Abstract
Brain age prediction algorithms using structural magnetic resonance imaging (MRI) aim to assess the biological age of the human brain. The difference between a person's chronological age and ...the estimated brain age is thought to reflect deviations from a normal aging trajectory, indicating a slower or accelerated biological aging process. Several pre‐trained software packages for predicting brain age are publicly available. In this study, we perform a comparison of such packages with respect to (1) predictive accuracy, (2) test–retest reliability, and (3) the ability to track age progression over time. We evaluated the six brain age prediction packages: brainageR, DeepBrainNet, brainage, ENIGMA, pyment, and mccqrnn. The accuracy and test–retest reliability were assessed on MRI data from 372 healthy people aged between 18.4 and 86.2 years (mean 38.7 ± 17.5 years). All packages showed significant correlations between predicted brain age and chronological age (
r
= 0.66–0.97,
p
< 0.001), with pyment displaying the strongest correlation. The mean absolute error was between 3.56 (pyment) and 9.54 years (ENIGMA). brainageR, pyment, and mccqrnn were superior in terms of reliability (ICC values between 0.94–0.98), as well as predicting age progression over a longer time span. Of the six packages, pyment and brainageR consistently showed the highest accuracy and test–retest reliability.
Adverse events (AEs) or complications may arise secondary to the treatment of aneurysmal subarachnoid haemorrhage (SAH). The aim of this study was to identify AEs associated with microsurgical ...occlusion of ruptured aneurysms, as well as to analyse their risk factors and impact on functional outcome.
Patients with aneurysmal SAH admitted to the neurosurgical centres in Sweden were prospectively registered during a 3.5-year period (2014-2018). AEs were categorised as intraoperative or postoperative. A range of variables from patient history and SAH characteristics were explored as potential risk factors for an AE. Functional outcome was assessed approximately 1 year after the bleeding using the extended Glasgow Outcome Scale.
In total, 1037 patients were treated for ruptured aneurysms, of which, 322 patients were treated with microsurgery. There were 105 surgical AEs in 97 patients (30%); 94 were intraoperative AEs in 79 patients (25%). Aneurysm rerupture occurred in 43 patients (13%), temporary occlusion of the parent artery >5 min in 26 patients (8%) and adjacent vessel injury in 25 patients (8%). High Fisher grade and brain oedema on CT were related to increased risk of AEs. At follow-up, 38% of patients had unfavourable outcome. Patients suffering AEs were more likely to have unfavourable outcome (OR 2.3, 95% CI 1.10 to 4.69).
Intraoperative AEs occurred in 25% of patients treated with microsurgery for ruptured intracerebral aneurysm in this nationwide survey. Although most operated patients had favourable outcome, AEs were associated with increased risk of unfavourable outcome.
Summary
Kidney transplant recipients (KTRs) have an increased cancer risk compared to the general population, but absolute risks that better reflect the clinical impact of cancer are seldom ...estimated. All KTRs in Sweden, Norway, Denmark, and Finland, with a first transplantation between 1995 and 2011, were identified through national registries. Post‐transplantation cancer occurrence was assessed through linkage with cancer registries. We estimated standardized incidence ratios (SIR), absolute excess risks (AER), and cumulative incidence of cancer in the presence of competing risks. Overall, 12 984 KTRs developed 2215 cancers. The incidence rate of cancer overall was threefold increased (SIR 3.3, 95% confidence interval CI: 3.2–3.4). The AER of any cancer was 1560 cases (95% CI: 1468–1656) per 100 000 person‐years. The highest AERs were observed for nonmelanoma skin cancer (838, 95% CI: 778–901), non‐Hodgkin lymphoma (145, 95% CI: 119–174), lung cancer (126, 95% CI: 98.2–149), and kidney cancer (122, 95% CI: 98.0–149). The five‐ and ten‐year cumulative incidence of any cancer was 8.1% (95% CI: 7.6–8.6%) and 16.8% (95% CI: 16.0–17.6%), respectively. Excess cancer risks were observed among Nordic KTRs for a wide range of cancers. Overall, 1 in 6 patients developed cancer within ten years, supporting extensive post‐transplantation cancer vigilance.
