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Development Of The International Spinal Cord Injury Basic Data Set For Informal Caregivers Oct 2022

Development Of The International Spinal Cord Injury Basic Data Set For Informal Caregivers

Faculty, Staff and Student Publications

STUDY DESIGN: Mixed-methods, including expert consensus for initial development and a multi-center repeated measures design for field testing.

OBJECTIVES: To develop an International Spinal Cord Injury Basic Data Set for caregivers of individuals with spinal cord injury/disorder (SCI/D) for use in research and clinical care settings.

SETTING: International, multi-disciplinary working group with field testing in five North American pediatric rehabilitation hospitals.

METHODS: The data set was developed iteratively through meetings and online surveys with a working group of experts in pediatric and adult SCI/D rehabilitation and caregivers of individuals with SCI/D. Initial reliability was examined through repeat administration of a …


Heterozygous Variants In Myh10 Associated With Neurodevelopmental Disorders And Congenital Anomalies With Evidence For Primary Cilia-Dependent Defects In Hedgehog Signaling, Kara Withrow, Richard Person, Maria J Guillen Sacoto, Yue Si, Ingrid M Wentzensen, Jada Pugh, Georgia Vasileiou, Melissa Rieger, André Reis, Emanuela Argilli, Elliott H Sherr, Kimberly A Aldinger, William B Dobyns, Theresa Brunet, Julia Hoefele, Matias Wagner, Benjamin Haber, Urania Kotzaeridou, Boris Keren, Delphine Heron, Cyril Mignot, Solveig Heide, Thomas Courtin, Julien Buratti, Serini Murugasen, Kirsten A Donald, Emily O'Heir, Shade Moody, Katherine H Kim, Barbara K Burton, Grace Yoon, Miguel Del Campo, Diane Masser-Frye, Mariya Kozenko, Christina Parkinson, Susan L Sell, Patricia L Gordon, Jeremy W Prokop, Amel Karaa, Caleb Bupp, Benjamin A Raby Oct 2022

Heterozygous Variants In Myh10 Associated With Neurodevelopmental Disorders And Congenital Anomalies With Evidence For Primary Cilia-Dependent Defects In Hedgehog Signaling, Kara Withrow, Richard Person, Maria J Guillen Sacoto, Yue Si, Ingrid M Wentzensen, Jada Pugh, Georgia Vasileiou, Melissa Rieger, André Reis, Emanuela Argilli, Elliott H Sherr, Kimberly A Aldinger, William B Dobyns, Theresa Brunet, Julia Hoefele, Matias Wagner, Benjamin Haber, Urania Kotzaeridou, Boris Keren, Delphine Heron, Cyril Mignot, Solveig Heide, Thomas Courtin, Julien Buratti, Serini Murugasen, Kirsten A Donald, Emily O'Heir, Shade Moody, Katherine H Kim, Barbara K Burton, Grace Yoon, Miguel Del Campo, Diane Masser-Frye, Mariya Kozenko, Christina Parkinson, Susan L Sell, Patricia L Gordon, Jeremy W Prokop, Amel Karaa, Caleb Bupp, Benjamin A Raby

Faculty, Staff and Student Publications

PURPOSE: Nonmuscle myosin II complexes are master regulators of actin dynamics that play essential roles during embryogenesis with vertebrates possessing 3 nonmuscle myosin II heavy chain genes, MYH9, MYH10, and MYH14. As opposed to MYH9 and MYH14, no recognizable disorder has been associated with MYH10. We sought to define the clinical characteristics and molecular mechanism of a novel autosomal dominant disorder related to MYH10.

METHODS: An international collaboration identified the patient cohort. CAS9-mediated knockout cell models were used to explore the mechanism of disease pathogenesis.

RESULTS: We identified a cohort of 16 individuals with heterozygous MYH10 variants presenting with a …


Early Versus Delayed Treatment With Glatiramer Acetate: Analysis Of Up To 27 Years Of Continuous Follow-Up In A Us Open-Label Extension Study, Robert P Lisak, Horea Rus, Jerry S Wolinsky, Shaul E Kadosh, Emily Bernstein-Hanlon, Yafit Stark, Jessica K Alexander Oct 2022

Early Versus Delayed Treatment With Glatiramer Acetate: Analysis Of Up To 27 Years Of Continuous Follow-Up In A Us Open-Label Extension Study, Robert P Lisak, Horea Rus, Jerry S Wolinsky, Shaul E Kadosh, Emily Bernstein-Hanlon, Yafit Stark, Jessica K Alexander

Faculty, Staff and Student Publications

BACKGROUND: Glatiramer acetate (GA) is US-approved for relapsing multiple sclerosis.

OBJECTIVES: To describe GA long-term clinical profile. To compare effectiveness of early start (ES) versus delayed start (DS; up to 3 years) with GA.

METHODS: Phase 3 trial participants entered a randomized placebo-controlled period then an open-label extension (OLE) with GA.

