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| 4. |
- Ederle, Joerg, et al.
(författare)
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Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial
- 2010
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Ingår i: The Lancet. - 1474-547X. ; 375:9719, s. 985-997
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Tidskriftsartikel (refereegranskat)abstract
- Background Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. Methods The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. Findings The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006), Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). Interpretation Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.
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| 5. |
- Meyer, H., et al.
(författare)
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Overview of physics results from MAST towards ITER/DEMO and the MAST Upgrade
- 2013
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 53:10, s. 104008-
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Tidskriftsartikel (refereegranskat)abstract
- New diagnostic, modelling and plant capability on the Mega Ampere Spherical Tokamak (MAST) have delivered important results in key areas for ITER/DEMO and the upcoming MAST Upgrade, a step towards future ST devices on the path to fusion currently under procurement. Micro-stability analysis of the pedestal highlights the potential roles of micro-tearing modes and kinetic ballooning modes for the pedestal formation. Mitigation of edge localized modes (ELM) using resonant magnetic perturbation has been demonstrated for toroidal mode numbers n = 3, 4, 6 with an ELM frequency increase by up to a factor of 9, compatible with pellet fuelling. The peak heat flux of mitigated and natural ELMs follows the same linear trend with ELM energy loss and the first ELM-resolved T-i measurements in the divertor region are shown. Measurements of flow shear and turbulence dynamics during L-H transitions show filaments erupting from the plasma edge whilst the full flow shear is still present. Off-axis neutral beam injection helps to strongly reduce the redistribution of fast-ions due to fishbone modes when compared to on-axis injection. Low-k ion-scale turbulence has been measured in L-mode and compared to global gyro-kinetic simulations. A statistical analysis of principal turbulence time scales shows them to be of comparable magnitude and reasonably correlated with turbulence decorrelation time. T-e inside the island of a neoclassical tearing mode allow the analysis of the island evolution without assuming specific models for the heat flux. Other results include the discrepancy of the current profile evolution during the current ramp-up with solutions of the poloidal field diffusion equation, studies of the anomalous Doppler resonance compressional Alfven eigenmodes, disruption mitigation studies and modelling of the new divertor design for MAST Upgrade. The novel 3D electron Bernstein synthetic imaging shows promising first data sensitive to the edge current profile and flows.
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| 6. |
- Valdes-Marquez, E., et al.
(författare)
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Relative effects of LDL-C on ischemic stroke and coronary disease A Mendelian randomization study
- 2019
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 92:11
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Tidskriftsartikel (refereegranskat)abstract
- Objective To examine the causal relevance of lifelong differences in low-density lipoprotein cholesterol (LDL-C) for ischemic stroke (IS) relative to that for coronary heart disease (CHD) using a Mendelian randomization approach. We undertook a 2-sample Mendelian randomization, based on summary data, to estimate the causal relevance of LDL-C for risk of IS and CHD. Information from 62 independent genetic variants with genome-wide significant effects on LDL-C levels was used to estimate the causal effects of LDL-C for IS and IS subtypes (based on 12,389 IS cases from METASTROKE) and for CHD (based on 60,801 cases from CARDIoGRAMplusC4D). We then assessed the effects of LDL-C on IS and CHD for heterogeneity. A 1 mmol/L higher genetically determined LDL-C was associated with a 50% higher risk of CHD (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.32-1.68, p = 1.1 x 10(-8)). By contrast, the causal effect of LDL-C was much weaker for IS (OR 1.12, 95% CI 0.96-1.30, p = 0.14; p for heterogeneity = 2.6 x 10(-3)) and, in particular, for cardioembolic stroke (OR 1.06, 95% CI 0.84-1.33, p = 0.64; p for heterogeneity = 8.6 x 10(-3)) when compared with that for CHD. In contrast with the consistent effects of LDL-C-lowering therapies on IS and CHD, genetic variants that confer lifelong LDL-C differences show a weaker effect on IS than on CHD. The relevance of etiologically distinct IS subtypes may contribute to the differences observed.
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| 9. |
- Pulit, SL, et al.
(författare)
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Loci associated with ischaemic stroke and its subtypes (SiGN): a genome-wide association study.
