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Alexander P Cole, David-Dan Nguyen, Akezhan Meirkhanov, Mehra Golshan, Nelya Melnitchouk, Stuart R Lipsitz, Kerry L Kilbridge, Adam S Kibel, Zara Cooper, Joel Weissman, Quoc-Dien Trinh
Importance: It is not known whether racial/ethnic differences in receipt of palliative care are attributable to different treatment of minorities or lower utilization of palliative care at the relatively small number of hospitals that treat a large portion of minority patients. Objective: To assess the association of receipt of palliative care among patients with metastatic cancer with receipt of treatment at minority-serving hospitals (MSHs) vs non-MSHs. Design, Setting, and Participants: This retrospective cohort study used Participant Use Files of the National Cancer Database, a prospectively maintained, hospital-based cancer registry consisting of all patients treated at more than 1500 US hospitals, to collect data from individuals older than 40 years with metastatic prostate, lung, colon, and breast cancer, diagnosed from January 1, 2004, to December 31, 2015...
February 1, 2019: JAMA network open
Xuzhou Li, Myrna Weissman, Ardesheer Talati, Connie Svob, Priya Wickramaratne, Jonathan Posner, Dongrong Xu
INTRODUCTION: Previously in a three-generation study of families at high risk for depression, we found that belief in the importance of religion/spirituality (R/S) was associated with thicker cortex in bilateral parietal and occipital regions. In the same sample using functional magnetic resonance imaging and electroencephalograph (EEG), we found that offspring at high familial risk had thinner cortices, increased default mode network connectivity, and reduced EEG power. These group differences were significantly diminished in offspring at high risk who reported high importance of R/S beliefs, suggesting a protective effect...
January 15, 2019: Brain and Behavior
Zheng-Rong Tiger Li, Veronika I Zarnitsyna, Anice C Lowen, Daniel Weissman, Katia Koelle, Jacob E Kohlmeier, Rustom Antia
The high-degree of conservation of CD8 T cell epitopes of influenza A virus (IAV) may allow for the development of T cell-inducing vaccines that provide protection across different strains and subtypes. This conservation is not fully explained by functional constraint, since additional mutation(s) can compensate the replicative fitness loss of IAV escape-variants. Here, we propose three additional mechanisms that contribute to the conservation of CD8 T cell epitopes of IAV. First, influenza-specific CD8 T cells may protect predominantly against severe pathology rather than infection and may have only a modest effect on transmission...
January 9, 2019: Journal of Virology
Hye-Sook Kwon, Aaron C Logan, Akanksha Chhabra, Wendy W Pang, Agnieszka Czechowicz, Keri Tate, Alan Le, Jessica Poyser, Roger Hollis, Benjamin V Kelly, Donald B Kohn, Irving L Weissman, Susan S Prohaska, Judith A Shizuru
No abstract text is available yet for this article.
January 7, 2019: Blood
Thomas Anderson, Rotem Petranker, Daniel Rosenbaum, Cory R Weissman, Le-Anh Dinh-Williams, Katrina Hui, Emma Hapke, Norman A S Farb
RATIONALE: Microdosing psychedelics-the regular consumption of small amounts of psychedelic substances such as LSD or psilocybin-is a growing trend in popular culture. Recent studies on full-dose psychedelic psychotherapy reveal promising benefits for mental well-being, especially for depression and end-of-life anxiety. While full-dose therapies include perception-distorting properties, microdosing mayprovide complementary clinical benefits using lower-risk, non-hallucinogenic doses. OBJECTIVES: This pre-registered study aimed to investigate whether microdosing psychedelics is related to differences in personality, mental health, and creativity...
January 2, 2019: Psychopharmacology
Gregor Hutter, Johanna Theruvath, Claus Moritz Graef, Michael Zhang, Matthew Kenneth Schoen, Eva Maria Manz, Mariko L Bennett, Andrew Olson, Tej D Azad, Rahul Sinha, Carmel Chan, Suzana Assad Kahn, Sharareh Gholamin, Christy Wilson, Gerald Grant, Joy He, Irving L Weissman, Siddhartha S Mitra, Samuel H Cheshier
Glioblastoma multiforme (GBM) is a highly aggressive malignant brain tumor with fatal outcome. Tumor-associated macrophages and microglia (TAMs) have been found to be major tumor-promoting immune cells in the tumor microenvironment. Hence, modulation and reeducation of tumor-associated macrophages and microglia in GBM is considered a promising antitumor strategy. Resident microglia and invading macrophages have been shown to have distinct origin and function. Whereas yolk sac-derived microglia reside in the brain, blood-derived monocytes invade the central nervous system only under pathological conditions like tumor formation...
