| 1. |
- Anwer, Danish M., et al.
(författare)
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A comparison of machine learning approaches for the quantification of microglial cells in the brain of mice, rats and non-human primates
- 2023
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Ingår i: PLoS ONE. - 1932-6203. ; 18:5 MAY
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Tidskriftsartikel (refereegranskat)abstract
- Microglial cells are brain-specific macrophages that swiftly react to disruptive events in the brain. Microglial activation leads to specific modifications, including proliferation, morphological changes, migration to the site of insult, and changes in gene expression profiles. A change in inflammatory status has been linked to many neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. For this reason, the investigation and quantification of microglial cells is essential for better understanding their role in disease progression as well as for evaluating the cytocompatibility of novel therapeutic approaches for such conditions. In the following study we implemented a machine learning-based approach for the fast and automatized quantification of microglial cells; this tool was compared with manual quantification (ground truth), and with alternative free-ware such as the threshold-based ImageJ and the machine learning-based Ilastik. We first trained the algorithms on brain tissue obtained from rats and non-human primate immunohistochemically labelled for microglia. Subsequently we validated the accuracy of the trained algorithms in a preclinical rodent model of Parkinson's disease and demonstrated the robustness of the algorithms on tissue obtained from mice, as well as from images provided by three collaborating laboratories. Our results indicate that machine learning algorithms can detect and quantify microglial cells in all the three mammalian species in a precise manner, equipotent to the one observed following manual counting. Using this tool, we were able to detect and quantify small changes between the hemispheres, suggesting the power and reliability of the algorithm. Such a tool will be very useful for investigation of microglial response in disease development, as well as in the investigation of compatible novel therapeutics targeting the brain. As all network weights and labelled training data are made available, together with our step-by-step user guide, we anticipate that many laboratories will implement machine learning-based quantification of microglial cells in their research.
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| 2. |
- Diller, Gerhard-Paul, et al.
(författare)
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Lifespan Perspective on CongenitalHeart Disease Research: JACC State-of-the-Art Review.
- 2021
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 1558-3597 .- 0735-1097. ; 77:17, s. 2219-2235
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Tidskriftsartikel (refereegranskat)abstract
- More than 90% of patients with congenital heart disease (CHD) are nowadays surviving to adulthood and adults account for over two-thirds of the contemporary CHD population in Western countries. Although outcomes are improved, surgery does not cure CHD. Decades of longitudinal observational data are currently motivating a paradigm shift toward a lifespan perspective and proactive approach to CHD care. The aim of this review is to operationalize these emerging concepts by presenting new constructs in CHD research. These concepts include long-term trajectories and a life course epidemiology framework. Focusing on a precision health, we propose to integrate our current knowledge on the genome, phenome, andenvironome across the CHD lifespan. We alsosummarize the potential of technology, especially machine learning,tofacilitate longitudinal researchbyembracing big data and multicenter lifelong data collection.
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| 3. |
- Huang, Liping, et al.
(författare)
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The contribution of sodium reduction and potassium increase to the blood pressure lowering observed in the Salt Substitute and Stroke Study
- 2024
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Ingår i: Journal of Human Hypertension. - : Springer Nature. - 0950-9240 .- 1476-5527. ; 38:4, s. 298-306
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Tidskriftsartikel (refereegranskat)abstract
- The Salt Substitute and Stroke Study (SSaSS) demonstrated significant reductions in systolic blood pressure (SBP), and the risk of stroke, major cardiovascular events and total mortality with the use of potassium-enriched salt. The contribution of sodium reduction versus potassium increase to these effects is unknown. We identified four different data sources describing the association between sodium reduction, potassium supplementation and change in SBP. We then fitted a series of models to estimate the SBP reductions expected for the differences in sodium and potassium intake in SSaSS, derived from 24-h urine collections. The proportions of the SBP reduction separately attributable to sodium reduction and potassium supplementation were calculated. The observed SBP reduction in SSaSS was -3.3 mmHg with a corresponding mean 15.2 mmol reduction in 24-h sodium excretion and a mean 20.6 mmol increase in 24-h potassium excretion. Assuming 90% of dietary sodium intake and 70% of dietary potassium intake were excreted through urine, the models projected falls in SBP of between -1.67 (95% confidence interval: -4.06 to +0.73) mmHg and -5.33 (95% confidence interval: -8.58 to -2.08) mmHg. The estimated proportional contribution of sodium reduction to the SBP fall ranged between 12 and 39% for the different models fitted. Sensitivity analyses assuming different proportional urinary excretion of dietary sodium and potassium intake showed similar results. In every model, the majority of the SBP lowering effect in SSaSS was estimated to be attributable to the increase in dietary potassium rather than the fall in dietary sodium.
