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Sean J. Morrison

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https://www.readbyqxmd.com/read/28887402/detection-of-long-repeat-expansions-from-pcr-free-whole-genome-sequence-data
#1
Egor Dolzhenko, Joke J F A van Vugt, Richard J Shaw, Mitchell A Bekritsky, Marka van Blitterswijk, Giuseppe Narzisi, Subramanian S Ajay, Vani Rajan, Bryan R Lajoie, Nathan H Johnson, Zoya Kingsbury, Sean J Humphray, Raymond D Schellevis, William J Brands, Matt Baker, Rosa Rademakers, Maarten Kooyman, Gijs H P Tazelaar, Michael A van Es, Russell McLaughlin, William Sproviero, Aleksey Shatunov, Ashley Jones, Ahmad Al Khleifat, Alan Pittman, Sarah Morgan, Orla Hardiman, Ammar Al-Chalabi, Chris Shaw, Bradley Smith, Edmund J Neo, Karen Morrison, Pamela J Shaw, Catherine Reeves, Lara Winterkorn, Nancy S Wexler, David E Housman, Christopher W Ng, Alina L Li, Ryan J Taft, Leonard H van den Berg, David R Bentley, Jan H Veldink, Michael A Eberle
Identifying large expansions of short tandem repeats (STRs), such as those that cause amyotrophic lateral sclerosis (ALS) and fragile X syndrome, is challenging for short-read whole-genome sequencing (WGS) data. A solution to this problem is an important step toward integrating WGS into precision medicine. We developed a software tool called ExpansionHunter that, using PCR-free WGS short-read data, can genotype repeats at the locus of interest, even if the expanded repeat is larger than the read length. We applied our algorithm to WGS data from 3001 ALS patients who have been tested for the presence of the C9orf72 repeat expansion with repeat-primed PCR (RP-PCR)...
September 8, 2017: Genome Research
https://www.readbyqxmd.com/read/28825709/ascorbate-regulates-haematopoietic-stem-cell-function-and-leukaemogenesis
#2
Michalis Agathocleous, Corbin E Meacham, Rebecca J Burgess, Elena Piskounova, Zhiyu Zhao, Genevieve M Crane, Brianna L Cowin, Emily Bruner, Malea M Murphy, Weina Chen, Gerald J Spangrude, Zeping Hu, Ralph J DeBerardinis, Sean J Morrison
Stem cell fate can be influenced by metabolite levels in culture but it is unknown whether physiological variations in metabolite levels in normal tissues regulate stem cell function in vivo. We developed a metabolomics method for analysis of rare cell populations isolated directly from tissues and used it to compare haematopoietic stem cells (HSCs) to restricted haematopoietic progenitors. Each haematopoietic cell type had a distinct metabolic signature. Human and mouse HSCs had unusually high levels of ascorbate, which declined with differentiation...
August 21, 2017: Nature
https://www.readbyqxmd.com/read/28817376/association-between-hospice-spending-on-patient-care-and-rates-of-hospitalization-and-medicare-expenditures-of-hospice-enrollees
#3
Melissa D Aldridge, Andrew J Epstein, Abraham A Brody, Eric J Lee, R Sean Morrison, Elizabeth H Bradley
BACKGROUND: Care at the end of life is increasingly fragmented and is characterized by multiple hospitalizations, even among patients enrolled with hospice. OBJECTIVE: To determine whether hospice spending on direct patient care (including the cost of home visits, drugs, equipment, and counseling) is associated with hospital utilization and Medicare expenditures of hospice enrollees. DESIGN: Longitudinal, observational cohort study (2008-2010)...
