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JOURNAL ARTICLE
Stephen Hermes, Janet Cady, Steven Armentrout, James O'Connor, Sarah Carlson Holdaway, Carlos Cruchaga, Thomas Wingo, Ellen McRae Greytak
BACKGROUND: Polygenic risk scores (PRS) are linear combinations of genetic markers weighted by effect size that are commonly used to predict disease risk. For complex heritable diseases such as late-onset Alzheimer's disease (LOAD), PRS models fail to capture much of the heritability. Additionally, PRS models are highly dependent on the population structure of the data on which effect sizes are assessed and have poor generalizability to new data. OBJECTIVE: The goal of this study is to construct a paragenic risk score that, in addition to single genetic marker data used in PRS, incorporates epistatic interaction features and machine learning methods to predict risk for LOAD...
May 23, 2024: Journal of Alzheimer's Disease: JAD
#2
JOURNAL ARTICLE
Calixto-Hope G Lucas, Kanish Mirchia, Kyounghee Seo, Hinda Najem, William C Chen, Naomi Zakimi, Kyla Foster, Charlotte D Eaton, Martha A Cady, Abrar Choudhury, S John Liu, Joanna J Phillips, Stephen T Magill, Craig M Horbinski, David A Solomon, Arie Perry, Harish N Vasudevan, Amy B Heimberger, David R Raleigh
Intratumor heterogeneity underlies cancer evolution and treatment resistance, but targetable mechanisms driving intratumor heterogeneity are poorly understood. Meningiomas are the most common primary intracranial tumors and are resistant to all medical therapies, and high-grade meningiomas have significant intratumor heterogeneity. Here we use spatial approaches to identify genomic, biochemical and cellular mechanisms linking intratumor heterogeneity to the molecular, temporal and spatial evolution of high-grade meningiomas...
May 17, 2024: Nature Genetics
#3
JOURNAL ARTICLE
Abrar Choudhury, Martha A Cady, Calixto-Hope G Lucas, Hinda Najem, Joanna J Phillips, Brisa Palikuqi, Naomi Zakimi, Tara Joseph, Janeth Ochoa Birrueta, William C Chen, Nancy Ann Oberheim Bush, Shawn L Hervey-Jumper, Ophir D Klein, Christine M Toedebusch, Craig M Horbinski, Stephen T Magill, Aparna Bhaduri, Arie Perry, Peter J Dickinson, Amy B Heimberger, Alan Ashworth, Elizabeth E Crouch, David R Raleigh
Meningiomas are the most common primary intracranial tumors. Treatments for patients with meningiomas are limited to surgery and radiotherapy, and systemic therapies remain ineffective or experimental. Resistance to radiotherapy is common in high-grade meningiomas and the cell types and signaling mechanisms that drive meningioma tumorigenesis and resistance to radiotherapy are incompletely understood. Here we report NOTCH3 drives meningioma tumorigenesis and resistance to radiotherapy and find that perivascular NOTCH3+ stem cells are conserved across meningiomas from humans, dogs, and mice...
May 14, 2024: Cancer Discovery
#4
Abrar Choudhury, Martha A Cady, Calixto-Hope G Lucas, Hinda Najem, Joanna J Phillips, Brisa Palikuqi, Naomi Zakimi, Tara Joseph, Janeth Ochoa Birrueta, William C Chen, Nancy Ann Oberheim Bush, Shawn L Hervey-Jumper, Ophir D Klein, Christine M Toedebusch, Craig M Horbinski, Stephen T Magill, Aparna Bhaduri, Arie Perry, Peter J Dickinson, Amy B Heimberger, Alan Ashworth, Elizabeth E Crouch, David R Raleigh
Meningiomas are the most common primary intracranial tumors 1-3 . Treatments for patients with meningiomas are limited to surgery and radiotherapy, and systemic therapies remain ineffective or experimental 4,5 . Resistance to radiotherapy is common in high-grade meningiomas 6 , and the cell types and signaling mechanisms driving meningioma tumorigenesis or resistance to radiotherapy are incompletely understood. Here we report NOTCH3 drives meningioma tumorigenesis and resistance to radiotherapy and find NOTCH3+ meningioma mural cells are conserved across meningiomas from humans, dogs, and mice...
