| 1. |
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| 2. |
- Abbafati, Cristiana, et al.
(författare)
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- 2020
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 4. |
- Santangelo, James S., et al.
(författare)
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Global urban environmental change drives adaptation in white clover
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375
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Tidskriftsartikel (refereegranskat)abstract
- Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural dines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale.
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| 5. |
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| 6. |
- Micah, Angela E., et al.
(författare)
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Tracking development assistance for health and for COVID-19 : a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050
- 2021
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 398:10308, s. 1317-1343
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Forskningsöversikt (refereegranskat)abstract
- Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$ per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. Findings In 2019, health spending globally reached $8. 8 trillion (95% uncertainty interval [UI] 8.7-8.8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total, $40.4 billion (0.5%, 95% UI 0.5-0.5) was development assistance for health provided to low-income and middle-income countries, which made up 24.6% (UI 24.0-25.1) of total spending in low-income countries. We estimate that $54.8 billion in development assistance for health was disbursed in 2020. Of this, $13.7 billion was targeted toward the COVID-19 health response. $12.3 billion was newly committed and $1.4 billion was repurposed from existing health projects. $3.1 billion (22.4%) of the funds focused on country-level coordination and $2.4 billion (17.9%) was for supply chain and logistics. Only $714.4 million (7.7%) of COVID-19 development assistance for health went to Latin America, despite this region reporting 34.3% of total recorded COVID-19 deaths in low-income or middle-income countries in 2020. Spending on health is expected to rise to $1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.
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| 7. |
- Sepanlou, Sadaf G., et al.
(författare)
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The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990-2017 : a systematic analysis for the Global Burden of Disease Study 2017
- 2020
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Ingår i: The Lancet Gastroenterology & Hepatology. - 2468-1253. ; 5:3, s. 245-266
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Tidskriftsartikel (refereegranskat)abstract
- Background Cirrhosis and other chronic liver diseases (collectively referred to as cirrhosis in this paper) are a major cause of morbidity and mortality globally, although the burden and underlying causes differ across locations and demographic groups. We report on results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 on the burden of cirrhosis and its trends since 1990, by cause, sex, and age, for 195 countries and territories. Methods We used data from vital registrations, vital registration samples, and verbal autopsies to estimate mortality. We modelled prevalence of total, compensated, and decompensated cirrhosis on the basis of hospital and claims data. Disability-adjusted life-years (DALYs) were calculated as the sum of years of life lost due to premature death and years lived with disability. Estimates are presented as numbers and age-standardised or age-specific rates per 100 000 population, with 95% uncertainty intervals (UIs). All estimates are presented for five causes of cirrhosis: hepatitis B, hepatitis C, alcohol-related liver disease, non-alcoholic steatohepatitis (NASH), and other causes. We compared mortality, prevalence, and DALY estimates with those expected according to the Socio-demographic Index (SDI) as a proxy for the development status of regions and countries. Findings In 2017, cirrhosis caused more than 1.32 million (95% UI 1.27-1.45) deaths (440000 [416 000-518 000; 33.3%] in females and 883 000 [838 000-967 000; 66.7%] in males) globally, compared with less than 899 000 (829 000-948 000) deaths in 1990. Deaths due to cirrhosis constituted 2.4% (2.3-2.6) of total deaths globally in 2017 compared with 1.9% (1.8-2.0) in 1990. Despite an increase in the number of deaths, the age-standardised death rate decreased from 21.0 (19.2-22.3) per 100 000 population in 1990 to 16.5 (15.8-18-1) per 100 000 population in 2017. Sub-Saharan Africa had the highest age-standardised death rate among GBD super-regions for all years of the study period (32.2 [25.8-38.6] deaths per 100 000 population in 2017), and the high-income super-region had the lowest (10.1 [9.8-10-5] deaths per 100 000 population in 2017). The age-standardised death rate decreased or remained constant from 1990 to 2017 in all GBD regions except eastern Europe and central Asia, where the age-standardised death rate increased, primarily due to increases in alcohol-related liver disease prevalence. At the national level, the age-standardised death rate of cirrhosis was lowest in Singapore in 2017 (3.7 [3.3-4.0] per 100 000 in 2017) and highest in Egypt in all years since 1990 (103.3 [64.4-133.4] per 100 000 in 2017). There were 10.6 million (10.3-10.9) prevalent cases of decompensated cirrhosis and 112 million (107-119) prevalent cases of compensated cirrhosis globally in 2017. There was a significant increase in age-standardised prevalence rate of decompensated cirrhosis between 1990 and 2017. Cirrhosis caused by NASH had a steady age-standardised death rate throughout the study period, whereas the other four causes showed declines in age-standardised death rate. The age-standardised prevalence of compensated and decompensated cirrhosis due to NASH increased more than for any other cause of cirrhosis (by 33.2% for compensated cirrhosis and 54.8% for decompensated cirrhosis) over the study period. From 1990 to 2017, the number of prevalent cases snore than doubled for compensated cirrhosis due to NASH and more than tripled for decompensated cirrhosis due to NASH. In 2017, age-standardised death and DALY rates were lower among countries and territories with higher SDI. Interpretation Cirrhosis imposes a substantial health burden on many countries and this burden has increased at the global level since 1990, partly due to population growth and ageing. Although the age-standardised death and DALY rates of cirrhosis decreased from 1990 to 2017, numbers of deaths and DALYs and the proportion of all global deaths due to cirrhosis increased. Despite the availability of effective interventions for the prevention and treatment of hepatitis B and C, they were still the main causes of cirrhosis burden worldwide, particularly in low-income countries. The impact of hepatitis B and C is expected to be attenuated and overtaken by that of NASH in the near future. Cost-effective interventions are required to continue the prevention and treatment of viral hepatitis, and to achieve early diagnosis and prevention of cirrhosis due to alcohol-related liver disease and NASH.