January 2, 2019: Proceedings of the National Academy of Sciences of the United States of America
Michael L Millenson, David B Muhlestein, Emily M O'Donnell, Daniel A Northam Jones, R Sterling Haring, Thomas Merrill, Joel S Weissman
Although there is a widespread belief that ACOs must be patient-centered to be successful, evidence to guide them in achieving that goal has been lacking. This case report examines four ACO innovators in patient-centered care that together represent urban, suburban and rural populations with a broad range of economic, racial, ethnic and geographic diversity. Seven patient-centeredness strategies emerged: transform primary care practices into patient-centered medical homes; move upstream to address social and economic issues; use both high-tech and high-touch to identify and engage high-risk patients; practice a whole-person orientation; optimize patient-reported measures; treat patients like valued customers; and incorporate patient voices into governance and operations...
December 26, 2018: Healthcare
Zoe T Cook, Nicole L Brockway, Zachary J C Tobias, Joy Pajarla, Isaac S Boardman, Helen Ippolito, Sylvia Nkombo-Nkoula, Tamily A Weissman
Fluorescent proteins are a powerful experimental tool, allowing the visualization of gene expression and cellular behaviors in a variety of systems. Multicolor combinations of fluorescent proteins, such as Brainbow, have expanded the range of possible research questions, and are useful for distinguishing and tracking cells. The addition of a separately driven color, however, would allow researchers to report expression of a manipulated gene within the multicolor context, to investigate mechanistic effects. A far-red or near-infrared protein could be particularly suitable in this context, as these can be distinguished spectrally from Brainbow...
December 26, 2018: Molecular Biology of the Cell
Judith D Weissman, David Russell, Fatemeh Haghighi, Lisa Dixon, Marianne Goodman
Objective: To examine sociodemographic characteristics and chronic health conditions in veterans across health coverage types including those without coverage. Design: The sample included cross-sectional data from veterans aged 18 years and over, collected in the 2016 National Health Interview Survey (n = 3487). Chronic health conditions and sociodemographic variables were examined across eleven health coverage types and combinations of health coverage types, as follows: No coverage, Medicare, Medicaid, Private, TRICARE (formerly known as the Civilian Health and Medical Program of the Uniformed Services (CHAMPUS)), TRICARE and Medicare, Veteran's Administration, Veteran's Administration and Medicare, Veteran's Administration and Private, Veteran's Administration and Private and Medicare...
March 2019: Preventive Medicine Reports
Xianglong Zhang, Ying Zhang, Xiaowei Zhu, Carolin Purmann, Michael S Haney, Thomas Ward, Arineh Khechaduri, Jie Yao, Sherman M Weissman, Alexander E Urban
Large copy number variants (CNVs) in the human genome are strongly associated with common neurodevelopmental, neuropsychiatric disorders such as schizophrenia and autism. Here we report on the epigenomic effects of the prominent large deletion CNVs on chromosome 22q11.2 and on chromosome 1q21.1. We use Hi-C analysis of long-range chromosome interactions, including haplotype-specific Hi-C analysis, ChIP-Seq analysis of regulatory histone marks, and RNA-Seq analysis of gene expression patterns. We observe changes on all the levels of analysis, within the deletion boundaries, in the deletion flanking regions, along chromosome 22q, and genome wide...
