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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...
November 5, 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
M Tessler, M Paul, S Halfon, B S Meyer, R Pardo, R Purtschert, K E Rehm, R Scott, M Weigand, L Weissman, S Almaraz-Calderon, M L Avila, D Baggenstos, P Collon, N Hazenshprung, Y Kashiv, D Kijel, A Kreisel, R Reifarth, D Santiago-Gonzalez, A Shor, I Silverman, R Talwar, D Veltum, R Vondrasek
The ^{36}Ar(n,γ)^{37}Ar (t_{1/2}=35  d) and ^{38}Ar(n,γ)^{39}Ar (269 yr) reactions were studied for the first time with a quasi-Maxwellian (kT∼47  keV) neutron flux for Maxwellian average cross section (MACS) measurements at stellar energies. Gas samples were irradiated at the high-intensity Soreq applied research accelerator facility-liquid-lithium target neutron source and the ^{37}Ar/^{36}Ar and ^{39}Ar/^{38}Ar ratios in the activated samples were determined by accelerator mass spectrometry at the ATLAS facility (Argonne National Laboratory)...
September 14, 2018: Physical Review Letters
Luke Gelinas, Joel S Weissman, Holly Fernandez Lynch, Avni Gupta, Ronen Rozenblum, Emily A Largent, I Glenn Cohen
A key aim of patient-centered outcomes research (PCOR) is to generate data that are important to patients by deliberately and extensively involving them in all aspects of research, from design to dissemination. However, certain elements of PCOR raise challenging and potentially novel ethical and regulatory issues for institutional review boards and oversight bodies. These challenges stem primarily from the engagement of patients in roles other than research subject, such as advisors, study personnel, and co-investigators, which gives rise to questions about appropriate levels of protection, training, and education, as well as identifying and managing conflicts of interest...
October 16, 2018: Annals of Internal Medicine
Charles K F Chan, Gunsagar S Gulati, Rahul Sinha, Justin Vincent Tompkins, Michael Lopez, Ava C Carter, Ryan C Ransom, Andreas Reinisch, Taylor Wearda, Matthew Murphy, Rachel E Brewer, Lauren S Koepke, Owen Marecic, Anoop Manjunath, Eun Young Seo, Tripp Leavitt, Wan-Jin Lu, Allison Nguyen, Stephanie D Conley, Ankit Salhotra, Thomas H Ambrosi, Mimi R Borrelli, Taylor Siebel, Karen Chan, Katharina Schallmoser, Jun Seita, Debashis Sahoo, Henry Goodnough, Julius Bishop, Michael Gardner, Ravindra Majeti, Derrick C Wan, Stuart Goodman, Irving L Weissman, Howard Y Chang, Michael T Longaker
Stem cell regulation and hierarchical organization of human skeletal progenitors remain largely unexplored. Here, we report the isolation of a self-renewing and multipotent human skeletal stem cell (hSSC) that generates progenitors of bone, cartilage, and stroma, but not fat. Self-renewing and multipotent hSSCs are present in fetal and adult bones and can also be derived from BMP2-treated human adipose stroma (B-HAS) and induced pluripotent stem cells (iPSCs). Gene expression analysis of individual hSSCs reveals overall similarity between hSSCs obtained from different sources and partially explains skewed differentiation toward cartilage in fetal and iPSC-derived hSSCs...
September 20, 2018: Cell
Linda Kimsey, Joel S Weissman, Avni Patel, Allison Drew, Tracey Koehlmoos, Jeffrey A Sparks
OBJECTIVE: To investigate factors associated with delay in initiation of initial disease-modifying antirheumatic drug (DMARD) in patients newly diagnosed with rheumatoid arthritis (RA). METHODS: We performed a retrospective cohort descriptive study using administrative data from the US military's TRICARE program (2007-2012). We identified incident RA cases using billing codes and initial DMARD receipt using prescription fill date. We quantified the time between RA presentation and initial DMARD receipt, evaluated temporal changes in delay over the study period, and investigated predictors of treatment delay (> 90 days) using logistic regression...
July 18, 2018: Seminars in Arthritis and Rheumatism
Erin A Bohula, Stephen D Wiviott, Darren K McGuire, Silvio E Inzucchi, Julia Kuder, KyungAh Im, Christina L Fanola, Arman Qamar, Conville Brown, Andrzej Budaj, Armando Garcia-Castillo, Milan Gupta, Lawrence A Leiter, Neil J Weissman, Harvey D White, Tushar Patel, Bruce Francis, Wenfeng Miao, Carlos Perdomo, Shobha Dhadda, Marc P Bonaca, Christian T Ruff, Anthony C Keech, Steven R Smith, Marc S Sabatine, Benjamin M Scirica
BACKGROUND: Lorcaserin, a selective serotonin 2C receptor agonist that modulates appetite, has proven efficacy for weight management in overweight or obese patients. The cardiovascular safety and efficacy of lorcaserin are undefined. METHODS: We randomly assigned 12,000 overweight or obese patients with atherosclerotic cardiovascular disease or multiple cardiovascular risk factors to receive either lorcaserin (10 mg twice daily) or placebo. The primary safety outcome of major cardiovascular events (a composite of cardiovascular death, myocardial infarction, or stroke) was assessed at an interim analysis to exclude a noninferiority boundary of 1...