RESULTS: Overall, 208 out of 251 (82.9%) randomized participants entered the OLE; 24 out of 101 (23.8%, ES) and 28 out of 107 (26.2%, DS) participants completed the OLE. Median GA treatment was 9.8 (0.1-26.3) years. Annualized change in Expanded Disability Status Scale (EDSS) score was lower with ES …


Public Health Information Seeking, Trust, And Covid-19 Prevention Behaviors: Cross-Sectional Study, Emmanuel Kwabena Tetteh, Todd Combs, Elvin Hsing Geng, Virginia Ruth Mckay Sep 2022

Public Health Information Seeking, Trust, And Covid-19 Prevention Behaviors: Cross-Sectional Study, Emmanuel Kwabena Tetteh, Todd Combs, Elvin Hsing Geng, Virginia Ruth Mckay

2020-Current year OA Pubs

BACKGROUND: Preventative health measures such as shelter in place and mask wearing have been widely encouraged to curb the spread of the COVID-19 disease. People's attitudes toward preventative behaviors may be dependent on their sources of information and trust in the information.

OBJECTIVE: The aim of this study was to understand the relationship between trusting in COVID-19 information and preventative behaviors in a racially and politically diverse metropolitan area in the United States.

METHODS: We conducted a web-based cross-sectional survey of residents in St. Louis City and County in Missouri. Individuals aged ≥18 years were eligible to participate. Participants were …


Help Is Available: Supporting Mental Wellness Through Peer Health Navigation With Young Black Men Who Have Sex With Men With Hiv, Donald R Gerke, Jeff Glotfelty, Maria Freshman, Julia Schlueter, Alex Ochs, Katie Plax Sep 2022

Help Is Available: Supporting Mental Wellness Through Peer Health Navigation With Young Black Men Who Have Sex With Men With Hiv, Donald R Gerke, Jeff Glotfelty, Maria Freshman, Julia Schlueter, Alex Ochs, Katie Plax

2020-Current year OA Pubs

Young black men who have sex with men (YBMSM) with HIV experience disproportionate rates of trauma, incarceration, poverty, racial discrimination, and homophobia. The synergistic effects of these adverse experiences, along with increased rates of mental health disorders, increase their risk for poor health. To address this need, the study authors adapted a current HIV service model to include a peer-health navigation intervention (WITH U) to attend to behavioral health, health literacy, linkage to services, and psychosocial support for YBMSM with HIV. This longitudinal, mixed-methods, nonexperimental study reports on the mental health burden among participants and the association between participation in …


Mixed Random And Nonrandom Allocation, And Group Randomization Have Been Mislabeled And Misanalysed, Necessitating Reanalysis Comment On Conner Et Al Kiwic For Vitality: Results Of A Randomized Placebo-Controlled Trial Testing The Effects Of Kiwifruit Or Vitamin C Tablets On Vitality In Adults With Low Vitamin C Levels, Colby J Vorland, Yasaman Jamshidi-Naeini, Lilian Golzarri-Arroyo, Andrew W Brown, David B Allison Sep 2022

Mixed Random And Nonrandom Allocation, And Group Randomization Have Been Mislabeled And Misanalysed, Necessitating Reanalysis Comment On Conner Et Al Kiwic For Vitality: Results Of A Randomized Placebo-Controlled Trial Testing The Effects Of Kiwifruit Or Vitamin C Tablets On Vitality In Adults With Low Vitamin C Levels, Colby J Vorland, Yasaman Jamshidi-Naeini, Lilian Golzarri-Arroyo, Andrew W Brown, David B Allison

Children’s Nutrition Research Center Staff Publications

We read the report by Conner and colleagues that tested whether kiwifruit or vitamin C affected measures of vitality [...].


Transcriptional And Immune Landscape Of Cardiac Sarcoidosis, Jing Liu, Pan Ma, Lulu Lai, Ana Villanueva, Andrew Koenig, Gregory R. Bean, Dawn E. Bowles, Carolyn Glass, Michael Watson, Kory J. Lavine, Chieh-Yu Lin Sep 2022

Transcriptional And Immune Landscape Of Cardiac Sarcoidosis, Jing Liu, Pan Ma, Lulu Lai, Ana Villanueva, Andrew Koenig, Gregory R. Bean, Dawn E. Bowles, Carolyn Glass, Michael Watson, Kory J. Lavine, Chieh-Yu Lin

2020-Current year OA Pubs

BACKGROUND: Cardiac involvement is an important determinant of mortality among sarcoidosis patients. Although granulomatous inflammation is a hallmark finding in cardiac sarcoidosis, the precise immune cell populations that comprise the granuloma remain unresolved. Furthermore, it is unclear how the cellular and transcriptomic landscape of cardiac sarcoidosis differs from other inflammatory heart diseases.