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| 4. |
- Jalloh, Mohamed F., et al.
(författare)
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Evidence of behaviour change during an Ebola virus disease outbreak, Sierra Leone
- 2020
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Ingår i: Bulletin of the World Health Organization. - : World Health Organization. - 0042-9686 .- 1564-0604. ; 98:5, s. 330-340
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Tidskriftsartikel (refereegranskat)abstract
- Objective To evaluate changes in Ebola-related knowledge, attitudes and prevention practices during the Sierra Leone outbreak between 2014 and 2015.Methods Four cluster surveys were conducted: two before the outbreak peak (3499 participants) and two after (7104 participants). We assessed the effect of temporal and geographical factors on 16 knowledge, attitude and practice outcomes.Findings Fourteen of 16 knowledge, attitude and prevention practice outcomes improved across all regions from before to after the outbreak peak. The proportion of respondents willing to: (i) welcome Ebola survivors back into the community increased from 60.0% to 89.4% (adjusted odds ratio, aOR: 6.0; 95% confidence interval, CI: 3.9–9.1); and (ii) wait for a burial team following a relative’s death increased from 86.0% to 95.9% (aOR: 4.4; 95% CI: 3.2–6.0). The proportion avoiding unsafe traditional burials increased from 27.3% to 48.2% (aOR: 3.1; 95% CI: 2.4–4.2) and the proportion believing spiritual healers can treat Ebola decreased from 15.9% to 5.0% (aOR: 0.2; 95% CI: 0.1–0.3). The likelihood respondents would wait for burial teams increased more in high-transmission (aOR: 6.2; 95% CI: 4.2–9.1) than low-transmission (aOR: 2.3; 95% CI: 1.4–3.8) regions. Self-reported avoidance of physical contact with corpses increased in high but not low-transmission regions, aOR: 1.9 (95% CI: 1.4–2.5) and aOR: 0.8 (95% CI: 0.6–1.2), respectively.Conclusion Ebola knowledge, attitudes and prevention practices improved during the Sierra Leone outbreak, especially in high-transmission regions. Behaviourally-targeted community engagement should be prioritized early during outbreaks.
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| 5. |
- Volz, Erik, et al.
(författare)
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Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity
- 2021
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Ingår i: Cell. - : Elsevier BV. - 1097-4172 .- 0092-8674. ; 184:1, s. 11-75
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Tidskriftsartikel (refereegranskat)abstract
- Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant.
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| 6. |
- Yin, Xuejun, et al.