- 2016
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Ingår i: The Lancet. Neurology. - 1474-4465. ; 15:2, s. 174-84
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of disease-associated loci through genome-wide association studies (GWAS) is the leading genetic approach to the identification of novel biological pathways underlying diseases in humans. Until recently, GWAS in ischaemic stroke have been limited by small sample sizes and have yielded few loci associated with ischaemic stroke. We did a large-scale GWAS to identify additional susceptibility genes for stroke and its subtypes.To identify genetic loci associated with ischaemic stroke, we did a two-stage GWAS. In the first stage, we included 16851 cases with state-of-the-art phenotyping data and 32473 stroke-free controls. Cases were aged 16 to 104 years, recruited between 1989 and 2012, and subtypes of ischaemic stroke were recorded by centrally trained and certified investigators who used the web-based protocol, Causative Classification of Stroke (CCS). We constructed case-control strata by identifying samples that were genotyped on nearly identical arrays and were of similar genetic ancestral background. We cleaned and imputed data by use of dense imputation reference panels generated from whole-genome sequence data. We did genome-wide testing to identify stroke-associated loci within each stratum for each available phenotype, and we combined summary-level results using inverse variance-weighted fixed-effects meta-analysis. In the second stage, we did in-silico lookups of 1372 single nucleotide polymorphisms identified from the first stage GWAS in 20941 cases and 364736 unique stroke-free controls. The ischaemic stroke subtypes of these cases had previously been established with the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification system, in accordance with local standards. Results from the two stages were then jointly analysed in a final meta-analysis.We identified a novel locus (G allele at rs12122341) at 1p13.2 near TSPAN2 that was associated with large artery atherosclerosis-related stroke (first stage odds ratio [OR] 1·21, 95% CI 1·13-1·30, p=4·50×10(-8); joint OR 1·19, 1·12-1·26, p=1·30×10(-9)). Our results also supported robust associations with ischaemic stroke for four other loci that have been reported in previous studies, including PITX2 (first stage OR 1·39, 1·29-1·49, p=3·26×10(-19); joint OR 1·37, 1·30-1·45, p=2·79×10(-32)) and ZFHX3 (first stage OR 1·19, 1·11-1·27, p=2·93×10(-7); joint OR 1·17, 1·11-1·23, p=2·29×10(-10)) for cardioembolic stroke, and HDAC9 (first stage OR 1·29, 1·18-1·42, p=3·50×10(-8); joint OR 1·24, 1·15-1·33, p=4·52×10(-9)) for large artery atherosclerosis stroke. The 12q24 locus near ALDH2, which has previously been associated with all ischaemic stroke but not with any specific subtype, exceeded genome-wide significance in the meta-analysis of small artery stroke (first stage OR 1·20, 1·12-1·28, p=6·82×10(-8); joint OR 1·17, 1·11-1·23, p=2·92×10(-9)). Other loci associated with stroke in previous studies, including NINJ2, were not confirmed.Our results suggest that all ischaemic stroke-related loci previously implicated by GWAS are subtype specific. We identified a novel gene associated with large artery atherosclerosis stroke susceptibility. Follow-up studies will be necessary to establish whether the locus near TSPAN2 can be a target for a novel therapeutic approach to stroke prevention. In view of the subtype-specificity of the associations detected, the rich phenotyping data available in the Stroke Genetics Network (SiGN) are likely to be crucial for further genetic discoveries related to ischaemic stroke.US National Institute of Neurological Disorders and Stroke, National Institutes of Health.
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| 11. |
- de Graauw, Th., et al.