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| 8. |
- Ekhtiari, Hamed, et al.
(författare)
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A methodological checklist for fMRI drug cue reactivity studies : development and expert consensus
- 2022
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Ingår i: Nature Protocols. - : Nature Portfolio. - 1754-2189 .- 1750-2799. ; 17:3, s. 567-595
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Tidskriftsartikel (refereegranskat)abstract
- Cue reactivity measured by functional magnetic resonance imaging is used in studies of substance-use disorders. This Consensus Statement is the result of a Delphi process to arrive at parameters that should be reported in describing these studies. Cue reactivity is one of the most frequently used paradigms in functional magnetic resonance imaging (fMRI) studies of substance use disorders (SUDs). Although there have been promising results elucidating the neurocognitive mechanisms of SUDs and SUD treatments, the interpretability and reproducibility of these studies is limited by incomplete reporting of participants characteristics, task design, craving assessment, scanning preparation and analysis decisions in fMRI drug cue reactivity (FDCR) experiments. This hampers clinical translation, not least because systematic review and meta-analysis of published work are difficult. This consensus paper and Delphi study aims to outline the important methodological aspects of FDCR research, present structured recommendations for more comprehensive methods reporting and review the FDCR literature to assess the reporting of items that are deemed important. Forty-five FDCR scientists from around the world participated in this study. First, an initial checklist of items deemed important in FDCR studies was developed by several members of the Enhanced NeuroImaging Genetics through Meta-Analyses (ENIGMA) Addiction working group on the basis of a systematic review. Using a modified Delphi consensus method, all experts were asked to comment on, revise or add items to the initial checklist, and then to rate the importance of each item in subsequent rounds. The reporting status of the items in the final checklist was investigated in 108 recently published FDCR studies identified through a systematic review. By the final round, 38 items reached the consensus threshold and were classified under seven major categories: Participants Characteristics, General fMRI Information, General Task Information, Cue Information, Craving Assessment Inside Scanner, Craving Assessment Outside Scanner and Pre- and Post-Scanning Considerations. The review of the 108 FDCR papers revealed significant gaps in the reporting of the items considered important by the experts. For instance, whereas items in the General fMRI Information category were reported in 90.5% of the reviewed papers, items in the Pre- and Post-Scanning Considerations category were reported by only 44.7% of reviewed FDCR studies. Considering the notable and sometimes unexpected gaps in the reporting of items deemed to be important by experts in any FDCR study, the protocols could benefit from the adoption of reporting standards. This checklist, a living document to be updated as the field and its methods advance, can help improve experimental design, reporting and the widespread understanding of the FDCR protocols. This checklist can also provide a sample for developing consensus statements for protocols in other areas of task-based fMRI.
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| 9. |
- Feigin, Valery L., et al.
(författare)
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Global, regional, and national burden of stroke and its risk factors, 1990-2019 : a systematic analysis for the Global Burden of Disease Study 2019
- 2021
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Ingår i: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 20:10, s. 795-820
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Tidskriftsartikel (refereegranskat)abstract
- Background Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings In 2019, there were 12.2 million (95% UI 11.0-13.6) incident cases of stroke, 101 million (93.2-111) prevalent cases of stroke, 143 million (133-153) DALYs due to stroke, and 6.55 million (6.00-7.02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11.6% [10.8-12.2] of total deaths) and the third-leading cause of death and disability combined (5.7% [5.1-6.2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70.0% (67.0-73.0), prevalent strokes increased by 85.0% (83.0-88.0), deaths from stroke increased by 43.0% (31.0-55.0), and DALYs due to stroke increased by 32.0% (22.0-42.0). During the same period, age-standardised rates of stroke incidence decreased by 17.0% (15.0-18.0), mortality decreased by 36.0% (31.0-42.0), prevalence decreased by 6.0% (5.0-7.0), and DALYs decreased by 36.0% (31.0-42.0). However, among people younger than 70 years, prevalence rates increased by 22.0% (21.0-24.0) and incidence rates increased by 15.0% (12.0-18.0). In 2019, the age-standardised stroke-related mortality rate was 3.6 (3.5-3.8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3.7 (3.5-3.9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62.4% of all incident strokes in 2019 (7.63 million [6.57-8.96]), while intracerebral haemorrhage constituted 27.9% (3.41 million [2.97-3.91]) and subarachnoid haemorrhage constituted 9.7% (1.18 million [1.01-1.39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79.6 million [67.7-90.8] DALYs or 55.5% [48.2-62.0] of total stroke DALYs), high body-mass index (34.9 million [22.3-48.6] DALYs or 24.3% [15.7-33.2]), high fasting plasma glucose (28.9 million [19.8-41.5] DALYs or 20.2% [13.8-29.1]), ambient particulate matter pollution (28.7 million [23.4-33.4] DALYs or 20.1% [16.6-23.0]), and smoking (25.3 million [22.6-28.2] DALYs or 17.6% [16.4-19.0]). Interpretation The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries.