Risks associated with metal contaminated sites are tightly linked to material leachability and contaminant mobility. In this study, metal solubility and transport were characterized within a glass ...waste landfill through i) lysimeter-collection of pore water and standardized batch leaching tests, ii) soil profiles extending from the landfill surface, through unsaturated soil underneath, and into the groundwater zone, and iii) groundwater samples upstream, at, and downstream of the landfill. The soil analyzes targeted both pseudo-total and geochemically active concentrations of contaminant metals (As, Cd, Pb, Sb) and basic soil geochemistry (pH, org. C, Fe, Mn). Water samples were analyzed for dissolved, colloid-bound and particulate metals, and speciation modelling of the aqueous phase was conducted. The results revealed a highly contaminated system, with mean metal concentrations in the waste zone between 90 and 250 times the regional background levels. Despite severe contamination of the waste zone and high geochemically active fractions (80–100%) of all contaminant metals as well as elevated concentrations in landfill pore water, the concentrations of Cd and Pb decrease abruptly at the transition between landfill and underlying natural soil and no indication of groundwater contamination was found. The efficient cation retention is likely due to the high pH. However, the sorption of As and Sb is weaker at such high pH, which explains their higher mobility from the pore water zone into groundwater. The field soil:solution partitioning (Kd) displayed a high spatial variability within the waste zone (the highest Kd variability was seen for Pb, ranging from 140 to 2,900,000 l kg−1), despite little variability in basic geochemical variables, which we suggest is due to waste material heterogeneity.
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•Metal solubility and transport from a contaminated landfill site were investigated.•Numerous methods were adopted in this high-resolution field- and laboratory study.•Efficient cation retention, likely due to high pH. As and Sb showed higher mobility.•Waste zone Kd values were highly variable but not correlated to basic geochemistry.•Soil metal concentrations decreased abruptly below the landfill.
Barley (Hordeum vulgare L.) is among the world's earliest domesticated and most important crop plants. It is diploid with a large haploid genome of 5.1 gigabases (Gb). Here we present an integrated ...and ordered physical, genetic and functional sequence resource that describes the barley gene-space in a structured whole-genome context. We developed a physical map of 4.98 Gb, with more than 3.90 Gb anchored to a high-resolution genetic map. Projecting a deep whole-genome shotgun assembly, complementary DNA and deep RNA sequence data onto this framework supports 79,379 transcript clusters, including 26,159 'high-confidence' genes with homology support from other plant genomes. Abundant alternative splicing, premature termination codons and novel transcriptionally active regions suggest that post-transcriptional processing forms an important regulatory layer. Survey sequences from diverse accessions reveal a landscape of extensive single-nucleotide variation. Our data provide a platform for both genome-assisted research and enabling contemporary crop improvement.
In patients with diabetes and obesity specifically, no studies have examined mortality after bariatric surgery. We did a nationwide study in Sweden to examine risks of cardiovascular disease and ...mortality in patients with obesity and diabetes who had undergone bariatric surgery (Roux-en-Y gastric bypass RYGB).
In this nationwide, matched, observational cohort study, we merged data for patients who had undergone RYGB registered in the Scandinavian Obesity Surgery Registry with other national databases, and identified matched controls (on the basis of sex, age, BMI, and calendar time year) who had not undergone bariatric surgery from the National Diabetes Registry. We assessed risks of cardiovascular disease and death using a Cox proportional-hazards regression model and other methods to examine the treatment effect while accounting for residual confounding. Primary outcomes were total mortality, cardiovascular death, and fatal or non-fatal myocardial infarction.
Between Jan 1, 2007, and Dec 31, 2014, we obtained data for 6132 patients who had undergone RYGB and 6132 control patients who had not. Median follow-up was 3·5 years (IQR 2·1-4·7). We noted a 58% relative risk reduction (hazard ratio HR 0·42, 95% CI 0·30-0·57; p<0·0001) in overall mortality in the RYGB group compared with the controls. The risk of fatal or non-fatal myocardial infarction was 49% lower (HR 0·51, 0·29-0·91; p=0·021) and that of cardiovascular death was 59% lower (0·41, 0·19-0·90; p=0·026) in the RYGB group than in the control group. 5 year absolute risks of death were 1·8% (95% CI 1·5-2·2) in the RYGB group and 5·8% (5·0-6·8) in the control group.