METHODS: We leveraged spatial transcriptomics (GeoMx digital spatial profiler) and single-nucleus RNA sequencing to elucidate the cellular and transcriptional landscape of cardiac sarcoidosis. Using GeoMX digital spatial profiler technology, we compared the transcriptomal profile of CD68

RESULTS: Despite overlapping histological features, spatial transcriptomics identified transcriptional signatures and associated …


Neurons Burdened By Dna Double-Strand Breaks Incite Microglia Activation Through Antiviral-Like Signaling In Neurodegeneration, Jose Davila-Velderrain, Matheus B Victor, Vishnu Dileep, P Lorenzo Bozzelli, Qiao Su, Jemmie D Cheng, Audrey Lee, Noelle S Leary, Andreas R Pfenning, Manolis Kellis, Li-Huei Tsai Sep 2022

Neurons Burdened By Dna Double-Strand Breaks Incite Microglia Activation Through Antiviral-Like Signaling In Neurodegeneration, Jose Davila-Velderrain, Matheus B Victor, Vishnu Dileep, P Lorenzo Bozzelli, Qiao Su, Jemmie D Cheng, Audrey Lee, Noelle S Leary, Andreas R Pfenning, Manolis Kellis, Li-Huei Tsai

Faculty, Staff and Students Publications

DNA double-strand breaks (DSBs) are linked to neurodegeneration and senescence. However, it is not clear how DSB-bearing neurons influence neuroinflammation associated with neurodegeneration. Here, we characterize DSB-bearing neurons from the CK-p25 mouse model of neurodegeneration using single-nucleus, bulk, and spatial transcriptomic techniques. DSB-bearing neurons enter a late-stage DNA damage response marked by nuclear factor κB (NFκB)-activated senescent and antiviral immune pathways. In humans, Alzheimer's disease pathology is closely associated with immune activation in excitatory neurons. Spatial transcriptomics reveal that regions of CK-p25 brain tissue dense with DSB-bearing neurons harbor signatures of inflammatory microglia, which is ameliorated by NFκB knockdown in …


Modeling Multivariate Age-Related Imaging Variables With Dependencies, Shuo Chen Sep 2022

Modeling Multivariate Age-Related Imaging Variables With Dependencies, Shuo Chen

Faculty, Staff and Student Publications

Neuroimaging techniques have been increasingly used to understand the neural biology of aging brains. The neuroimaging variables from distinct brain locations and modalities can exhibit age-related patterns that reflect localized neural decline. However, it is a challenge to identify the impacts of risk factors (eg, mental disorders) on multivariate imaging variables while simultaneously accounting for the dependence structure and nonlinear age trajectories using existing tools. We propose a mixed-effects model to address this challenge by building random effects based on the latent brain aging status. We develop computationally efficient algorithms to estimate the parameters of new random effects. The simulations …


Cardiac Structure And Function In Adults With Down Syndrome., Fadi M. Azar, Victor D Y Beck, Alice M. Matthews, Daniel Forsha, Thessa I M Hilgenkamp Sep 2022

Cardiac Structure And Function In Adults With Down Syndrome., Fadi M. Azar, Victor D Y Beck, Alice M. Matthews, Daniel Forsha, Thessa I M Hilgenkamp

Manuscripts, Articles, Book Chapters and Other Papers

Various factors may alter the risk for cardiovascular disease in adults with Down syndrome (Ds), yet few studies have examined differences in cardiac physiology in this population. Previous research suggested lower systolic and diastolic function, but inconsistent methodologies and younger samples warrant research in adults with Ds. Our aim is to compare the cardiac structure and function of adults with Ds to age- and sex-matched adults without Ds. Echocardiography was used to assess systolic function, diastolic function, and cardiac structure in n = 19 adults (Ds n = 9, control n = 10). Regarding cardiac structure, adults with Ds had …


Tigit Is The Central Player In T-Cell Suppression Associated With Car T-Cell Relapse In Mantle Cell Lymphoma, Vivian Changying Jiang, Dapeng Hao, Preetesh Jain, Yijing Li, Qingsong Cai, Lei Nie, Jingling Jin, Wei Wang, Heng-Huan Lee, Yuxuan Che, Enyu Dai, Guangchun Han, Ruiping Wang, Kunal Rai, Andrew Futreal, Christopher Flowers, Linghua Wang, Michael Wang Sep 2022

Tigit Is The Central Player In T-Cell Suppression Associated With Car T-Cell Relapse In Mantle Cell Lymphoma, Vivian Changying Jiang, Dapeng Hao, Preetesh Jain, Yijing Li, Qingsong Cai, Lei Nie, Jingling Jin, Wei Wang, Heng-Huan Lee, Yuxuan Che, Enyu Dai, Guangchun Han, Ruiping Wang, Kunal Rai, Andrew Futreal, Christopher Flowers, Linghua Wang, Michael Wang

Faculty, Staff and Student Publications

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy using brexucabtagene autoleucel (BA) induces remission in many patients with mantle cell lymphoma (MCL), and BA is the only CAR T-cell therapy approved by the FDA for MCL. However, development of relapses to BA is recognized with poor patient outcomes. Multiple CAR T-cell therapies have been approved for other lymphomas and the resistance mechanisms have been investigated. However, the mechanisms underlying BA relapse in MCL have not been investigated and whether any previously reported resistance mechanisms apply to BA-relapsed patients with MCL is unknown.

METHODS: To interrogate BA resistance mechanisms in MCL, we …


Il-6 And Tnf-Α Responses To Acute And Regular Exercise In Adult Individuals With Multiple Sclerosis (Ms): A Systematic Review And Meta-Analysis, Antônio L Teixeira Sep 2022

Il-6 And Tnf-Α Responses To Acute And Regular Exercise In Adult Individuals With Multiple Sclerosis (Ms): A Systematic Review And Meta-Analysis, Antônio L Teixeira

Faculty, Staff and Student Publications

Background: In both the general population and people with multiple sclerosis (PwMS), physical exercise is associated with improved mental well-being. Moreover, there is evidence of the possible protection of physical activity against disease progression in multiple sclerosis (MS). However, the question arises if acute or regular exercise has any impact on the immune system in PwMS. To answer this question, we performed a systematic review and meta-analysis on both plasma and serum cytokine levels (IL-6 and TNF-α) before and after acute and regular exercise among PwMS and compared to healthy controls.