August 17, 2017: Journal of Palliative Medicine
https://www.readbyqxmd.com/read/28806994/patterns-of-locoregional-failure-following-post-operative-intensity-modulated-radiotherapy-to-oral-cavity-cancer-quantitative-spatial-and-dosimetric-analysis-using-a-deformable-image-registration-workflow
#4
Abdallah S R Mohamed, Andrew J Wong, Clifton D Fuller, Mona Kamal, Gary B Gunn, Jack Phan, William H Morrison, Beth M Beadle, Heath Skinner, Stephen Y Lai, Sean R Quinlan-Davidson, Abdelaziz M Belal, Ahmed G El-Gowily, Steven J Frank, David I Rosenthal, Adam S Garden
BACKGROUND: We sought to identify spatial/dosimetric patterns of failure for oral cavity cancer patients receiving post-operative IMRT (PO-IMRT). METHODS: Two hundred eighty-nine OCC patients receiving PO-IMRT were retrospectively reviewed from 2000 to 2012. Diagnostic CT documenting recurrence (rCT) was co-registered with planning CT (pCT) using a validated deformable image registration software. Manually segmented recurrent gross disease (rGTV) was deformed to co-registered pCTs...
August 15, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/28797467/outcomes-of-oral-cavity-cancer-patients-treated-with-surgery-followed-by-postoperative-intensity-modulated-radiation-therapy
#5
Sean R Quinlan-Davidson, Abdallah S R Mohamed, Jeffrey N Myers, Gary B Gunn, Faye M Johnson, Heath Skinner, Beth M Beadle, Ann M Gillenwater, Jack Phan, Steven J Frank, William N William, Andrew J Wong, Stephen Y Lai, Clifton D Fuller, William H Morrison, David I Rosenthal, Adam S Garden
OBJECTIVES: Although treatment paradigms have not changed significantly, radiotherapy, surgery, and imaging techniques have improved, leading us to investigate oncologic and survival outcomes for oral cavity squamous cell cancer (OCSCC) patients treated with surgery followed by postoperative IMRT. MATERIAL AND METHODS: Records of patients with pathological diagnosis of OCSCC treated between 2000 and 2012 were retrospectively reviewed. Patients' demographic, disease, and treatment criteria were extracted...
September 2017: Oral Oncology
https://www.readbyqxmd.com/read/28783041/27-hydroxycholesterol-induces-hematopoietic-stem-cell-mobilization-and-extramedullary-hematopoiesis-during-pregnancy
#6
Hideyuki Oguro, Jeffrey G McDonald, Zhiyu Zhao, Michihisa Umetani, Philip W Shaul, Sean J Morrison
Extramedullary hematopoiesis (EMH) is induced during pregnancy to support rapid expansion of maternal blood volume. EMH activation requires hematopoietic stem cell (HSC) proliferation and mobilization, processes that depend upon estrogen receptor α (ERα) in HSCs. Here we show that treating mice with estradiol to model estradiol increases during pregnancy induced HSC proliferation in the bone marrow but not HSC mobilization. Treatment with the alternative ERα ligand 27-hydroxycholesterol (27HC) induced ERα-dependent HSC mobilization and EMH but not HSC division in the bone marrow...
August 7, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28732051/cd4-is-expressed-on-a-heterogeneous-subset-of-hematopoietic-progenitors-which-persistently-harbor-cxcr4-and-ccr5-tropic-hiv-proviral-genomes-in-vivo
#7
Nadia T Sebastian, Thomas D Zaikos, Valeri Terry, Frances Taschuk, Lucy A McNamara, Adewunmi Onafuwa-Nuga, Ryan Yucha, Robert A J Signer, James Riddell Iv, Dale Bixby, Norman Markowitz, Sean J Morrison, Kathleen L Collins
Latent HIV infection of long-lived cells is a barrier to viral clearance. Hematopoietic stem and progenitor cells are a heterogeneous population of cells, some of which are long-lived. CXCR4-tropic HIVs infect a broad range of HSPC subtypes, including hematopoietic stem cells, which are multi-potent and long-lived. However, CCR5-tropic HIV infection is limited to more differentiated progenitor cells with life spans that are less well understood. Consistent with emerging data that restricted progenitor cells can be long-lived, we detected persistent HIV in restricted HSPC populations from optimally treated people...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28714970/bone-marrow-adipocytes-promote-the-regeneration-of-stem-cells-and-haematopoiesis-by-secreting-scf
#8
COMPARATIVE STUDY
Bo O Zhou, Hua Yu, Rui Yue, Zhiyu Zhao, Jonathan J Rios, Olaia Naveiras, Sean J Morrison
Endothelial cells and leptin receptor(+) (LepR(+)) stromal cells are critical sources of haematopoietic stem cell (HSC) niche factors, including stem cell factor (SCF), in bone marrow. After irradiation or chemotherapy, these cells are depleted while adipocytes become abundant. We discovered that bone marrow adipocytes synthesize SCF. They arise from Adipoq-Cre/ER(+) progenitors, which represent ∼5% of LepR(+) cells, and proliferate after irradiation. Scf deletion using Adipoq-Cre/ER inhibited haematopoietic regeneration after irradiation or 5-fluorouracil treatment, depleting HSCs and reducing mouse survival...
