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- Nelson, G., et al.
(författare)
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QUAREP-LiMi: A community-driven initiative to establish guidelines for quality assessment and reproducibility for instruments and images in light microscopy
- 2021
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Ingår i: Journal of Microscopy. - : Wiley. - 0022-2720 .- 1365-2818. ; 284:1, s. 56-73
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Tidskriftsartikel (refereegranskat)abstract
- A modern day light microscope has evolved from a tool devoted to making primarily empirical observations to what is now a sophisticated , quantitative device that is an integral part of both physical and life science research. Nowadays, microscopes are found in nearly every experimental laboratory. However, despite their prevalent use in capturing and quantifying scientific phenomena, neither a thorough understanding of the principles underlying quantitative imaging techniques nor appropriate knowledge of how to calibrate, operate and maintain microscopes can be taken for granted. This is clearly demonstrated by the well-documented and widespread difficulties that are routinely encountered in evaluating acquired data and reproducing scientific experiments. Indeed, studies have shown that more than 70% of researchers have tried and failed to repeat another scientist's experiments, while more than half have even failed to reproduce their own experiments. One factor behind the reproducibility crisis of experiments published in scientific journals is the frequent underreporting of imaging methods caused by a lack of awareness and/or a lack of knowledge of the applied technique. Whereas quality control procedures for some methods used in biomedical research, such as genomics (e.g. DNA sequencing, RNA-seq) or cytometry, have been introduced (e.g. ENCODE), this issue has not been tackled for optical microscopy instrumentation and images. Although many calibration standards and protocols have been published, there is a lack of awareness and agreement on common standards and guidelines for quality assessment and reproducibility. In April 2020, the QUality Assessment and REProducibility for instruments and images in Light Microscopy (QUAREP-LiMi) initiative was formed. This initiative comprises imaging scientists from academia and industry who share a common interest in achieving a better understanding of the performance and limitations of microscopes and improved quality control (QC) in light microscopy. The ultimate goal of the QUAREP-LiMi initiative is to establish a set of common QC standards, guidelines, metadata models and tools, including detailed protocols, with the ultimate aim of improving reproducible advances in scientific research. This White Paper (1) summarizes the major obstacles identified in the field that motivated the launch of the QUAREP-LiMi initiative; (2) identifies the urgent need to address these obstacles in a grassroots manner, through a community of stakeholders including, researchers, imaging scientists, bioimage analysts, bioimage informatics developers, corporate partners, funding agencies, standards organizations, scientific publishers and observers of such; (3) outlines the current actions of the QUAREP-LiMi initiative and (4) proposes future steps that can be taken to improve the dissemination and acceptance of the proposed guidelines to manage QC. To summarize, the principal goal of the QUAREP-LiMi initiative is to improve the overall quality and reproducibility of light microscope image data by introducing broadly accepted standard practices and accurately captured image data metrics.
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| 2. |
- Gao, YX, et al.
(författare)
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Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis
- 2020
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 12184-
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Tidskriftsartikel (refereegranskat)abstract
- We employed Mendelian randomization (MR) to evaluate the causal relationship between leukocyte telomere length (LTL) and amyotrophic lateral sclerosis (ALS) with summary statistics from genome-wide association studies (n = ~ 38,000 for LTL and ~ 81,000 for ALS in the European population; n = ~ 23,000 for LTL and ~ 4,100 for ALS in the Asian population). We further evaluated mediation roles of lipids in the pathway from LTL to ALS. The odds ratio per standard deviation decrease of LTL on ALS was 1.10 (95% CI 0.93–1.31, p = 0.274) in the European population and 0.75 (95% CI 0.53–1.07, p = 0.116) in the Asian population. This null association was also detected between LTL and frontotemporal dementia in the European population. However, we found that an indirect effect of LTL on ALS might be mediated by low density lipoprotein (LDL) or total cholesterol (TC) in the European population. These results were robust against extensive sensitivity analyses. Overall, our MR study did not support the direct causal association between LTL and the ALS risk in neither population, but provided suggestive evidence for the mediation role of LDL or TC on the influence of LTL and ALS in the European population.
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| 3. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)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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| 4. |
- Bethlehem, RAI, et al.
(författare)
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Brain charts for the human lifespan
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 604:79057906, s. 525-
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Tidskriftsartikel (refereegranskat)abstract
- Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data (http://www.brainchart.io/). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes.
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| 7. |
- Kubica, Jacek, et al.
