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- Beal, Jacob, et al.
(author)
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Robust estimation of bacterial cell count from optical density
- 2020
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In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Journal article (peer-reviewed)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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- Hansson, Oskar, et al.
(author)
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The Alzheimer's Association appropriate use recommendations for blood biomarkers in Alzheimer's disease
- 2022
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In: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 18:12, s. 2669-2686
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Journal article (peer-reviewed)abstract
- Blood-based markers (BBMs) have recently shown promise to revolutionize the diagnostic and prognostic work-up of Alzheimer's disease (AD), as well as to improve the design of interventional trials. Here we discuss in detail further research needed to be performed before widespread use of BBMs. We already now recommend use of BBMs as (pre-)screeners to identify individuals likely to have AD pathological changes for inclusion in trials evaluating disease-modifying therapies, provided the AD status is confirmed with positron emission tomography (PET) or cerebrospinal fluid (CSF) testing. We also encourage studying longitudinal BBM changes in ongoing as well as future interventional trials. However, BBMs should not yet be used as primary endpoints in pivotal trials. Further, we recommend to cautiously start using BBMs in specialized memory clinics as part of the diagnostic work-up of patients with cognitive symptoms and the results should be confirmed whenever possible with CSF or PET. Additional data are needed before use of BBMs as stand-alone diagnostic AD markers, or before considering use in primary care.
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- Zicha, S., et al.
(author)
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Comparative analytical performance of multiple plasma A beta 42 and A beta 40 assays and their ability to predict positron emission tomography amyloid positivity
- 2022
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In: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279.
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Journal article (peer-reviewed)abstract
- Introduction This report details the approach taken to providing a dataset allowing for analyses on the performance of recently developed assays of amyloid beta (A beta) peptides in plasma and the extent to which they improve the prediction of amyloid positivity. Methods Alzheimer's Disease Neuroimaging Initiative plasma samples with corresponding amyloid positron emission tomography (PET) data were run on six plasma A beta assays. Statistical tests were performed to determine whether the plasma A beta measures significantly improved the area under the receiver operating characteristic curve for predicting amyloid PET status compared to age and apolipoprotein E (APOE) genotype. Results The age and APOE genotype model predicted amyloid status with an area under the curve (AUC) of 0.75. Three assays improved AUCs to 0.81, 0.81, and 0.84 (P < .05, uncorrected for multiple comparisons). Discussion Measurement of A beta in plasma contributes to addressing the amyloid component of the ATN (amyloid/tau/neurodegeneration) framework and could be a first step before or in place of a PET or cerebrospinal fluid screening study. Highlights The Foundation of the National Institutes of Health Biomarkers Consortium evaluated six plasma amyloid beta (A beta) assays using Alzheimer's Disease Neuroimaging Initiative samples. Three assays improved prediction of amyloid status over age and apolipoprotein E (APOE) genotype. Plasma A beta 42/40 predicted amyloid positron emission tomography status better than A beta 42 or A beta 40 alone.
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- Verberk, Inge M.W., et al.
(author)
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Characterization of pre-analytical sample handling effects on a panel of Alzheimer's disease–related blood-based biomarkers : Results from the Standardization of Alzheimer's Blood Biomarkers (SABB) working group
- 2022
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In: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 18:8, s. 1484-1497
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Journal article (peer-reviewed)abstract
- Introduction: Pre-analytical sample handling might affect the results of Alzheimer's disease blood-based biomarkers. We empirically tested variations of common blood collection and handling procedures. Methods: We created sample sets that address the effect of blood collection tube type, and of ethylene diamine tetraacetic acid plasma delayed centrifugation, centrifugation temperature, aliquot volume, delayed storage, and freeze–thawing. We measured amyloid beta (Aβ)42 and 40 peptides with six assays, and Aβ oligomerization-tendency (OAβ), amyloid precursor protein (APP)699-711, glial fibrillary acidic protein (GFAP), neurofilament light (NfL), total tau (t-tau), and phosphorylated tau181. Results: Collection tube type resulted in different values of all assessed markers. Delayed plasma centrifugation and storage affected Aβ and t-tau; t-tau was additionally affected by centrifugation temperature. The other markers were resistant to handling variations. Discussion: We constructed a standardized operating procedure for plasma handling, to facilitate introduction of blood-based biomarkers into the research and clinical settings.
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