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Murray grossman

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https://www.readbyqxmd.com/read/29878075/neurodegenerative-disease-concomitant-proteinopathies-are-prevalent-age-related-and-apoe4-associated
#1
John L Robinson, Edward B Lee, Sharon X Xie, Lior Rennert, EunRan Suh, Colin Bredenberg, Carrie Caswell, Vivianna M Van Deerlin, Ning Yan, Ahmed Yousef, Howard I Hurtig, Andrew Siderowf, Murray Grossman, Corey T McMillan, Bruce Miller, John E Duda, David J Irwin, David Wolk, Lauren Elman, Leo McCluskey, Alice Chen-Plotkin, Daniel Weintraub, Steven E Arnold, Johannes Brettschneider, Virginia M-Y Lee, John Q Trojanowski
Lewy bodies commonly occur in Alzheimer's disease, and Alzheimer's disease pathology is frequent in Lewy body diseases, but the burden of co-pathologies across neurodegenerative diseases is unknown. We assessed the extent of tau, amyloid-β, α-synuclein and TDP-43 proteinopathies in 766 autopsied individuals representing a broad spectrum of clinical neurodegenerative disease. We interrogated pathological Alzheimer's disease (n = 247); other tauopathies (n = 95) including Pick's disease, corticobasal disease and progressive supranuclear palsy; the synucleinopathies (n = 164) including multiple system atrophy and Lewy body disease; the TDP-43 proteinopathies (n = 188) including frontotemporal lobar degeneration with TDP-43 inclusions and amyotrophic lateral sclerosis; and a minimal pathology group (n = 72)...
June 5, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29851876/primary-progressive-aphasia-and-stroke-aphasia
#2
Murray Grossman, David J Irwin
PURPOSE OF REVIEW: This article summarizes the clinical and anatomic features of the three named variants of primary progressive aphasia (PPA): semantic variant PPA, nonfluent/agrammatic variant PPA, and logopenic variant PPA. Three stroke aphasia syndromes that resemble the PPA variants (Broca aphasia, Wernicke aphasia, and conduction aphasia) are also presented. RECENT FINDINGS: Semantic variant PPA and Wernicke aphasia are characterized by fluent speech with naming and comprehension difficulty; these syndromes are associated with disease in different portions of the left temporal lobe...
June 2018: Continuum: Lifelong Learning in Neurology
https://www.readbyqxmd.com/read/29751289/perfusion-alterations-converge-with-patterns-of-pathological-spread-in-transactive-response-dna-binding-protein-43-proteinopathies
#3
Pilar M Ferraro, Charles Jester, Christopher A Olm, Katerina Placek, Federica Agosta, Lauren Elman, Leo McCluskey, David J Irwin, John A Detre, Massimo Filippi, Murray Grossman, Corey T McMillan
Amyotrophic lateral sclerosis (ALS) and the behavioral variant of frontotemporal dementia (bvFTD) commonly share the presence of transactive response DNA-binding protein 43 (TDP-43) inclusions. Structural magnetic resonance imaging studies demonstrated evidence for TDP-43 pathology spread, but while structural imaging usually reveals overt neuronal loss, perfusion imaging may detect more subtle neural activity alterations. We evaluated perfusion as an early marker for incipient pathology-associated brain alterations in TDP-43 proteinopathies...
