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Articles 3721 - 3750 of 7437
Full-Text Articles in Entire DC Network
Recruiting A Prospective Community Cohort To Study Alzheimer's Disease And Structural And Social Determinants Of Health Among Adults Racialized As Black: The Arches Cohort, Alexis I B Walker, Jean-Francois Trani, Christian F Banks, Samantha A Murphy, Wenqing Zha, Monique M Williams, Gregory S Day, Yiqi Zhu, Beau M Ances, Carl V Hill, Darrell L Hudson, Ganesh M Babulal
Recruiting A Prospective Community Cohort To Study Alzheimer's Disease And Structural And Social Determinants Of Health Among Adults Racialized As Black: The Arches Cohort, Alexis I B Walker, Jean-Francois Trani, Christian F Banks, Samantha A Murphy, Wenqing Zha, Monique M Williams, Gregory S Day, Yiqi Zhu, Beau M Ances, Carl V Hill, Darrell L Hudson, Ganesh M Babulal
2020-Current year OA Pubs
INTRODUCTION: This ongoing, prospective study examines the effectiveness of methods used to successfully recruit and retain 238 Black older adults in a longitudinal, observational Alzheimer's disease (AD) study.
METHODS: Recruitment strategies included traditional media, established research registries, speaking engagements, community events, and snowball sampling. Participants were asked to complete an annual office testing session, blood-based biomarker collection, optional one-time magnetic resonance imaging (MRI) scan, and community workshop.
RESULTS: Within the first 22 months of active recruitment, 629 individuals expressed interest in participating, and 238 enrolled in the ongoing study. Of the recruitment methods used, snowball sampling, community events, and speaking …
Cognitive And Functional Performance And Plasma Biomarkers Of Early Alzheimer's Disease In Down Syndrome, Emily K Schworer, Beau M Ances, Et Al.
Cognitive And Functional Performance And Plasma Biomarkers Of Early Alzheimer's Disease In Down Syndrome, Emily K Schworer, Beau M Ances, Et Al.
2020-Current year OA Pubs
INTRODUCTION: People with Down syndrome (DS) have a 75% to 90% lifetime risk of Alzheimer's disease (AD). AD pathology begins a decade or more prior to onset of clinical AD dementia in people with DS. It is not clear if plasma biomarkers of AD pathology are correlated with early cognitive and functional impairments in DS, and if these biomarkers could be used to track the early stages of AD in DS or to inform inclusion criteria for clinical AD treatment trials.
METHODS: This large cross-sectional cohort study investigated the associations between plasma biomarkers of amyloid beta (Aβ)42/40, total tau, and …
Impahct: A Randomized Phase 2b/3 Study Of Inhaled Imatinib For Pulmonary Arterial Hypertension, Hunter Gillies, Murali M Chakinala, Benjamin T Dake, Jeremy P Feldman, Marius M Hoeper, Marc Humbert, Zhi-Cheng Jing, Jonathan Langley, Vallerie V Mclaughlin, Ralph W Niven, Stephan Rosenkranz, Xiaosha Zhang, Nicholas S Hill
Impahct: A Randomized Phase 2b/3 Study Of Inhaled Imatinib For Pulmonary Arterial Hypertension, Hunter Gillies, Murali M Chakinala, Benjamin T Dake, Jeremy P Feldman, Marius M Hoeper, Marc Humbert, Zhi-Cheng Jing, Jonathan Langley, Vallerie V Mclaughlin, Ralph W Niven, Stephan Rosenkranz, Xiaosha Zhang, Nicholas S Hill
2020-Current year OA Pubs
AV-101 (imatinib) powder for inhalation, an investigational dry powder inhaled formulation of imatinib designed to target the underlying pathobiology of pulmonary arterial hypertension, was generally well tolerated in healthy adults in a phase 1 single and multiple ascending dose study.