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| 10. |
- Jhun, Mina-A, et al.
(författare)
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A multi-ethnic epigenome-wide association study of leukocyte DNA methylation and blood lipids
- 2021
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Here we examine the association between DNA methylation in circulating leukocytes and blood lipids in a multi-ethnic sample of 16,265 subjects. We identify 148, 35, and 4 novel associations among Europeans, African Americans, and Hispanics, respectively, and an additional 186 novel associations through a trans-ethnic meta-analysis. We observe a high concordance in the direction of effects across racial/ethnic groups, a high correlation of effect sizes between high-density lipoprotein and triglycerides, a modest overlap of associations with epigenome-wide association studies of other cardio-metabolic traits, and a largely non-overlap with lipid loci identified to date through genome-wide association studies. Thirty CpGs reached significance in at least 2 racial/ethnic groups including 7 that showed association with the expression of an annotated gene. CpGs annotated to CPT1A showed evidence of being influenced by triglycerides levels. DNA methylation levels of circulating leukocytes show robust and consistent association with blood lipid levels across multiple racial/ethnic groups. Abnormal blood lipid levels are important risk factors for cardiovascular and other various diseases. Here the authors conduct a large-scale multi-ethnic epigenome-wide association study combined with epigenetic (cis-QTL and eQTM) data, and identify CpG-lipid traits associations that are specific to or common across racial/ethnic groups.
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| 11. |
- Rabiee, Navid, et al.
(författare)
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Green Biomaterials : fundamental principles
- 2023
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Ingår i: Green Biomaterials. - : Taylor & Francis. - 2993-4168. ; 1:1, s. 1-4
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 12. |
- Sangchooli, Arshiya, et al.
(författare)
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Parameter Space and Potential for Biomarker Development in 25 Years of fMRI Drug Cue Reactivity
- 2024
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Ingår i: JAMA psychiatry. - : AMER MEDICAL ASSOC. - 2168-6238 .- 2168-622X.
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Forskningsöversikt (refereegranskat)abstract
- Importance In the last 25 years, functional magnetic resonance imaging drug cue reactivity (FDCR) studies have characterized some core aspects in the neurobiology of drug addiction. However, no FDCR-derived biomarkers have been approved for treatment development or clinical adoption. Traversing this translational gap requires a systematic assessment of the FDCR literature evidence, its heterogeneity, and an evaluation of possible clinical uses of FDCR-derived biomarkers. Objective To summarize the state of the field of FDCR, assess their potential for biomarker development, and outline a clear process for biomarker qualification to guide future research and validation efforts. Evidence Review The PubMed and Medline databases were searched for every original FDCR investigation published from database inception until December 2022. Collected data covered study design, participant characteristics, FDCR task design, and whether each study provided evidence that might potentially help develop susceptibility, diagnostic, response, prognostic, predictive, or severity biomarkers for 1 or more addictive disorders. Findings There were 415 FDCR studies published between 1998 and 2022. Most focused on nicotine (122 [29.6%]), alcohol (120 [29.2%]), or cocaine (46 [11.1%]), and most used visual cues (354 [85.3%]). Together, these studies recruited 19 311 participants, including 13 812 individuals with past or current substance use disorders. Most studies could potentially support biomarker development, including diagnostic (143 [32.7%]), treatment response (141 [32.3%]), severity (84 [19.2%]), prognostic (30 [6.9%]), predictive (25 [5.7%]), monitoring (12 [2.7%]), and susceptibility (2 [0.5%]) biomarkers. A total of 155 interventional studies used FDCR, mostly to investigate pharmacological (67 [43.2%]) or cognitive/behavioral (51 [32.9%]) interventions; 141 studies used FDCR as a response measure, of which 125 (88.7%) reported significant interventional FDCR alterations; and 25 studies used FDCR as an intervention outcome predictor, with 24 (96%) finding significant associations between FDCR markers and treatment outcomes. Conclusions and Relevance Based on this systematic review and the proposed biomarker development framework, there is a pathway for the development and regulatory qualification of FDCR-based biomarkers of addiction and recovery. Further validation could support the use of FDCR-derived measures, potentially accelerating treatment development and improving diagnostic, prognostic, and predictive clinical judgments.
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| 13. |
- Gorski, Mathias, et al.
(författare)
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Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies
- 2022
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Ingår i: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 102:3, s. 624-639
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Tidskriftsartikel (refereegranskat)abstract
- Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genomewide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR- baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant- by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with agedependency of genetic cross- section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in- silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03- 1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics.