July 11, 2023: bioRxiv
#5
JOURNAL ARTICLE
Peter O Dunn, Insiyaa Ahmed, Elise Armstrong, Natasha Barlow, Malcolm A Barnard, Marc Bélisle, Thomas J Benson, Lisha L Berzins, Chloe K Boynton, T Anders Brown, Melissa Cady, Kyle Cameron, Xuan Chen, Robert G Clark, Ethan D Clotfelter, Kara Cromwell, Russell D Dawson, Elsie Denton, Andrew Forbes, Kendrick Fowler, Kevin C Fraser, Kamal J K Gandhi, Dany Garant, Megan Hiebert, Claire Houchen, Jennifer Houtz, Tara L Imlay, Brian D Inouye, David W Inouye, Michelle Jackson, Andrew P Jacobson, Kristin Jayd, Christy Juteau, Andrea Kautz, Caroline Killian, Elliot Kinnear, Kimberly J Komatsu, Kirk Larsen, Andrew Laughlin, Valerie Levesque-Beaudin, Ryan Leys, Elizabeth Long, Stephen C Lougheed, Stuart Mackenzie, Jen Marangelo, Colleen Miller, Brenda Molano-Flores, Christy A Morrissey, Emony Nicholls, Jessica M Orlofske, Ian S Pearse, Fanie Pelletier, Amber L Pitt, Joseph P Poston, Danielle M Racke, Jeannine A Randall, Matthew L Richardson, Olivia Rooney, A Rose Ruegg, Scott Rush, Sadie Ryan, Mitchell Sadowski, Ivana Schoepf, Lindsay Schulz, Brenna Shea, Thomas N Sheehan, Lynn Siefferman, Derek Sikes, Mark Stanback, John D Styrsky, Conor C Taff, Jennifer J Uehling, Kathleen Uvino, Thomas Wassmer, Kathryn Weglarz, Megan Weinberger, John Wenzel, Linda A Whittingham
Climate change models often assume similar responses to temperatures across a species range, but local adaptation or phenotypic plasticity can lead plants and animals to respond differently to temperature in different parts of their range. To date, there have been few tests of this assumption at the scale of continents, so it is unclear if this is a large-scale problem. Here, we examined the assumption that insect taxa show similar responses to temperature at 96 sites in grassy habitats across North America...
March 21, 2023: Ecology
#6
Stephen Hermes, Janet Cady, Steven Armentrout, James O'Connor, Sarah Carlson, Carlos Cruchaga, Thomas Wingo, Ellen McRae Greytak
BACKGROUND: Polygenic risk scores (PRS) are linear combinations of genetic markers weighted by effect size that are commonly used to predict disease risk. For complex heritable diseases such as late onset Alzheimer's disease (LOAD), PRS models fail to capture much of the heritability. Additionally, PRS models are highly dependent on the population structure of data on which effect sizes are assessed, and have poor generalizability to new data. OBJECTIVE: The goal of this study is to construct a paragenic risk score that, in addition to single genetic marker data used in PRS, incorporates epistatic interaction features and machine learning methods to predict lifetime risk for LOAD...
February 11, 2023: medRxiv
#7
JOURNAL ARTICLE
Hansen Cao, Daven K Henze, Liye Zhu, Mark W Shephard, Karen Cady-Pereira, Enrico Dammers, Michael Sitwell, Nicholas Heath, Chantelle Lonsdale, Jesse O Bash, Kazuyuki Miyazaki, Christophe Flechard, Yannick Fauvel, Roy Wichink Kruit, Stefan Feigenspan, Christian Brümmer, Frederik Schrader, Marsailidh M Twigg, Sarah Leeson, Yuk S Tang, Amy C M Stephens, Christine Braban, Keith Vincent, Mario Meier, Eva Seitler, Camilla Geels, Thomas Ellermann, Agnieszka Sanocka, Shannon L Capps
We conduct the first 4D-Var inversion of NH3 accounting for NH3 bi-directional flux, using CrIS satellite NH3 observations over Europe in 2016. We find posterior NH3 emissions peak more in springtime than prior emissions at continental to national scales, and annually they are generally smaller than the prior emissions over central Europe, but larger over most of the rest of Europe. Annual posterior anthropogenic NH3 emissions for 25 European Union members (EU25) are 25% higher than the prior emissions and very close (<2% difference) to other inventories...
