| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Yuh, Esther L, et al.
(author)
-
Pathological computed tomography features associated with adverse outcomes after mild traumatic brain injury : A TRACK-TBI study with external validation in CENTER-TBI.
- 2021
-
In: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 78:9, s. 1137-1148
-
Journal article (peer-reviewed)abstract
- IMPORTANCE: A head computed tomography (CT) with positive results for acute intracranial hemorrhage is the gold-standard diagnostic biomarker for acute traumatic brain injury (TBI). In moderate to severe TBI (Glasgow Coma Scale [GCS] scores 3-12), some CT features have been shown to be associated with outcomes. In mild TBI (mTBI; GCS scores 13-15), distribution and co-occurrence of pathological CT features and their prognostic importance are not well understood.OBJECTIVE: To identify pathological CT features associated with adverse outcomes after mTBI.DESIGN, SETTING, AND PARTICIPANTS: The longitudinal, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study enrolled patients with TBI, including those 17 years and older with GCS scores of 13 to 15 who presented to emergency departments at 18 US level 1 trauma centers between February 26, 2014, and August 8, 2018, and underwent head CT imaging within 24 hours of TBI. Evaluations of CT imaging used TBI Common Data Elements. Glasgow Outcome Scale-Extended (GOSE) scores were assessed at 2 weeks and 3, 6, and 12 months postinjury. External validation of results was performed via the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Data analyses were completed from February 2020 to February 2021.EXPOSURES: Acute nonpenetrating head trauma.MAIN OUTCOMES AND MEASURES: Frequency, co-occurrence, and clustering of CT features; incomplete recovery (GOSE scores <8 vs 8); and an unfavorable outcome (GOSE scores <5 vs ≥5) at 2 weeks and 3, 6, and 12 months.RESULTS: In 1935 patients with mTBI (mean [SD] age, 41.5 [17.6] years; 1286 men [66.5%]) in the TRACK-TBI cohort and 2594 patients with mTBI (mean [SD] age, 51.8 [20.3] years; 1658 men [63.9%]) in an external validation cohort, hierarchical cluster analysis identified 3 major clusters of CT features: contusion, subarachnoid hemorrhage, and/or subdural hematoma; intraventricular and/or petechial hemorrhage; and epidural hematoma. Contusion, subarachnoid hemorrhage, and/or subdural hematoma features were associated with incomplete recovery (odds ratios [ORs] for GOSE scores <8 at 1 year: TRACK-TBI, 1.80 [95% CI, 1.39-2.33]; CENTER-TBI, 2.73 [95% CI, 2.18-3.41]) and greater degrees of unfavorable outcomes (ORs for GOSE scores <5 at 1 year: TRACK-TBI, 3.23 [95% CI, 1.59-6.58]; CENTER-TBI, 1.68 [95% CI, 1.13-2.49]) out to 12 months after injury, but epidural hematoma was not. Intraventricular and/or petechial hemorrhage was associated with greater degrees of unfavorable outcomes up to 12 months after injury (eg, OR for GOSE scores <5 at 1 year in TRACK-TBI: 3.47 [95% CI, 1.66-7.26]). Some CT features were more strongly associated with outcomes than previously validated variables (eg, ORs for GOSE scores <5 at 1 year in TRACK-TBI: neuropsychiatric history, 1.43 [95% CI .98-2.10] vs contusion, subarachnoid hemorrhage, and/or subdural hematoma, 3.23 [95% CI 1.59-6.58]). Findings were externally validated in 2594 patients with mTBI enrolled in the CENTER-TBI study.CONCLUSIONS AND RELEVANCE: In this study, pathological CT features carried different prognostic implications after mTBI to 1 year postinjury. Some patterns of injury were associated with worse outcomes than others. These results support that patients with mTBI and these CT features need TBI-specific education and systematic follow-up.
|
|
| 9. |
- Bowden, John A., et al.
(author)
-
Harmonizing lipidomics : NIST interlaboratory comparison exercise for lipidomics using SRM 1950-Metabolites in Frozen Human Plasma
- 2017
-
In: Journal of Lipid Research. - 0022-2275 .- 1539-7262. ; 58:12, s. 2275-2288
-
Journal article (peer-reviewed)abstract
- As the lipidomics field continues to advance, self-evaluation within the community is critical. Here, we performed an interlaboratory comparison exercise for lipidomics using Standard Reference Material (SRM) 1950-Metabolites in Frozen Human Plasma, a commercially available reference material. The interlaboratory study comprised 31 diverse laboratories, with each laboratory using a different lipidomics workflow. A total of 1,527 unique lipids were measured across all laboratories and consensus location estimates and associated uncertainties were determined for 339 of these lipids measured at the sum composition level by five or more participating laboratories. These evaluated lipids detected in SRM 1950 serve as community-wide benchmarks for intra-and interlaboratory quality control and method validation. These analyses were performed using nonstandardized laboratory-independent workflows. The consensus locations were also compared with a previous examination of SRM 1950 by the LIPID MAPS consortium.jlr While the central theme of the interlaboratory study was to provide values to help harmonize lipids, lipid mediators, and precursor measurements across the community, it was also initiated to stimulate a discussion regarding areas in need of improvement.
|
|
| 10. |
|
|
| 11. |
- Kotronen, A., et al.
(author)
-
Serum saturated fatty acids containing triacylglycerols are better markers of insulin resistance than total serum triacylglycerol concentrations
- 2009
-
In: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 52:4, s. 684-690
-
Journal article (peer-reviewed)abstract
- AIMS/HYPOTHESIS: The weak relationship between insulin resistance and total serum triacylglycerols (TGs) could be in part due to heterogeneity of TG molecules and their distribution within different lipoproteins. We determined concentrations of individual TGs and the fatty acid composition of serum and major lipoprotein particles and analysed how changes in different TGs and fatty acid composition are related to features of insulin resistance and abdominal obesity.METHODS: We performed lipidomic analyses of all major lipoprotein fractions using two analytical platforms in 16 individuals, who exhibited a broad range of insulin sensitivity.RESULTS: We identified 45 different TGs in serum. Serum TGs containing saturated and monounsaturated fatty acids were positively, while TGs containing essential linoleic acid (18:2 n-6) were negatively correlated with HOMA-IR. Specific serum TGs that correlated positively with HOMA-IR were also significantly positively related to HOMA-IR when measured in very-low-density lipoproteins (VLDLs), intermediate-density lipoproteins (IDLs) and LDL, but not in HDL subfraction 2 (HDL(2)) or 3 (HDL(3)). Analyses of proportions of esterified fatty acids within lipoproteins revealed that palmitic acid (16:0) was positively related to HOMA-IR when measured in VLDL, IDL and LDL, but not in HDL(2) or HDL(3). Monounsaturated palmitoleic (16:1 n-7) and oleic (18:1 n-9) acids were positively related to HOMA-IR when measured in HDL(2) and HDL(3), but not in VLDL, IDL or LDL. Linoleic acid was negatively related to HOMA-IR in all lipoproteins.CONCLUSIONS/INTERPRETATION: Serum concentrations of specific TGs, such as TG(16:0/16:0/18:1) or TG(16:0/18:1/18:0), may be more precise markers of insulin resistance than total serum TG concentrations.
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
- Dijkland, Simone A., et al.
