD) syndromes are among the most common primary immunodeficiency disorders in adults and are characterized by hypogammaglobulinemia and impaired ability to mount robust antibody responses following infection or vaccination.

METHODS: Here, we present an analysis of both the B and T cell response in a prospective cohort of 30 individuals with PAD up to 150 days following initial COVID-19 vaccination and 150 days post mRNA booster vaccination. …


Postnatal Osterix But Not Dmp1 Lineage Cells Significantly Contribute To Intramembranous Ossification In Three Preclinical Models Of Bone Injury, Evan G Buettmann, Susumu Yoneda, Pei Hu, Jennifer A Mckenzie, Matthew J Silva Jan 2022

Postnatal Osterix But Not Dmp1 Lineage Cells Significantly Contribute To Intramembranous Ossification In Three Preclinical Models Of Bone Injury, Evan G Buettmann, Susumu Yoneda, Pei Hu, Jennifer A Mckenzie, Matthew J Silva

2020-Current year OA Pubs

Murine models of long-bone fracture, stress fracture, and cortical defect are used to discern the cellular and molecular mediators of intramembranous and endochondral bone healing. Previous work has shown that Osterix (Osx


3d Bi-Directional Transformer U-Net For Medical Image Segmentation, Xiyao Fu, Zhexian Sun, Haoteng Tang, Eric M Zou, Heng Huang, Yong Wang, Liang Zhan Jan 2022

3d Bi-Directional Transformer U-Net For Medical Image Segmentation, Xiyao Fu, Zhexian Sun, Haoteng Tang, Eric M Zou, Heng Huang, Yong Wang, Liang Zhan

2020-Current year OA Pubs

As one of the popular deep learning methods, deep convolutional neural networks (DCNNs) have been widely adopted in segmentation tasks and have received positive feedback. However, in segmentation tasks, DCNN-based frameworks are known for their incompetence in dealing with global relations within imaging features. Although several techniques have been proposed to enhance the global reasoning of DCNN, these models are either not able to gain satisfying performances compared with traditional fully-convolutional structures or not capable of utilizing the basic advantages of CNN-based networks (namely the ability of local reasoning). In this study, compared with current attempts to combine FCNs and …


Mortality In Pediatric Oncology And Stem Cell Transplant Patients With Bloodstream Infections, Daniel N Willis, Mary Claire Mcglynn, Patrick J Reich, Robert J Hayashi Jan 2022

Mortality In Pediatric Oncology And Stem Cell Transplant Patients With Bloodstream Infections, Daniel N Willis, Mary Claire Mcglynn, Patrick J Reich, Robert J Hayashi

2020-Current year OA Pubs

BACKGROUND: Bloodstream infections (BSI) continue to represent a significant source of morbidity for pediatric oncology patients, however less is known regarding this population's risk of death. We sought to evaluate the risk of BSI and death at a large pediatric cancer center.

METHODS: We retrospectively collected inpatient data from pediatric oncology and hematopoietic stem cell transplant (HSCT) patients over a 9-year period. We performed univariate and multivariable modeling to assess risk of BSI and mortality examining the following variables: demographics, underlying malignancy, history of HSCT, central line type, and febrile neutropenia (FN).

RESULTS: During the study period, 6763 admissions from …


Top-Down And Bottom-Up Propagation Of Disease In The Neuronal Ceroid Lipofuscinoses, John R Ostergaard, Hemanth R Nelvagal, Jonathan D Cooper Jan 2022

Top-Down And Bottom-Up Propagation Of Disease In The Neuronal Ceroid Lipofuscinoses, John R Ostergaard, Hemanth R Nelvagal, Jonathan D Cooper

2020-Current year OA Pubs

BACKGROUND: The Neuronal Ceroid Lipofuscinoses (NCLs) may be considered distinct neurodegenerative disorders with separate underlying molecular causes resulting from monogenetic mutations. An alternative hypothesis is to consider the NCLs as related diseases that share lipofuscin pathobiology as the common core feature, but otherwise distinguished by different a) initial anatomic location, and b) disease propagation.

METHODS: We have tested this hypothesis by comparing known differences in symptomatology and pathology of the CLN1 phenotype caused by complete loss of

RESULTS: Despite displaying similar pathological endpoints, the clinical phenotypes and the evidence of imaging and

DISCUSSION: The propagation of disease in these two …


Decision-Making Factors For An Autologous Stem Cell Transplant For Older Adults With Newly Diagnosed Multiple Myeloma: A Qualitative Analysis, Owais Mian, Martine Puts, Arleigh Mccurdy, Tanya M Wildes, Mark A Fiala, Matthew Kang, Mary Salib, Shabbir Alibhai, Hira Mian Jan 2022

Decision-Making Factors For An Autologous Stem Cell Transplant For Older Adults With Newly Diagnosed Multiple Myeloma: A Qualitative Analysis, Owais Mian, Martine Puts, Arleigh Mccurdy, Tanya M Wildes, Mark A Fiala, Matthew Kang, Mary Salib, Shabbir Alibhai, Hira Mian

2020-Current year OA Pubs

PURPOSE: A utologous stem cell transplant (ASCT) remains a standard of care among older adults (aged ≥65) with multiple myeloma (MM). However, heterogeneity in the eligibility and utilization of ASCT remains. We identified decision-making factors that influence ASCT eligibility and utilization among older adults with MM.