May 16, 2022: Journal of Geophysical Research. Atmospheres: JGR
#8
JOURNAL ARTICLE
Abrar Choudhury, Stephen T Magill, Charlotte D Eaton, Briana C Prager, William C Chen, Martha A Cady, Kyounghee Seo, Calixto-Hope G Lucas, Tim J Casey-Clyde, Harish N Vasudevan, S John Liu, Javier E Villanueva-Meyer, Tai-Chung Lam, Jenny Kan-Suen Pu, Lai-Fung Li, Gilberto Ka-Kit Leung, Danielle L Swaney, Michael Y Zhang, Jason W Chan, Zhixin Qiu, Michael V Martin, Matthew S Susko, Steve E Braunstein, Nancy Ann Oberheim Bush, Jessica D Schulte, Nicholas Butowski, Penny K Sneed, Mitchel S Berger, Nevan J Krogan, Arie Perry, Joanna J Phillips, David A Solomon, Joseph F Costello, Michael W McDermott, Jeremy N Rich, David R Raleigh
Meningiomas are the most common primary intracranial tumors. There are no effective medical therapies for meningioma patients, and new treatments have been encumbered by limited understanding of meningioma biology. Here, we use DNA methylation profiling on 565 meningiomas integrated with genetic, transcriptomic, biochemical, proteomic and single-cell approaches to show meningiomas are composed of three DNA methylation groups with distinct clinical outcomes, biological drivers and therapeutic vulnerabilities...
May 2022: Nature Genetics
#9
JOURNAL ARTICLE
Emily A Scherer, Stephen A Metcalf, Cady L Whicker, Sophia M Bartels, Michael Grabinski, Sunny Jung Kim, Mary Ann Sweeney, Shea M Lemley, Hannah Lavoie, Haiyi Xie, Patrick G Bissett, Jesse Dallery, Michaela Kiernan, Michael R Lowe, Lisa Onken, Judith J Prochaska, Luke E Stoeckel, Russell A Poldrack, David P MacKinnon, Lisa A Marsch
Introduction: Self-regulation has been implicated in health risk behaviors and is a target of many health behavior interventions. Despite most prior research focusing on self-regulation as an individual-level trait, we hypothesize that self-regulation is a time-varying mechanism of health and risk behavior that may be influenced by momentary contexts to a substantial degree. Because most health behaviors (e.g., eating, drinking, smoking) occur in the context of everyday activities, digital technologies may help us better understand and influence these behaviors in real time...
2022: Frontiers in digital health
#10
JOURNAL ARTICLE
Wai H Lim, Brigitte Adams, Stephen Alexander, Antonia H M Bouts, Frans Claas, Michael Collins, Elisabeth Cornelissen, Heather Dunckley, Huib de Jong, Lloyd D'Orsogna, Anna Francis, Sebastiaan Heidt, Jean Herman, Rhonda Holdsworth, Joshua Kausman, Rabia Khalid, Jon Jin Kim, Siah Kim, Noël Knops, Vasilis Kosmoliaptsis, Cynthia Kramer, Dirk Kuypers, Nicholas Larkins, Suetonia C Palmer, Chanel Prestidge, Agnieszka Prytula, Ankit Sharma, Meena Shingde, Anne Taverniti, Armando Teixeira-Pinto, Peter Trnka, Francis Willis, Daniel Wong, Germaine Wong
BACKGROUND: Parental donor kidney transplantation is the most common treatment option for children and adolescents with kidney failure. Emerging data from observational studies have reported improved short- and medium-term allograft outcomes in recipients of paternal compared to maternal donors. The INCEPTION study aims to identify potential differences in immunological compatibility between maternal and paternal donor kidneys and ascertain how this affects kidney allograft outcomes in children and adolescents with kidney failure...