(author)
-
Outcome Prediction after Moderate and Severe Traumatic Brain Injury : External Validation of Two Established Prognostic Models in 1742 European Patients
- 2021
-
In: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 38:10, s. 1377-1388
-
Journal article (peer-reviewed)abstract
- The International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) and Corticoid Randomisation After Significant Head injury (CRASH) prognostic models predict functional outcome after moderate and severe traumatic brain injury (TBI). We aimed to assess their performance in a contemporary cohort of patients across Europe. The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) core study is a prospective, observational cohort study in patients presenting with TBI and an indication for brain computed tomography. The CENTER-TBI core cohort consists of 4509 TBI patients available for analyses from 59 centers in 18 countries across Europe and Israel. The IMPACT validation cohort included 1173 patients with GCS ≤12, age ≥14, and 6-month Glasgow Outcome Scale-Extended (GOSE) available. The CRASH validation cohort contained 1742 patients with GCS ≤14, age ≥16, and 14-day mortality or 6-month GOSE available. Performance of the three IMPACT and two CRASH model variants was assessed with discrimination (area under the receiver operating characteristic curve; AUC) and calibration (comparison of observed vs. predicted outcome rates). For IMPACT, model discrimination was good, with AUCs ranging between 0.77 and 0.85 in 1173 patients and between 0.80 and 0.88 in the broader CRASH selection (n = 1742). For CRASH, AUCs ranged between 0.82 and 0.88 in 1742 patients and between 0.66 and 0.80 in the stricter IMPACT selection (n = 1173). Calibration of the IMPACT and CRASH models was generally moderate, with calibration-in-the-large and calibration slopes ranging between -2.02 and 0.61 and between 0.48 and 1.39, respectively. The IMPACT and CRASH models adequately identify patients at high risk for mortality or unfavorable outcome, which supports their use in research settings and for benchmarking in the context of quality-of-care assessment.
|
|
| 16. |
- Galimberti, Stefania, et al.
(author)
-
Effect of frailty on 6-month outcome after traumatic brain injury : a multicentre cohort study with external validation
- 2022
-
In: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 21:2, s. 153-162
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Frailty is known to be associated with poorer outcomes in individuals admitted to hospital for medical conditions requiring intensive care. However, little evidence is available for the effect of frailty on patients' outcomes after traumatic brain injury. Many frailty indices have been validated for clinical practice and show good performance to predict clinical outcomes. However, each is specific to a particular clinical context. We aimed to develop a frailty index to predict 6-month outcomes in patients after a traumatic brain injury.METHODS: A cumulative deficit approach was used to create a novel frailty index based on 30 items dealing with disease states, current medications, and laboratory values derived from data available from CENTER-TBI, a prospective, longitudinal observational study of patients with traumatic brain injury presenting within 24 h of injury and admitted to a ward or an intensive care unit at 65 centres in Europe between Dec 19, 2014, and Dec 17, 2017. From the individual cumulative CENTER-TBI frailty index (range 0-30), we obtained a standardised value (range 0-1), with high scores indicating higher levels of frailty. The effect of frailty on 6-month outcome evaluated with the extended Glasgow Outcome Scale (GOSE) was assessed through a proportional odds logistic model adjusted for known outcome predictors. An unfavourable outcome was defined as death or severe disability (GOSE score ≤4). External validation was performed on data from TRACK-TBI, a prospective observational study co-designed with CENTER-TBI, which enrolled patients with traumatic brain injury at 18 level I trauma centres in the USA from Feb 26, 2014, to July 27, 2018. CENTER-TBI is registered with ClinicalTrials.gov, NCT02210221; TRACK-TBI is registered at ClinicalTrials.gov, NCT02119182.FINDINGS: 2993 participants (median age was 51 years [IQR 30-67], 2058 [69%] were men) were included in this analysis. The overall median CENTER-TBI frailty index score was 0·07 (IQR 0·03-0·15), with a median score of 0·17 (0·08-0·27) in older adults (aged ≥65 years). The CENTER-TBI frailty index score was significantly associated with the probability of an increasingly unfavourable outcome (cumulative odds ratio [OR] 1·03, 95% CI 1·02-1·04; p<0·0001), and the association was stronger for participants admitted to hospital wards (1·04, 1·03-1·06, p<0·0001) compared with those admitted to the intensive care unit (1·02, 1·01-1·03 p<0·0001). External validation of the CENTER-TBI frailty index in data from the TRACK-TBI (n=1667) cohort supported the robustness and reliability of these findings. The overall median TRACK-TBI frailty index score was 0·03 (IQR 0-0·10), with the frailty index score significantly associated with the risk of an increasingly unfavourable outcome in patients admitted to hospital wards (cumulative OR 1·05, 95% CI 1·03-1·08; p<0·0001), but not in those admitted to the intensive care unit (1·01, 0·99-1·03; p=0·43).INTERPRETATION: We developed and externally validated a frailty index specific to traumatic brain injury. Risk of unfavourable outcome was significantly increased in participants with a higher CENTER-TBI frailty index score, regardless of age. Frailty identification could help to individualise rehabilitation approaches aimed at mitigating effects of frailty in patients with traumatic brain injury.FUNDING: European Union, Hannelore Kohl Stiftung, OneMind, Integra LifeSciences Corporation, NeuroTrauma Sciences, NIH-NINDS-TRACK-TBI, US Department of Defense.
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
- Huie, J. Russell, et al.
(author)
-
Biomarkers for Traumatic Brain Injury : Data Standards and Statistical Considerations
- 2021
-
In: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 38:18, s. 2514-2529
-
Journal article (peer-reviewed)abstract
- Recent biomarker innovations hold potential for transforming diagnosis, prognostic modeling, and precision therapeutic targeting of traumatic brain injury (TBI). However, many biomarkers, including brain imaging, genomics, and proteomics, involve vast quantities of high-throughput and high-content data. Management, curation, analysis, and evidence synthesis of these data are not trivial tasks. In this review, we discuss data management concepts and statistical and data sharing strategies when dealing with biomarker data in the context of TBI research. We propose that application of biomarkers involves three distinct steps-discovery, evaluation, and evidence synthesis. First, complex/big data has to be reduced to useful data elements at the stage of biomarker discovery. Second, inferential statistical approaches must be applied to these biomarker data elements for assessment of biomarker clinical utility and validity. Last, synthesis of relevant research is required to support practice guidelines and enable health decisions informed by the highest quality, up-to-date evidence available. We focus our discussion around recent experiences from the International Traumatic Brain Injury Research (InTBIR) initiative, with a specific focus on four major clinical projects (Transforming Research and Clinical Knowledge in TBI, Collaborative European NeuroTrauma Effectiveness Research in TBI, Collaborative Research on Acute Traumatic Brain Injury in Intensive Care Medicine in Europe, and Approaches and Decisions in Acute Pediatric TBI Trial), which are currently enrolling subjects in North America and Europe. We discuss common data elements, data collection efforts, data-sharing opportunities, and challenges, as well as examine the statistical techniques required to realize successful adoption and use of biomarkers in the clinic as a foundation for precision medicine in TBI.
|
|
| 20. |
- Kovacs, Gabor G., et al.
