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Sean J. Morrison

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https://www.readbyqxmd.com/read/29743104/predicting-response-to-checkpoint-inhibitors-in-melanoma-beyond-pd-l1-and-mutational-burden
#1
Carl Morrison, Sarabjot Pabla, Jeffrey M Conroy, Mary K Nesline, Sean T Glenn, Devin Dressman, Antonios Papanicolau-Sengos, Blake Burgher, Jonathan Andreas, Vincent Giamo, Moachun Qin, Yirong Wang, Felicia L Lenzo, Angela Omilian, Wiam Bshara, Matthew Zibelman, Pooja Ghatalia, Konstantin Dragnev, Keisuke Shirai, Katherine G Madden, Laura J Tafe, Neel Shah, Deepa Kasuganti, Luis de la Cruz-Merino, Isabel Araujo, Yvonne Saenger, Margaret Bogardus, Miguel Villalona-Calero, Zuanel Diaz, Roger Day, Marcia Eisenberg, Steven M Anderson, Igor Puzanov, Lorenzo Galluzzi, Mark Gardner, Marc S Ernstoff
BACKGROUND: Immune checkpoint inhibitors (ICIs) have changed the clinical management of melanoma. However, not all patients respond, and current biomarkers including PD-L1 and mutational burden show incomplete predictive performance. The clinical validity and utility of complex biomarkers have not been studied in melanoma. METHODS: Cutaneous metastatic melanoma patients at eight institutions were evaluated for PD-L1 expression, CD8+ T-cell infiltration pattern, mutational burden, and 394 immune transcript expression...
May 9, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29720224/assessing-brain-volume-changes-in-older-women-with-breast-cancer-receiving-adjuvant-chemotherapy-a-brain-magnetic-resonance-imaging-pilot-study
#2
Bihong T Chen, Sean K Sethi, Taihao Jin, Sunita K Patel, Ningrong Ye, Can-Lan Sun, Russell C Rockne, E Mark Haacke, James C Root, Andrew J Saykin, Tim A Ahles, Andrei I Holodny, Neal Prakash, Joanne Mortimer, James Waisman, Yuan Yuan, George Somlo, Daneng Li, Richard Yang, Heidi Tan, Vani Katheria, Rachel Morrison, Arti Hurria
BACKGROUND: Cognitive decline is among the most feared treatment-related outcomes of older adults with cancer. The majority of older patients with breast cancer self-report cognitive problems during and after chemotherapy. Prior neuroimaging research has been performed mostly in younger patients with cancer. The purpose of this study was to evaluate longitudinal changes in brain volumes and cognition in older women with breast cancer receiving adjuvant chemotherapy. METHODS: Women aged ≥ 60 years with stage I-III breast cancer receiving adjuvant chemotherapy and age-matched and sex-matched healthy controls were enrolled...
May 2, 2018: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/29710177/economics-of-palliative-care-for-hospitalized-adults-with-serious-illness-a-meta-analysis
#3
Peter May, Charles Normand, J Brian Cassel, Egidio Del Fabbro, Robert L Fine, Reagan Menz, Corey A Morrison, Joan D Penrod, Chessie Robinson, R Sean Morrison
Importance: Economics of care for adults with serious illness is a policy priority worldwide. Palliative care may lower costs for hospitalized adults, but the evidence has important limitations. Objective: To estimate the association of palliative care consultation (PCC) with direct hospital costs for adults with serious illness. Data Sources: Systematic searches of the Embase, PsycINFO, CENTRAL, PubMed, CINAHL, and EconLit databases were performed for English-language journal articles using keywords in the domains of palliative care (eg, palliative, terminal) and economics (eg, cost, utilization), with limiters for hospital and consultation...
April 30, 2018: JAMA Internal Medicine
https://www.readbyqxmd.com/read/29660039/trial-readiness-in-cavernous-angiomas-with-symptomatic-hemorrhage-cash
#4
Sean P Polster, Ying Cao, Timothy Carroll, Kelly Flemming, Romuald Girard, Daniel Hanley, Nicholas Hobson, Helen Kim, James Koenig, Janne Koskimäki, Karen Lane, Jennifer J Majersik, Nichol McBee, Leslie Morrison, Robert Shenkar, Agnieszka Stadnik, Richard E Thompson, Joseph Zabramski, Hussein A Zeineddine, Issam A Awad
BACKGROUND: Brain cavernous angiomas with symptomatic hemorrhage (CASH) are uncommon but exact a heavy burden of neurological disability from recurrent bleeding, for which there is no proven therapy. Candidate drugs to stabilize the CASH lesion and prevent rebleeding will ultimately require testing of safety and efficacy in multisite clinical trials. Much progress has been made in understanding the epidemiology of CASH, and novel biomarkers have been linked to the biological mechanisms and clinical activity in lesions...
