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- Bowden, John A., et al.
(author)
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Harmonizing lipidomics : NIST interlaboratory comparison exercise for lipidomics using SRM 1950-Metabolites in Frozen Human Plasma
- 2017
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In: Journal of Lipid Research. - 0022-2275 .- 1539-7262. ; 58:12, s. 2275-2288
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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.
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- Ganda, Anjali, et al.
(author)
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Plasma metabolite profiles, cellular cholesterol efflux, and non-traditional cardiovascular risk in patients with CKD
- 2017
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In: Journal of Molecular and Cellular Cardiology. - : Elsevier BV. - 1095-8584 .- 0022-2828. ; 112, s. 114-122
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Journal article (peer-reviewed)abstract
- BACKGROUND: Patients with chronic kidney disease (CKD) experience high rates of atherosclerotic cardiovascular disease and death that are not fully explained by traditional risk factors. In animal studies, defective cellular cholesterol efflux pathways which are mediated by the ATP binding cassette transporters ABCA1 and ABCG1 are associated with accelerated atherosclerosis. We hypothesized that cholesterol efflux in humans would vary in terms of cellular components, with potential implications for cardiovascular disease.METHODS: We recruited 120 CKD patients (eGFR<30mL/min/1.73m(2)) and 120 control subjects (eGFR ≥60mL/min/1.73m(2)) in order to measure cholesterol efflux using either patients' HDL and THP-1 macrophages or patients' monocytes and a flow cytometry based cholesterol efflux assay. We also measured cell-surface levels of the common β subunit of the IL-3/GM-CSF receptor (IL-3Rβ) which has been linked to defective cholesterol homeostasis and may promote monocytosis. In addition, we measured plasma inflammatory cytokines and plasma metabolite profiles.RESULTS: There was a strong positive correlation between cell-surface IL-3Rβ levels and monocyte counts in CKD (P<0.001). ABCA1 mRNA was reduced in CKD vs. control monocytes (P<0.05), across various etiologies of CKD. Cholesterol efflux to apolipoprotein A1 was impaired in monocytes from CKD patients with diabetic nephropathy (P<0.05), but we found no evidence for a circulating HDL-mediated defect in cholesterol efflux in CKD. Profiling of plasma metabolites showed that medium-chain acylcarnitines were both independently associated with lower levels of cholesterol transporter mRNA in CKD monocytes at baseline (P<0.05), and with cardiovascular events in CKD patients after median 2.6years of follow-up.CONCLUSIONS: Cholesterol efflux in humans varies in terms of cellular components. We report a cellular defect in ABCA1-mediated cholesterol efflux in monocytes from CKD patients with diabetic nephropathy. Unlike several traditional risk factors for atherosclerotic cardiovascular disease, plasma metabolites inversely associated with endogenous cholesterol transporters predicted cardiovascular events in CKD patients. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.).
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- Paul, Elisabeth R., 1991-, et al.
(author)
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Functional Connectivity Between Extrastriate Body Area and Default Mode Network Predicts Depersonalization Symptoms in Major Depression : Findings From an A Priori Specified Multinetwork Comparison
- 2019
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In: Biological Psychiatry. - : Elsevier. - 2451-9022. ; 4:7, s. 627-635
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Journal article (peer-reviewed)abstract
- BackgroundDepersonalization/derealization disorder is a dissociative disorder characterized by feelings of unreality and detachment from the self and surroundings. Depersonalization/derealization disorder is classified as a primary disorder, but depersonalization symptoms are frequently observed in mood and anxiety disorders. In the context of major depressive disorder (MDD), depersonalization symptoms are associated with greater depressive severity as indexed by treatment resistance, inpatient visits, and duration of depressive episodes. In the current investigation, we tested four network-based, neural-functional hypotheses of depersonalization in MDD. These hypotheses were framed in terms of functional relationships between 1) extrastriate body area and default mode network (DMN); 2) hippocampus and DMN; 3) medial prefrontal cortex and ventral striatum; and 4) posterior and anterior insular cortex.MethodsWe conducted functional magnetic resonance imaging during resting state on 28 female patients with MDD and 27 control subjects with no history of a psychiatric disorder. Functional connectivity between seed and target regions as specified by our network-level hypotheses was computed and correlated with scores on the Cambridge Depersonalization Scale. We used a conservative, unbiased bootstrapping procedure to test the significance of neural-behavioral correlations observed under each of the four models tested.ResultsOf the four neural-functional models of depersonalization symptoms tested, only the model proposing that reduced connectivity between the extrastriate body area and DMN predicts higher levels of depersonalization symptoms in MDD was confirmed.ConclusionsOur results indicate that depersonalization/derealization disorder symptoms in patients with depression are related to reduced functional connectivity between brain regions that are proposed to support processing of body-related (extrastriate body area) and autobiographical (DMN) information.
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- Ahvenniemi, Esko, et al.