Method: We performed an online search via PubMed, EMBASE, …


Study Protocol For An Adapted Personal Project Analysis To Measure Vertical Inter-Goal Relations On Physical Activity And Diet, Sara Kassas, Catherine Culot, Geert Crombez, Annique Smeding, Christophe Leys, Debbe Thompson, Ann Desmet Sep 2022

Study Protocol For An Adapted Personal Project Analysis To Measure Vertical Inter-Goal Relations On Physical Activity And Diet, Sara Kassas, Catherine Culot, Geert Crombez, Annique Smeding, Christophe Leys, Debbe Thompson, Ann Desmet

Children’s Nutrition Research Center Staff Publications

Background: The promotion of multiple healthy lifestyles has been implemented as part of public health efforts to prevent and reduce the burden of non-communicable diseases. However, these interventions have shown a heterogeneity in their effectiveness. The pursuit of multiple daily goals may influence overall progress in achieving health goals. Horizontal inter-goal relations can be conflicting (due to time constraints) or facilitating (due to goal compatibility) and impact progress towards goal achievement. Personal values also play an important role in health promotion. Personal values direct attention towards accomplishing a higher-level goal through goal setting. Identifying the conflicting or facilitating relationships between …


Leading The Way: Competencies Of Leadership To Prevent Mis-Implementation Of Public Health Programs, Sarah Moreland-Russell, Louise Farah Saliba, Emily Rodriguez Weno, Romario Smith, Margaret Padek, Ross C Brownson Sep 2022

Leading The Way: Competencies Of Leadership To Prevent Mis-Implementation Of Public Health Programs, Sarah Moreland-Russell, Louise Farah Saliba, Emily Rodriguez Weno, Romario Smith, Margaret Padek, Ross C Brownson

2020-Current year OA Pubs

Public health agencies are increasingly concerned with ensuring that they are maximizing limited resources by delivering effective programs to enhance population-level health outcomes. Preventing mis-implementation (ending effective activities prematurely or continuing ineffective ones) is necessary to sustain public health efforts and resources needed to improve health and well-being. The purpose of this paper is to identify the important qualities of leadership in preventing mis-implementation of public health programs. In 2019, 45 state health department chronic disease employees were interviewed via phone and audio-recorded, and the conversations were transcribed verbatim. Thematic analysis focused on items related to mis-implementation and the manners …


Islet Primary Cilia Motility Controls Insulin Secretion, Jung Hoon Cho, Zipeng A Li, Lifei Zhu, Brian D Muegge, Henry F Roseman, Eun Young Lee, Toby Utterback, Louis G Woodhams, Philip V Bayly, Jing W Hughes Sep 2022

Islet Primary Cilia Motility Controls Insulin Secretion, Jung Hoon Cho, Zipeng A Li, Lifei Zhu, Brian D Muegge, Henry F Roseman, Eun Young Lee, Toby Utterback, Louis G Woodhams, Philip V Bayly, Jing W Hughes

2020-Current year OA Pubs

Primary cilia are specialized cell-surface organelles that mediate sensory perception and, in contrast to motile cilia and flagella, are thought to lack motility function. Here, we show that primary cilia in human and mouse pancreatic islets exhibit movement that is required for glucose-dependent insulin secretion. Islet primary cilia contain motor proteins conserved from those found in classic motile cilia, and their three-dimensional motion is dynein-driven and dependent on adenosine 5'-triphosphate and glucose metabolism. Inhibition of cilia motion blocks beta cell calcium influx and insulin secretion. Human beta cells have enriched ciliary gene expression, and motile cilia genes are altered in …


Glycemia Reduction In Type 2 Diabetes - Glycemic Outcomes, Henry B Burch, John B Buse, Nicole M Butera, Robert M Cohen, Jill P Crandall, Steven E Kahn, Heidi Krause-Steinrauf, Mary E Larkin, Neda Rasouli, Margaret Tiktin, Deborah J Wexler, Naji Younes Sep 2022

Glycemia Reduction In Type 2 Diabetes - Glycemic Outcomes, Henry B Burch, John B Buse, Nicole M Butera, Robert M Cohen, Jill P Crandall, Steven E Kahn, Heidi Krause-Steinrauf, Mary E Larkin, Neda Rasouli, Margaret Tiktin, Deborah J Wexler, Naji Younes

Faculty, Staff and Students Publications

BACKGROUND: The comparative effectiveness of glucose-lowering medications for use with metformin to maintain target glycated hemoglobin levels in persons with type 2 diabetes is uncertain.