Awareness, Access, And Communication: Provider Perspectives On Early Intervention Services For Children With Sickle Cell Disease, Andrew M Heitzer, Erin Macarthur, Mollie Tamboli, Ashley Wilson, Jane S Hankins, Catherine R Hoyt
Awareness, Access, And Communication: Provider Perspectives On Early Intervention Services For Children With Sickle Cell Disease, Andrew M Heitzer, Erin Macarthur, Mollie Tamboli, Ashley Wilson, Jane S Hankins, Catherine R Hoyt
2020-Current year OA Pubs
PURPOSE: This study aimed to identify determinants influencing the utilization of early intervention services among young children with sickle cell disease (SCD) based on perspectives from medical and early intervention providers.
DESIGN AND METHODS: Early intervention and medical providers from the catchment area surrounding St. Jude Children's Research Hospital and Washington University were recruited (20 total providers). Interviews were completed over the phone and audio recorded. All interviews were transcribed verbatim, coded, and analyzed using inductive thematic analysis.
RESULTS: Three overarching themes were identified from both groups: Awareness (e.g., lack of awareness about the EI system and SCD), Access (e.g., …
Children With Non-Central Nervous System Tumors Treated With Platinum-Based Chemotherapy Are At Risk For Hearing Loss And Cognitive Impairments, Allison J L'Hotta, Anne Spence, Taniya E Varughese, Kara Felts, Susan S Hayashi, Megan Jones-White, Emily Lafentres, Judith E C Lieu, Robert J Hayashi, Allison A King
Children With Non-Central Nervous System Tumors Treated With Platinum-Based Chemotherapy Are At Risk For Hearing Loss And Cognitive Impairments, Allison J L'Hotta, Anne Spence, Taniya E Varughese, Kara Felts, Susan S Hayashi, Megan Jones-White, Emily Lafentres, Judith E C Lieu, Robert J Hayashi, Allison A King
2020-Current year OA Pubs
BACKGROUND: Childhood cancer survivors (CCS) with chemotherapy induced sensorineural hearing loss (SNHL) are at risk for neurocognitive impairments. The purpose of this study was to determine the relationship between SNHL and cognitive function among CCS.
PROCEDURE: Inclusion: non-CNS solid tumor diagnosis; history of platinum chemotherapy (cisplatin and/or carboplatin); 8-17 years of age; off anti-cancer treatment for ≥6 months; and English speaking. Exclusion: history of intrathecal chemotherapy, cranial radiation, or baseline neurocognitive disorder. Participants completed the NIH Toolbox Cognition Battery at enrollment.
RESULTS: Fifty-seven individuals enrolled; 52 completed full cognitive testing. Participants were on average 12.2 years of age and 7.0 …
Early Detection Of Myocardial Involvement By Non-Contrast T1Ρ Mapping Of Cardiac Magnetic Resonance In Type 2 Diabetes Mellitus, Hongmin Shu, Huimin Xu, Zixiang Pan, Yan Liu, Wei Deng, Ren Zhao, Yan Sun, Zhen Wang, Jinxiu Yang, Hui Gao, Kaixuan Yao, Jie Zheng, Yongqiang Yu, Xiaohu Li
Early Detection Of Myocardial Involvement By Non-Contrast T1Ρ Mapping Of Cardiac Magnetic Resonance In Type 2 Diabetes Mellitus, Hongmin Shu, Huimin Xu, Zixiang Pan, Yan Liu, Wei Deng, Ren Zhao, Yan Sun, Zhen Wang, Jinxiu Yang, Hui Gao, Kaixuan Yao, Jie Zheng, Yongqiang Yu, Xiaohu Li
2020-Current year OA Pubs
OBJECTIVE: This study aims to determine the effectiveness of T1ρ in detecting myocardial fibrosis in type 2 diabetes mellitus (T2DM) patients by comparing with native T1 and extracellular volume (ECV) fraction.
METHODS: T2DM patients (n = 35) and healthy controls (n = 30) underwent cardiac magnetic resonance. ECV, T1ρ, native T1, and global longitudinal strain (GLS) values were assessed. Diagnostic performance was analyzed using receiver operating curves.