(author)
-
Aging-related tau astrogliopathy (ARTAG) : harmonized evaluation strategy
- 2016
-
In: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 131:1, s. 87-102
-
Journal article (peer-reviewed)abstract
- Pathological accumulation of abnormally phosphorylated tau protein in astrocytes is a frequent, but poorly characterized feature of the aging brain. Its etiology is uncertain, but its presence is sufficiently ubiquitous to merit further characterization and classification, which may stimulate clinicopathological studies and research into its pathobiology. This paper aims to harmonize evaluation and nomenclature of aging-related tau astrogliopathy (ARTAG), a term that refers to a morphological spectrum of astroglial pathology detected by tau immunohistochemistry, especially with phosphorylation-dependent and 4R isoform-specific antibodies. ARTAG occurs mainly, but not exclusively, in individuals over 60 years of age. Tau-immunoreactive astrocytes in ARTAG include thorn-shaped astrocytes at the glia limitans and in white matter, as well as solitary or clustered astrocytes with perinuclear cytoplasmic tau immunoreactivity that extends into the astroglial processes as fine fibrillar or granular immunopositivity, typically in gray matter. Various forms of ARTAG may coexist in the same brain and might reflect different pathogenic processes. Based on morphology and anatomical distribution, ARTAG can be distinguished from primary tauopathies, but may be concurrent with primary tauopathies or other disorders. We recommend four steps for evaluation of ARTAG: (1) identification of five types based on the location of either morphologies of tau astrogliopathy: subpial, subependymal, perivascular, white matter, gray matter; (2) documentation of the regional involvement: medial temporal lobe, lobar (frontal, parietal, occipital, lateral temporal), subcortical, brainstem; (3) documentation of the severity of tau astrogliopathy; and (4) description of subregional involvement. Some types of ARTAG may underlie neurological symptoms; however, the clinical significance of ARTAG is currently uncertain and awaits further studies. The goal of this proposal is to raise awareness of astroglial tau pathology in the aged brain, facilitating communication among neuropathologists and researchers, and informing interpretation of clinical biomarkers and imaging studies that focus on tau-related indicators.
|
|
| 21. |
- Kovacs, Gabor G., et al.
(author)
-
Multisite Assessment of Aging-Related Tau Astrogliopathy (ARTAG)
- 2017
-
In: Journal of Neuropathology and Experimental Neurology. - : Oxford University Press (OUP). - 0022-3069 .- 1554-6578. ; 76:7, s. 605-619
-
Journal article (peer-reviewed)abstract
- Aging-related tau astrogliopathy (ARTAG) is a recently introduced terminology. To facilitate the consistent identification of ARTAG and to distinguish it from astroglial tau pathologies observed in the primary frontotemporal lobar degeneration tauopathies we evaluated how consistently neuropathologists recognize (1) different astroglial tau immunoreactivities, including those of ARTAG and those associated with primary tauopathies (Study 1); (2) ARTAG types (Study 2A); and (3) ARTAG severity (Study 2B). Microphotographs and scanned sections immunostained for phosphorylated tau (AT8) were made available for download and preview. Percentage of agreement and kappa values with 95% confidence interval (CI) were calculated for each evaluation. The overall agreement for Study 1 was > 60% with a kappa value of 0.55 (95% CI 0.433-0.645). Moderate agreement (> 90%, kappa 0.48, 95% CI 0.457-0.900) was reached in Study 2A for the identification of ARTAG pathology for each ARTAG subtype (kappa 0.37-0.72), whereas fair agreement (kappa 0.40, 95% CI 0.341-0.445) was reached for the evaluation of ARTAG severity. The overall assessment of ARTAG showed moderate agreement (kappa 0.60, 95% CI 0.534-0.653) among raters. Our study supports the application of the current harmonized evaluation strategy for ARTAG with a slight modification of the evaluation of its severity.
|
|
| 22. |
- Lembrechts, Jonas J., et al.
(author)
-
SoilTemp : A global database of near-surface temperature
- 2020
-
In: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 26:11, s. 6616-6629
-
Journal article (peer-reviewed)abstract
- Current analyses and predictions of spatially explicit patterns and processes in ecology most often rely on climate data interpolated from standardized weather stations. This interpolated climate data represents long-term average thermal conditions at coarse spatial resolutions only. Hence, many climate-forcing factors that operate at fine spatiotemporal resolutions are overlooked. This is particularly important in relation to effects of observation height (e.g. vegetation, snow and soil characteristics) and in habitats varying in their exposure to radiation, moisture and wind (e.g. topography, radiative forcing or cold-air pooling). Since organisms living close to the ground relate more strongly to these microclimatic conditions than to free-air temperatures, microclimatic ground and near-surface data are needed to provide realistic forecasts of the fate of such organisms under anthropogenic climate change, as well as of the functioning of the ecosystems they live in. To fill this critical gap, we highlight a call for temperature time series submissions to SoilTemp, a geospatial database initiative compiling soil and near-surface temperature data from all over the world. Currently, this database contains time series from 7,538 temperature sensors from 51 countries across all key biomes. The database will pave the way toward an improved global understanding of microclimate and bridge the gap between the available climate data and the climate at fine spatiotemporal resolutions relevant to most organisms and ecosystem processes.
|
|
| 23. |
- López, Miguel, et al.
(author)
-
Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance
- 2010
-
In: Nature Medicine. - : Nature Publishing Group. - 1078-8956 .- 1546-170X. ; 16:9, s. 1001-1008
-
Journal article (peer-reviewed)abstract
- Thyroid hormones have widespread cellular effects; however it is unclear whether their effects on the central nervous system (CNS) contribute to global energy balance. Here we demonstrate that either whole-body hyperthyroidism or central administration of triiodothyronine (T3) decreases the activity of hypothalamic AMP-activated protein kinase (AMPK), increases sympathetic nervous system (SNS) activity and upregulates thermogenic markers in brown adipose tissue (BAT). Inhibition of the lipogenic pathway in the ventromedial nucleus of the hypothalamus (VMH) prevents CNS-mediated activation of BAT by thyroid hormone and reverses the weight loss associated with hyperthyroidism. Similarly, inhibition of thyroid hormone receptors in the VMH reverses the weight loss associated with hyperthyroidism. This regulatory mechanism depends on AMPK inactivation, as genetic inhibition of this enzyme in the VMH of euthyroid rats induces feeding-independent weight loss and increases expression of thermogenic markers in BAT. These effects are reversed by pharmacological blockade of the SNS. Thus, thyroid hormone-induced modulation of AMPK activity and lipid metabolism in the hypothalamus is a major regulator of whole-body energy homeostasis.
|
|
| 24. |
- Mikolić, Ana, et al.
(author)
-
Prediction of Global Functional Outcome and Post-Concussive Symptoms after Mild Traumatic Brain Injury : External Validation of Prognostic Models in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Study
- 2021
-
In: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 38:2, s. 196-209
-
Journal article (peer-reviewed)abstract
- The majority of traumatic brain injuries (TBIs) are categorized as mild, according to a baseline Glasgow Coma Scale (GCS) score of 13-15. Prognostic models that were developed to predict functional outcome and persistent post-concussive symptoms (PPCS) after mild TBI have rarely been externally validated. We aimed to externally validate models predicting 3-12-month Glasgow Outcome Scale Extended (GOSE) or PPCS in adults with mild TBI. We analyzed data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) project, which included 2862 adults with mild TBI, with 6-month GOSE available for 2374 and Rivermead Post-Concussion Symptoms Questionnaire (RPQ) results available for 1605 participants. Model performance was evaluated based on calibration (graphically and characterized by slope and intercept) and discrimination (C-index). We validated five published models for 6-month GOSE and three for 6-month PPCS scores. The models used different cutoffs for outcome and some included symptoms measured 2 weeks post-injury. Discriminative ability varied substantially (C-index between 0.58 and 0.79). The models developed in the Corticosteroid Randomisation After Significant Head Injury (CRASH) trial for prediction of GOSE <5 discriminated best (C-index 0.78 and 0.79), but were poorly calibrated. The best performing models for PPCS included 2-week symptoms (C-index 0.75 and 0.76). In conclusion, none of the prognostic models for early prediction of GOSE and PPCS has both good calibration and discrimination in persons with mild TBI. In future studies, prognostic models should be tailored to the population with mild TBI, predicting relevant end-points based on readily available predictors.
|
|
| 25. |
|
|
| 26. |
- Thomas, Ilias, 1987-, et al.