(författare)
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The Herschel-Heterodyne Instrument for the Far-Infrared (HIFI)
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518, s. L6-
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Tidskriftsartikel (refereegranskat)abstract
- Aims: This paper describes the Heterodyne Instrument for the Far-Infrared (HIFI) that was launched onboard ESA's Herschel Space Observatory in May 2009. Methods: The instrument is a set of 7 heterodyne receivers that are electronically tuneable, covering 480-1250 GHz with SIS mixers and the 1410-1910 GHz range with hot electron bolometer (HEB) mixers. The local oscillator (LO) subsystem comprises a Ka-band synthesizer followed by 14 chains of frequency multipliers and 2 chains for each frequency band. A pair of auto-correlators and a pair of acousto-optical spectrometers process the two IF signals from the dual-polarization, single-pixel front-ends to provide instantaneous frequency coverage of 2 × 4 GHz, with a set of resolutions (125 kHz to 1 MHz) that are better than 0.1 km s-1. Results: After a successful qualification and a pre-launch TB/TV test program, the flight instrument is now in-orbit and completed successfully the commissioning and performance verification phase. The in-orbit performance of the receivers matches the pre-launch sensitivities. We also report on the in-orbit performance of the receivers and some first results of HIFI's operations. Herschel is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation from NASA.
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| 14. |
- Willeit, P., et al.
(författare)
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Carotid Intima-Media Thickness Progression as Surrogate Marker for Cardiovascular Risk: Meta-Analysis of 119 Clinical Trials Involving 100 667 Patients
- 2020
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Ingår i: Circulation. - 1524-4539. ; 142:7, s. 621-642
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To quantify the association between effects of interventions on carotid intima-media thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk. METHODS: We systematically collated data from randomized, controlled trials. cIMT was assessed as the mean value at the common-carotid-artery; if unavailable, the maximum value at the common-carotid-artery or other cIMT measures were used. The primary outcome was a combined CVD end point defined as myocardial infarction, stroke, revascularization procedures, or fatal CVD. We estimated intervention effects on cIMT progression and incident CVD for each trial, before relating the 2 using a Bayesian meta-regression approach. RESULTS: We analyzed data of 119 randomized, controlled trials involving 100 667 patients (mean age 62 years, 42% female). Over an average follow-up of 3.7 years, 12 038 patients developed the combined CVD end point. Across all interventions, each 10 μm/y reduction of cIMT progression resulted in a relative risk for CVD of 0.91 (95% Credible Interval, 0.87-0.94), with an additional relative risk for CVD of 0.92 (0.87-0.97) being achieved independent of cIMT progression. Taken together, we estimated that interventions reducing cIMT progression by 10, 20, 30, or 40 μm/y would yield relative risks of 0.84 (0.75-0.93), 0.76 (0.67-0.85), 0.69 (0.59-0.79), or 0.63 (0.52-0.74), respectively. Results were similar when grouping trials by type of intervention, time of conduct, time to ultrasound follow-up, availability of individual-participant data, primary versus secondary prevention trials, type of cIMT measurement, and proportion of female patients. CONCLUSIONS: The extent of intervention effects on cIMT progression predicted the degree of CVD risk reduction. This provides a missing link supporting the usefulness of cIMT progression as a surrogate marker for CVD risk in clinical trials.
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| 15. |
- Joss, D. T., et al.
(författare)
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Evolving collective structures in the transitional nuclei W-162 and W-164
- 2016
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Ingår i: PHYSICAL REVIEW C. - : American Physical Society. - 2469-9985. ; 93:2
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Tidskriftsartikel (refereegranskat)abstract
- Excited states in the neutron-deficient nuclides(74)(162)W(88) and W-164(74)90 were investigated by using the gamma-ray spectrometer Jurogam. A change in structure is apparent from the first rotational alignments in W-162 and W-164, whose rotationally aligned bands are interpreted as nu(h(9/2))(2) and nu(i(13/2))(2) configurations, respectively. The level schemes have been extended using recoil (-decay) correlations with the observation of excited collective structures. Configuration assignments have been made on the basis of comparisons of the deduced aligned angular momentum, as a function of rotational frequency, with the predictions of the cranked shell model.
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| 16. |
- Scherer, SW, et al.
(författare)
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Human chromosome 7: DNA sequence and biology
- 2003
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 300:5620, s. 767-772
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Tidskriftsartikel (refereegranskat)abstract
- DNA sequence and annotation of the entire human chromosome 7, encompassing nearly 158 million nucleotides of DNA and 1917 gene structures, are presented. To generate a higher order description, additional structural features such as imprinted genes, fragile sites, and segmental duplications were integrated at the level of the DNA sequence with medical genetic data, including 440 chromosome rearrangement breakpoints associated with disease. This approach enabled the discovery of candidate genes for developmental diseases including autism.