December 19, 2021: BMC Nephrology
#11
COMMENT
Anne P Pribonic, Bryna C Torre, Chelsea N Cady, Stephen M McHugh
No abstract text is available yet for this article.
February 1, 2021: Anesthesia and Analgesia
#12
JOURNAL ARTICLE
Yu Wang, Indu Aravind, Zhi Cai, Lang Shen, George N Gibson, Jihan Chen, Bo Wang, Haotian Shi, Boxiang Song, Ernest F Guignon, Nathaniel C Cady, William D Page, Arturo Pilar, Stephen B Cronin
We demonstrate hot electron injection of photoexcited carriers in Ag-based plasmon resonant grating structure. By varying the incident angle of irradiation, sharp dips are observed in the reflectance with p-polarized light (electric field perpendicular to grating lines) when there is wavevector matching between the incident light and the plasmon resonant modes of the grating, and no angle dependence is observed with s-polarized light. This configuration enables us to compare photoelectrochemical current produced by plasmon resonant excitation with that of bulk metal interband absorption simply by rotating the polarization of the incident light while keeping all other parameters of the measurement fixed...
March 26, 2020: ACS Applied Materials & Interfaces
#13
JOURNAL ARTICLE
William E Pelham, Oscar Gonzalez, Stephen A Metcalf, Cady L Whicker, Katie Witkiewitz, Lisa A Marsch, David P Mackinnon
OBJECTIVE: Nearly all studies treat the Five Facet Mindfulness Questionnaire as five independent scales (one measuring each of the five facets), yet almost no methodological work has examined the psychometric structure of the facets independently. We address this gap using factor analytic methods. METHODS: Exploratory and confirmatory factor models were fit to item response data from a sample of 522 adults recruited online. Findings were replicated in a sample of 454 adults receiving aftercare for substance use disorder...
December 2019: Mindfulness
#14
JOURNAL ARTICLE
William E Pelham, Oscar Gonzalez, Stephen A Metcalf, Cady L Whicker, Emily A Scherer, Katie Witkiewitz, Lisa A Marsch, David P Mackinnon
Objectives: The Five Facet Mindfulness Questionnaire (FFMQ) is a self-report measure of mindfulness with forms of several different lengths, including the FFMQ-39, FFMQ-24, and FFMQ-15. We use item response theory analysis to directly compare the functioning of these three forms. Methods: Data were drawn from a non-clinical Amazon Mechanical Turk study ( N = 522) and studies of aftercare treatment of individuals with substance use disorders (combined N = 454). The item and test functioning of the three FFMQ forms were studied and compared...
August 2019: Mindfulness
#15
RANDOMIZED CONTROLLED TRIAL
David W Dodick, Richard B Lipton, Stephen Silberstein, Peter J Goadsby, David Biondi, Joe Hirman, Roger Cady, Jeff Smith
BACKGROUND: Calcitonin gene-related peptide plays an important role in migraine pathophysiology. We evaluated eptinezumab, an intravenous (IV) anti-calcitonin gene-related peptide monoclonal antibody, for the prevention of chronic migraine. OBJECTIVE: To determine the safety, tolerability, and effectiveness of four dose levels of eptinezumab and to inform the phase 3 development program. METHODS: This was a phase 2b, parallel-group, double-blind, randomized, placebo-controlled, dose-ranging clinical trial...
August 2019: Cephalalgia: An International Journal of Headache
#16
JOURNAL ARTICLE
Yi Wang, Lang Shen, Yu Wang, Bingya Hou, George N Gibson, Nirakar Poudel, Jihan Chen, Haotian Shi, Ernest Guignon, Nathaniel C Cady, William D Page, Arturo Pilar, Jahan Dawlaty, Stephen B Cronin
Plasmon resonant grating structures provide an effective platform for distinguishing between the effects of plasmon resonant excitation and bulk metal absorption via interband transitions. By simply rotating the polarization of the incident light, we can switch between resonant excitation and non-resonant excitation, while keeping all other parameters of the measurement constant. With light polarized perpendicular to the lines in the grating (i.e., TE-polarization), the photocatalytic reaction rate (i.e., photocurrent) is measured as the angle of the incident laser light is tuned through the resonance with the grating...