(author)
-
Serum metabolome associated with severity of acute traumatic brain injury
- 2022
-
In: Nature Communications. - : Nature Research. - 2041-1723. ; 13:1
-
Journal article (peer-reviewed)abstract
- Complex metabolic disruption is a crucial aspect of the pathophysiology of traumatic brain injury (TBI). Associations between this and systemic metabolism and their potential prognostic value are poorly understood. Here, we aimed to describe the serum metabolome (including lipidome) associated with acute TBI within 24 h post-injury, and its relationship to severity of injury and patient outcome. We performed a comprehensive metabolomics study in a cohort of 716 patients with TBI and non-TBI reference patients (orthopedic, internal medicine, and other neurological patients) from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) cohort. We identified panels of metabolites specifically associated with TBI severity and patient outcomes. Choline phospholipids (lysophosphatidylcholines, ether phosphatidylcholines and sphingomyelins) were inversely associated with TBI severity and were among the strongest predictors of TBI patient outcomes, which was further confirmed in a separate validation dataset of 558 patients. The observed metabolic patterns may reflect different pathophysiological mechanisms, including protective changes of systemic lipid metabolism aiming to maintain lipid homeostasis in the brain.
|
|
| 27. |
- van der Vlegel, Marjolein, et al.
(author)
-
Health care utilization and outcomes in older adults after Traumatic Brain Injury : a CENTER-TBI study
- 2022
-
In: Injury. - : Elsevier. - 0020-1383 .- 1879-0267. ; 53:8, s. 2774-2782
-
Journal article (peer-reviewed)abstract
- INTRODUCTION: The incidence of Traumatic Brain Injury (TBI) is increasingly common in older adults aged ≥65 years, forming a growing public health problem. However, older adults are underrepresented in TBI research. Therefore, we aimed to provide an overview of health-care utilization, and of six-month outcomes after TBI and their determinants in older adults who sustained a TBI.METHODS: We used data from the prospective multi-center Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. In-hospital and post-hospital health care utilization and outcomes were described for patients aged ≥65 years. Ordinal and linear regression analyses were performed to identify determinants of the Glasgow Outcome Scale Extended (GOSE), health-related quality of life (HRQoL), and mental health symptoms six-months post-injury.RESULTS: Of 1254 older patients, 45% were admitted to an ICU with a mean length of stay of 9 days. Nearly 30% of the patients received inpatient rehabilitation. In total, 554/1254 older patients completed the six-month follow-up questionnaires. The mortality rate was 9% after mild and 60% after moderate/severe TBI, and full recovery based on GOSE was reported for 44% of patients after mild and 6% after moderate/severe TBI. Higher age and increased injury severity were primarily associated with functional impairment, while pre-injury systemic disease, psychiatric conditions and lower educational level were associated with functional impairment, lower generic and disease-specific HRQoL and mental health symptoms.CONCLUSION: The rate of impairment and disability following TBI in older adults is substantial, and poorer outcomes across domains are associated with worse preinjury health. Nonetheless, a considerable number of patients fully or partially returns to their preinjury functioning. There should not be pessimism about outcomes in older adults who survive.
|
|
| 28. |
- Ylipaasto, P., et al.
(author)
-
Enterovirus-induced gene expression profile is critical for human pancreatic islet destruction
- 2012
-
In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 55:12, s. 3273-3283
-
Journal article (peer-reviewed)abstract
- Aims/hypothesis Virally induced inflammatory responses, beta cell destruction and release of beta cell autoantigens may lead to autoimmune reactions culminating in type 1 diabetes. Therefore, viral capability to induce beta cell death and the nature of virus-induced immune responses are among key determinants of diabetogenic viruses. We hypothesised that enterovirus infection induces a specific gene expression pattern that results in islet destruction and that such a host response pattern is not shared among all enterovirus infections but varies between virus strains. Methods The changes in global gene expression and secreted cytokine profiles induced by lytic or benign enterovirus infections were studied in primary human pancreatic islet using DNA microarrays and viral strains either isolated at the clinical onset of type 1 diabetes or capable of causing a diabetes-like condition in mice. Results The expression of pro-inflammatory cytokine genes (IL-1-a, IL-1-β and TNF-a) that also mediate cytokineinduced beta cell dysfunction correlated with the lytic potential of a virus. Temporally increasing gene expression levels of double-stranded RNArecognition receptors, antiviral molecules, cytokines and chemokines were detected for all studied virus strains. Lytic coxsackievirus B5 (CBV-5)-DS infection also downregulated genes involved in glycolysis and insulin secretion. Conclusions/interpretation The results suggest a distinct, virusstrain- specific, gene expression pattern leading to pancreatic islet destruction and pro-inflammatory effects after enterovirus infection. However, neither viral replication nor cytotoxic cytokine production alone are sufficient to induce necrotic cell death. More likely the combined effect of these and possibly cellular energy depletion lie behind the enterovirus-induced necrosis of islets.
|
|
| 29. |
- Ahrens, Angelica P., et al.
(author)
-
Infant microbes and metabolites point to childhood neurodevelopmental disorders
- 2024
-
In: Cell. - : Cell Press. - 0092-8674 .- 1097-4172. ; 187:8, s. 1853-1873.e15
-
Journal article (peer-reviewed)abstract
- This study has followed a birth cohort for over 20 years to find factors associated with neurodevelopmental disorder (ND) diagnosis. Detailed, early-life longitudinal questionnaires captured infection and antibiotic events, stress, prenatal factors, family history, and more. Biomarkers including cord serum metabolome and lipidome, human leukocyte antigen (HLA) genotype, infant microbiota, and stool metabolome were assessed. Among the 16,440 Swedish children followed across time, 1,197 developed an ND. Significant associations emerged for future ND diagnosis in general and for specific ND subtypes, spanning intellectual disability, speech disorder, attention-deficit/hyperactivity disorder, and autism. This investigation revealed microbiome connections to future diagnosis as well as early emerging mood and gastrointestinal problems. The findings suggest links to immunodysregulation and metabolism, compounded by stress, early-life infection, and antibiotics. The convergence of infant biomarkers and risk factors in this prospective, longitudinal study on a large-scale population establishes a foundation for early-life prediction and intervention in neurodevelopment.
|
|
| 30. |
- Burla, Bo, et al.
(author)
-
MS-based lipidomics of human blood plasma : a community-initiated position paper to develop accepted guidelines
- 2018
-
In: Journal of Lipid Research. - : American Society for Biochemistry and Molecular Biology. - 0022-2275 .- 1539-7262. ; 59:10, s. 2001-2017
-
Journal article (peer-reviewed)abstract
- Human blood is a self-regenerating lipid-rich biological fluid that is routinely collected in hospital settings. The inventory of lipid molecules found in blood plasma (plasma lipidome) offers insights into individual metabolism and physiology in health and disease. Disturbances in the plasma lipidome also occur in conditions that are not directly linked to lipid metabolism; therefore, plasma lipidomics based on MS is an emerging tool in an array of clinical diagnostics and disease management. However, challenges exist in the translation of such lipidomic data to clinical applications. These relate to the reproducibility, accuracy, and precision of lipid quantitation, study design, sample handling, and data sharing. This position paper emerged from a workshop that initiated a community-led process to elaborate and define a set of generally accepted guidelines for quantitative MS-based lipidomics of blood plasma or serum, with harmonization of data acquired on different instrumentation platforms across independent laboratories as an ultimate goal. We hope that other fields may benefit from and follow such a precedent.
|
|
| 31. |
- Curtis, R. Keira, et al.