September 20, 2018: New England Journal of Medicine
John R Weisz, Ana M Ugueto, Jenny Herren, Lauren K Marchette, Sarah Kate Bearman, Erica H Lee, Kristel Thomassin, Alisha Alleyne, Daniel M Cheron, J Lindsey Tweed, Jacqueline Hersh, Jacquelyn N Raftery-Helmer, Adam S Weissman, Amanda Jensen-Doss
OBJECTIVE: We assessed sustainability of an empirically supported, transdiagnostic youth psychotherapy program when therapist supervision was shifted from external experts to internal clinic staff. METHOD: One hundred sixty-eight youths, aged 6-15 years, 59.5% male, 85.1% Caucasian, were treated for anxiety, depression, traumatic stress, or conduct problems by clinicians employed in community mental health clinics. In Phase 1 (2.7 years), 1 group of clinicians, the Sustain group, received training in Child STEPs (a modular transdiagnostic treatment + weekly feedback on youth response) and treated clinic-referred youths, guided by weekly supervision from external STEPs experts...
September 2018: Journal of Consulting and Clinical Psychology
Michael J Mack, William T Abraham, JoAnn Lindenfeld, Steven F Bolling, Ted E Feldman, Paul A Grayburn, Samir R Kapadia, Patrick M McCarthy, D Scott Lim, James E Udelson, Michael R Zile, James S Gammie, A Marc Gillinov, Donald D Glower, David A Heimansohn, Rakesh M Suri, Jeffrey T Ellis, Yu Shu, Saibal Kar, Neil J Weissman, Gregg W Stone
BACKGROUND: Patients with heart failure (HF) and symptomatic secondary mitral regurgitation (SMR) have a poor prognosis, with morbidity and mortality directly correlated with MR severity. Correction of isolated SMR with surgery is not well established in this population, and medical management remains the preferred approach in most patients. The Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trial was designed to determine whether transcatheter mitral valve (MV) repair with the MitraClip device is safe and effective in patients with symptomatic HF and clinically significant SMR...
August 1, 2018: American Heart Journal
Rebecca T Hahn, Philippe Pibarot, Jonathon Leipsic, Philipp Blanke, Pamela S Douglas, Neil J Weissman, Samir Kapadia, Vinod H Thourani, Howard C Herrmann, Tamim Nazif, Thomas McAndrew, John G Webb, Martin B Leon, Susheel Kodali
OBJECTIVES: The purpose of this study was to understand the effects of balloon post-dilatation on outcomes following transcatheter aortic valve replacement with the SAPIEN 3 valve. BACKGROUND: Hemodynamics and outcomes with balloon post-dilatation for the SAPIEN 3 valve have not been previously reported. METHODS: The effects of balloon post-dilatation (BPD) in 1,661 intermediate (S3i cohort) and high surgical risk (S3HR cohort) patients with aortic stenosis enrolled in the PARTNER (Placement of Aortic Transcatheter Valves) 2, SAPIEN 3 observational study on outcomes, as well as procedural complications, were assessed...
September 10, 2018: JACC. Cardiovascular Interventions
Elizabeth A Whitcomb, Yien Che Tsai, Johnvesly Basappa, Ke Liu, Aurélie K Le Feuvre, Allan M Weissman, Allen Taylor
Ubiquitinylation drives many cellular processes by targeting proteins for proteasomal degradation. Ubiquitin conjugation enzymes promote ubiquitinylation and, thus, degradation of protein substrates. Ubiquitinylation is a well-known posttranslational modification controlling cell-cycle transitions and levels or/and activation levels of ubiquitin-conjugating enzymes change during development and cell cycle. Progression through the cell cycle is tightly controlled by CDK inhibitors such as p27Kip1 . Here we show that, in contrast to promoting its degradation, the ubiquitin-conjugating enzyme UBCH7/UBE2L3 specifically protects p27Kip1 from degradation...
August 16, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Jie Yang, Mengru Zhang, Hongshik Ahn, Qing Zhang, Tony B Jin, Ien Li, Matthew Nemesure, Nandita Joshi, Haoran Jiang, Jeffrey M Miller, Robert Todd Ogden, Eva Petkova, Matthew S Milak, Mary Elizabeth Sublette, Gregory M Sullivan, Madhukar H Trivedi, Myrna Weissman, Patrick J McGrath, Maurizio Fava, Benji T Kurian, Diego A Pizzagalli, Crystal M Cooper, Melvin McInnis, Maria A Oquendo, Joseph John Mann, Ramin V Parsey, Christine DeLorenzo
This study aimed to identify biomarkers of major depressive disorder (MDD), by relating neuroimage-derived measures to binary (MDD/control), ordinal (severe MDD/mild MDD/control), or continuous (depression severity) outcomes. To address MDD heterogeneity, factors (severity of psychic depression, motivation, anxiety, psychosis, and sleep disturbance) were also used as outcomes. A multisite, multimodal imaging (diffusion MRI [dMRI] and structural MRI [sMRI]) cohort (52 controls and 147 MDD patients) and several modeling techniques-penalized logistic regression, random forest, and support vector machine (SVM)-were used...
November 2018: Human Brain Mapping
Mingye Feng, Kristopher D Marjon, Fangfang Zhu, Rachel Weissman-Tsukamoto, Aaron Levett, Katie Sullivan, Kevin S Kao, Maxim Markovic, Paul A Bump, Hannah M Jackson, Timothy S Choi, Jing Chen, Allison M Banuelos, Jie Liu, Phung Gip, Lei Cheng, Denong Wang, Irving L Weissman
Macrophage-mediated programmed cell removal (PrCR) is a process essential for the clearance of unwanted (damaged, dysfunctional, aged, or harmful) cells. The detection and recognition of appropriate target cells by macrophages is a critical step for successful PrCR, but its molecular mechanisms have not been delineated. Here using the models of tissue turnover, cancer immunosurveillance, and hematopoietic stem cells, we show that unwanted cells such as aging neutrophils and living cancer cells are susceptible to "labeling" by secreted calreticulin (CRT) from macrophages, enabling their clearance through PrCR...
August 10, 2018: Nature Communications
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