RESULTS: The global ECV and T1ρ of T2DM group (ECV = 32.1 ± 3.2%, T1ρ = 51.6 ± 3.8 msec) were significantly higher than those of controls (ECV = 26.2 ± 1.6%, T1ρ …
Assessing Quality Of Life In Childhood Cancer Survivors At Risk For Hearing Loss: A Comparison Of Hear-Ql And Promis Measures, Anne Spence, Allison J L'Hotta, Susan S Hayashi, Kara Felts, Emily Lafentres, Megan Jones-White, Judith E C Lieu, Allison A King, Robert J Hayashi
Assessing Quality Of Life In Childhood Cancer Survivors At Risk For Hearing Loss: A Comparison Of Hear-Ql And Promis Measures, Anne Spence, Allison J L'Hotta, Susan S Hayashi, Kara Felts, Emily Lafentres, Megan Jones-White, Judith E C Lieu, Allison A King, Robert J Hayashi
2020-Current year OA Pubs
BACKGROUND: Childhood cancer survivors (CCS) exposed to platinum chemotherapy are at an increased risk of developing hearing loss and reporting decreased quality of life (QOL). This study compared two QOL measures; one developed for children with hearing loss, The Hearing Environments and Refection on Quality of Life (HEAR-QL), and one validated in CCS, the Patient-Reported Outcomes Measurement Information System (PROMIS), to assess their ability to evaluate QOL deficits in this population.
METHODS: Subject eligibility were restricted to CCS exposed to platinum-based chemotherapy but who were free of known risk factors for cognitive impairment, (non-central nervous system tumor, no cranial radiation, …
Case Report: Long-Term Follow-Up Of Patients Who Received A Fimch Vaccine For Prevention Of Recurrent Urinary Tract Infections Caused By Antibiotic Resistant Enterobacteriaceae: A Case Report Series, Elise Perer, Helen Stacey, Terri Eichorn, Heidi Hughey, Julie Lawrence, Eric Cunningham, Mark O'Neil Johnson, Kevin Bacon, Andrew Kau, Scott J Hultgren, Thomas M Hooton, Jennifer L Harris
Case Report: Long-Term Follow-Up Of Patients Who Received A Fimch Vaccine For Prevention Of Recurrent Urinary Tract Infections Caused By Antibiotic Resistant Enterobacteriaceae: A Case Report Series, Elise Perer, Helen Stacey, Terri Eichorn, Heidi Hughey, Julie Lawrence, Eric Cunningham, Mark O'Neil Johnson, Kevin Bacon, Andrew Kau, Scott J Hultgren, Thomas M Hooton, Jennifer L Harris
2020-Current year OA Pubs
Urinary tract infections (UTI) caused by carbapenem-resistant Enterobacteriaceae (CRE) are considered one of the most urgent health threats to humans according to the Centers for Disease Control (CDC), and the World Health Organization (WHO). A FimCH Vaccine expanded access study is being conducted in patients with a history of antibiotic resistant UTIs who are considered to be at risk for development of CRE UTI. This case series describes the clinical, safety and immunogenicity findings for four participants who received a FimCH four-vaccine series. Participants were followed for 12 months after administration of the fourth vaccine for safety, general health status …
Post-Traumatic Stress And Future Substance Use Outcomes: Leveraging Antecedent Factors To Stratify Risk, Henri M Garrison-Desany, Stacey L House, Et Al.
Post-Traumatic Stress And Future Substance Use Outcomes: Leveraging Antecedent Factors To Stratify Risk, Henri M Garrison-Desany, Stacey L House, Et Al.
2020-Current year OA Pubs
BACKGROUND: Post-traumatic stress disorder (PTSD) and substance use (tobacco, alcohol, and cannabis) are highly comorbid. Many factors affect this relationship, including sociodemographic and psychosocial characteristics, other prior traumas, and physical health. However, few prior studies have investigated this prospectively, examining new substance use and the extent to which a wide range of factors may modify the relationship to PTSD.