December 17, 2018: Nature Communications
Rakesh M Suri, Hoda Javadikasgari, David A Heimansohn, Neil J Weissman, Gorav Ailawadi, Niv Ad, Gabriel S Aldea, Vinod H Thourani, Wilson Y Szeto, Robert E Michler, Hector I Michelena, Reza Dabir, Gregory P Fontana, William F Kessler, Michael G Moront, Louis A Brunsting, Bartley P Griffith, Alvaro Montoya, Sreekumar Subramanian, Mark A Mostovych, Eric E Roselli
OBJECTIVES: We performed a prospective, single-arm clinical trial approved under a Food and Drug Administration Investigational Device Exemption to assess safety and efficacy of Perceval, a sutureless bovine pericardial aortic valve representing the initial US experience. METHODS: From June 2013 to January 2015, 300 patients (mean age 76.7 ± 7.7 years, 54.3% men, 37.3% ≥80 years, median Society of Thoracic Surgeons Predicted Risk of Mortality 2.8%), underwent Perceval valve implantation at 18 centers across the United States...
October 23, 2018: Journal of Thoracic and Cardiovascular Surgery
Yasmin A Zerhouni, Dan C Krupka, Jove Graham, Adam Landman, Angela Li, Deepak L Bhatt, Louis L Nguyen, Kevin Capatch, Kevin Concheri, Amanda J Reich, Natalia Wilson, Joel S Weissman
BACKGROUND: In response to problems with the current postmarket surveillance of medical devices, the U.S. Food and Drug Administration mandated device labelers to include a unique device identifier (UDI), composed of a device identifier (DI) and production identifier. Including the DI in insurance claims could be a potent method to monitor implanted devices, yet implementation has lagged because of questions of benefit and operational concerns. METHODS: To illustrate the potential benefit of including DIs in claims, rates of 90-day adverse events after implantation using an electronic health record (EHR) were compared with the EHR plus claims, which capture utilization outside that EHR's health system...
November 21, 2018: Journal of Patient Safety
Michelle P Lin, Shaw Natsui, Corine Sinnette, Alexis Ball, Joel S Weissman, Jeremiah D Schuur
BACKGROUND: Chest pain of possible cardiac etiology is a leading reason for emergency department (ED) visits and hospitalizations nationwide. Evidence suggests outpatient management is safe and effective for low-risk patients; however, ED admission rates for chest pain vary widely. To identify barriers and facilitators to outpatient management after ED visits, we performed a multicenter qualitative study of key stakeholders. METHODS AND RESULTS: We identified Massachusetts hospitals with below-average admission rates for adult ED chest pain visits from 2010 to 2011...
December 2018: Critical Pathways in Cardiology
Rachel Kohn, Michael O Harhay, Gary E Weissman, George L Anesi, Brian Bayes, S Ryan Greysen, Sarah J Ratcliffe, Scott D Halpern, Meeta Prasad Kerlin
No abstract text is available yet for this article.
November 8, 2018: Annals of the American Thoracic Society
Michael S Haney, Christopher J Bohlen, David W Morgens, James A Ousey, Amira A Barkal, C Kimberly Tsui, Braeden K Ego, Roni Levin, Roarke A Kamber, Hannah Collins, Andrew Tucker, Amy Li, Daan Vorselen, Lorenzo Labitigan, Emily Crane, Evan Boyle, Lihua Jiang, Joanne Chan, Esther Rincón, William J Greenleaf, Billy Li, Michael P Snyder, Irving L Weissman, Julie A Theriot, Sean R Collins, Ben A Barres, Michael C Bassik
Phagocytosis is required for a broad range of physiological functions, from pathogen defense to tissue homeostasis, but the mechanisms required for phagocytosis of diverse substrates remain incompletely understood. Here, we developed a rapid magnet-based phenotypic screening strategy, and performed eight genome-wide CRISPR screens in human cells to identify genes regulating phagocytosis of distinct substrates. After validating select hits in focused miniscreens, orthogonal assays and primary human macrophages, we show that (1) the previously uncharacterized gene NHLRC2 is a central player in phagocytosis, regulating RhoA-Rac1 signaling cascades that control actin polymerization and filopodia formation, (2) very-long-chain fatty acids are essential for efficient phagocytosis of certain substrates and (3) the previously uncharacterized Alzheimer's disease-associated gene TM2D3 can preferentially influence uptake of amyloid-β aggregates...