(author)
-
Pathways to the analysis of microarray data
- 2005
-
In: Trends in Biotechnology. - : Elsevier. - 0167-7799 .- 1879-3096. ; 23:8, s. 429-435
-
Research review (peer-reviewed)abstract
- The development of microarray technology allows the simultaneous measurement of the expression of many thousands of genes. The information gained offers an unprecedented opportunity to fully characterize biological processes. However, this challenge will only be successful if new tools for the efficient integration and interpretation of large datasets are available. One of these tools, pathway analysis, involves looking for consistent but subtle changes in gene expression by incorporating either pathway or functional annotations. We review several methods of pathway analysis and compare the performance of three, the binomial distribution, z scores, and gene set enrichment analysis, on two microarray datasets. Pathway analysis is a promising tool to identify the mechanisms that underlie diseases, adaptive physiological compensatory responses and new avenues for investigation.
|
|
| 32. |
- Davidov, Eugene, et al.
(author)
-
Methods for the differential integrative omic analysis of plasma from a transgenic disease animal model
- 2004
-
In: Omics. - : Mary Ann Liebert. - 1536-2310 .- 1557-8100. ; 8:4, s. 267-288
-
Journal article (peer-reviewed)abstract
- Multitiered quantitative analysis of biological systems is rapidly becoming the desired approach to study hierarchical functional interactions between proteins and metabolites. We describe here a novel systematic approach to analyze organisms with complex metabolic regulatory networks. By using precise analytical methods to measure biochemical constituents and their relative abundance in whole plasma of transgenic ApoE*3-Leiden mice and an isogenic wild-type control group, simultaneous snapshots of metabolic and protein states were obtained. Novel data processing and multivariate analysis tools such as Impurity Resolution Software (IMPRESS) and Windows-based linear fit program (WINLIN) were used to compare protein and metabolic profiles in parallel. Canonical correlations of the resulting data show quantitative relationships between heterogeneous components in the TG animals. These results, obtained solely from whole plasma analysis allowed us, in a rapid manner, to corroborate previous findings as well as find new events pertaining to dominant and peripheral events in lipoprotein metabolism of a genetically modified mammalian organism in relation to ApoE3, a key mediator of lipoprotein metabolism.
|
|
| 33. |
- Elo, Laura L., et al.
(author)
-
Genome-wide profiling of interleukin-4 and STAT6 transcription factor regulation of human Th2 cell programming
- 2010
-
In: Immunity. - : Cell Press. - 1074-7613 .- 1097-4180. ; 32:6, s. 852-862
-
Journal article (peer-reviewed)abstract
- Dissecting the molecular mechanisms by which T helper (Th) cells differentiate to effector Th2 cells is important for understanding the pathogenesis of immune-mediated diseases, such as asthma and allergy. Because the STAT6 transcription factor is an upstream mediator required for interleukin-4 (IL-4)-induced Th2 cell differentiation, its targets include genes important for this process. Using primary human CD4(+) T cells, and by blocking STAT6 with RNAi, we identified a number of direct and indirect targets of STAT6 with ChIP sequencing. The integration of these data sets with detailed kinetics of IL-4-driven transcriptional changes showed that STAT6 was predominantly needed for the activation of transcription leading to the Th2 cell phenotype. This integrated genome-wide data on IL-4- and STAT6-mediated transcription provide a unique resource for studies on Th cell differentiation and, in particular, for designing interventions of human Th2 cell responses.
|
|
| 34. |
- Fan, Y., et al.
(author)
-
The gut microbiota contributes to the pathogenesis of anorexia nervosa in humans and mice
- 2023
-
In: Nature Microbiology. - : Nature Publishing Group. - 2058-5276. ; 8, s. 787-802
-
Journal article (peer-reviewed)abstract
- Anorexia nervosa (AN) is an eating disorder with a high mortality. About 95% of cases are women and it has a population prevalence of about 1%, but evidence-based treatment is lacking. The pathogenesis of AN probably involves genetics and various environmental factors, and an altered gut microbiota has been observed in individuals with AN using amplicon sequencing and relatively small cohorts. Here we investigated whether a disrupted gut microbiota contributes to AN pathogenesis. Shotgun metagenomics and metabolomics were performed on faecal and serum samples, respectively, from a cohort of 77 females with AN and 70 healthy females. Multiple bacterial taxa (for example, Clostridium species) were altered in AN and correlated with estimates of eating behaviour and mental health. The gut virome was also altered in AN including a reduction in viral-bacterial interactions. Bacterial functional modules associated with the degradation of neurotransmitters were enriched in AN and various structural variants in bacteria were linked to metabolic features of AN. Serum metabolomics revealed an increase in metabolites associated with reduced food intake (for example, indole-3-propionic acid). Causal inference analyses implied that serum bacterial metabolites are potentially mediating the impact of an altered gut microbiota on AN behaviour. Further, we performed faecal microbiota transplantation from AN cases to germ-free mice under energy-restricted feeding to mirror AN eating behaviour. We found that the reduced weight gain and induced hypothalamic and adipose tissue gene expression were related to aberrant energy metabolism and eating behaviour. Our 'omics' and mechanistic studies imply that a disruptive gut microbiome may contribute to AN pathogenesis. Faecal metagenomics and serum metabolomics reveal compositional and functional alterations in the gut microbiota of women with anorexia nervosa, and faecal transplants could transfer an anorexia-associated phenotype to germ-free mice.
|
|
| 35. |
- Feng, Junfeng, et al.
(author)
-
Comparison of Care System and Treatment Approaches for Patients with Traumatic Brain Injury in China versus Europe : A CENTER-TBI Survey Study
- 2020
-
In: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 37:16, s. 1806-1817
-
Journal article (peer-reviewed)abstract
- Traumatic brain injury (TBI) poses a huge public health and societal problem worldwide. Uncertainty exists on how care system and treatment approaches for TBI worked in China may differ from those in Europe. Better knowledge on this is important to facilitate interpretation of findings reported by Chinese researchers and to inform opportunities for collaborative studies. We aimed to investigate concordance and variations in TBI care between Chinese and European neurotrauma centers. Investigators from 52 centers in China and 68 in Europe involved in the Collaborative European Neuro Trauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study were invited to complete provider profiling (PP) questionnaires, which covered the main aspects of care system and treatment approaches of TBI care. Participating Chinese and European centers were mainly publicly funded and academic. More centers in China indicated available dedicated neuro-intensive care than those in Europe (98% vs. 60%), and treatment decisions in the ICU were mainly determined by neurosurgeons (58%) in China while in Europe, (neuro)intensivists often took the lead (61%). The ambulance dispatching system was automatic in half of Chinese centers (49%), whereas selective dispatching was more common in European centers (74%). For treatment of refractory intracranial hypertension, a decompressive craniectomy was more frequently regarded as general policy in China compared with in Europe (89% vs. 45%). We observed both concordance and substantial variations with regard to the various aspects of TBI care between Chinese and European centers. These findings are fundamental to guide future research and offer opportunities for collaborative comparative effectiveness research to identify best practices.
|
|
| 36. |
- Franks, P. W., et al.
(author)
-
Technological readiness and implementation of genomic-driven precision medicine for complex diseases
- 2021
-
In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 290:3, s. 602-620
-
Research review (peer-reviewed)abstract
- The fields of human genetics and genomics have generated considerable knowledge about the mechanistic basis of many diseases. Genomic approaches to diagnosis, prognostication, prevention and treatment - genomic-driven precision medicine (GDPM) - may help optimize medical practice. Here, we provide a comprehensive review of GDPM of complex diseases across major medical specialties. We focus on technological readiness: how rapidly a test can be implemented into health care. Although these areas of medicine are diverse, key similarities exist across almost all areas. Many medical areas have, within their standards of care, at least one GDPM test for a genetic variant of strong effect that aids the identification/diagnosis of a more homogeneous subset within a larger disease group or identifies a subset with different therapeutic requirements. However, for almost all complex diseases, the majority of patients do not carry established single-gene mutations with large effects. Thus, research is underway that seeks to determine the polygenic basis of many complex diseases. Nevertheless, most complex diseases are caused by the interplay of genetic, behavioural and environmental risk factors, which will likely necessitate models for prediction and diagnosis that incorporate genetic and non-genetic data.
|
|
| 37. |
- Gopalacharyulu, Peddinti V., et al.