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| 14. |
- Gorski, Mathias, et al.
(författare)
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Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline
- 2021
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Ingår i: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 99:4, s. 926-939
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Tidskriftsartikel (refereegranskat)abstract
- Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m2/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m2 at follow-up among those with eGFRcrea 60 mL/min/1.73m2 or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or LARP4B. Individuals at high compared to those at low genetic risk (8-14 vs 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
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| 15. |
- Agardh, Emilie E., et al.
(författare)
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Disease Burden Attributed to Drug use in the Nordic Countries : a Systematic Analysis for the Global Burden of Diseases, Injuries, and Risk Factors Study 2019
- 2023
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Ingår i: International Journal of Mental Health and Addiction. - 1557-1874 .- 1557-1882.
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Tidskriftsartikel (refereegranskat)abstract
- The Nordic countries share similarities in many social and welfare domains, but drug policies have varied over time and between countries. We wanted to compare differences in mortality and disease burden attributed to drug use over time. Using results from the Global Burden of Disease (GBD) study, we extracted age-standardized estimates of deaths, DALYs, YLLs and YLDs per 100 000 population for Denmark, Finland, Iceland, Norway, and Sweden during the years 1990 to 2019. Among males, DALY rates in 2019 were highest in Finland and lowest in Iceland. Among females, DALY rates in 2019 were highest in Iceland and lowest in Sweden. Sweden have had the highest increase in burden since 1990, from 252 DALYs to 694 among males, and from 111 to 193 among females. Norway had a peak with highest level of all countries in 2001-2004 and thereafter a strong decline. Denmark have had the most constant burden over time, 566-600 DALYs among males from 1990 to 2010 and 210-240 DALYs among females. Strict drug policies in Nordic countries have not prevented an increase in some countries, so policies need to be reviewed.
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| 16. |
- Asnicar, Francesco, et al.
(författare)
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Blue poo : Impact of gut transit time on the gut microbiome using a novel marker
- 2021
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 70:9, s. 1665-1674
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Gut transit time is a key modulator of host-microbiome interactions, yet this is often overlooked, partly because reliable methods are typically expensive or burdensome. The aim of this single-arm, single-blinded intervention study is to assess (1) the relationship between gut transit time and the human gut microbiome, and (2) the utility of the a € blue dye' method as an inexpensive and scalable technique to measure transit time. Methods: We assessed interactions between the taxonomic and functional potential profiles of the gut microbiome (profiled via shotgun metagenomic sequencing), gut transit time (measured via the blue dye method), cardiometabolic health and diet in 863 healthy individuals from the PREDICT 1 study. Results: We found that gut microbiome taxonomic composition can accurately discriminate between gut transit time classes (0.82 area under the receiver operating characteristic curve) and longer gut transit time is linked with specific microbial species such as Akkermansia muciniphila, Bacteroides spp and Alistipes spp (false discovery rate-adjusted p values <0.01). The blue dye measure of gut transit time had the strongest association with the gut microbiome over typical transit time proxies such as stool consistency and frequency. Conclusions: Gut transit time, measured via the blue dye method, is a more informative marker of gut microbiome function than traditional measures of stool consistency and frequency. The blue dye method can be applied in large-scale epidemiological studies to advance diet-microbiome-health research. Clinical trial registry website https://clinicaltrials.gov/ct2/show/NCT03479866 and trial number NCT03479866.
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| 17. |
- Climaco Pinto, Rui, et al.
(författare)
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Finding Correspondence between Metabolomic Features in Untargeted Liquid Chromatography-Mass Spectrometry Metabolomics Datasets.
- 2022
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Ingår i: Analytical chemistry. - : American Chemical Society (ACS). - 1520-6882 .- 0003-2700. ; 94:14, s. 5493-5503
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Tidskriftsartikel (refereegranskat)abstract
- Integration of multiple datasets can greatly enhance bioanalytical studies, for example, by increasing power to discover and validate biomarkers. In liquid chromatography-mass spectrometry (LC-MS) metabolomics, it is especially hard to combine untargeted datasets since the majority of metabolomic features are not annotated and thus cannot be matched by chemical identity. Typically, the information available for each feature is retention time (RT), mass-to-charge ratio (m/z), and feature intensity (FI). Pairs of features from the same metabolite in separate datasets can exhibit small but significant differences, making matching very challenging. Current methods to address this issue are too simple or rely on assumptions that cannot be met in all cases. We present a method to find feature correspondence between two similar LC-MS metabolomics experiments or batches using only the features' RT, m/z, and FI. We demonstrate the method on both real and synthetic datasets, using six orthogonal validation strategies to gauge the matching quality. In our main example, 4953 features were uniquely matched, of which 585 (96.8%) of 604 manually annotated features were correct. In a second example, 2324 features could be uniquely matched, with 79 (90.8%) out of 87 annotated features correctly matched. Most of the missed annotated matches are between features that behave very differently from modeled inter-dataset shifts of RT, MZ, and FI. In a third example with simulated data with 4755 features per dataset, 99.6% of the matches were correct. Finally, the results of matching three other dataset pairs using our method are compared with a published alternative method, metabCombiner, showing the advantages of our approach. The method can be applied using M2S (Match 2 Sets), a free, open-source MATLAB toolbox, available at https://github.com/rjdossan/M2S.