METHODS: In this trial involving participants with type 2 diabetes of less than 10 years' duration who were receiving metformin and had glycated hemoglobin levels of 6.8 to 8.5%, we compared the effectiveness of four commonly used glucose-lowering medications. We randomly assigned participants to receive insulin glargine U-100 (hereafter, glargine), the sulfonylurea glimepiride, the glucagon-like peptide-1 receptor agonist liraglutide, or sitagliptin, a dipeptidyl peptidase 4 inhibitor. The primary metabolic outcome was a glycated hemoglobin level, …


High Prevalence Of Chronic Viral Hepatitis B And C In Minnesota Somalis Contributes To Rising Hepatocellular Carcinoma Incidence, Essa A Mohamed, Joyce E Balls-Berry, Et Al. Sep 2022

High Prevalence Of Chronic Viral Hepatitis B And C In Minnesota Somalis Contributes To Rising Hepatocellular Carcinoma Incidence, Essa A Mohamed, Joyce E Balls-Berry, Et Al.

2020-Current year OA Pubs

BACKGROUND: Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are known risk factors for liver disease, cirrhosis and hepatocellular carcinoma (HCC). There is substantial global variation in HBV and HCV prevalence resulting in variations in cirrhosis and HCC. We previously reported high prevalence of HBV and HCV infections in Somali immigrants seen at an academic medical center in Minnesota.

AIM: To determine the prevalence of chronic viral hepatitis in Somali immigrants in Minnesota through a community-based screening program.

METHODS: We conducted a prospective community-based participatory research study in the Somali community in Minnesota in partnership with community …


Insular Cortical Circuits As An Executive Gateway To Decipher Threat Or Extinction Memory Via Distinct Subcortical Pathways, Qi Wang, Jia-Jie Zhu, Lizhao Wang, Yan-Peng Kan, Yan-Mei Liu, Xue Gu, Ze-Jie Lin, Qin Wang, Jian-Fei Lu, Qin Jiang, Ying Li, Ming-Gang Liu, Nan-Jie Xu, Michael X Zhu, Lu-Yang Wang, Siyu Zhang, Wei-Guang Li, Tian-Le Xu Sep 2022

Insular Cortical Circuits As An Executive Gateway To Decipher Threat Or Extinction Memory Via Distinct Subcortical Pathways, Qi Wang, Jia-Jie Zhu, Lizhao Wang, Yan-Peng Kan, Yan-Mei Liu, Xue Gu, Ze-Jie Lin, Qin Wang, Jian-Fei Lu, Qin Jiang, Ying Li, Ming-Gang Liu, Nan-Jie Xu, Michael X Zhu, Lu-Yang Wang, Siyu Zhang, Wei-Guang Li, Tian-Le Xu

Faculty, Staff and Student Publications

Threat and extinction memories are crucial for organisms' survival in changing environments. These memories are believed to be encoded by separate ensembles of neurons in the brain, but their whereabouts remain elusive. Using an auditory fear-conditioning and extinction paradigm in male mice, here we discovered that two distinct projection neuron subpopulations in physical proximity within the insular cortex (IC), targeting the central amygdala (CeA) and nucleus accumbens (NAc), respectively, to encode fear and extinction memories. Reciprocal intracortical inhibition of these two IC subpopulations gates the emergence of either fear or extinction memory. Using rabies-virus-assisted tracing, we found IC-NAc projection neurons …


Effect Of The Tokyo 2020 Summer Olympic Games On Covid-19 Incidence In Japan: A Synthetic Control Approach, Daisuke Yoneoka, Akifumi Eguchi, Kentato Fukumoto, Takayuki Kawashima, Yuta Tanoue, Takahiro Tabuchi, Hiroaki Miyata, Cyrus Ghaznavi, Kenji Shibuya, Shuhei Nomura Sep 2022

Effect Of The Tokyo 2020 Summer Olympic Games On Covid-19 Incidence In Japan: A Synthetic Control Approach, Daisuke Yoneoka, Akifumi Eguchi, Kentato Fukumoto, Takayuki Kawashima, Yuta Tanoue, Takahiro Tabuchi, Hiroaki Miyata, Cyrus Ghaznavi, Kenji Shibuya, Shuhei Nomura

2020-Current year OA Pubs

BACKGROUND: The Tokyo 2020 Summer Olympic Games (23 July-8 August 2021) were held in the middle of Japan's fifth wave of COVID-19, when the number of cases was on the rise, and coincided with the fourth state of emergency implemented by the host city, Tokyo.

AIM: This study aimed to assess whether the hosting of the Games was associated with a change in the number of COVID-19 cases in Japan using a synthetic control method.

METHODS: A weighted average of control countries with a variety of predictors was used to estimate the counterfactual trajectory of daily COVID-19 cases per 1 …


Integrated Stem Cell Signature And Cytomolecular Risk Determination In Pediatric Acute Myeloid Leukemia., Benjamin J. Huang, Jenny L. Smith, Jason E. Farrar, Yi-Cheng Wang, Masayuki Umeda, Rhonda E. Ries, Amanda R. Leonti, Erin Crowgey, Scott N. Furlan, Katherine Tarlock, Marcos Armendariz, Yanling Liu, Timothy I. Shaw, Lisa Wei, Robert B. Gerbing, Todd M. Cooper, Alan S. Gamis, Richard Aplenc, E Anders Kolb, Jeffrey Rubnitz, Jing Ma, Jeffery M. Klco, Xiaotu Ma, Todd A. Alonzo, Timothy Triche, Soheil Meshinchi Sep 2022