METHODS: The Advancing Understanding of RecOvery afteR traumA (AURORA) study is a prospective cohort of adults presenting at emergency departments (N = 2,943). Participants self-reported PTSD symptoms and the frequency and quantity of tobacco, alcohol, and cannabis use at six total …
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
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
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
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 …
An Internet Mantram Repetition Program To Promote Well-Being In Breast Cancer Survivors: A Feasibility Randomized Controlled Trial, Jennifer M Hulett, An-Lin Cheng, Jill E Bormann, Allison B Anbari, Jane M Armer, Brooke M Hartman, B Ann Bettencourt, Leeanne B Sherwin, Edie L Sperling, Natsayakarn Narkthong, Carol Reinero, Hans Rindt, Kathy Schreiber, Lindsay L Peterson, Emily Albright
An Internet Mantram Repetition Program To Promote Well-Being In Breast Cancer Survivors: A Feasibility Randomized Controlled Trial, Jennifer M Hulett, An-Lin Cheng, Jill E Bormann, Allison B Anbari, Jane M Armer, Brooke M Hartman, B Ann Bettencourt, Leeanne B Sherwin, Edie L Sperling, Natsayakarn Narkthong, Carol Reinero, Hans Rindt, Kathy Schreiber, Lindsay L Peterson, Emily Albright
2020-Current year OA Pubs
No abstract provided.
Comparison Of Cerebrospinal Fluid, Plasma And Neuroimaging Biomarker Utility In Alzheimer's Disease, Karin L Meeker, Patrick H Luckett, Nicolas R Barthélemy, Diana A Hobbs, Charles Chen, James Bollinger, Vitaliy Ovod, Shaney Flores, Sarah Keefe, Rachel L Henson, Elizabeth M Herries, Eric Mcdade, Jason J Hassenstab, Chengjie Xiong, Carlos Cruchaga, Tammie L S Benzinger, David M Holtzman, Suzanne E Schindler, Randall J Bateman, John C Morris, Brian A Gordon, Beau M Ances
Comparison Of Cerebrospinal Fluid, Plasma And Neuroimaging Biomarker Utility In Alzheimer's Disease, Karin L Meeker, Patrick H Luckett, Nicolas R Barthélemy, Diana A Hobbs, Charles Chen, James Bollinger, Vitaliy Ovod, Shaney Flores, Sarah Keefe, Rachel L Henson, Elizabeth M Herries, Eric Mcdade, Jason J Hassenstab, Chengjie Xiong, Carlos Cruchaga, Tammie L S Benzinger, David M Holtzman, Suzanne E Schindler, Randall J Bateman, John C Morris, Brian A Gordon, Beau M Ances
2020-Current year OA Pubs
Alzheimer's disease biomarkers are crucial to understanding disease pathophysiology, aiding accurate diagnosis and identifying target treatments. Although the number of biomarkers continues to grow, the relative utility and uniqueness of each is poorly understood as prior work has typically calculated serial pairwise relationships on only a handful of markers at a time. The present study assessed the cross-sectional relationships among 27 Alzheimer's disease biomarkers simultaneously and determined their ability to predict meaningful clinical outcomes using machine learning. Data were obtained from 527 community-dwelling volunteers enrolled in studies at the Charles F. and Joanne Knight Alzheimer Disease Research Center at Washington …
Transcriptional Precision In Photoreceptor Development And Diseases - Lessons From 25 Years Of Crx Research, Yiqiao Zheng, Shiming Chen
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
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
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 …
Disentangling Socioeconomic Status And Race In Infant Brain, Birth Weight, And Gestational Age At Birth: A Neural Network Analysis, Kathryn Sarullo, Deanna M Barch, Christopher D Smyser, Cynthia Rogers, Barbara B Warner, J Philip Miller, Sarah K England, Joan Luby, S Joshua Swamidass
Disentangling Socioeconomic Status And Race In Infant Brain, Birth Weight, And Gestational Age At Birth: A Neural Network Analysis, Kathryn Sarullo, Deanna M Barch, Christopher D Smyser, Cynthia Rogers, Barbara B Warner, J Philip Miller, Sarah K England, Joan Luby, S Joshua Swamidass
2020-Current year OA Pubs
BACKGROUND: Race is commonly used as a proxy for multiple features including socioeconomic status. It is critical to dissociate these factors, to identify mechanisms that affect infant outcomes, such as birth weight, gestational age, and brain development, and to direct appropriate interventions and shape public policy.