April 17, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29724592/potential-genetic-modifiers-of-disease-risk-and-age-at-onset-in-patients-with-frontotemporal-lobar-degeneration-and-grn-mutations-a-genome-wide-association-study
#4
Cyril Pottier, Xiaolai Zhou, Ralph B Perkerson, Matt Baker, Gregory D Jenkins, Daniel J Serie, Roberta Ghidoni, Luisa Benussi, Giuliano Binetti, Adolfo López de Munain, Miren Zulaica, Fermin Moreno, Isabelle Le Ber, Florence Pasquier, Didier Hannequin, Raquel Sánchez-Valle, Anna Antonell, Albert Lladó, Tammee M Parsons, NiCole A Finch, Elizabeth C Finger, Carol F Lippa, Edward D Huey, Manuela Neumann, Peter Heutink, Matthis Synofzik, Carlo Wilke, Robert A Rissman, Jaroslaw Slawek, Emilia Sitek, Peter Johannsen, Jørgen E Nielsen, Yingxue Ren, Marka van Blitterswijk, Mariely DeJesus-Hernandez, Elizabeth Christopher, Melissa E Murray, Kevin F Bieniek, Bret M Evers, Camilla Ferrari, Sara Rollinson, Anna Richardson, Elio Scarpini, Giorgio G Fumagalli, Alessandro Padovani, John Hardy, Parastoo Momeni, Raffaele Ferrari, Francesca Frangipane, Raffaele Maletta, Maria Anfossi, Maura Gallo, Leonard Petrucelli, EunRan Suh, Oscar L Lopez, Tsz H Wong, Jeroen G J van Rooij, Harro Seelaar, Simon Mead, Richard J Caselli, Eric M Reiman, Marwan Noel Sabbagh, Mads Kjolby, Anders Nykjaer, Anna M Karydas, Adam L Boxer, Lea T Grinberg, Jordan Grafman, Salvatore Spina, Adrian Oblak, M-Marsel Mesulam, Sandra Weintraub, Changiz Geula, John R Hodges, Olivier Piguet, William S Brooks, David J Irwin, John Q Trojanowski, Edward B Lee, Keith A Josephs, Joseph E Parisi, Nilüfer Ertekin-Taner, David S Knopman, Benedetta Nacmias, Irene Piaceri, Silvia Bagnoli, Sandro Sorbi, Marla Gearing, Jonathan Glass, Thomas G Beach, Sandra E Black, Mario Masellis, Ekaterina Rogaeva, Jean-Paul Vonsattel, Lawrence S Honig, Julia Kofler, Amalia C Bruni, Julie Snowden, David Mann, Stuart Pickering-Brown, Janine Diehl-Schmid, Juliane Winkelmann, Daniela Galimberti, Caroline Graff, Linn Öijerstedt, Claire Troakes, Safa Al-Sarraj, Carlos Cruchaga, Nigel J Cairns, Jonathan D Rohrer, Glenda M Halliday, John B Kwok, John C van Swieten, Charles L White, Bernardino Ghetti, Jill R Murell, Ian R A Mackenzie, Ging-Yuek R Hsiung, Barbara Borroni, Giacomina Rossi, Fabrizio Tagliavini, Zbigniew K Wszolek, Ronald C Petersen, Eileen H Bigio, Murray Grossman, Vivianna M Van Deerlin, William W Seeley, Bruce L Miller, Neill R Graff-Radford, Bradley F Boeve, Dennis W Dickson, Joanna M Biernacka, Rosa Rademakers
BACKGROUND: Loss-of-function mutations in GRN cause frontotemporal lobar degeneration (FTLD). Patients with GRN mutations present with a uniform subtype of TAR DNA-binding protein 43 (TDP-43) pathology at autopsy (FTLD-TDP type A); however, age at onset and clinical presentation are variable, even within families. We aimed to identify potential genetic modifiers of disease onset and disease risk in GRN mutation carriers. METHODS: The study was done in three stages: a discovery stage, a replication stage, and a meta-analysis of the discovery and replication data...
April 30, 2018: Lancet Neurology
https://www.readbyqxmd.com/read/29700597/cerebrospinal-fluid-neurogranin-concentration-in-neurodegeneration-relation-to-clinical-phenotypes-and-neuropathology
#5
Erik Portelius, Bob Olsson, Kina Höglund, Nicholas C Cullen, Hlin Kvartsberg, Ulf Andreasson, Henrik Zetterberg, Åsa Sandelius, Leslie M Shaw, Virginia M Y Lee, David J Irwin, Murray Grossman, Daniel Weintraub, Alice Chen-Plotkin, David A Wolk, Leo McCluskey, Lauren Elman, Jennifer McBride, Jon B Toledo, John Q Trojanowski, Kaj Blennow
Neurogranin (Ng) is a post-synaptic protein that previously has been shown to be a biomarker for synaptic function when measured in cerebrospinal fluid (CSF). The CSF concentration of Ng is increased in Alzheimer's disease dementia (ADD), and even in the pre-dementia stage. In this prospective study, we used an enzyme-linked immunosorbent assay that quantifies Ng in CSF to test the performance of Ng as a marker of synaptic function. In 915 patients, CSF Ng was evaluated across several different neurodegenerative diseases...