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| 18. |
- Hurley, Carolyn K., et al.
(författare)
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Common, intermediate and well-documented HLA alleles in world populations : CIWD version 3.0.0
- 2020
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Ingår i: HLA. - : WILEY. - 2059-2302 .- 2059-2310. ; 95:6, s. 516-531
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Tidskriftsartikel (refereegranskat)abstract
- A catalog of common, intermediate and well-documented (CIWD) HLA-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5, -DQB1 and -DPB1 alleles has been compiled from over 8 million individuals using data from 20 unrelated hematopoietic stem cell volunteer donor registries. Individuals are divided into seven geographic/ancestral/ethnic groups and data are summarized for each group and for the total population. P (two-field) and G group assignments are divided into one of four frequency categories: common (>= 1 in 10 000), intermediate (>= 1 in 100 000), well-documented (>= 5 occurrences) or not-CIWD. Overall 26% of alleles in IPD-IMGT/HLA version 3.31.0 at P group resolution fall into the three CIWD categories. The two-field catalog includes 18% (n = 545) common, 17% (n = 513) intermediate, and 65% (n = 1997) well-documented alleles. Full-field allele frequency data are provided but are limited in value by the variations in resolution used by the registries. A recommended CIWD list is based on the most frequent category in the total or any of the seven geographic/ancestral/ethnic groups. Data are also provided so users can compile a catalog specific to the population groups that they serve. Comparisons are made to three previous CWD reports representing more limited population groups. This catalog, CIWD version 3.0.0, is a step closer to the collection of global HLA frequencies and to a clearer view of HLA diversity in the human population as a whole.
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| 19. |
- Khaghanifard, Jalal, et al.
(författare)
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Nonlinear modelling of unimorph and bimorph magneto-electro-elastic energy harvesters
- 2023
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Ingår i: Applied Mathematical Modelling. - : Elsevier BV. - 0307-904X. ; 119, s. 803-830
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Tidskriftsartikel (refereegranskat)abstract
- This paper nonlinearly models cantilever-based functionally graded magneto-electro-elastic energy harvesters (FGMEEEH) for the first time. The coupled magneto-electro-mechanical model is obtained on the basis of the Euler-Bernoulli beam theory. A hybrid procedure including Ritz's method is then utilized to generate reduced order models for both asymmetric unimorph and symmetric bimorph configurations. The resulting sets of initial value problems, whose convergence will be examined, are then analytically solved using the method of multiple time scales for both the free vibrations and primary resonance cases. The analytical time-histories of the system are compared by those obtained numerically and excellent agreements between them are observed. In addition, simplifying the frequency response function of the system in the primary resonance case, the present findings are validated by those available in the literature for linear unimorph systems. The influences of the harvester configurations, base acceleration amplitude, the value of the tip mass, the material gradation index as well as the resistances of the piezoelectric and magnetic circuits on the nonlinear response of the system are also studied in detail. It is observed that FGMEEEEHs enjoy much more efficiency in comparison to piezoelectric-based systems.
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| 20. |
- Kim, Min Seo, et al.
(författare)
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Global burden of peripheral artery disease and its risk factors, 1990-2019 : a systematic analysis for the Global Burden of Disease Study 2019
- 2023
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Ingår i: The Lancet Global Health. - : Elsevier. - 2214-109X. ; 11:10, s. E1553-E1565
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Tidskriftsartikel (refereegranskat)abstract
- Background: Peripheral artery disease is a growing public health problem. We aimed to estimate the global disease burden of peripheral artery disease, its risk factors, and temporospatial trends to inform policy and public measures.Methods: Data on peripheral artery disease were modelled using the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2019 database. Prevalence, disability-adjusted life years (DALYs), and mortality estimates of peripheral artery disease were extracted from GBD 2019. Total DALYs and age-standardised DALY rate of peripheral artery disease attributed to modifiable risk factors were also assessed.Findings: In 2019, the number of people aged 40 years and older with peripheral artery disease was 113 million (95% uncertainty interval [UI] 99 center dot 2-128 center dot 4), with a global prevalence of 1 center dot 52% (95% UI 1 center dot 33-1 center dot 72), of which 42 center dot 6% was in countries with low to middle Socio-demographic Index (SDI). The global prevalence of peripheral artery disease was higher in older people, (14 center dot 91% [12 center dot 41-17 center dot 87] in those aged 80-84 years), and was generally higher in females than in males. Globally, the total number of DALYs attributable to modifiable risk factors in 2019 accounted for 69 center dot 4% (64 center dot 2-74 center dot 3) of total peripheral artery disease DALYs. The prevalence of peripheral artery disease was highest in countries with high SDI and lowest in countries with low SDI, whereas DALY and mortality rates showed U-shaped curves, with the highest burden in the high and low SDI quintiles.Interpretation: The total number of people with peripheral artery disease has increased globally from 1990 to 2019. Despite the lower prevalence of peripheral artery disease in males and low-income countries, these groups showed similar DALY rates to females and higher-income countries, highlighting disproportionate burden in these groups. Modifiable risk factors were responsible for around 70% of the global peripheral artery disease burden. Public measures could mitigate the burden of peripheral artery disease by modifying risk factors.