METHODS: Demographic, socioeconomic, and clinical variables were used to model infant outcomes. There were 351 participants included in the analysis for birth weight and gestational age. For the analysis using brain volumes, 280 participants were included after removing participants with missing magnetic resonance imaging scans and those matching our exclusion criteria. We modeled these …
A Structure-Function Analysis Of Hepatocyte Arginase 2 Reveals Mitochondrial Ureahydrolysis As A Determinant Of Glucose Oxidation, Yiming Zhang, Jiameng Sun, Henry D Wasserman, Joshua A Adams, Cassandra B Higgins, Shannon C Kelly, Louise Lantier, Brian J Debosch
A Structure-Function Analysis Of Hepatocyte Arginase 2 Reveals Mitochondrial Ureahydrolysis As A Determinant Of Glucose Oxidation, Yiming Zhang, Jiameng Sun, Henry D Wasserman, Joshua A Adams, Cassandra B Higgins, Shannon C Kelly, Louise Lantier, Brian J Debosch
2020-Current year OA Pubs
BACKGROUND & AIMS: Restoring hepatic and peripheral insulin sensitivity is critical to prevent or reverse metabolic syndrome and type 2 diabetes. Glucose homeostasis comprises in part the complex regulation of hepatic glucose production and insulin-mediated glucose uptake and oxidation in peripheral tissues. We previously identified hepatocyte arginase 2 (Arg2) as an inducible ureahydrolase that improves glucose homeostasis and enhances glucose oxidation in multiple obese, insulin-resistant models. We therefore examined structure-function determinants through which hepatocyte Arg2 governs systemic insulin action and glucose oxidation.
METHODS: To do this, we generated mice expressing wild-type murine Arg2, enzymatically inactive Arg2 (Arg2
RESULTS: We show …
Intrusive Traumatic Re-Experiencing Domain: Functional Connectivity Feature Classification By The Enigma Ptsd Consortium, Benjamin Suarez-Jimenez, Evan M Gordon, Et Al.
Intrusive Traumatic Re-Experiencing Domain: Functional Connectivity Feature Classification By The Enigma Ptsd Consortium, Benjamin Suarez-Jimenez, Evan M Gordon, Et Al.
2020-Current year OA Pubs
BACKGROUND: Intrusive traumatic re-experiencing domain (ITRED) was recently introduced as a novel perspective on posttraumatic psychopathology, proposing to focus research of posttraumatic stress disorder (PTSD) on the unique symptoms of intrusive and involuntary re-experiencing of the trauma, namely, intrusive memories, nightmares, and flashbacks. The aim of the present study was to explore ITRED from a neural network connectivity perspective.
METHODS: Data were collected from 9 sites taking part in the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) PTSD Consortium (
RESULTS: rsFC signatures differentiated TE-only participants from PTSD and ITRED-only participants at about 60% accuracy. Conversely, rsFC signatures did …
Multiple Genes Core To Erad, Macroautophagy And Lysosomal Degradation Pathways Participate In The Proteostasis Response In Α1-Antitrypsin Deficiency, Jie Li, Tunda Hidvegi, Sanja Sviben, James A J Fitzpatrick, Hemalatha Sundaramoorthi, Stephen C Pak, Gary A Silverman, David H Perlmutter, Et Al.
Multiple Genes Core To Erad, Macroautophagy And Lysosomal Degradation Pathways Participate In The Proteostasis Response In Α1-Antitrypsin Deficiency, Jie Li, Tunda Hidvegi, Sanja Sviben, James A J Fitzpatrick, Hemalatha Sundaramoorthi, Stephen C Pak, Gary A Silverman, David H Perlmutter, Et Al.