April 26, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29604263/cerebrospinal-fluid-%C3%AE-synuclein-contributes-to-the-differential-diagnosis-of-alzheimer-s-disease
#6
Min Shi, Lu Tang, Jon B Toledo, Carmen Ginghina, Hua Wang, Patrick Aro, Poul H Jensen, Daniel Weintraub, Alice S Chen-Plotkin, David J Irwin, Murray Grossman, Leo McCluskey, Lauren B Elman, David A Wolk, Edward B Lee, Leslie M Shaw, John Q Trojanowski, Jing Zhang
INTRODUCTION: The ability of Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers (amyloid β peptide 1-42, total tau, and phosphorylated tau) to discriminate AD from related disorders is limited. Biomarkers for other concomitant pathologies (e.g., CSF α-synuclein [α-syn] for Lewy body pathology) may be needed to further improve the differential diagnosis. METHODS: CSF total α-syn, phosphorylated α-syn at Ser129, and AD CSF biomarkers were evaluated with Luminex immunoassays in 367 participants, followed by validation in 74 different neuropathologically confirmed cases...
March 28, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29592955/characterizing-the-human-hippocampus-in-aging-and-alzheimer-s-disease-using-a-computational-atlas-derived-from-ex-vivo-mri-and-histology
#7
Daniel H Adler, Laura E M Wisse, Ranjit Ittyerah, John B Pluta, Song-Lin Ding, Long Xie, Jiancong Wang, Salmon Kadivar, John L Robinson, Theresa Schuck, John Q Trojanowski, Murray Grossman, John A Detre, Mark A Elliott, Jon B Toledo, Weixia Liu, Stephen Pickup, Michael I Miller, Sandhitsu R Das, David A Wolk, Paul A Yushkevich
Although the hippocampus is one of the most studied structures in the human brain, limited quantitative data exist on its 3D organization, anatomical variability, and effects of disease on its subregions. Histological studies provide restricted reference information due to their 2D nature. In this paper, high-resolution (∼200 × 200 × 200 μm3 ) ex vivo MRI scans of 31 human hippocampal specimens are combined using a groupwise diffeomorphic registration approach into a 3D probabilistic atlas that captures average anatomy and anatomic variability of hippocampal subfields...
April 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29559904/longitudinal-diffusion-tensor-imaging-resembles-patterns-of-pathology-progression-in-behavioral-variant-frontotemporal-dementia-bvftd
#8
Jan Kassubek, Hans-Peter Müller, Kelly Del Tredici, Michael Hornberger, Matthias L Schroeter, Karsten Müller, Sarah Anderl-Straub, Ingo Uttner, Murray Grossman, Heiko Braak, John R Hodges, Olivier Piguet, Markus Otto, Albert C Ludolph
Objective: Recently, the characteristic longitudinal distribution pattern of the underlying phosphorylated TDP-43 (pTDP-43) pathology in the behavioral variant of frontotemporal dementia (bvFTD) excluding Pick's disease (PiD) across specific brain regions was described. The aim of the present study was to investigate whether in vivo investigations of bvFTD patients by use of diffusion tensor imaging (DTI) were consistent with these proposed patterns of progression. Methods: Sixty-two bvFTD patients and 47 controls underwent DTI in a multicenter study design...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29554190/a-2-step-cerebrospinal-algorithm-for-the-selection-of-frontotemporal-lobar-degeneration-subtypes
#9
Alberto Lleó, David J Irwin, Ignacio Illán-Gala, Corey T McMillan, David A Wolk, Edward B Lee, Vivianna M Van Deerlin, Leslie M Shaw, John Q Trojanowski, Murray Grossman
Importance: Cerebrospinal fluid (CSF) core Alzheimer disease (AD) biomarkers have shown an excellent capacity for the in vivo detection of AD. Previous studies have shown that CSF levels of phosphorylated tau (p-tau) also correlate with tau pathology in frontotemporal lobar degeneration (FTLD) after accounting for AD copathology. Objective: To develop an algorithm based on core AD CSF measures to exclude cases with AD pathology and then differentiate between FTLD-tau and FTLD transactive response DNA-binding protein of approximately 43kDa (FTLD-TDP)...