(author)
-
Dynamic network topology changes in functional modules predict responses to oxidative stress in yeast
- 2009
-
In: Molecular Biosystems. - : Royal Society of Chemistry. - 1742-206X .- 1742-2051. ; 5:3, s. 276-287
-
Journal article (peer-reviewed)abstract
- In response to environmental challenges, biological systems respond with dynamic adaptive changes in order to maintain the functionality of the system. Such adaptations may lead to cumulative stress over time, possibly leading to global failure of the system. When studying such systems responses, it is therefore important to understand them in system-wide and dynamic context. Here we hypothesize that dynamic changes in the topology of functional modules of integrated biological networks reflect their activity under specific environmental challenges. We introduce topological enrichment analysis of functional subnetworks (TEAFS), a method for the analysis of integrated molecular profile and interactome data, which we validated by comprehensive metabolomic analysis of dynamic yeast response under oxidative stress. TEAFS identified activation of multiple stress response related mechanisms, such as lipid metabolism and phospholipid biosynthesis. We identified, among others, a fatty acid elongase IFA38 as a hub protein which was absent at all time points under oxidative stress conditions. The deletion mutant of the IFA38 encoding gene is known for the accumulation of ceramides. By applying a comprehensive metabolomic analysis, we confirmed the increased concentrations over time of ceramides and palmitic acid, a precursor of de novo ceramide biosynthesis. Our results imply that the connectivity of the system is being dynamically modulated in response to oxidative stress, progressively leading to the accumulation of (lipo)toxic lipids such as ceramides. Studies of local network topology dynamics can be used to investigate as well as predict the activity of biological processes and the system's responses to environmental challenges and interventions.
|
|
| 38. |
- Gravesteijn, Benjamin Y., et al.
(author)
-
Toward a New Multi-Dimensional Classification of Traumatic Brain Injury : A Collaborative European NeuroTrauma Effectiveness Research for Traumatic Brain Injury Study
- 2020
-
In: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 37:7, s. 1002-1010
-
Journal article (peer-reviewed)abstract
- Traumatic brain injury (TBI) is currently classified as mild, moderate, or severe TBI by trichotomizing the Glasgow Coma Scale (GCS). We aimed to explore directions for a more refined multidimensional classification system. For that purpose, we performed a hypothesis-free cluster analysis in the Collaborative European NeuroTrauma Effectiveness Research for TBI (CENTER-TBI) database: a European all-severity TBI cohort (n = 4509). The first building block consisted of key imaging characteristics, summarized using principal component analysis from 12 imaging characteristics. The other building blocks were demographics, clinical severity, secondary insults, and cause of injury. With these building blocks, the patients were clustered into four groups. We applied bootstrap resampling with replacement to study the stability of cluster allocation. The characteristics that predominantly defined the clusters were injury cause, major extracranial injury, and GCS. The clusters consisted of 1451, 1534, 1006, and 518 patients, respectively. The clustering method was quite stable: the proportion of patients staying in one cluster after resampling and reclustering was 97.4% (95% confidence interval [CI]: 85.6-99.9%). These clusters characterized groups of patients with different functional outcomes: from mild to severe, 12%, 19%, 36%, and 58% of patients had unfavorable 6 month outcome. Compared with the mild and the upper intermediate cluster, the lower intermediate and the severe cluster received more key interventions. To conclude, four types of TBI patients may be defined by injury mechanism, presence of major extracranial injury and GCS. Describing patients according to these three characteristics could potentially capture differences in etiology and care pathways better than with GCS only.
|
|
| 39. |
- Hall, Diana, et al.
(author)
-
Peroxisomal and microsomal lipid pathways associated with resistance to hepatic steatosis and reduced pro-inflammatory state
- 2010
-
In: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 285:40, s. 31011-31023
-
Journal article (peer-reviewed)abstract
- Accumulation of fat in the liver increases the risk to develop fibrosis and cirrhosis and is associated with development of the metabolic syndrome. Here, to identify genes or gene pathways that may underlie the genetic susceptibility to fat accumulation in liver, we studied A/J and C57Bl/6 mice that are resistant and sensitive to diet-induced hepatosteatosis and obesity, respectively. We performed comparative transcriptomic and lipidomic analysis of the livers of both strains of mice fed a high fat diet for 2, 10, and 30 days. We found that resistance to steatosis in A/J mice was associated with the following: (i) a coordinated up-regulation of 10 genes controlling peroxisome biogenesis and β-oxidation; (ii) an increased expression of the elongase Elovl5 and desaturases Fads1 and Fads2. In agreement with these observations, peroxisomal β-oxidation was increased in livers of A/J mice, and lipidomic analysis showed increased concentrations of long chain fatty acid-containing triglycerides, arachidonic acid-containing lysophosphatidylcholine, and 2-arachidonylglycerol, a cannabinoid receptor agonist. We found that the anti-inflammatory CB2 receptor was the main hepatic cannabinoid receptor, which was highly expressed in Kupffer cells. We further found that A/J mice had a lower pro-inflammatory state as determined by lower plasma levels and IL-1β and granulocyte-CSF and reduced hepatic expression of their mRNAs, which were found only in Kupffer cells. This suggests that increased 2-arachidonylglycerol production may limit Kupffer cell activity. Collectively, our data suggest that genetic variations in the expression of peroxisomal β-oxidation genes and of genes controlling the production of an anti-inflammatory lipid may underlie the differential susceptibility to diet-induced hepatic steatosis and pro-inflammatory state.
|
|
| 40. |
- Hernández-Alvarez, María Isabel, et al.
(author)
-
Deficient Endoplasmic Reticulum-Mitochondrial Phosphatidylserine Transfer Causes Liver Disease
- 2019
-
In: Cell. - : Cell Press. - 0092-8674 .- 1097-4172. ; 177:4, s. 881-895.e17
-
Journal article (peer-reviewed)abstract
- Non-alcoholic fatty liver is the most common liver disease worldwide. Here, we show that the mitochondrial protein mitofusin 2 (Mfn2) protects against liver disease. Reduced Mfn2 expression was detected in liver biopsies from patients with non-alcoholic steatohepatitis (NASH). Moreover, reduced Mfn2 levels were detected in mouse models of steatosis or NASH, and its re-expression in a NASH mouse model ameliorated the disease. Liver-specific ablation of Mfn2 in mice provoked inflammation, triglyceride accumulation, fibrosis, and liver cancer. We demonstrate that Mfn2 binds phosphatidylserine (PS) and can specifically extract PS into membrane domains, favoring PS transfer to mitochondria and mitochondrial phosphatidylethanolamine (PE) synthesis. Consequently, hepatic Mfn2 deficiency reduces PS transfer and phospholipid synthesis, leading to endoplasmic reticulum (ER) stress and the development of a NASH-like phenotype and liver cancer. Ablation of Mfn2 in liver reveals that disruption of ER-mitochondrial PS transfer is a new mechanism involved in the development of liver disease.
|
|
| 41. |
- Koikkalainen, Juha R., et al.