METHODS: A qualitative study across two academic and two community centres in Ontario was conducted between July 2019-July 2020. Older adults with MM (newly diagnosed MM aged 65-75 in whom a decision had been made about ASCT in <12 months) and treating oncologists completed a baseline survey and a subsequent interview, which was analyzed using thematic analysis.

RESULTS: Eighteen patients completed the survey and 9 follow-up interviews were conducted. Patients were happy with …


Stat3 Gain-Of-Function Syndrome, Tiphanie P Vogel, Jennifer W Leiding, Megan A Cooper, Lisa R Forbes Satter Jan 2022

Stat3 Gain-Of-Function Syndrome, Tiphanie P Vogel, Jennifer W Leiding, Megan A Cooper, Lisa R Forbes Satter

2020-Current year OA Pubs

STAT3 gain-of-function (GOF) syndrome is a multi-organ primary immune regulatory disorder characterized by early onset autoimmunity. Patients present early in life, most commonly with lymphoproliferation, autoimmune cytopenias, and growth delay. However, disease is often progressive and can encompass a wide range of clinical manifestations such as: enteropathy, skin disease, pulmonary disease, endocrinopathy, arthritis, autoimmune hepatitis, and rarely neurologic disease, vasculopathy, and malignancy. Treatment of the autoimmune and immune dysregulatory features of STAT3-GOF patients relies heavily on immunosuppression and is often challenging and fraught with complications including severe infections. Defects in the T cell compartment leading to effector T cell accumulation …


"Provider Discretionary Power Practices To Support Implementation Of Patient-Centered Hiv Care In Lusaka, Zambia", Chanda Mwamba, Njekwa Mukamba, Anjali Sharma, Kasapo Lumbo, Marksman Foloko, Herbert Nyirenda, Sandra Simbeza, Kombatende Sikombe, Charles B Holmes, Izukanji Sikazwe, Carolyn Bolton Moore, Aaloke Mody, Elvin Geng, Laura K Beres Jan 2022

"Provider Discretionary Power Practices To Support Implementation Of Patient-Centered Hiv Care In Lusaka, Zambia", Chanda Mwamba, Njekwa Mukamba, Anjali Sharma, Kasapo Lumbo, Marksman Foloko, Herbert Nyirenda, Sandra Simbeza, Kombatende Sikombe, Charles B Holmes, Izukanji Sikazwe, Carolyn Bolton Moore, Aaloke Mody, Elvin Geng, Laura K Beres

2020-Current year OA Pubs

INTRODUCTION: Traditional patient-provider relationships privilege the providers, as they possess the formal authority and clinical knowledge applied to address illness, but providers also have discretion over how they exercise their power to influence patients' services, benefits, and sanctions. In this study, we assessed providers' exercise of discretionary power in implementing patient-centered care (PCC) practices in Lusaka, Zambia.

METHODS: HIV clinical encounters between patients on antiretroviral therapy (ART) and providers across 24 public health facilities in Lusaka Province were audio recorded and transcribed verbatim. Using qualitative content analysis, we identified practices of discretionary power (DP) employed in the implementation of PCC …


Sustainability In Pediatric Hospitals: An Exploration At The Intersection Of Quality Improvement And Implementation Science, Sara Malone, Jason Newland, Sapna R Kudchadkar, Kim Prewitt, Virginia Mckay, Beth Prusaczyk, Enola Proctor, Ross C Brownson, Douglas A Luke Jan 2022

Sustainability In Pediatric Hospitals: An Exploration At The Intersection Of Quality Improvement And Implementation Science, Sara Malone, Jason Newland, Sapna R Kudchadkar, Kim Prewitt, Virginia Mckay, Beth Prusaczyk, Enola Proctor, Ross C Brownson, Douglas A Luke

2020-Current year OA Pubs

BACKGROUND: Although new evidence-based practices are frequently implemented in clinical settings, many are not sustained, limiting the intended impact. Within implementation science, there is a gap in understanding sustainability. Pediatric healthcare settings have a robust history of quality improvement (QI), which includes a focus on continuation of change efforts. QI capability and sustainability capacity, therefore, serve as a useful concept for connecting the broader fields of QI and implementation science to provide insights on improving care. This study addresses these gaps in understanding of sustainability in pediatric settings and its relationship to QI.

METHODS: This is a cross-sectional observational study …