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| 18. |
- Baudena, M., et al.
(författare)
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Forests, savannas, and grasslands: bridging the knowledge gap between ecology and Dynamic Global Vegetation Models
- 2015
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Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4189. ; 12:6, s. 1833-1848
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Tidskriftsartikel (refereegranskat)abstract
- The forest, savanna, and grassland biomes, and the transitions between them, are expected to undergo major changes in the future due to global climate change. Dynamic global vegetation models (DGVMs) are very useful for understanding vegetation dynamics under the present climate, and for predicting its changes under future conditions. However, several DGVMs display high uncertainty in predicting vegetation in tropical areas. Here we perform a comparative analysis of three different DGVMs (JSBACH, LPJ-GUESS-SPITFIRE and aDGVM) with regard to their representation of the ecological mechanisms and feedbacks that determine the forest, savanna, and grassland biomes, in an attempt to bridge the knowledge gap between ecology and global modeling. The outcomes of the models, which include different mechanisms, are compared to observed tree cover along a mean annual precipitation gradient in Africa. By drawing on the large number of recent studies that have delivered new insights into the ecology of tropical ecosystems in general, and of savannas in particular, we identify two main mechanisms that need improved representation in the examined DGVMs. The first mechanism includes water limitation to tree growth, and tree grass competition for water, which are key factors in determining savanna presence in arid and semi-arid areas. The second is a grass fire feedback, which maintains both forest and savanna presence in mesic areas. Grasses constitute the majority of the fuel load, and at the same time benefit from the openness of the landscape after fires, since they recover faster than trees. Additionally, these two mechanisms are better represented when the models also include tree life stages (adults and seedlings), and distinguish between fire-prone and shade-tolerant forest trees, and fire-resistant and shade-intolerant savanna trees. Including these basic elements could improve the predictive ability of the DGVMs, not only under current climate conditions but also and especially under future scenarios.
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| 19. |
- Roelfsema, P. R., et al.
(författare)
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In-orbit performance of Herschel-HIFI
- 2012
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 537
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Tidskriftsartikel (refereegranskat)abstract
- Aims: In this paper the calibration and in-orbit performance of the Heterodyne Instrument for the Far-Infrared (HIFI) is described.Methods: The calibration of HIFI is based on a combination of ground and in-flight tests. Dedicated ground tests to determine those instrument parameters that can only be measured accurately using controlled laboratory stimuli were carried out in the instrument level test (ILT) campaign. Special in-flight tests during the commissioning phase (CoP) and performance verification (PV) allowed the determination of the remaining instrument parameters. The various instrument observing modes, as specified in astronomical observation templates (AOTs), were validated in parallel during PV by observing selected celestial sources.Results: The initial calibration and in-orbit performance of HIFI has been established. A first estimate of the calibration budget is given. The overall in-flight instrument performance agrees with the original specification. Issues remain at only a few frequencies. Herschel is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation from NASA.
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| 22. |
- Biel, D., et al.