(author)
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Recommended reading list of early publications on atomic layer deposition-Outcome of the "Virtual Project on the History of ALD"
- 2017
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In: Journal of Vacuum Science & Technology. A. Vacuum, Surfaces, and Films. - : American Vacuum Society. - 0734-2101 .- 1520-8559. ; 35:1
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Research review (peer-reviewed)abstract
- Atomic layer deposition (ALD), a gas-phase thin film deposition technique based on repeated, self-terminating gas-solid reactions, has become the method of choice in semiconductor manufacturing and many other technological areas for depositing thin conformal inorganic material layers for various applications. ALD has been discovered and developed independently, at least twice, under different names: atomic layer epitaxy (ALE) and molecular layering. ALE, dating back to 1974 in Finland, has been commonly known as the origin of ALD, while work done since the 1960s in the Soviet Union under the name "molecular layering" (and sometimes other names) has remained much less known. The virtual project on the history of ALD (VPHA) is a volunteer-based effort with open participation, set up to make the early days of ALD more transparent. In VPHA, started in July 2013, the target is to list, read and comment on all early ALD academic and patent literature up to 1986. VPHA has resulted in two essays and several presentations at international conferences. This paper, based on a poster presentation at the 16th International Conference on Atomic Layer Deposition in Dublin, Ireland, 2016, presents a recommended reading list of early ALD publications, created collectively by the VPHA participants through voting. The list contains 22 publications from Finland, Japan, Soviet Union, United Kingdom, and United States. Up to now, a balanced overview regarding the early history of ALD has been missing; the current list is an attempt to remedy this deficiency.
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- Bas-Hoogendam, Janna Marie, et al.
(author)
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Voxel-based morphometry multi-center mega-analysis of brain structure in social anxiety disorder
- 2017
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In: NeuroImage. - : Elsevier BV. - 2213-1582. ; 16, s. 678-688
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Journal article (peer-reviewed)abstract
- Social anxiety disorder (SAD) is a prevalent and disabling mental disorder, associated with significant psychiatric co-morbidity. Previous research on structural brain alterations associated with SAD has yielded inconsistent results concerning the direction of the changes in gray matter (GM) in various brain regions, as well as on the relationship between brain structure and SAD-symptomatology. These heterogeneous findings are possibly due to limited sample sizes. Multi-site imaging offers new opportunities to investigate SAD-related alterations in brain structure in larger samples.An international multi-center mega-analysis on the largest database of SAD structural T1-weighted 3T MRI scans to date was performed to compare GM volume of SAD-patients (n = 174) and healthy control (HC)-participants (n = 213) using voxel-based morphometry. A hypothesis-driven region of interest (ROI) approach was used, focusing on the basal ganglia, the amygdala-hippocampal complex, the prefrontal cortex, and the parietal cortex. SAD-patients had larger GM volume in the dorsal striatum when compared to HC-participants. This increase correlated positively with the severity of self-reported social anxiety symptoms. No SAD-related differences in GM volume were present in the other ROIs. Thereby, the results of this mega-analysis suggest a role for the dorsal striatum in SAD, but previously reported SAD-related changes in GM in the amygdala, hippocampus, precuneus, prefrontal cortex and parietal regions were not replicated. Our findings emphasize the importance of large sample imaging studies and the need for meta-analyses like those performed by the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium.
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- Cremers, Ruben G., et al.
(author)
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The role of the prostate cancer gene 3 urine test in addition to serum prostate-specific antigen level in prostate cancer screening among breast cancer, early-onset gene mutation carriers
- 2015
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In: Urologic Oncology: Seminars and Original Investigations. - : Elsevier BV. - 1078-1439. ; 33:5, s. 19-202
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Journal article (peer-reviewed)abstract
- Objective: To evaluate the additive value of the prostate cancer gene 3 (PCA3) urine test to serum prostate-specific antigen (PSA) in prostate cancer (PC) screening among breast cancer, early-onset gene (BRCA) mutation carriers. This study was performed among the Dutch participants of IMPACT, a large international study on the effectiveness of PSA screening among BRCA mutation carriers. Materials and methods: Urinary PCA3 was measured in 191 BRCA1 mutation carriers, 75 BRCA2 mutation carriers, and 308 noncarriers. The physicians and participants were blinded for the results. Serum PSA level≥3.0. ng/ml was used to indicate prostate biopsies. PCA3 was evaluated (1) as an independent indicator for prostate biopsies and (2) as an indicator for prostate biopsies among men with an elevated PSA level. PC detected up to the 2-year screening was used as gold standard as end-of-study biopsies were not performed. Results: Overall, 23 PCs were diagnosed, 20 of which were in men who had an elevated PSA level in the initial screening round. (1) PCA3, successfully determined in 552 participants, was elevated in 188 (cutoff≥25; 34%) or 134 (cutoff≥35; 24%) participants, including 2 of the 3 PCs missed by PSA. PCA3 would have added 157 (≥25; 28%) or 109 (≥35; 20%) biopsy sessions to screening with PSA only. (2) Elevated PCA3 as a requirement for biopsies in addition to PSA would have saved 37 (cutoff≥25) or 43 (cutoff≥35) of the 68 biopsy sessions, and 7 or 11 PCs would have been missed, respectively, including multiple high-risk PCs. So far, PCA3 performed best among BRCA2 mutation carriers, but the numbers are still small. Because PCA3 was not used to indicate prostate biopsies, its true diagnostic value cannot be calculated. Conclusions: The results do not provide evidence for PCA3 as a useful additional indicator of prostate biopsies in BRCA mutation carriers, as many participants had an elevated PCA3 in the absence of PC. This must be interpreted with caution because PCA3 was not used to indicate biopsies. Many participants diagnosed with PC had low PCA3, making it invalid as a restrictive marker for prostate biopsies in men with elevated PSA levels.
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