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| 21. |
- Louca, Panayiotis, et al.
(författare)
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Modest effects of dietary supplements during the COVID-19 pandemic : Insights from 445 850 users of the COVID-19 Symptom Study app
- 2021
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Ingår i: BMJ Nutrition, Prevention and Health. - : BMJ. - 2516-5542. ; 4:1, s. 149-157
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Dietary supplements may ameliorate SARS-CoV-2 infection, although scientific evidence to support such a role is lacking. We investigated whether users of the COVID-19 Symptom Study app who regularly took dietary supplements were less likely to test positive for SARS-CoV-2 infection. Design App-based community survey. Setting 445 850 subscribers of an app that was launched to enable self-reported information related to SARS-CoV-2 infection for use in the general population in the UK (n=372 720), the USA (n=45 757) and Sweden (n=27 373). Main exposure Self-reported regular dietary supplement usage (constant use during previous 3 months) in the first waves of the pandemic up to 31 July 2020. Main outcome measures SARS-CoV-2 infection confirmed by viral RNA reverse transcriptase PCR test or serology test before 31 July 2020. Results In 372 720 UK participants (175 652 supplement users and 197 068 non-users), those taking probiotics, omega-3 fatty acids, multivitamins or vitamin D had a lower risk of SARS-CoV-2 infection by 14% (95% CI (8% to 19%)), 12% (95% CI (8% to 16%)), 13% (95% CI (10% to 16%)) and 9% (95% CI (6% to 12%)), respectively, after adjusting for potential confounders. No effect was observed for those taking vitamin C, zinc or garlic supplements. On stratification by sex, age and body mass index (BMI), the protective associations in individuals taking probiotics, omega-3 fatty acids, multivitamins and vitamin D were observed in females across all ages and BMI groups, but were not seen in men. The same overall pattern of association was observed in both the US and Swedish cohorts. Conclusion In women, we observed a modest but significant association between use of probiotics, omega-3 fatty acid, multivitamin or vitamin D supplements and lower risk of testing positive for SARS-CoV-2. We found no clear benefits for men nor any effect of vitamin C, garlic or zinc. Randomised controlled trials are required to confirm these observational findings before any therapeutic recommendations can be made.
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| 22. |
- Mazidi, Mohsen, et al.
(författare)
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Diet and lifestyle behaviour disruption related to the pandemic was varied and bidirectional among US and UK adults participating in the ZOE COVID Study
- 2021
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Ingår i: Nature Food. - : Springer Science and Business Media LLC. - 2662-1355. ; 2:12, s. 957-969
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Tidskriftsartikel (refereegranskat)abstract
- Evidence of the impact of the COVID-19 pandemic on health behaviours in the general population is limited. In this retrospective longitudinal study including UK and US participants, we collected diet and lifestyle data pre-pandemic (896,286) and peri-pandemic (291,871) using a mobile health app, and we computed a bidirectional health behaviour disruption index. Disruption of health behaviour was higher in younger, female and socio-economically deprived participants. Loss in body weight was greater in highly disrupted individuals than in those with low disruption. There were large inter-individual changes observed in 46 health and diet behaviours measured peri-pandemic compared with pre-pandemic, but no mean change in the total population. Individuals most adherent to less healthy pre-pandemic health behaviours improved their diet quality and weight compared with those reporting healthier pre-pandemic behaviours, irrespective of relative deprivation; therefore, for a proportion of the population, the pandemic may have provided an impetus to improve health behaviours. Public policies to tackle health inequalities widened by the pandemic should continue to prioritize diet and physical activity for all, as well as more targeted approaches to support younger females and those living in economically deprived areas.
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| 23. |
- Merino, Jordi, et al.
(författare)
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Diet quality and risk and severity of COVID-19 : a prospective cohort study
- 2021
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 70:11, s. 2096-2104
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Poor metabolic health and unhealthy lifestyle factors have been associated with risk and severity of COVID-19, but data for diet are lacking. We aimed to investigate the association of diet quality with risk and severity of COVID-19 and its interaction with socioeconomic deprivation. DESIGN: We used data from 592 571 participants of the smartphone-based COVID-19 Symptom Study. Diet information was collected for the prepandemic period using a short food frequency questionnaire, and diet quality was assessed using a healthful Plant-Based Diet Score, which emphasises healthy plant foods such as fruits or vegetables. Multivariable Cox models were fitted to calculate HRs and 95% CIs for COVID-19 risk and severity defined using a validated symptom-based algorithm or hospitalisation with oxygen support, respectively. RESULTS: Over 3 886 274 person-months of follow-up, 31 815 COVID-19 cases were documented. Compared with individuals in the lowest quartile of the diet score, high diet quality was associated with lower risk of COVID-19 (HR 0.91; 95% CI 0.88 to 0.94) and severe COVID-19 (HR 0.59; 95% CI 0.47 to 0.74). The joint association of low diet quality and increased deprivation on COVID-19 risk was higher than the sum of the risk associated with each factor alone (Pinteraction=0.005). The corresponding absolute excess rate per 10 000 person/months for lowest vs highest quartile of diet score was 22.5 (95% CI 18.8 to 26.3) among persons living in areas with low deprivation and 40.8 (95% CI 31.7 to 49.8) among persons living in areas with high deprivation. CONCLUSIONS: A diet characterised by healthy plant-based foods was associated with lower risk and severity of COVID-19. This association may be particularly evident among individuals living in areas with higher socioeconomic deprivation.