(författare)
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Combining tau-PET and fMRI meta-analyses for patient-centered prediction of cognitive decline in Alzheimer's disease
- 2022
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Ingår i: Alzheimers Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Tau-PET is a prognostic marker for cognitive decline in Alzheimer's disease, and the heterogeneity of tau-PET patterns matches cognitive symptom heterogeneity. Thus, tau-PET may allow precision-medicine prediction of individual tau-related cognitive trajectories, which can be important for determining patient-specific cognitive endpoints in clinical trials. Here, we aimed to examine whether tau-PET in cognitive-domain-specific brain regions, identified via fMRI meta-analyses, allows the prediction of domain-specific cognitive decline. Further, we aimed to determine whether tau-PET-informed personalized cognitive composites capture patient-specific cognitive trajectories more sensitively than conventional cognitive measures. Methods We included Alzheimer's Disease Neuroimaging Initiative (ADNI) participants classified as controls (i.e., amyloid-negative, cognitively normal, n = 121) or Alzheimer's disease-spectrum (i.e., amyloid-positive, cognitively normal to dementia, n = 140), plus 111 AVID-1451-A05 participants for independent validation (controls/Alzheimer's disease-spectrum=46/65). All participants underwent baseline F-18-flortaucipir tau-PET, amyloid-PET, and longitudinal cognitive testing to assess annual cognitive changes (i.e., episodic memory, language, executive functioning, visuospatial). Cognitive changes were calculated using linear mixed models. Independent meta-analytical task-fMRI activation maps for each included cognitive domain were obtained from the Neurosynth database and applied to tau-PET to determine tau-PET signal in cognitive-domain-specific brain regions. In bootstrapped linear regression, we assessed the strength of the relationship (i.e., partial R-2) between cognitive-domain-specific tau-PET vs. global or temporal-lobe tau-PET and cognitive changes. Further, we used tau-PET-based prediction of domain-specific decline to compose personalized cognitive composites that were tailored to capture patient-specific cognitive decline. Results In both amyloid-positive cohorts (ADNI [age = 75.99 +/- 7.69] and A05 [age = 74.03 +/- 9.03]), cognitive-domain-specific tau-PET outperformed global and temporal-lobe tau-PET for predicting future cognitive decline in episodic memory, language, executive functioning, and visuospatial abilities. Further, a tau-PET-informed personalized cognitive composite across cognitive domains enhanced the sensitivity to assess cognitive decline in amyloid-positive subjects, yielding lower sample sizes required for detecting simulated intervention effects compared to conventional cognitive endpoints (i.e., memory composite, global cognitive composite). However, the latter effect was less strong in A05 compared to the ADNI cohort. Conclusion Combining tau-PET with task-fMRI-derived maps of major cognitive domains facilitates the prediction of domain-specific cognitive decline. This approach may help to increase the sensitivity to detect Alzheimer's disease-related cognitive decline and to determine personalized cognitive endpoints in clinical trials.
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| 24. |
- Casares, L., et al.
(författare)
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The synthetic triterpenoids CDDO-TFEA and CDDO-Me, but not CDDO, promote nuclear exclusion of BACH1 impairing its activity
- 2022
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Ingår i: Redox Biology. - : Elsevier BV. - 2213-2317. ; 51
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Tidskriftsartikel (refereegranskat)abstract
- The transcription factor BACH1 is a potential therapeutic target for a variety of chronic conditions linked to oxidative stress and inflammation, as well as cancer metastasis. However, only a few BACH1 degraders/inhibitors have been described. BACH1 is a transcriptional repressor of heme oxygenase 1 (HMOX1), which is positively regulated by transcription factor NRF2 and is highly inducible by derivatives of the synthetic oleanane triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO). Most of the therapeutic activities of these compounds are due to their anti-inflammatory and antioxidant properties, which are widely attributed to their ability to activate NRF2. However, with such a broad range of action, these compounds have other molecular targets that have not been fully identified and could also be of importance for their therapeutic profile. Herein we identified BACH1 as a target of two CDDO-derivatives (CDDO-Me and CDDO-TFEA), but not of CDDO. While both CDDO and CDDO-derivatives activate NRF2 similarly, only CDDO-Me and CDDO-TFEA inhibit BACH1, which explains the much higher potency of these CDDO-derivatives as HMOX1 inducers compared with unmodified CDDO. Notably, we demonstrate that CDDO-Me and CDDO-TFEA inhibit BACH1 via a novel mechanism that reduces BACH1 nuclear levels while accumulating its cytoplasmic form. In an in vitro model, both CDDO-derivatives impaired lung cancer cell invasion in a BACH1-dependent and NRF2-independent manner, while CDDO was inactive. Altogether, our study identifies CDDO-Me and CDDO-TFEA as dual KEAP1/BACH1 inhibitors, providing a rationale for further therapeutic uses of these drugs.
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| 25. |
- Higgins, D., et al.