May 23, 2019: Faraday Discussions
#17
JOURNAL ARTICLE
Rameez A Qudsi, Faith Selzer, Stephen C Hill, Ariel Lerner, Jean Wildric Hippolyte, Eldine Jacques, Francel Alexis, Collin J May, Robert B Cady, Elena Losina
PURPOSE: The Ponseti Method has dramatically altered the management of clubfoot, with particular implications for limited-resource settings. We sought to describe outcomes of care and risk factors for sub-optimal results using the Ponseti Method in Haiti. METHODS: We conducted a records review of patients presenting from 2011-2015 to a CURE Clubfoot clinic in Port-au-Prince, Haiti. We report patient characteristics (demographics and clinical), treatment patterns (cast number/duration and tenotomy rates), and outcomes (relapse and complications)...
2019: PloS One
#18
MULTICENTER STUDY
Philip J O'Connell, Weijia Zhang, Madhav C Menon, Zhengzi Yi, Bernd Schröppel, Lorenzo Gallon, Yi Luan, Ivy A Rosales, Yongchao Ge, Bojan Losic, Caixia Xi, Christopher Woytovich, Karen L Keung, Chengguo Wei, Ilana Greene, Jessica Overbey, Emilia Bagiella, Nader Najafian, Milagros Samaniego, Arjang Djamali, Stephen I Alexander, Brian J Nankivell, Jeremy R Chapman, Rex Neal Smith, Robert Colvin, Barbara Murphy
BACKGROUND: Chronic injury in kidney transplants remains a major cause of allograft loss. The aim of this study was to identify a gene set capable of predicting renal allografts at risk of progressive injury due to fibrosis. METHODS: This Genomics of Chronic Allograft Rejection (GoCAR) study is a prospective, multicentre study. We prospectively collected biopsies from renal allograft recipients (n=204) with stable renal function 3 months after transplantation. We used microarray analysis to investigate gene expression in 159 of these tissue samples...
September 3, 2016: Lancet
#19
RANDOMIZED CONTROLLED TRIAL
Stephen D Silberstein, Anne H Calhoun, Richard B Lipton, Brian M Grosberg, Roger K Cady, Stefanie Dorlas, Kristy A Simmons, Chris Mullin, Eric J Liebler, Peter J Goadsby, Joel R Saper
OBJECTIVE: To evaluate the feasibility, safety, and tolerability of noninvasive vagus nerve stimulation (nVNS) for the prevention of chronic migraine (CM) attacks. METHODS: In this first prospective, multicenter, double-blind, sham-controlled pilot study of nVNS in CM prophylaxis, adults with CM (≥15 headache d/mo) entered the baseline phase (1 month) and were subsequently randomized to nVNS or sham treatment (2 months) before receiving open-label nVNS treatment (6 months)...
August 2, 2016: Neurology
#20
RANDOMIZED CONTROLLED TRIAL
Hong Sun, David W Dodick, Stephen Silberstein, Peter J Goadsby, Uwe Reuter, Messoud Ashina, Joel Saper, Roger Cady, Yun Chon, Julie Dietrich, Robert Lenz
BACKGROUND: The calcitonin gene-related peptide (CGRP) pathway is a promising target for preventive therapies in patients with migraine. We assessed the safety and efficacy of AMG 334, a fully human monoclonal antibody against the CGRP receptor, for migraine prevention. METHODS: In this multicentre, randomised, double-blind, placebo-controlled, phase 2 trial, patients aged 18-60 years with 4 to 14 migraine days per month were enrolled at 59 headache and clinical research centres in North America and Europe, and randomly assigned in a 3:2:2:2 ratio to monthly subcutaneous placebo, AMG 334 7 mg, AMG 334 21 mg, or AMG 334 70 mg using a sponsor-generated randomisation sequence centrally executed by an interactive voice response or interactive web response system...
April 2016: Lancet Neurology
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