April 11, 2018: Neurosurgery
https://www.readbyqxmd.com/read/29462149/the-ino80-chromatin-remodeler-sustains-metabolic-stability-by-promoting-tor-signaling-and-regulating-histone-acetylation
#5
Sean L Beckwith, Erin K Schwartz, Pablo E García-Nieto, Devin A King, Graeme J Gowans, Ka Man Wong, Tessa L Eckley, Alexander P Paraschuk, Egan L Peltan, Laura R Lee, Wei Yao, Ashby J Morrison
Chromatin remodeling complexes are essential for gene expression programs that coordinate cell function with metabolic status. However, how these remodelers are integrated in metabolic stability pathways is not well known. Here, we report an expansive genetic screen with chromatin remodelers and metabolic regulators in Saccharomyces cerevisiae. We found that, unlike the SWR1 remodeler, the INO80 chromatin remodeling complex is composed of multiple distinct functional subunit modules. We identified a strikingly divergent genetic signature for the Ies6 subunit module that links the INO80 complex to metabolic homeostasis...
February 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29452642/the-yeast-ino80-complex-operates-as-a-tunable-dna-length-sensitive-switch-to-regulate-nucleosome-sliding
#6
Coral Y Zhou, Stephanie L Johnson, Laura J Lee, Adam D Longhurst, Sean L Beckwith, Matthew J Johnson, Ashby J Morrison, Geeta J Narlikar
The yeast INO80 chromatin remodeling complex plays essential roles in regulating DNA damage repair, replication, and promoter architecture. INO80's role in these processes is likely related to its ability to slide nucleosomes, but the underlying mechanism is poorly understood. Here we use ensemble and single-molecule enzymology to study INO80-catalyzed nucleosome sliding. We find that the rate of nucleosome sliding by INO80 increases ∼100-fold when the flanking DNA length is increased from 40 to 60 bp. Furthermore, once sliding is initiated, INO80 moves the nucleosome rapidly at least 20 bp without pausing to re-assess flanking DNA length, and it can change the direction of nucleosome sliding without dissociation...
February 15, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29169346/social-and-clinical-determinants-of-preferences-and-their-achievement-at-the-end-of-life-prospective-cohort-study-of-older-adults-receiving-palliative-care-in-three-countries
#7
Irene J Higginson, Barbara A Daveson, R Sean Morrison, Deokhee Yi, Diane Meier, Melinda Smith, Karen Ryan, Regina McQuillan, Bridget M Johnston, Charles Normand
BACKGROUND: Achieving choice is proposed as a quality marker. But little is known about what influences preferences especially among older adults. We aimed to determine and compare, across three countries, factors associated with preferences for place of death and treatment, and actual site of death. METHODS: We recruited adults aged ≥65-years from hospital-based multiprofessional palliative care services in London, Dublin, New York, and followed them for >17 months...
November 23, 2017: BMC Geriatrics
https://www.readbyqxmd.com/read/29109980/the-abundance-of-metabolites-related-to-protein-methylation-correlates-with-the-metastatic-capacity-of-human-melanoma-xenografts
#8
Xiaolei Shi, Alpaslan Tasdogan, Fang Huang, Zeping Hu, Sean J Morrison, Ralph J DeBerardinis
Metabolic reprogramming is a major factor in transformation, and particular metabolic phenotypes correlate with oncogenotype, tumor progression, and metastasis. By profiling metabolites in 17 patient-derived xenograft melanoma models, we identified durable metabolomic signatures that correlate with biological features of the tumors. BRAF mutant tumors had metabolomic and metabolic flux features of enhanced glycolysis compared to BRAF wild-type tumors. Tumors that metastasized efficiently from their primary sites had elevated levels of metabolites related to protein methylation, including trimethyllysine (TML)...
November 2017: Science Advances
https://www.readbyqxmd.com/read/28887402/detection-of-long-repeat-expansions-from-pcr-free-whole-genome-sequence-data
#9
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)...
November 2017: Genome Research
https://www.readbyqxmd.com/read/28825709/ascorbate-regulates-haematopoietic-stem-cell-function-and-leukaemogenesis
#10
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 not known whether physiological variations in metabolite levels in normal tissues regulate stem-cell function in vivo. Here we describe a metabolomics method for the analysis of rare cell populations isolated directly from tissues and use it to compare mouse 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 decreased with differentiation...
September 28, 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
#11
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)...
January 2018: 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
#12
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
#13
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
#14
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...
September 1, 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
#15
Nadia T Sebastian, Thomas D Zaikos, Valeri Terry, Frances Taschuk, Lucy A McNamara, Adewunmi Onafuwa-Nuga, Ryan Yucha, Robert A J Signer, James Riddell, 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
#16
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
#17
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
#18
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
#19
MULTICENTER STUDY
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
#20
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
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