(författare)
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Application of high-throughput pyrosequencing in the analysis of microbiota of food commodities procured from small and large retail outlets in a U.S. metropolitan area – A pilot study
- 2018
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Ingår i: Food Research International. - : Elsevier BV. - 0963-9969. ; 105, s. 29-40
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Tidskriftsartikel (refereegranskat)abstract
- With the advent of high-throughput sequencing technologies, it is possible to comprehensively analyze the microbial community of foods without culturing them in the laboratory. The estimation of all microbes inhabiting a food commodity (food microbiota) therefore may shed light on the microbial quality and safety of foods. In this study, we utilized high-throughput pyrosequencing of 16S rRNA genes as well as traditional microbiological methods to evaluate the bacterial diversity and the predicted metabolic pathways associated with the bacterial communities of selected foods (romaine lettuce, cabbage, deli meat, and chicken legs, total 200 samples) procured from small and large retail outlets located in Memphis-Shelby County, Tennessee, USA. For high-throughput sequencing, microbial genomic DNA was directly extracted from the food products and subjected to genetic sequencing. Aerobic plate count of all food samples was also performed. Foods from small stores (such as corner stores) were found to contain higher bacterial counts as compared to large stores (such as supermarkets). High-throughput pyrosequencing in tandem with bioinformatics analyses revealed a comprehensive picture of the bacterial ecology of foods at different taxonomic levels. Firmicutes and Proteobacteria were the most abundant phyla across all products. At the genus level, Enterobacter and Pantoea in vegetables, and Bacillus and Aeromonas in animal products were found to be the most abundant. The bacterial predicted metabolic pathways such as inosine-5′-phosphate biosynthesis I, methylglyoxal (MG) degradation pathways, urea cycle, dTDP-L-rhamnose biosynthesis I, and mevalonate pathway I differed in foods procured from small stores as compared to large groceries or supermarkets. The results from this study revealed that the bacterial ecology (both in terms of numbers and types of bacteria) of food commodities might differ based on the vending outlet type (large vs. small) of retail stores. The overall estimation bacterial communities in foods by high-throughput sequencing method may be useful to identify potential taxa responsible for food spoilage. Moreover, the data from pyrosequencing of 16S rRNA genes can also be applied to infer major metabolic pathways in bacteria inhabiting different foods. This may reflect the role of these pathways in food-bacteria interaction and adaptation.
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| 26. |
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| 27. |
- Zheng, L. K., et al.
(författare)
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Combined Connectomics, MAPT Gene Expression, and Amyloid Deposition to Explain Regional Tau Deposition in Alzheimer Disease
- 2024
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Ingår i: Annals of Neurology. - 0364-5134. ; 95:2, s. 274-287
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We aimed to test whether region-specific factors, including spatial expression patterns of the tau-encoding gene MAPT and regional levels of amyloid positron emission tomography (PET), enhance connectivity-based modeling of the spatial variability in tau-PET deposition in the Alzheimer disease (AD) spectrum.Methods: We included 685 participants (395 amyloid-positive participants within AD spectrum and 290 amyloid-negative controls) with tau-PET and amyloid-PET from 3 studies (Alzheimer's Disease Neuroimaging Initiative, F-18-AV-1451-A05, and BioFINDER-1). Resting-state functional magnetic resonance imaging was obtained in healthy controls (n = 1,000) from the Human Connectome Project, and MAPT gene expression from the Allen Human Brain Atlas. Based on a brain-parcellation atlas superimposed onto all modalities, we obtained region of interest (ROI)-to-ROI functional connectivity, ROI-level PET values, and MAPT gene expression. In stepwise regression analyses, we tested connectivity, MAPT gene expression, and amyloid-PET as predictors of group-averaged and individual tau-PET ROI values in amyloid-positive participants.Results: Connectivity alone explained 21.8 to 39.2% (range across 3 studies) of the variance in tau-PET ROI values averaged across amyloid-positive participants. Stepwise addition of MAPT gene expression and amyloid-PET increased the proportion of explained variance to 30.2 to 46.0% and 45.0 to 49.9%, respectively. Similarly, for the prediction of patient-level tau-PET ROI values, combining all 3 predictors significantly improved the variability explained (mean adjusted R-2 range across studies = 0.118-0.148, 0.156-0.196, and 0.251-0.333 for connectivity alone, connectivity plus MAPT expression, and all 3 modalities combined, respectively).Interpretation: Across 3 study samples, combining the functional connectome and molecular properties substantially enhanced the explanatory power compared to single modalities, providing a valuable tool to explain regional susceptibility to tau deposition in AD.
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