Integrated Stem Cell Signature And Cytomolecular Risk Determination In Pediatric Acute Myeloid Leukemia., Benjamin J. Huang, Jenny L. Smith, Jason E. Farrar, Yi-Cheng Wang, Masayuki Umeda, Rhonda E. Ries, Amanda R. Leonti, Erin Crowgey, Scott N. Furlan, Katherine Tarlock, Marcos Armendariz, Yanling Liu, Timothy I. Shaw, Lisa Wei, Robert B. Gerbing, Todd M. Cooper, Alan S. Gamis, Richard Aplenc, E Anders Kolb, Jeffrey Rubnitz, Jing Ma, Jeffery M. Klco, Xiaotu Ma, Todd A. Alonzo, Timothy Triche, Soheil Meshinchi

Manuscripts, Articles, Book Chapters and Other Papers

Relapsed or refractory pediatric acute myeloid leukemia (AML) is associated with poor outcomes and relapse risk prediction approaches have not changed significantly in decades. To build a robust transcriptional risk prediction model for pediatric AML, we perform RNA-sequencing on 1503 primary diagnostic samples. While a 17 gene leukemia stem cell signature (LSC17) is predictive in our aggregated pediatric study population, LSC17 is no longer predictive within established cytogenetic and molecular (cytomolecular) risk groups. Therefore, we identify distinct LSC signatures on the basis of AML cytomolecular subtypes (LSC47) that were more predictive than LSC17. Based on these findings, we build a …


A Small Molecule Antagonist Of Smn Disrupts The Interaction Between Smn And Rnap Ii, Yanli Liu, Aman Iqbal, Weiguo Li, Zuyao Ni, Yalong Wang, Karan Joshua Abraham, Dorothy Yanling Zhao, Su Qin, Peter Loppnau, Honglv Jiang, Xinghua Guo, Peter J Brown, Xuechu Zhen, Guoqiang Xu, Karim Mekhail, Xingyue Ji, Mark T Bedford, Jack F Greenblatt, Jinrong Min Sep 2022

A Small Molecule Antagonist Of Smn Disrupts The Interaction Between Smn And Rnap Ii, Yanli Liu, Aman Iqbal, Weiguo Li, Zuyao Ni, Yalong Wang, Karan Joshua Abraham, Dorothy Yanling Zhao, Su Qin, Peter Loppnau, Honglv Jiang, Xinghua Guo, Peter J Brown, Xuechu Zhen, Guoqiang Xu, Karim Mekhail, Xingyue Ji, Mark T Bedford, Jack F Greenblatt, Jinrong Min

Faculty, Staff and Student Publications

Survival of motor neuron (SMN) functions in diverse biological pathways via recognition of symmetric dimethylarginine (Rme2s) on proteins by its Tudor domain, and deficiency of SMN leads to spinal muscular atrophy. Here we report a potent and selective antagonist with a 4-iminopyridine scaffold targeting the Tudor domain of SMN. Our structural and mutagenesis studies indicate that both the aromatic ring and imino groups of compound 1 contribute to its selective binding to SMN. Various on-target engagement assays support that compound 1 specifically recognizes SMN in a cellular context and prevents the interaction of SMN with the R1810me2s of RNA polymerase …


Targeting Ras Mutant Colorectal Cancer With Dual Inhibition Of Mek And Cdk4/6, Alexey V Sorokin, Preeti Kanikarla Marie, Lea Bitner, Muddassir Syed, Melanie Woods, Lawrence N Kwong, Van K Morris, Philip Jones, David G Menter, Michael S Lee, Scott Kopetz Sep 2022

Targeting Ras Mutant Colorectal Cancer With Dual Inhibition Of Mek And Cdk4/6, Alexey V Sorokin, Preeti Kanikarla Marie, Lea Bitner, Muddassir Syed, Melanie Woods, Lawrence N Kwong, Van K Morris, Philip Jones, David G Menter, Michael S Lee, Scott Kopetz

Faculty, Staff and Student Publications

UNLABELLED: KRAS and NRAS mutations occur in 45% of colorectal cancers, with combined MAPK pathway and CDK4/6 inhibition identified as a potential therapeutic strategy. In the current study, this combinatorial treatment approach was evaluated in a co-clinical trial in patient-derived xenografts (PDX), and safety was established in a clinical trial of binimetinib and palbociclib in patients with metastatic colorectal cancer with RAS mutations. Across 18 PDX models undergoing dual inhibition of MEK and CDK4/6, 60% of tumors regressed, meeting the co-clinical trial primary endpoint. Prolonged duration of response occurred predominantly in TP53 wild-type models. Clinical evaluation of binimetinib and palbociclib …


Risk And Incidence Of Head And Neck Cancers In Veterans Living With Hiv And Matched Hiv-Negative Veterans, Jennifer R Kramer, Donna L White, Kathryn E Royse, Suchismita Raychaudhury, Vlad C Sandulache, Sarah T Ahmed, Jose P Zevallos, Peter A Richardson, Andrew G Sikora, Elizabeth Y Chiao Sep 2022

Risk And Incidence Of Head And Neck Cancers In Veterans Living With Hiv And Matched Hiv-Negative Veterans, Jennifer R Kramer, Donna L White, Kathryn E Royse, Suchismita Raychaudhury, Vlad C Sandulache, Sarah T Ahmed, Jose P Zevallos, Peter A Richardson, Andrew G Sikora, Elizabeth Y Chiao

Faculty, Staff and Students Publications

BACKGROUND: Persons living with HIV/AIDS have a higher incidence of virus-related and tobacco/alcohol-related cancers. This study is the first to estimate the effect of HIV versus HIV-negative veterans on the risk of head and neck squamous cell carcinoma incidence in a large retrospective cohort study.