(författare)
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Prolonged antithrombotic therapy in patients after acute coronary syndrome : A critical appraisal of current European Society of Cardiology guidelines
- 2020
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Ingår i: CARDIOLOGY JOURNAL. - : VM Media SP. zo.o VM Group SK. - 1897-5593 .- 1898-018X. ; 27:6, s. 661-676
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Tidskriftsartikel (refereegranskat)abstract
- The increased risk of non-cardiovascular death in patients receiving clopidogrel or prasugrel in comparison with the placebo group in the Dual Antiplatelet Therapy (DAPT) trial in contrast to the decreased risk of cardiovascular death and all-cause death seen in patients treated with low-dose ticagrelor in the EU label population of the PEGASUS-TIMI 54 trial, resulted in inclusion in the 2020 ESC NSTE-ACS guidelines the recommendation for use of clopidogrel or prasugrel only if the patient is not eligible for treatment with ticagrelor. The prevalence of the primary outcome composed of cardiovascular death, stroke, or myocardial infarction was lower in the low-dose rivaroxaban and acetylsalicylic acid (ASA) group than in the ASA-alone group in the COMPASS trial. Moreover, all-cause mortality and cardiovascular mortality rates were lower in the rivaroxaban-plus-ASA group. Comparison of the PEGASUS-TIMI 54 and COMPASS trial patient characteristics clearly shows that each of these treatment strategies should be addressed at different groups of patients. A greater benefit in post-acute coronary syndrome (ACS) patients with a high risk of ischemic events and without high bleeding risk may be expected with ASA and ticagrelor 60 mg b.i.d. when the therapy is continued without interruption or with short interruption only after ACS. On the other hand, ASA and rivaroxaban 2.5 mg b.i.d. seems to be a better option when indications for dual antithrombotic therapy (DATT) appear after a longer time from ACS (more than 2 years) and/or from cessation of DAPT (more than 1 year) and in patients with multiple vascular bed atherosclerosis. Thus, both options of DATTs complement each other rather than compete, as can be presumed from the recommendations. However, a direct comparison between these strategies should be tested in future clinical trials.
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| 8. |
- Saddiki, H., et al.
(författare)
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Age and the association between apolipoprotein E genotype and Alzheimer disease: A cerebrospinal fluid biomarker-based case-control study
- 2020
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Ingår i: Plos Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 17:8
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Tidskriftsartikel (refereegranskat)abstract
- Background The epsilon 4 allele of apolipoprotein E (APOE) gene and increasing age are two of the most important known risk factors for developing Alzheimer disease (AD). The diagnosis of AD based on clinical symptoms alone is known to have poor specificity; recently developed diagnostic criteria based on biomarkers that reflect underlying AD neuropathology allow better assessment of the strength of the associations of risk factors with AD. Accordingly, we examined the global and age-specific association betweenAPOEgenotype and AD by using the A/T/N classification, relying on the cerebrospinal fluid (CSF) levels of beta-amyloid peptide (A, beta-amyloid deposition), phosphorylated tau (T, pathologic tau), and total tau (N, neurodegeneration) to identify patients with AD. Methods and findings This case-control study included 1,593 white AD cases (55.4% women; mean age 72.8 [range = 44-96] years) with abnormal values of CSF biomarkers from nine European memory clinics and the American Alzheimer's Disease Neuroimaging Initiative (ADNI) study. A total of 11,723 dementia-free controls (47.1% women; mean age 65.6 [range = 44-94] years) were drawn from two longitudinal cohort studies (Whitehall II and Three-City), in which incident cases of dementia over the follow-up were excluded from the control population. Odds ratio (OR) and population attributable fraction (PAF) for AD associated withAPOEgenotypes were determined, overall and by 5-year age categories. In total, 63.4% of patients with AD and 22.6% of population controls carried at least oneAPOE epsilon 4 allele. Compared with non-epsilon 4 carriers, heterozygous epsilon 4 carriers had a 4.6 (95% confidence interval 4.1-5.2;p< 0.001) and epsilon 4/epsilon 4 homozygotes a 25.4 (20.4-31.2;p< 0.001) higher OR of AD in unadjusted analysis. This association was modified by age (pfor interaction < 0.001). The PAF associated with carrying at least one epsilon 4 allele was greatest in the 65-70 age group (69.7%) and weaker before 55 years (14.2%) and after 85 years (22.6%). The protective effect ofAPOE epsilon 2 allele for AD was unaffected by age. Main study limitations are that analyses were based on white individuals and AD cases were drawn from memory centers, which may not be representative of the general population of patients with AD. Conclusions In this study, we found that AD diagnosis based on biomarkers was associated with APOE epsilon 4 carrier status, with a higher OR than previously reported from studies based on only clinical AD criteria. This association differs according to age, with the strongest effect at 65-70 years. These findings highlight the need for early interventions for dementia prevention to mitigate the effect ofAPOE epsilon 4 at the population level. Author summaryWhy was this study done? The epsilon 4 allele of apolipoprotein E () gene () and increasing age are two of the most important known risk factors for developing Alzheimer disease (AD). The recent development of diagnostic criteria based on biomarkers that reflect brain beta-amyloid and tau lesions (beta-amyloid deposition, pathologic tau, neurodegeneration [A/T/N] classification]) increases homogeneity in diagnosed cases. The strength of association of AD with risk factors can be better determined using biomarker-based AD compared with AD diagnosis based only on clinical criteria because the latter are known to lack specificity as a result of difficulties in ruling out other causes of dementia. What did the researchers do and find? We compared the overall and age-specific association between and AD using a case-control study that included 1,593 AD cases from memory clinics with positive cerebrospinal fluid biomarkers and 11,723 dementia-free controls drawn from two longitudinal cohort studies. The use of a large number of cases and controls allows assessment of whether the association between and AD is dependent on age. Compared with controls, patients with AD were more likely to carry one (odds ratio [OR] = 4.6) or two (OR = 25.3). This association was significantly modified by age, with the strongest association seen between 65 and 70 years of age and weaker associations at the two tails of the age distribution. What do these findings mean? Incorporating biomarkers for diagnosis of AD identified an association with that is apparently greater than has been previously reported using clinical diagnosis of the disease. The impact of on the risk of AD was strongest between the 65 and 70 years of age, earlier than the mean age at diagnosis in this study, which was 72.8 years.
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