August 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28698301/prdm16-is-required-for-the-maintenance-of-neural-stem-cells-in-the-postnatal-forebrain-and-their-differentiation-into-ependymal-cells
#9
Issei S Shimada, Melih Acar, Rebecca J Burgess, Zhiyu Zhao, Sean J Morrison
We and others showed previously that PR domain-containing 16 (Prdm16) is a transcriptional regulator required for stem cell function in multiple fetal and neonatal tissues, including the nervous system. However, Prdm16 germline knockout mice died neonatally, preventing us from testing whether Prdm16 is also required for adult stem cell function. Here we demonstrate that Prdm16 is required for neural stem cell maintenance and neurogenesis in the adult lateral ventricle subventricular zone and dentate gyrus. We also discovered that Prdm16 is required for the formation of ciliated ependymal cells in the lateral ventricle...
June 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28686011/glucosylceramide-and-glucosylsphingosine-quantitation-by-liquid-chromatography-tandem-mass-spectrometry-to-enable-in-vivo-preclinical-studies-of-neuronopathic-gaucher-disease
#10
Rick Hamler, Nastry Brignol, Sean W Clark, Sean Morrison, Leo B Dungan, Hui H Chang, Richie Khanna, Michelle Frascella, Kenneth J Valenzano, Elfrida R Benjamin, Robert E Boyd
Gaucher disease (GD) is caused by mutations in the GBA1 gene that encodes the lysosomal enzyme acid β-glucosidase (GCase). Reduced GCase activity primarily leads to the accumulation of two substrates, glucosylceramide (GlcCer) and glucosylsphingosine (GlcSph). Current treatment options have not been shown to ameliorate the neurological pathology observed in the most severe forms of GD, clearly representing an unmet medical need. To better understand the relationship between GlcCer and GlcSph accumulation and ultimately their connection with the progression of neurological pathology, we developed LC-MS/MS methods to quantify GlcCer and GlcSph in mouse brain tissue...
July 26, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28637734/pregnancy-specific-stress-fetoplacental-haemodynamics-and-neonatal-outcomes-in-women-with-small-for-gestational-age-pregnancies-a-secondary-analysis-of-the-multicentre-prospective-observational-trial-to-optimise-paediatric-health-in-intrauterine-growth-restriction
#11
Terri A Levine, Ruth E Grunau, Ricardo Segurado, Sean Daly, Michael P Geary, Mairead M Kennelly, Keelin O'Donoghue, Alyson Hunter, John J Morrison, Gerard Burke, Patrick Dicker, Elizabeth C Tully, Fergal D Malone, Fiona A Alderdice, Fionnuala M McAuliffe
OBJECTIVES: To examine associations between maternal pregnancy-specific stress and umbilical (UA PI) and middle cerebral artery pulsatility indices (MCA PI), cerebroplacental ratio, absent end diastolic flow (AEDF), birthweight, prematurity, neonatal intensive care unit admission and adverse obstetric outcomes in women with small for gestational age pregnancies. It was hypothesised that maternal pregnancy-specific stress would be associated with fetoplacental haemodynamics and neonatal outcomes...