2020-Current year OA Pubs
BACKGROUND & AIMS: In the classic form of α1-antitrypsin deficiency (ATD), the misfolded α1-antitrypsin Z (ATZ) variant accumulates in the endoplasmic reticulum (ER) of liver cells. A gain-of-function proteotoxic mechanism is responsible for chronic liver disease in a subgroup of homozygotes. Proteostatic response pathways, including conventional endoplasmic reticulum-associated degradation and autophagy, have been proposed as the mechanisms that allow cellular adaptation and presumably protection from the liver disease phenotype. Recent studies have concluded that a distinct lysosomal pathway called endoplasmic reticulum-to-lysosome completely supplants the role of the conventional macroautophagy pathway in degradation of ATZ. Here, we used several state-of-the-art approaches …
Bradykinin Receptor Expression And Bradykinin-Mediated Sensitization Of Human Sensory Neurons, Jiwon Yi, Zachariah Bertels, John Smith Del Rosario, Allie J. Widman, Richard A. Slivicki, Maria Payne, Henry M. Susser, Bryan A. Copits, Robert W. Gereau 4th
Bradykinin Receptor Expression And Bradykinin-Mediated Sensitization Of Human Sensory Neurons, Jiwon Yi, Zachariah Bertels, John Smith Del Rosario, Allie J. Widman, Richard A. Slivicki, Maria Payne, Henry M. Susser, Bryan A. Copits, Robert W. Gereau 4th
2020-Current year OA Pubs
Bradykinin is a peptide implicated in inflammatory pain in both humans and rodents. In rodent sensory neurons, activation of B1 and B2 bradykinin receptors induces neuronal hyperexcitability. Recent evidence suggests that human and rodent dorsal root ganglia (DRG), which contain the cell bodies of sensory neurons, differ in the expression and function of key GPCRs and ion channels; whether bradykinin receptor expression and function are conserved across species has not been studied in depth. In this study, we used human DRG tissue from organ donors to provide a detailed characterization of bradykinin receptor expression and bradykinin-induced changes in the excitability …
Harmonization Of Csf And Imaging Biomarkers In Alzheimer's Disease: Need And Practical Applications For Genetics Studies And Preclinical Classification, Jigyasha Timsina, Muhammad Ali, Anh Do, Lihua Wang, Daniel Western, Yun Ju Sung, Carlos Cruchaga
Harmonization Of Csf And Imaging Biomarkers In Alzheimer's Disease: Need And Practical Applications For Genetics Studies And Preclinical Classification, Jigyasha Timsina, Muhammad Ali, Anh Do, Lihua Wang, Daniel Western, Yun Ju Sung, Carlos Cruchaga
2020-Current year OA Pubs
In Alzheimer's disease (AD) research, cerebrospinal fluid (CSF) Amyloid beta (Aβ), Tau and pTau are the most accepted and well validated biomarkers. Several methods and platforms exist to measure those biomarkers, leading to challenges in combining data across studies. Thus, there is a need to identify methods that harmonize and standardize these values. We used a Z-score based approach to harmonize CSF and amyloid imaging data from multiple cohorts and compared GWAS results using this approach with currently accepted methods. We also used a generalized mixture model to calculate the threshold for biomarker-positivity. Based on our findings, our normalization approach …
Accuracy Of True-Net In Comparison To Established White Matter Hyperintensity Segmentation Methods: An Independent Validation Study, Jeremy F Strain, Maryam Rahmani, Donna Dierker, Christopher Owen, Hussain Jafri, Andrei G Vlassenko, Kyle Womack, Jurgen Fripp, Duygu Tosun, Tammie L S Benzinger, Michael Weiner, Colin Masters, Jin-Moo Lee, John C Morris, Manu S Goyal, Adopic And Adni Investigators