March 19, 2018: JAMA Neurology
https://www.readbyqxmd.com/read/29542053/occupational-attainment-influences-longitudinal-decline-in-behavioral-variant-frontotemporal-degeneration
#10
Lauren Massimo, Sharon X Xie, Lior Rennert, Donna M Fick, Amy Halpin, Katerina Placek, Andrew Williams, Katya Rascovsky, David J Irwin, Murray Grossman, Corey T McMillan
To evaluate whether occupational attainment influences the trajectory of longitudinal cognitive decline in behavioral variant frontotemporal degeneration (bvFTD). Single-center, retrospective, longitudinal study. Sixty-three patients meeting consensus criteria for bvFTD underwent evaluation at the University of Pennsylvania Frontotemporal Degeneration Center. All patients were studied longitudinally on letter-guided fluency, category-naming fluency and Boston Naming Test (BNT). Occupational attainment was defined categorically by assigning each individual's occupation to a professional or non-professional category...
March 14, 2018: Brain Imaging and Behavior
https://www.readbyqxmd.com/read/29467305/csf-tau-and-%C3%AE-amyloid-predict-cerebral-synucleinopathy-in-autopsied-lewy-body-disorders
#11
David J Irwin, Sharon X Xie, David Coughlin, Naomi Nevler, Rizwan S Akhtar, Corey T McMillan, Edward B Lee, David A Wolk, Daniel Weintraub, Alice Chen-Plotkin, John E Duda, Meredith Spindler, Andrew Siderowf, Howard I Hurtig, Leslie M Shaw, Murray Grossman, John Q Trojanowski
OBJECTIVE: To test the association of antemortem CSF biomarkers with postmortem pathology in Lewy body disorders (LBD). METHODS: Patients with autopsy-confirmed LBD (n = 24) and autopsy-confirmed Alzheimer disease (AD) (n = 23) and cognitively normal (n = 36) controls were studied. In LBD, neuropathologic criteria defined Lewy body α-synuclein (SYN) stages with medium/high AD copathology (SYN + AD = 10) and low/no AD copathology (SYN - AD = 14). Ordinal pathology scores for tau, β-amyloid (Aβ), and SYN pathology were averaged across 7 cortical regions to obtain a global cerebral score for each pathology...
March 20, 2018: Neurology
https://www.readbyqxmd.com/read/29228211/asymmetry-of-post-mortem-neuropathology-in-behavioural-variant-frontotemporal-dementia
#12
David J Irwin, Corey T McMillan, Sharon X Xie, Katya Rascovsky, Vivianna M Van Deerlin, H Branch Coslett, Roy Hamilton, Geoffrey K Aguirre, Edward B Lee, Virginia M Y Lee, John Q Trojanowski, Murray Grossman
Antemortem behavioural and anatomic abnormalities have largely been associated with right hemisphere disease in behavioural-variant frontotemporal dementia, but post-mortem neuropathological examination of bilateral hemispheres remains to be defined. Here we measured the severity of post-mortem pathology in both grey and white matter using a validated digital image analysis method in four cortical regions sampled from each hemisphere in 26 patients with behavioural-variant frontotemporal dementia, including those with frontotemporal degeneration (i...