June 21, 2017: BMJ Open
https://www.readbyqxmd.com/read/28604734/adult-haematopoietic-stem-cell-niches
#12
REVIEW
Genevieve M Crane, Elise Jeffery, Sean J Morrison
Stem cell niches are specialized microenvironments that promote the maintenance of stem cells and regulate their function. Recent advances have improved our understanding of the niches that maintain adult haematopoietic stem cells (HSCs). These advances include new markers for HSCs and niche cells, systematic analyses of the expression patterns of niche factors, genetic tools for functionally identifying niche cells in vivo, and improved imaging techniques. Together, they have shown that HSC niches are perivascular in the bone marrow and spleen...
September 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/28574529/prospective-cohort-study-of-hospitalized-adults-with-advanced-cancer-associations-between-complications-comorbidity-and-utilization
#13
Peter May, Melissa M Garrido, Melissa D Aldridge, J Brian Cassel, Amy S Kelley, Diane E Meier, Charles Normand, Joan D Penrod, Thomas J Smith, R Sean Morrison
BACKGROUND: Inpatient hospital stays account for more than a third of direct medical cancer care costs. Evidence on factors driving these costs can inform planning of services, as well as consideration of equity in access. OBJECTIVE: To measure the association between hospital costs, and demographic, clinical, and system factors, for a cohort of adults with advanced cancer. DESIGN: Prospective multisite cohort study. SETTING: Four medical and cancer centers...
June 2017: Journal of Hospital Medicine: An Official Publication of the Society of Hospital Medicine
https://www.readbyqxmd.com/read/28465357/identification-of-hair-shaft-progenitors-that-create-a-niche-for-hair-pigmentation
#14
Chung-Ping Liao, Reid C Booker, Sean J Morrison, Lu Q Le
Hair differentiates from follicle stem cells through progenitor cells in the matrix. In contrast to stem cells in the bulge, the identities of the progenitors and the mechanisms by which they regulate hair shaft components are poorly understood. Hair is also pigmented by melanocytes in the follicle. However, the niche that regulates follicular melanocytes is not well characterized. Here, we report the identification of hair shaft progenitors in the matrix that are differentiated from follicular epithelial cells expressing transcription factor KROX20...
April 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28460020/tnf-%C3%AE-and-stnf-rii-are-associated-with-pain-following-hip-fracture-surgery-in-older-adults
#15
Fred C Ko, William J Rubenstein, Eric J Lee, Albert L Siu, R Sean Morrison
Objective.:  To explore whether plasma inflammatory mediators on postoperative day 3 (POD3) are associated with pain scores in older adults after hip fracture surgery. Design.:  Cross-sectional study. Setting. : Mount Sinai Hospital, New York, New York. Subjects. : Forty patients age 60 years or older who presented with acute hip fracture at Mount Sinai Hospital between November 2011 and April 2013. Methods...
April 28, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/28278423/digoxin-plus-trametinib-therapy-achieves-disease-control-in-braf-wild-type-metastatic-melanoma-patients
#16
Arthur E Frankel, Ugur Eskiocak, Jennifer G Gill, Stacy Yuan, Vijayashree Ramesh, Thomas W Froehlich, Chul Ahn, Sean J Morrison
This is the first prospective study of a combination therapy involving a cardenolide and a MEK inhibitor for metastatic melanoma. Whereas BRAF mutant melanomas can exhibit profound responses to treatment with BRAF and MEK inhibitors, there are fewer options for BRAF wild-type melanomas. In preclinical studies, we discovered that cardenolides synergize with MEK inhibitor to promote the regression of patient-derived xenografts irrespective of BRAF mutation status. We therefore conducted a phase 1B study of digoxin 0...