Accuracy Of True-Net In Comparison To Established White Matter Hyperintensity Segmentation Methods: An Independent Validation Study, Jeremy F Strain, Maryam Rahmani, Donna Dierker, Christopher Owen, Hussain Jafri, Andrei G Vlassenko, Kyle Womack, Jurgen Fripp, Duygu Tosun, Tammie L S Benzinger, Michael Weiner, Colin Masters, Jin-Moo Lee, John C Morris, Manu S Goyal, Adopic And Adni Investigators
2020-Current year OA Pubs
White matter hyperintensities (WMH) are nearly ubiquitous in the aging brain, and their topography and overall burden are associated with cognitive decline. Given their numerosity, accurate methods to automatically segment WMH are needed. Recent developments, including the availability of challenge data sets and improved deep learning algorithms, have led to a new promising deep-learning based automated segmentation model called TrUE-Net, which has yet to undergo rigorous independent validation. Here, we compare TrUE-Net to six established automated WMH segmentation tools, including a semi-manual method. We evaluated the techniques at both global and regional level to compare their ability to detect the …
Targeting Of Oncogenic Aaa-Atpase Trip13 Reduces Progression Of Pancreatic Ductal Adenocarcinoma, Farrukh Afaq, Sumit Agarwal, Prachi Bajpai, Sameer Al Diffalha, Hyung-Gyoon Kim, Shajan Peter, Moh'd Khushman, Subhash C Chauhan, Priyabrata Mukherjee, Sooryanarayana Varambally, Upender Manne
Targeting Of Oncogenic Aaa-Atpase Trip13 Reduces Progression Of Pancreatic Ductal Adenocarcinoma, Farrukh Afaq, Sumit Agarwal, Prachi Bajpai, Sameer Al Diffalha, Hyung-Gyoon Kim, Shajan Peter, Moh'd Khushman, Subhash C Chauhan, Priyabrata Mukherjee, Sooryanarayana Varambally, Upender Manne
2020-Current year OA Pubs
Thyroid hormone receptor-interacting protein 13 (TRIP13) is involved in cancer progression, but its role in pancreatic ductal adenocarcinoma (PDAC) is unknown. Thus, we assessed the expression, functional role, and mechanism of action of TRIP13 in PDAC. We further examined the efficacy of TRIP13 inhibitor, DCZ0415, alone or in combination with gemcitabine on malignant phenotypes, tumor progression, and immune response. We found that TRIP13 was overexpressed in human PDACs relative to corresponding normal pancreatic tissues. TRIP13 knockdown or treatment of PDAC cells with DCZ0415 reduced proliferation and colony formation, and induced G2/M cell cycle arrest and apoptosis. Additionally, TRIP13 knockdown or …
Leveraging Murine Models Of The Neurofibromatosis Type 1 Cancer Predisposition Syndrome To Elucidate The Cellular Circuits That Drive Pediatric Low-Grade Glioma Formation And Progression, David H Gutmann
2020-Current year OA Pubs
Brain tumors are the leading cause of cancer-related death in children, where low-grade gliomas (LGGs) predominate. One common hereditary cause for LGGs involves neurofibromatosis-1 (NF1) gene mutation, as seen in individuals with the NF1 cancer predisposition syndrome. As such, children with NF1 are at increased risk of developing LGGs of the optic pathway, brainstem, cerebellum, and midline brain structures. Using genetically engineered mouse models, studies have revealed both cell-intrinsic (MEK signaling) and stromal dependencies that underlie their formation and growth. Importantly, these dependencies represent vulnerabilities against which targeted agents can be used for preclinical investigation prior to clinical translation.