January 1, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29223682/neocortical-origin-and-progression-of-gray-matter-atrophy-in-nonamnestic-alzheimer-s-disease
#13
Jeffrey S Phillips, Fulvio Da Re, Laynie Dratch, Sharon X Xie, David J Irwin, Corey T McMillan, Sanjeev N Vaishnavi, Carlo Ferrarese, Edward B Lee, Leslie M Shaw, John Q Trojanowski, David A Wolk, Murray Grossman
Amnestic Alzheimer's disease (AD) is characterized by early atrophy of the hippocampus and medial temporal lobes before spreading to the neocortex. In contrast, nonamnestic Alzheimer's patients have relative sparing of the hippocampus, but the pattern in which the disease spreads is unclear. We examined spreading disease in nonamnestic AD using a novel magnetic resonance imaging-based analysis adapted from pathologic staging studies, applied here to cross-sectional imaging data. We selected 240 T1-weighted scans from 129 patients with pathology confirmed by autopsy or cerebrospinal fluid, and atrophy maps were computed relative to 238 scans from 115 elderly controls...
March 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29121998/circulating-brain-enriched-micrornas-as-novel-biomarkers-for-detection-and-differentiation-of-neurodegenerative-diseases
#14
Kira S Sheinerman, Jon B Toledo, Vladimir G Tsivinsky, David Irwin, Murray Grossman, Daniel Weintraub, Howard I Hurtig, Alice Chen-Plotkin, David A Wolk, Leo F McCluskey, Lauren B Elman, John Q Trojanowski, Samuil R Umansky
BACKGROUND: Minimally invasive specific biomarkers of neurodegenerative diseases (NDs) would facilitate patient selection and disease progression monitoring. We describe the assessment of circulating brain-enriched microRNAs as potential biomarkers for Alzheimer's disease (AD), frontotemporal dementia (FTD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). METHODS: In this case-control study, the plasma samples were collected from 250 research participants with a clinical diagnosis of AD, FTD, PD, and ALS, as well as from age- and sex-matched control subjects (n = 50 for each group), recruited from 2003 to 2015 at the University of Pennsylvania Health System, including the Alzheimer's Disease Center, the Parkinson's Disease and Movement Disorders Center, the Frontotemporal Degeneration Center, and the Amyotrophic Lateral Sclerosis Clinic...
November 9, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29105977/tau-pet-imaging-predicts-cognition-in-atypical-variants-of-alzheimer-s-disease
#15
Jeffrey S Phillips, Sandhitsu R Das, Corey T McMillan, David J Irwin, Emily E Roll, Fulvio Da Re, Ilya M Nasrallah, David A Wolk, Murray Grossman
Accumulation of paired helical filament tau contributes to neurodegeneration in Alzheimer's disease (AD).18 F-flortaucipir is a positron emission tomography (PET) radioligand sensitive to tau in AD, but its clinical utility will depend in part on its ability to predict cognitive symptoms in diverse dementia phenotypes associated with selective, regional uptake. We examined associations between18 F-flortaucipir and cognition in 14 mildly-impaired patients (12 with cerebrospinal fluid analytes consistent with AD pathology) who had amnestic (n = 5) and non-amnestic AD syndromes, including posterior cortical atrophy (PCA, n = 5) and logopenic-variant primary progressive aphasia (lvPPA, n = 4)...
February 2018: Human Brain Mapping
https://www.readbyqxmd.com/read/28980714/-18-f-flortaucipir-tau-positron-emission-tomography-distinguishes-established-progressive-supranuclear-palsy-from-controls-and-parkinson-disease-a-multicenter-study
#16
MULTICENTER STUDY
Daniel R Schonhaut, Corey T McMillan, Salvatore Spina, Bradford C Dickerson, Andrew Siderowf, Michael D Devous, Richard Tsai, Joseph Winer, David S Russell, Irene Litvan, Erik D Roberson, William W Seeley, Lea T Grinberg, Joel H Kramer, Bruce L Miller, Peter Pressman, Ilya Nasrallah, Suzanne L Baker, Stephen N Gomperts, Keith A Johnson, Murray Grossman, William J Jagust, Adam L Boxer, Gil D Rabinovici
OBJECTIVE: 18 F-flortaucipir (formerly 18 F-AV1451 or 18 F-T807) binds to neurofibrillary tangles in Alzheimer disease, but tissue studies assessing binding to tau aggregates in progressive supranuclear palsy (PSP) have yielded mixed results. We compared in vivo 18 F-flortaucipir uptake in patients meeting clinical research criteria for PSP (n = 33) to normal controls (n = 46) and patients meeting criteria for Parkinson disease (PD; n = 26). METHODS: Participants underwent magnetic resonance imaging and positron emission tomography for amyloid-β (11 C-PiB or 18 F-florbetapir) and tau (18 F-flortaucipir)...