April 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28213060/prediction-of-cesarean-delivery-in-the-term-nulliparous-woman-results-from-the-prospective-multicenter-genesis%C3%A2-study
#17
MULTICENTER STUDY
Naomi Burke, Gerard Burke, Fionnuala Breathnach, Fionnuala McAuliffe, John J Morrison, Michael Turner, Samina Dornan, John R Higgins, Amanda Cotter, Michael Geary, Peter McParland, Sean Daly, Fiona Cody, Pat Dicker, Elizabeth Tully, Fergal D Malone
BACKGROUND: In contemporary practice many nulliparous women require intervention during childbirth such as operative vaginal delivery or cesarean delivery (CD). Despite the knowledge that the increasing rate of CD is associated with increasing maternal age, obesity and larger infant birthweight, we lack a reliable method to predict the requirement for such potentially hazardous obstetric procedures during labor and delivery. This issue is important, as there are greater rates of morbidity and mortality associated with unplanned CD performed in labor compared with scheduled CDs...
June 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28156192/cost-analysis-of-a-prospective-multi-site-cohort-study-of-palliative-care-consultation-teams-for-adults-with-advanced-cancer-where-do-cost-savings-come-from
#18
Peter May, Melissa M Garrido, J Brian Cassel, Amy S Kelley, Diane E Meier, Charles Normand, Thomas J Smith, R Sean Morrison
BACKGROUND: Studies report cost-savings from hospital-based palliative care consultation teams compared to usual care only, but drivers of observed differences are unclear. AIM: To analyse cost-differences associated with palliative care consultation teams using two research questions: (Q1) What is the association between early palliative care consultation team intervention, and intensity of services and length of stay, compared to usual care only? (Q2) What is the association between early palliative care consultation team intervention and day-to-day hospital costs, compared to a later intervention? DESIGN: Prospective multi-site cohort study (2007-2011)...
April 2017: Palliative Medicine
https://www.readbyqxmd.com/read/28122244/distinct-brca1-mutations-differentially-reduce-hematopoietic-stem-cell-function
#19
Victoria E Mgbemena, Robert A J Signer, Ranjula Wijayatunge, Travis Laxson, Sean J Morrison, Theodora S Ross
BRCA1 is a well-known DNA repair pathway component and a tissue-specific tumor suppressor. However, its role in hematopoiesis is uncertain. Here, we report that a cohort of patients heterozygous for BRCA1 mutations experienced more hematopoietic toxicity from chemotherapy than those with BRCA2 mutations. To test whether this reflects a requirement for BRCA1 in hematopoiesis, we generated mice with Brca1 mutations in hematopoietic cells. Mice homozygous for a null Brca1 mutation in the embryonic hematopoietic system (Vav1-iCre;Brca1(F22-24/F22-24)) developed hematopoietic defects in early adulthood that included reduced hematopoietic stem cells (HSCs)...
January 24, 2017: Cell Reports
https://www.readbyqxmd.com/read/28052317/prenatal-prediction-of-significant-intertwin-birthweight-discordance-using-standard-second-and-third-trimester-sonographic-parameters
#20
Mark P Hehir, Fionnuala M Breathnach, Jennifer L Hogan, Fionnuala M Mcauliffe, Michael P Geary, Sean Daly, John Higgins, Alyson Hunter, John J Morrison, Gerard Burke, Rhona Mahony, Patrick Dicker, Elizabeth Tully, Fergal D Malone
INTRODUCTION: Our study aim was to evaluate standard ultrasound-derived fetal biometric parameters in the prediction of clinically significant intertwin birthweight discordance defined as ≥18%. MATERIAL AND METHODS: This was a secondary analysis of a prospective cohort study of 1028 unselected twin pairs recruited over a two-year period. Dichorionic twins underwent two-weekly ultrasonographic surveillance from 24 weeks' gestation, with surveillance of monochorionic twins two-weekly from 16 weeks...
April 2017: Acta Obstetricia et Gynecologica Scandinavica
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