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| 24. |
- Moshtaghian, Hanieh, et al.
(författare)
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Application of Oyster Mushroom Cultivation Residue as an Upcycled Ingredient for Developing Bread
- 2022
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Ingår i: Applied Sciences. - : MDPI. - 2076-3417. ; 12:21
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Tidskriftsartikel (refereegranskat)abstract
- Oyster mushroom (OM) cultivation generates residue that needs to be managed; otherwise, it will be converted into waste. One of the substrates for OM cultivation is the food industry by-product, e.g., a mixture of the brewer’s spent grain (BSG) and wheat bran. This study assesses the OM cultivation residue’s physical and nutritional characteristics as a potential upcycled food ingredient and also considers developing bread from this cultivation residue. The OM was cultivated in a mixture of 55% BSG and 45% wheat bran. After the OM harvest, the cultivation residue (mixture of BSG, wheat bran and mycelium) had a lighter colour and a pleasant aroma compared to the initial substrate. It contained protein (10.8%) and had high niacin (42.4 mg/100 g), fibre (59.2%) and beta-glucan (6.6%). Thiamine, riboflavin and pyridoxine were also present in the cultivation residue. The bread was developed from 50% cultivation residue and 50% wheat flour, and its scores for darkness, dryness, sponginess, sour taste, bitter aftertaste, and aromatic aroma differed from white bread (p-value < 0.05). However, its overall acceptability and liking scores were not significantly different from white bread (p-value > 0.05). Therefore, this OM cultivation residue can be used as a nutritious ingredient; nevertheless, product development should be further explored.
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| 25. |
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| 26. |
- Pirkis, Jane, et al.
(författare)
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Suicide numbers during the first 9-15 months of the COVID-19 pandemic compared with pre-existing trends : An interrupted time series analysis in 33 countries
- 2022
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Ingår i: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 51
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Tidskriftsartikel (refereegranskat)abstract
- Background Predicted increases in suicide were not generally observed in the early months of the COVID-19 pandemic. However, the picture may be changing and patterns might vary across demographic groups. We aimed to provide a timely, granular picture of the pandemic's impact on suicides globally. Methods We identified suicide data from official public-sector sources for countries/areas-within-countries, searching websites and academic literature and contacting data custodians and authors as necessary. We sent our first data request on 22nd June 2021 and stopped collecting data on 31st October 2021. We used interrupted time series (ITS) analyses to model the association between the pandemic's emergence and total suicides and suicides by sex-, age-and sex-by-age in each country/area-within-country. We compared the observed and expected numbers of suicides in the pandemic's first nine and first 10-15 months and used meta-regression to explore sources of variation. Findings We sourced data from 33 countries (24 high-income, six upper-middle-income, three lower-middle-income; 25 with whole-country data, 12 with data for area(s)-within-the-country, four with both). There was no evidence of greater-than-expected numbers of suicides in the majority of countries/areas-within-countries in any analysis; more commonly, there was evidence of lower-than-expected numbers. Certain sex, age and sex-by-age groups stood out as potentially concerning, but these were not consistent across countries/areas-within-countries. In the meta-regression, different patterns were not explained by countries' COVID-19 mortality rate, stringency of public health response, economic support level, or presence of a national suicide prevention strategy. Nor were they explained by countries' income level, although the meta-regression only included data from high-income and upper-middle-income countries, and there were suggestions from the ITS analyses that lower-middle-income countries fared less well. Interpretation Although there are some countries/areas-within-countries where overall suicide numbers and numbers for certain sex- and age-based groups are greater-than-expected, these countries/areas-within-countries are in the minority. Any upward movement in suicide numbers in any place or group is concerning, and we need to remain alert to and respond to changes as the pandemic and its mental health and economic consequences continue. Copyright (C) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
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| 27. |
- Recknagel, Hans, et al.