METHODS: The authors constructed a retrospective cohort study using patient data from 1999 to 2016 from the National Veterans Administration Corporate Data Warehouse and the VA Central Cancer Registry. This cohort study included 45,052 veterans living with HIV/AIDS and 162,486 HIV-negative patients matched by age, sex, and index visit (i.e., HIV diagnosis date or clinic …


Where Have All The Flowers Gone? A Multicenter Investigation Of Frequent Users Of Midwest Emergency Department Services During The Covid-19 Stay-At-Home Orders., Howard W Levitin, Bruce G Jones, Marie M Lockhart, Christopher M Lloyd, Meenal D Sharkey, Paul A Willette, Andrew F Kalnow Sep 2022

Where Have All The Flowers Gone? A Multicenter Investigation Of Frequent Users Of Midwest Emergency Department Services During The Covid-19 Stay-At-Home Orders., Howard W Levitin, Bruce G Jones, Marie M Lockhart, Christopher M Lloyd, Meenal D Sharkey, Paul A Willette, Andrew F Kalnow

Ambulatory and Primary Care Articles

INTRODUCTION: In this study we aimed to determine the impact of the mandatory coronavirus disease 2019 (COVID-19) pandemic stay-at-home order on the proportional makeup of emergency department (ED) visits by frequent users and super users.

METHODS: We conducted a secondary analysis of existing data using a multisite review of the medical records of 280,053 patients to measure the impact of the COVID-19 pandemic stay-at-home order on ED visits. The primary outcomes included analysis before and during the lockdown in determining ED use and unique characteristics of non-frequent, frequent, and super users of emergency services.

RESULTS: During the mandatory COVID-19 stay-at-home …


Inhibition Of Uba6 By Inosine Augments Tumour Immunogenicity And Responses, Lei Zhang, Li Jiang, Liang Yu, Qin Li, Xiangjun Tian, Ling Zeng, Chaoran Wang, Yuhan Wei, Xiaoyue Jiang, Jing Li, Xiaolu Ge, Qisheng Gu, Jikun Li, Di Wu, Anthony J Sadler, Di Yu, Dakang Xu, Yue Gao, Xiangliang Yuan, Baokun He Sep 2022

Inhibition Of Uba6 By Inosine Augments Tumour Immunogenicity And Responses, Lei Zhang, Li Jiang, Liang Yu, Qin Li, Xiangjun Tian, Ling Zeng, Chaoran Wang, Yuhan Wei, Xiaoyue Jiang, Jing Li, Xiaolu Ge, Qisheng Gu, Jikun Li, Di Wu, Anthony J Sadler, Di Yu, Dakang Xu, Yue Gao, Xiangliang Yuan, Baokun He

Faculty, Staff and Student Publications

Anti-cancer immunity and response to immune therapy is influenced by the metabolic states of the tumours. Immune checkpoint blockade therapy (ICB) is known to involve metabolic adaptation, however, the mechanism is not fully known. Here we show, by metabolic profiling of plasma samples from melanoma-bearing mice undergoing anti-PD1 and anti-CTLA4 combination therapy, that higher levels of purine metabolites, including inosine, mark ICB sensitivity. Metabolic profiles of ICB-treated human cancers confirm the association between inosine levels and ICB sensitivity. In mouse models, inosine supplementation sensitizes tumours to ICB, even if they are intrinsically ICB resistant, by enhancing T cell-mediated cytotoxicity and …


A Review Of The Effectiveness, Feasibility, And Acceptability Of Art Therapy For Children And Adolescents During The Covid-19 Pandemic, Stefan Kohler, Nhan Trong Huynh Vo, Linh Mai Vu Nguyen, Linh Gia Vu, Vu Anh Trong Dam, Thomy Duong, Dan Linh Nguyen Do, Ngoc Minh Do, Roger S Mclntyre, Carl Latkin, Roger Chun Man Ho, Cyrus Su Hui Ho Sep 2022

A Review Of The Effectiveness, Feasibility, And Acceptability Of Art Therapy For Children And Adolescents During The Covid-19 Pandemic, Stefan Kohler, Nhan Trong Huynh Vo, Linh Mai Vu Nguyen, Linh Gia Vu, Vu Anh Trong Dam, Thomy Duong, Dan Linh Nguyen Do, Ngoc Minh Do, Roger S Mclntyre, Carl Latkin, Roger Chun Man Ho, Cyrus Su Hui Ho