(author)
-
Early familial dilated cardiomyopathy : identification with determination of disease state parameter from cine MR image data
- 2008
-
In: Radiology. - : Radiological Society of North America, Inc. - 0033-8419 .- 1527-1315. ; 249:1, s. 88-96
-
Journal article (peer-reviewed)abstract
- PURPOSE: To characterize early changes in cardiac anatomy and function for lamin A/C gene (LMNA) mutation carriers by using magnetic resonance (MR) imaging and to develop tools to analyze and visualize the findings.MATERIALS AND METHODS: The ethical review board of the institution approved the study, and informed written consent was obtained. The patient group consisted of 12 subjects, seven women (mean age, 36 years; age range, 18-54 years) and five men (mean age, 28 years; age range, 18-39 years) of Finnish origin, who were each heterozygotes with one LMNA mutation that may cause familial dilated cardiomyopathy (DCM). All the subjects were judged to be healthy with transthoracic echocardiography. The control group consisted of 14 healthy subjects, 11 women (mean age, 41 years; range, 23-54 years) and three men (mean age, 45 years; range, 34-57 years), of Finnish origin. Cine steady state free precession MR imaging was performed with a 1.5-T system. The volumes, wall thickness, and wall motion of both left ventricle (LV) and right ventricle were assessed. A method combining multiple MR image parameters was used to generate a global cardiac function index, the disease state parameter (DSP). A visual fingerprint was generated to assess the severity of familial DCM.RESULTS: The mean DSP of the patient group (0.69 +/- 0.15 [standard deviation]) was significantly higher than that of the control group (0.32 +/- 0.13) (P = .00002). One subject had an enlarged LV.CONCLUSION: Subclinical familial DCM was identified by determination of the DSP with MR imaging, and this method might be used to recognize familial DCM at an early stage.
|
|
| 42. |
- Kolak, Maria, et al.
(author)
-
Adipose tissue inflammation and increased ceramide content characterize subjects with high liver fat content independent of obesity
- 2007
-
In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 56:8, s. 1960-1968
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: We sought to determine whether adipose tissue is inflamed in individuals with increased liver fat (LFAT) independently of obesity.RESEARCH DESIGN AND METHODS: A total of 20 nondiabetic, healthy, obese women were divided into normal and high LFAT groups based on their median LFAT level (2.3 +/- 0.3 vs. 14.4 +/- 2.9%). Surgical subcutaneous adipose tissue biopsies were studied using quantitative PCR, immunohistochemistry, and a lipidomics approach to search for putative mediators of insulin resistance and inflammation. The groups were matched for age and BMI. The high LFAT group had increased insulin (P = 0.0025) and lower HDL cholesterol (P = 0.02) concentrations.RESULTS: Expression levels of the macrophage marker CD68, the chemokines monocyte chemoattractant protein-1 and macrophage inflammatory protein-1alpha, and plasminogen activator inhibitor-1 were significantly increased, and those of peroxisome proliferator-activated receptor-gamma and adiponectin decreased in the high LFAT group. CD68 expression correlated with the number of macrophages and crown-like structures (multiple macrophages fused around dead adipocytes). Concentrations of 154 lipid species in adipose tissue revealed several differences between the groups, with the most striking being increased concentrations of triacylglycerols, particularly long chain, and ceramides, specifically Cer(d18:1/24:1) (P = 0.01), in the high LFAT group. Expression of sphingomyelinases SMPD1 and SMPD3 were also significantly increased in the high compared with normal LFAT group.CONCLUSIONS: Adipose tissue is infiltrated with macrophages, and its content of long-chain triacylglycerols and ceramides is increased in subjects with increased LFAT compared with equally obese subjects with normal LFAT content. Ceramides or their metabolites could contribute to adverse effects of long-chain fatty acids on insulin resistance and inflammation.
|
|
| 43. |
- Kristan, Matej, et al.
(author)
-
The Sixth Visual Object Tracking VOT2018 Challenge Results
- 2019
-
In: Computer Vision – ECCV 2018 Workshops. - Cham : Springer Publishing Company. - 9783030110086 - 9783030110093 ; , s. 3-53
-
Conference paper (peer-reviewed)abstract
- The Visual Object Tracking challenge VOT2018 is the sixth annual tracker benchmarking activity organized by the VOT initiative. Results of over eighty trackers are presented; many are state-of-the-art trackers published at major computer vision conferences or in journals in the recent years. The evaluation included the standard VOT and other popular methodologies for short-term tracking analysis and a “real-time” experiment simulating a situation where a tracker processes images as if provided by a continuously running sensor. A long-term tracking subchallenge has been introduced to the set of standard VOT sub-challenges. The new subchallenge focuses on long-term tracking properties, namely coping with target disappearance and reappearance. A new dataset has been compiled and a performance evaluation methodology that focuses on long-term tracking capabilities has been adopted. The VOT toolkit has been updated to support both standard short-term and the new long-term tracking subchallenges. Performance of the tested trackers typically by far exceeds standard baselines. The source code for most of the trackers is publicly available from the VOT page. The dataset, the evaluation kit and the results are publicly available at the challenge website (http://votchallenge.net).
|
|
| 44. |
- Kristan, Matej, et al.
(author)
-
The Visual Object Tracking VOT2013 challenge results
- 2013
-
In: 2013 IEEE INTERNATIONAL CONFERENCE ON COMPUTER VISION WORKSHOPS (ICCVW). - : IEEE. - 9781479930227 ; , s. 98-111
-
Conference paper (peer-reviewed)abstract
- Visual tracking has attracted a significant attention in the last few decades. The recent surge in the number of publications on tracking-related problems have made it almost impossible to follow the developments in the field. One of the reasons is that there is a lack of commonly accepted annotated data-sets and standardized evaluation protocols that would allow objective comparison of different tracking methods. To address this issue, the Visual Object Tracking (VOT) workshop was organized in conjunction with ICCV2013. Researchers from academia as well as industry were invited to participate in the first VOT2013 challenge which aimed at single-object visual trackers that do not apply pre-learned models of object appearance (model-free). Presented here is the VOT2013 benchmark dataset for evaluation of single-object visual trackers as well as the results obtained by the trackers competing in the challenge. In contrast to related attempts in tracker benchmarking, the dataset is labeled per-frame by visual attributes that indicate occlusion, illumination change, motion change, size change and camera motion, offering a more systematic comparison of the trackers. Furthermore, we have designed an automated system for performing and evaluating the experiments. We present the evaluation protocol of the VOT2013 challenge and the results of a comparison of 27 trackers on the benchmark dataset. The dataset, the evaluation tools and the tracker rankings are publicly available from the challenge website(1).
|
|
| 45. |
- Kristan, Matej, et al.
(author)
-
The Visual Object Tracking VOT2016 Challenge Results
- 2016
-
In: COMPUTER VISION - ECCV 2016 WORKSHOPS, PT II. - Cham : SPRINGER INT PUBLISHING AG. - 9783319488813 - 9783319488806 ; , s. 777-823
-
Conference paper (peer-reviewed)abstract
- The Visual Object Tracking challenge VOT2016 aims at comparing short-term single-object visual trackers that do not apply pre-learned models of object appearance. Results of 70 trackers are presented, with a large number of trackers being published at major computer vision conferences and journals in the recent years. The number of tested state-of-the-art trackers makes the VOT 2016 the largest and most challenging benchmark on short-term tracking to date. For each participating tracker, a short description is provided in the Appendix. The VOT2016 goes beyond its predecessors by (i) introducing a new semi-automatic ground truth bounding box annotation methodology and (ii) extending the evaluation system with the no-reset experiment.
|
|
| 46. |
- Kristan, Matej, et al.