(författare)
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The functional genetic architecture of egg-laying and live-bearing reproduction in common lizards
- 2021
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Ingår i: Nature Ecology & Evolution. - : Springer Nature. - 2397-334X. ; 5:11, s. 1546-1556
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Tidskriftsartikel (refereegranskat)abstract
- All amniotes reproduce either by egg-laying (oviparity), which is ancestral to vertebrates or by live-bearing (viviparity), which has evolved many times independently. However, the genetic basis of these parity modes has never been resolved and, consequently, its convergence across evolutionary scales is currently unknown. Here, we leveraged natural hybridizations between oviparous and viviparous common lizards (Zootoca vivipara) to describe the functional genes and genetic architecture of parity mode and its key traits, eggshell and gestation length, and compared our findings across vertebrates. In these lizards, parity trait genes were associated with progesterone-binding functions and enriched for tissue remodelling and immune system pathways. Viviparity involved more genes and complex gene networks than did oviparity. Angiogenesis, vascular endothelial growth and adrenoreceptor pathways were enriched in the viviparous female reproductive tissue, while pathways for transforming growth factor were enriched in the oviparous. Natural selection on these parity mode genes was evident genome-wide. Our comparison to seven independent origins of viviparity in mammals, squamates and fish showed that genes active in pregnancy were related to immunity, tissue remodelling and blood vessel generation. Therefore, our results suggest that pre-established regulatory networks are repeatedly recruited for viviparity and that these are shared at deep evolutionary scales. Using natural hybrids between oviparous and viviparous common lizards, the authors describe the genetic architecture of parity mode and conduct a comparative analysis of genes associated with viviparity in mammals, squamates and fish.
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| 28. |
- Rezaee, Khosro, et al.
(författare)
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An Autonomous UAV-Assisted Distance-Aware Crowd Sensing Platform Using Deep ShuffleNet Transfer Learning
- 2022
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Ingår i: IEEE transactions on intelligent transportation systems (Print). - : Institute of Electrical and Electronics Engineers (IEEE). - 1524-9050 .- 1558-0016. ; 23:7, s. 9404-9413
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Tidskriftsartikel (refereegranskat)abstract
- Autonomous unmanned aerial vehicles (UAVs) are essential for detecting and tracking specific events, such as automatic navigation. The intelligent monitoring of people’s social distances in crowds is one of the most significant events caused by the coronavirus. The virus is spreading more quickly among the crowds, and the disease cycle continues in congested areas. Due to the error that occurs when humans monitor their activity, an automated model is required to alert to social distance violations in crowds. As a result, this article proposes a two-step framework based on autonomous UAV videos, including human tracking and deep learning-based recognition of the crowd’s social distance. The deep architecture is a modified-fast and lightweight ShuffleNet learning structure. First, the Kalman filter is used to determine the positions of individuals, and then the modified ShuffleNet is used to refine the bounding boxes obtained and determine the social distance. The social distance is calculated using the initial refinement of the bounding box obtained during the tracking step and the scale in frames of the human body. The observed average accuracy, average processing time (APT), and processed frame per second (FPS) for three congestion datasets were 97.5%, 84 milliseconds, and 11.5 FPS, respectively. Real-time decision-making was achieved by reducing the size and resolution of the frames. Additionally, the frames were re-labeled to reduce the computational complexity associated with detecting social distancing. The experimental results demonstrated that the proposed method could operate more quickly and accurately on various resolution frames of UAV videos with difficult conditions.
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| 29. |
- Simoes, R., et al.
(författare)
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Scratch behavior of reinforced HDPE through molecular dynamics simulations
- 2021
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Ingår i: Mrs Communications. - : Springer Science and Business Media LLC. - 2159-6859 .- 2159-6867. ; 11, s. 628-634
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Tidskriftsartikel (refereegranskat)abstract
- To better understand the tribological behavior of polymer-based materials under scratching, we studied the effect of including a second phase in the form of liquid-crystalline (LC) islands in an amorphous matrix emulating high-density polyethylene. We employ molecular dynamics computer simulations with a coarse-grain model. The effects of the indenter diameter and force magnitude on the tribological properties (scratch resistance) were evaluated. The LC islands have a significant effect on the scratching depth, more significantly from 10 to 20% than from 0 to 10% concentration, and that the influence of the second phase is more pronounced for larger indenters and lower forces.
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| 30. |
- Zheleznyakova, Galina Yurevna, et al.
(författare)
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Small noncoding RNA profiling across cellular and biofluid compartments and their implications for multiple sclerosis immunopathology
- 2021
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 118:17
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease affecting the central nervous system (CNS). Small non-coding RNAs (sncRNAs) and, in particular, microRNAs (miRNAs) have frequently been associated with MS. Here, we performed a comprehensive analysis of all classes of sncRNAs in matching samples of peripheral blood mononuclear cells (PBMCs), plasma, cerebrospinal fluid (CSF) cells, and cell-free CSF from relapsing-remitting (RRMS, n = 12 in relapse and n = 11 in remission) patients, secondary progressive (SPMS, n = 6) MS patients, and noninflammatory and inflammatory neurological disease controls (NINDC, n = 11; INDC, n = 5). We show widespread changes in miRNAs and sncRNA-derived fragments of small nuclear, nucleolar, and transfer RNAs. In CSF cells, 133 out of 133 and 115 out of 117 differentially expressed sncRNAs were increased in RRMS relapse compared to remission and RRMS compared to NINDC, respectively. In contrast, 65 out of 67 differentially expressed PBMC sncRNAs were decreased in RRMS compared to NINDC. The striking contrast between the periphery and CNS suggests that sncRNA-mediated mechanisms, including alternative splicing, RNA degradation, and mRNA translation, regulate the transcriptome of pathogenic cells primarily in the CNS target organ.
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