Faculty, Staff and Student Publications

Art therapy has been widely offered to reduce symptoms of psychological disturbance. Pooled evidence about its effectiveness in epidemic contexts, particularly during the COVID-19 pandemic, has not been yet established. This study reviewed the effectiveness, feasibility, and acceptability of art therapy on children and adolescents during the COVID-19 pandemic and past epidemics. We searched PubMed/Medline, PsycINFO, CENTRAL (Cochrane Library), and CINAHL for articles on art therapy during COVID-19. Included studies reported improvements in measures of mental health, sleep quality, and psychological well-being in children with or without disabilities in the epidemic context. Results also showed that art therapy was highly …


Epigenetic Activation Of The Flt3 Gene By Znf384 Fusion Confers A Therapeutic Susceptibility In Acute Lymphoblastic Leukemia., Xujie Zhao, Ping Wang, Jonathan D Diedrich, Brandon Smart, Noemi Reyes, Satoshi Yoshimura, Jingliao Zhang, Wentao Yang, Kelly Barnett, Beisi Xu, Zhenhua Li, Xin Huang, Jiyang Yu, Kristine Crews, Allen Eng Juh Yeoh, Marina Konopleva, Chia-Lin Wei, Ching-Hon Pui, Daniel Savic, Jun J Yang Sep 2022

Epigenetic Activation Of The Flt3 Gene By Znf384 Fusion Confers A Therapeutic Susceptibility In Acute Lymphoblastic Leukemia., Xujie Zhao, Ping Wang, Jonathan D Diedrich, Brandon Smart, Noemi Reyes, Satoshi Yoshimura, Jingliao Zhang, Wentao Yang, Kelly Barnett, Beisi Xu, Zhenhua Li, Xin Huang, Jiyang Yu, Kristine Crews, Allen Eng Juh Yeoh, Marina Konopleva, Chia-Lin Wei, Ching-Hon Pui, Daniel Savic, Jun J Yang

Faculty Research 2022

FLT3 is an attractive therapeutic target in acute lymphoblastic leukemia (ALL) but the mechanism for its activation in this cancer is incompletely understood. Profiling global gene expression in large ALL cohorts, we identify over-expression of FLT3 in ZNF384-rearranged ALL, consistently across cases harboring different fusion partners with ZNF384. Mechanistically, we discover an intergenic enhancer element at the FLT3 locus that is exclusively activated in ZNF384-rearranged ALL, with the enhancer-promoter looping directly mediated by the fusion protein. There is also a global enrichment of active enhancers within ZNF384 binding sites across the genome in ZNF384-rearranged ALL cells. Downregulation of ZNF384 blunts …


The Effects On Gait Of 4-Wheeled Walker Use In People With Alzheimer's Disease Dementia And Gait Impairment: A Pilot Study, Humberto Omaña, Edward Madou, Susan W. Hunter Sep 2022

The Effects On Gait Of 4-Wheeled Walker Use In People With Alzheimer's Disease Dementia And Gait Impairment: A Pilot Study, Humberto Omaña, Edward Madou, Susan W. Hunter

Physical Therapy Publications

In people with dementia, provision of mobility aids is standard treatment for those with impaired gait. However, mobility aid use is independently associated with increased falls risk. In this short communication, gait velocity and stride time variability were recorded in eleven adults with Alzheimer's disease dementia. Three conditions were tested: single-task (no aid), walking with a walker, and dual-task (walker use and counting backwards) under both a straight path and Figure-of-8 walking configuration. Gait velocity increased when using a walker compared to no aid in the Figure-of-8 walking configuration. Walker use improved gait in simple walking, but benefits diminished upon …


Transplant Outcomes After Cpx-351 Vs 7 + 3 In Older Adults With Newly Diagnosed High-Risk And/Or Secondary Aml, Geoffrey L Uy, Laura F Newell, Tara L Lin, Stuart L Goldberg, Matthew J Wieduwilt, Robert J Ryan, Stefan Faderl, Jeffrey E Lancet Sep 2022

Transplant Outcomes After Cpx-351 Vs 7 + 3 In Older Adults With Newly Diagnosed High-Risk And/Or Secondary Aml, Geoffrey L Uy, Laura F Newell, Tara L Lin, Stuart L Goldberg, Matthew J Wieduwilt, Robert J Ryan, Stefan Faderl, Jeffrey E Lancet

2020-Current year OA Pubs

No abstract provided.


American Society Of Hematology Living Guidelines On The Use Of Anticoagulation For Thromboprophylaxis In Patients With Covid-19: January 2022 Update On The Use Of Therapeutic-Intensity Anticoagulation In Acutely Ill Patients, Adam Cuker, Kristen M Sanfilippo, Et Al Sep 2022

American Society Of Hematology Living Guidelines On The Use Of Anticoagulation For Thromboprophylaxis In Patients With Covid-19: January 2022 Update On The Use Of Therapeutic-Intensity Anticoagulation In Acutely Ill Patients, Adam Cuker, Kristen M Sanfilippo, Et Al

2020-Current year OA Pubs

BACKGROUND: COVID-19-related acute illness is associated with an increased risk of venous thromboembolism (VTE).

OBJECTIVE: These evidence-based guidelines from the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in making decisions about the use of anticoagulation in patients with COVID-19.

METHODS: ASH formed a multidisciplinary guideline panel that included patient representatives and applied strategies to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process and performed systematic evidence reviews (through November 2021). The panel prioritized clinical questions and outcomes according to their importance for …