(author)
-
The Visual Object Tracking VOT2017 challenge results
- 2017
-
In: 2017 IEEE INTERNATIONAL CONFERENCE ON COMPUTER VISION WORKSHOPS (ICCVW 2017). - : IEEE. - 9781538610343 ; , s. 1949-1972
-
Conference paper (peer-reviewed)abstract
- The Visual Object Tracking challenge VOT2017 is the fifth annual tracker benchmarking activity organized by the VOT initiative. Results of 51 trackers are presented; many are state-of-the-art published at major computer vision conferences or journals in recent years. The evaluation included the standard VOT and other popular methodologies and a new "real-time" experiment simulating a situation where a tracker processes images as if provided by a continuously running sensor. Performance of the tested trackers typically by far exceeds standard baselines. The source code for most of the trackers is publicly available from the VOT page. The VOT2017 goes beyond its predecessors by (i) improving the VOT public dataset and introducing a separate VOT2017 sequestered dataset, (ii) introducing a realtime tracking experiment and (iii) releasing a redesigned toolkit that supports complex experiments. The dataset, the evaluation kit and the results are publicly available at the challenge website(1).
|
|
| 47. |
- Kyle, Jennifer E., et al.
(author)
-
Interpreting the lipidome : bioinformatic approaches to embrace the complexity
- 2021
-
In: Metabolomics. - : Springer-Verlag New York. - 1573-3882 .- 1573-3890. ; 17:6
-
Research review (peer-reviewed)abstract
- BACKGROUND: Improvements in mass spectrometry (MS) technologies coupled with bioinformatics developments have allowed considerable advancement in the measurement and interpretation of lipidomics data in recent years. Since research areas employing lipidomics are rapidly increasing, there is a great need for bioinformatic tools that capture and utilize the complexity of the data. Currently, the diversity and complexity within the lipidome is often concealed by summing over or averaging individual lipids up to (sub)class-based descriptors, losing valuable information about biological function and interactions with other distinct lipids molecules, proteins and/or metabolites.AIM OF REVIEW: To address this gap in knowledge, novel bioinformatics methods are needed to improve identification, quantification, integration and interpretation of lipidomics data. The purpose of this mini-review is to summarize exemplary methods to explore the complexity of the lipidome.KEY SCIENTIFIC CONCEPTS OF REVIEW: Here we describe six approaches that capture three core focus areas for lipidomics: (1) lipidome annotation including a resolvable database identifier, (2) interpretation via pathway- and enrichment-based methods, and (3) understanding complex interactions to emphasize specific steps in the analytical process and highlight challenges in analyses associated with the complexity of lipidome data.
|
|
| 48. |
- Laajala, Essi, et al.
(author)
-
Umbilical cord blood DNA methylation in children who later develop type 1 diabetes
- 2022
-
In: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 65:9, s. 1534-1540
-
Journal article (peer-reviewed)abstract
- AIMS/HYPOTHESIS: Distinct DNA methylation patterns have recently been observed to precede type 1 diabetes in whole blood collected from young children. Our aim was to determine whether perinatal DNA methylation is associated with later progression to type 1 diabetes.METHODS: Reduced representation bisulphite sequencing (RRBS) analysis was performed on umbilical cord blood samples collected within the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Study. Children later diagnosed with type 1 diabetes and/or who tested positive for multiple islet autoantibodies (n = 43) were compared with control individuals (n = 79) who remained autoantibody-negative throughout the DIPP follow-up until 15 years of age. Potential confounding factors related to the pregnancy and the mother were included in the analysis.RESULTS: No differences in the umbilical cord blood methylation patterns were observed between the cases and controls at a false discovery rate <0.05.CONCLUSIONS/INTERPRETATION: Based on our results, differences between children who progress to type 1 diabetes and those who remain healthy throughout childhood are not yet present in the perinatal DNA methylome. However, we cannot exclude the possibility that such differences would be found in a larger dataset.
|
|
| 49. |
- Madrid-Gambin, Francisco, et al.
(author)
-
Integrated Lipidomics and Proteomics Point to Early Blood-Based Changes in Childhood Preceding Later Development of Psychotic Experiences : Evidence From the Avon Longitudinal Study of Parents and Children
- 2019
-
In: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 86:1, s. 25-34
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The identification of early biomarkers of psychotic experiences (PEs) is of interest because early diagnosis and treatment of those at risk of future disorder is associated with improved outcomes. The current study investigated early lipidomic and coagulation pathway protein signatures of later PEs in subjects from the Avon Longitudinal Study of Parents and Children cohort.METHODS: Plasma of 115 children (12 years of age) who were first identified as experiencing PEs at 18 years of age (48 cases and 67 controls) were assessed through integrated and targeted lipidomics and semitargeted proteomics approaches. We assessed the lipids, lysophosphatidylcholines (n = 11) and phosphatidylcholines (n = 61), and the protein members of the coagulation pathway (n = 22) and integrated these data with complement pathway protein data already available on these subjects.RESULTS: Twelve phosphatidylcholines, four lysophosphatidylcholines, and the coagulation protein plasminogen were altered between the control and PEs groups after correction for multiple comparisons. Lipidomic and proteomic datasets were integrated into a multivariate network displaying a strong relationship between most lipids that were significantly associated with PEs and plasminogen. Finally, an unsupervised clustering approach identified four different clusters, with one of the clusters presenting the highest case-control ratio (p < .01) and associated with a higher concentration of smaller low-density lipoprotein cholesterol particles.CONCLUSIONS: Our findings indicate that the lipidome and proteome of subjects who report PEs at 18 years of age are already altered at 12 years of age, indicating that metabolic dysregulation may contribute to an early vulnerability to PEs and suggesting crosstalk between these lysophosphatidylcholines, phosphatidylcholines, and coagulation and complement proteins.
|
|
| 50. |
- Marto, João Pedro, et al.
(author)
-
Safety and Outcome of Revascularization Treatment in Patients With Acute Ischemic Stroke and COVID-19: The Global COVID-19 Stroke Registry.
- 2023
-
In: Neurology. - 1526-632X. ; 100:7
-
Journal article (peer-reviewed)abstract
- COVID-19-related inflammation, endothelial dysfunction, and coagulopathy may increase the bleeding risk and lower the efficacy of revascularization treatments in patients with acute ischemic stroke (AIS). We aimed to evaluate the safety and outcomes of revascularization treatments in patients with AIS and COVID-19.This was a retrospective multicenter cohort study of consecutive patients with AIS receiving intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) between March 2020 and June 2021 tested for severe acute respiratory syndrome coronavirus 2 infection. With a doubly robust model combining propensity score weighting and multivariate regression, we studied the association of COVID-19 with intracranial bleeding complications and clinical outcomes. Subgroup analyses were performed according to treatment groups (IVT-only and EVT).Of a total of 15,128 included patients from 105 centers, 853 (5.6%) were diagnosed with COVID-19; of those, 5,848 (38.7%) patients received IVT-only and 9,280 (61.3%) EVT (with or without IVT). Patients with COVID-19 had a higher rate of symptomatic intracerebral hemorrhage (SICH) (adjusted OR 1.53; 95% CI 1.16-2.01), symptomatic subarachnoid hemorrhage (SSAH) (OR 1.80; 95% CI 1.20-2.69), SICH and/or SSAH combined (OR 1.56; 95% CI 1.23-1.99), 24-hour mortality (OR 2.47; 95% CI 1.58-3.86), and 3-month mortality (OR 1.88; 95% CI 1.52-2.33). Patients with COVID-19 also had an unfavorable shift in the distribution of the modified Rankin score at 3 months (OR 1.42; 95% CI 1.26-1.60).Patients with AIS and COVID-19 showed higher rates of intracranial bleeding complications and worse clinical outcomes after revascularization treatments than contemporaneous non-COVID-19 patients receiving treatment. Current available data do not allow direct conclusions to be drawn on the effectiveness of revascularization treatments in patients with COVID-19 or to establish different treatment recommendations in this subgroup of patients with ischemic stroke. Our findings can be taken into consideration for treatment decisions, patient monitoring, and establishing prognosis.The study was registered under ClinicalTrials.gov identifier NCT04895462.
|
|