Efficacy And Health-Related Quality Of Life Impact Of Fecal Microbiota, Live-Jslm: A Post Hoc Analysis Of Punch Cd3 Patients At First Recurrence Of Clostridioides Difficile Infection, Paul Feuerstadt, Jessica R Allegretti, Erik R Dubberke, Amy Guo, Adam Harvey, Min Yang, Viviana Garcia-Horton, Mirko Fillbrunn, Glenn Tillotson, Lindy L Bancke, Kerry Laplante, Kevin W Garey, Sahil Khanna
Efficacy And Health-Related Quality Of Life Impact Of Fecal Microbiota, Live-Jslm: A Post Hoc Analysis Of Punch Cd3 Patients At First Recurrence Of Clostridioides Difficile Infection, Paul Feuerstadt, Jessica R Allegretti, Erik R Dubberke, Amy Guo, Adam Harvey, Min Yang, Viviana Garcia-Horton, Mirko Fillbrunn, Glenn Tillotson, Lindy L Bancke, Kerry Laplante, Kevin W Garey, Sahil Khanna
2020-Current year OA Pubs
INTRODUCTION: Clostridioides difficile infection (CDI) causes symptoms of varying severity and negatively impacts patients' health-related quality of life (HRQL). Despite antibiotic treatment, recurrence of CDI (rCDI) is common and imposes clinical and economic burdens on patients. Fecal microbiota, live-jslm (REBYOTA [RBL]) is newly approved in the USA for prevention of rCDI following antibiotic treatments. We analyzed efficacy and HRQL impact of RBL vs. placebo in patients at first rCDI using data from the phase 3 randomized, double-blind placebo-controlled clinical trial, PUNCH CD3.
METHODS: This post hoc analysis included patients at first rCDI fromPUNCH CD3. Treatment success (i.e., absence of diarrhea …
Disruption Of The Nascent Polypeptide-Associated Complex Leads To Reduced Polyglutamine Aggregation And Toxicity, Leeran B. Dublin-Ryan, Ankan K. Bhadra, Heather L. True
Disruption Of The Nascent Polypeptide-Associated Complex Leads To Reduced Polyglutamine Aggregation And Toxicity, Leeran B. Dublin-Ryan, Ankan K. Bhadra, Heather L. True
2020-Current year OA Pubs
The nascent polypeptide-associate complex (NAC) is a heterodimeric chaperone complex that binds near the ribosome exit tunnel and is the first point of chaperone contact for newly synthesized proteins. Deletion of the NAC induces embryonic lethality in many multi-cellular organisms. Previous work has shown that the deletion of the NAC rescues cells from prion-induced cytotoxicity. This counterintuitive result led us to hypothesize that NAC disruption would improve viability in cells expressing human misfolding proteins. Here, we show that NAC disruption improves viability in cells expressing expanded polyglutamine and also leads to delayed and reduced aggregation of expanded polyglutamine and changes …
Optic Chiasm Glioma In An Older Adult Patient, Ulviyya Gasimova, Osasu Adah, Matahi Muradova, Kaleigh Roberts, Sonika Dahiya, Rashmi Verma, Lokesh Rukmangadachar
Optic Chiasm Glioma In An Older Adult Patient, Ulviyya Gasimova, Osasu Adah, Matahi Muradova, Kaleigh Roberts, Sonika Dahiya, Rashmi Verma, Lokesh Rukmangadachar
2020-Current year OA Pubs
We present a case of an adult patient experiencing progressive visual loss. An initial presentation was concerning for neuromyelitis optica with optic chiasm involvement. However, persistent contrast enhancement observed in follow-up brain and orbit images raised suspicion for optic tract malignant neoplasm. Histopathological evolution of optic nerve biopsy confirmed the diagnosis of an optic chiasm glioma. The patient was then referred to oncology for chemotherapy.
A Global Multicohort Study To Map Subcortical Brain Development And Cognition In Infancy And Early Childhood, Ann M Alex, Kelly Botteron, Et Al.
A Global Multicohort Study To Map Subcortical Brain Development And Cognition In Infancy And Early Childhood, Ann M Alex, Kelly Botteron, Et Al.
2020-Current year OA Pubs
The human brain grows quickly during infancy and early childhood, but factors influencing brain maturation in this period remain poorly understood. To address this gap, we harmonized data from eight diverse cohorts, creating one of the largest pediatric neuroimaging datasets to date focused on birth to 6 years of age. We mapped the developmental trajectory of intracranial and subcortical volumes in ∼2,000 children and studied how sociodemographic factors and adverse birth outcomes influence brain structure and cognition. The amygdala was the first subcortical volume to mature, whereas the thalamus exhibited protracted development. Males had larger brain volumes than females, and …
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
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 …