December 2018: Nature Genetics
Suzana A Kahn, Xin Wang, Ryan T Nitta, Sharareh Gholamin, Johanna Theruvath, Gregor Hutter, Tej D Azad, Lina Wadi, Sara Bolin, Vijay Ramaswamy, Rogelio Esparza, Kun-Wei Liu, Michael Edwards, Fredrik J Swartling, Debashis Sahoo, Gordon Li, Robert J Wechsler-Reya, Jüri Reimand, Yoon-Jae Cho, Michael D Taylor, Irving L Weissman, Siddhartha S Mitra, Samuel H Cheshier
The original version of this Article omitted Suzana A. Kahn, Siddhartha S. Mitra & Samuel H. Cheshier as jointly supervising authors. This has now been corrected in both the PDF and HTML versions of the Article.
November 2, 2018: Nature Communications
Sandip A Shelke, Yaming Shao, Artur Laski, Deepak Koirala, Benjamin P Weissman, James R Fuller, Xiaohong Tan, Tudor P Constantin, Alan S Waggoner, Marcel P Bruchez, Bruce A Armitage, Joseph A Piccirilli
The DIR2s RNA aptamer, a second-generation, in-vitro selected binder to dimethylindole red (DIR), activates the fluorescence of cyanine dyes, DIR and oxazole thiazole blue (OTB), allowing detection of two well-resolved emission colors. Using Fab BL3-6 and its cognate hairpin as a crystallization module, we solved the crystal structures of both the apo and OTB-SO3 bound forms of DIR2s at 2.0 Å and 1.8 Å resolution, respectively. DIR2s adopts a compact, tuning fork-like architecture comprised of a helix and two short stem-loops oriented in parallel to create the ligand binding site through tertiary interactions...
October 31, 2018: Nature Communications
Hamideh Parhiz, Vladimir V Shuvaev, Norbert Pardi, Makan Khoshnejad, Raisa Yu Kiseleva, Jacob S Brenner, Thomas Uhler, Steven Tuyishime, Barbara L Mui, Ying K Tam, Thomas D Madden, Michael J Hope, Drew Weissman, Vladimir R Muzykantov
Systemic administration of lipid nanoparticle (LNP)-encapsulated messenger RNA (mRNA) leads predominantly to hepatic uptake and expression. Here, we conjugated nucleoside-modified mRNA-LNPs with antibodies (Abs) specific to vascular cell adhesion molecule, PECAM-1. Systemic (intravenous) administration of Ab/LNP-mRNAs resulted in profound inhibition of hepatic uptake concomitantly with ~200-fold and 25-fold elevation of mRNA delivery and protein expression in the lungs compared to non-targeted counterparts...
December 10, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Suzana A Kahn, Xin Wang, Ryan T Nitta, Sharareh Gholamin, Johanna Theruvath, Gregor Hutter, Tej D Azad, Lina Wadi, Sara Bolin, Vijay Ramaswamy, Rogelio Esparza, Kun-Wei Liu, Michael Edwards, Fredrik J Swartling, Debashis Sahoo, Gordon Li, Robert J Wechsler-Reya, Jüri Reimand, Yoon-Jae Cho, Michael D Taylor, Irving L Weissman, Siddhartha S Mitra, Samuel H Cheshier
Medulloblastoma is the most common malignant brain tumor of childhood. Group 3 medulloblastoma, the most aggressive molecular subtype, frequently disseminates through the leptomeningeal cerebral spinal fluid (CSF) spaces in the brain and spinal cord. The mechanism of dissemination through the CSF remains poorly understood, and the molecular pathways involved in medulloblastoma metastasis and self-renewal are largely unknown. Here we show that NOTCH1 signaling pathway regulates both the initiation of metastasis and the self-renewal of medulloblastoma...
October 8, 2018: Nature Communications
Jin Liu, Ning Jiang, Amy Z Fan, Rebecca Weissman
Purpose: Identification of mental healthcare disparities through scales or questionnaires is an initial step to improve mental healthcare equity. This study was designed to investigate the performance of a single-item question relative to two psychiatric scales with multiple items in assessing mental healthcare disparities among U.S. adults using the Behavioral Risk Factor Surveillance System (BRFSS) data. Methods: The current depression (CD) and serious psychological distress (SPD) were analyzed in 2010 and 2012 with the BRFSS using two multiple-item scales in selected states...
2018: Health Equity
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