October 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28969902/production-of-verbs-related-to-body-movement-in-amyotrophic-lateral-sclerosis-als-and-parkinson-s-disease-pd
#17
Katheryn A Q Cousins, Sharon Ash, Murray Grossman
Theories of grounded cognition propose that action verb knowledge relies in part on motor processing regions, including premotor cortex. Accordingly, impaired action verb knowledge in patients with amyotrophic lateral sclerosis (ALS) and Parkinson's Disease (PD) is thought to be due to motor system degeneration. Upper motor neuron disease in ALS degrades the motor cortex and related pyramidal motor system, while disease in PD is centered in the basal ganglia and can spread to frontostriatal areas that are important to language functioning...
March 2018: Cortex; a Journal Devoted to the Study of the Nervous System and Behavior
https://www.readbyqxmd.com/read/28914737/evidence-of-semantic-processing-impairments-in-behavioural-variant-frontotemporal-dementia-and-parkinson-s-disease
#18
REVIEW
Katheryn A Q Cousins, Murray Grossman
PURPOSE OF REVIEW: Category-specific impairments caused by brain damage can provide important insights into how semantic concepts are organized in the brain. Recent research has demonstrated that disease to sensory and motor cortices can impair perceptual feature knowledge important to the representation of semantic concepts. This evidence supports the grounded cognition theory of semantics, the view that lexical knowledge is partially grounded in perceptual experience and that sensory and motor regions support semantic representations...
December 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28887373/optical-coherence-tomography-identifies-outer-retina-thinning-in-frontotemporal-degeneration
#19
Benjamin J Kim, David J Irwin, Delu Song, Ebenezer Daniel, Jennifer D Leveque, Aaishah R Raquib, Wei Pan, Gui-Shuang Ying, Tomas S Aleman, Joshua L Dunaief, Murray Grossman
OBJECTIVE: Whereas Alzheimer disease (AD) is associated with inner retina thinning visualized by spectral-domain optical coherence tomography (SD-OCT), we sought to determine if the retina has a distinguishing biomarker for frontotemporal degeneration (FTD). METHODS: Using a cross-sectional design, we examined retinal structure in 38 consecutively enrolled patients with FTD and 44 controls using a standard SD-OCT protocol. Retinal layers were segmented with the Iowa Reference Algorithm...
October 10, 2017: Neurology
https://www.readbyqxmd.com/read/28877758/neuron-loss-and-degeneration-in-the-progression-of-tdp-43-in-frontotemporal-lobar-degeneration
#20
Ahmed Yousef, John L Robinson, David J Irwin, Matthew D Byrne, Linda K Kwong, Edward B Lee, Yan Xu, Sharon X Xie, Lior Rennert, EunRan Suh, Vivianna M Van Deerlin, Murray Grossman, Virginia M-Y Lee, John Q Trojanowski
Frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) is associated with the accumulation of pathological neuronal and glial intracytoplasmic inclusions as well as accompanying neuron loss. We explored if cortical neurons detected by NeuN decreased with increasing TDP-43 inclusion pathology in the postmortem brains of 63 patients with sporadic and familial FTLD-TDP. Semi-automated quantitative algorithms to quantify histology in tissue sections stained with antibodies specific for pathological or phosphorylated TDP-43 (pTDP-43) and NeuN were developed and validated in affected (cerebral cortex) and minimally affected (cerebellar cortex) brain regions of FTLD-TDP cases...
September 6, 2017: Acta Neuropathologica Communications
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