(författare)
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Availability, Formulation, Labeling, and Price of Low-sodium Salt Worldwide : Environmental Scan
- 2021
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Ingår i: JMIR Public Health and Surveillance. - : JMIR Publications. - 2369-2960. ; 7:7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Regular salt is about 100% sodium chloride. Low-sodium salts have reduced sodium chloride content, most commonly through substitution with potassium chloride. Low-sodium salts have a potential role in reducing the population's sodium intake levels and blood pressure, but their availability in the global market is unknown.OBJECTIVE: The aim of this study is to assess the availability, formulation, labeling, and price of low-sodium salts currently available to consumers worldwide.METHODS: Low-sodium salts were identified through a systematic literature review, Google search, online shopping site searches, and inquiry of key informants. The keywords "salt substitute," "low-sodium salt," "potassium salt," "mineral salt," and "sodium reduced salt" in six official languages of the United Nations were used for the search. Information about the brand, formula, labeling, and price was extracted and analyzed.RESULTS: A total of 87 low-sodium salts were available in 47 out of 195 (24%) countries worldwide, including 28 high-income countries, 13 upper-middle-income countries, and 6 lower-middle-income countries. The proportion of sodium chloride varied from 0% (sodium-free) to 88% (as percent of weight; regular salt is 100% sodium chloride). Potassium chloride was the most frequent component with levels ranging from 0% to 100% (potassium chloride salt). A total of 43 (49%) low-sodium salts had labels with the potential health risks, and 33 (38%) had labels with the potential health benefits. The median price of low-sodium salts in high-income, upper-middle-income, and lower-middle-income countries was US $15.00/kg (IQR 6.4-22.5), US $2.70/kg (IQR 1.7-5.5), and US $2.90/kg (IQR 0.50-22.2), respectively. The price of low-sodium salts was between 1.1 and 14.6 times that of regular salts.CONCLUSIONS: Low-sodium salts are not widely available and are commonly more expensive than regular salts. Policies that promote the availability, affordability, and labeling of low-sodium salts should increase uptake, helping populations reduce blood pressure and prevent cardiovascular diseases.INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1111/jch.14054.
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| 7. |
- Zhong, Jun, et al.
(författare)
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A Transcriptome-Wide Association Study Identifies Novel Candidate Susceptibility Genes for Pancreatic Cancer
- 2020
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 112:10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although 20 pancreatic cancer susceptibility loci have been identified through genome-wide association studies in individuals of European ancestry, much of its heritability remains unexplained and the genes responsible largely unknown. Methods: To discover novel pancreatic cancer risk loci and possible causal genes, we performed a pancreatic cancer transcriptome-wide association study in Europeans using three approaches: FUSION, MetaXcan, and Summary-MulTiXcan. We integrated genome-wide association studies summary statistics from 9040 pancreatic cancer cases and 12 496 controls, with gene expression prediction models built using transcriptome data from histologically normal pancreatic tissue samples (NCI Laboratory of Translational Genomics [n = 95] and Genotype-Tissue Expression v7 [n = 174] datasets) and data from 48 different tissues (Genotype-Tissue Expression v7, n = 74-421 samples). Results: We identified 25 genes whose genetically predicted expression was statistically significantly associated with pancreatic cancer risk (false discovery rate < .05), including 14 candidate genes at 11 novel loci (1p36.12: CELA3B; 9q31.1: SMC2, SMC2-AS1; 10q23.31: RP11-80H5.9; 12q13.13: SMUG1; 14q32.33: BTBD6; 15q23: HEXA; 15q26.1: RCCD1; 17q12: PNMT, CDK12, PGAP3; 17q22: SUPT4H1; 18q11.22: RP11-888D10.3; and 19p13.11: PGPEPI) and 11 at six known risk loci (5p15.33: TERT, CLPTMIL, ZDHHCIIB; 7p14.1: INHBA; 9q34.2: ABO; 13q12.2: PDX1; 13q22.1: KLF5; and 16q23.1: WDR59, CFDP1, BCAR1, TMEM170A). The association for 12 of these genes (CELA3B, SMC2, and PNMT at novel risk loci and TERT, CLPTMIL, INHBA, ABO, PDX1, KLF5, WDR59, CFDP1, and BCAR1 at known loci) remained statistically significant after Bonferroni correction. Conclusions: By integrating gene expression and genotype data, we identified novel pancreatic cancer risk loci and candidate functional genes that warrant further investigation.
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