Our findings provide support for the benefits of RYGB surgery for patients with obesity and type 2 diabetes. The causes of these beneficial effects may be the weight reduction per se, changes in physiology and metabolism, improved care and treatment, improvements in lifestyle and risk factors, or combinations of these factors.
Swedish Association of Local Authorities and Regions and Region Västra Götaland.
Conifers have dominated forests for more than 200 million years and are of huge ecological and economic importance. Here we present the draft assembly of the 20-gigabase genome of Norway spruce ...(Picea abies), the first available for any gymnosperm. The number of well-supported genes (28,354) is similar to the >100 times smaller genome of Arabidopsis thaliana, and there is no evidence of a recent whole-genome duplication in the gymnosperm lineage. Instead, the large genome size seems to result from the slow and steady accumulation of a diverse set of long-terminal repeat transposable elements, possibly owing to the lack of an efficient elimination mechanism. Comparative sequencing of Pinus sylvestris, Abies sibirica, Juniperus communis, Taxus baccata and Gnetum gnemon reveals that the transposable element diversity is shared among extant conifers. Expression of 24-nucleotide small RNAs, previously implicated in transposable element silencing, is tissue-specific and much lower than in other plants. We further identify numerous long (>10,000 base pairs) introns, gene-like fragments, uncharacterized long non-coding RNAs and short RNAs. This opens up new genomic avenues for conifer forestry and breeding.
The oxygen-isotope records from Greenland ice cores show a very strong, reproducible pattern of alternation between warm Greenland Interstadials (GI) and cold Greenland Stadials (GS) at ...millennial-scale during the last glacial period. Here we summarise what is known about this variability from ice core records. The typical cycle has a sawtooth pattern, with a very rapid warming event (occurring in a few decades), a slow cooling trend, and then a final fast cooling. 25 such events have been numbered in the last glacial. The recent GICC05 age scale provides the best available age scale that can be directly applied to this stratigraphy, and we summarise the timing of the warming events, and the length and strength of each event. The Greenland stratigraphy can be transferred to other records if we make assumptions about the contemporaneous nature of rapid events in different archives. Other parameters, such as the snow accumulation rate, and the concentration of terrestrial dust and sea salt recorded in the Greenland cores, also show a strong contrasting pattern between GI and GS. Methane concentrations are generally high during GI and lower during GS, with the increase from GS to GI occurring within a century. Antarctic ice cores show a different pattern: each GI has an Antarctic counterpart, but Antarctica appears to warm while Greenland is in a GS, and cool during GI. These changes are consistent with a mechanism involving ocean heat transport, but the rapid nature of warmings poses a challenge for modellers, while the rapid methane changes pose questions about the pattern of land biosphere emissions during the glacial that are also relevant for understanding glacial-interglacial methane variability.
The cytoplasmic phosphatase PTPN22 (protein tyrosine phosphatase nonreceptor type 22) plays a key role in regulating lymphocyte homeostasis, which ensures that the total number of lymphocytes in the ...periphery remains relatively constant. Mutations in PTPN22 confer an increased risk of developing autoimmune diseases; however, the precise function of PTPN22 and how mutations contribute to autoimmunity remain controversial. Loss-of-function mutations in PTPN22 are associated with increased numbers of effector T cells and autoreactive B cells in humans and mice; however, the complete absence of PTPN22 in mice does not result in spontaneous autoimmunity. We found that PTPN22 was a key regulator of regulatory T cell (T(reg)) function that fine-tuned the signaling of the T cell receptor and integrins. PTPN22(-/-) T(regs) were more effective at immunosuppression than were wild-type T(regs), and they suppressed the activity of PTPN22(-/-) effector T cells, preventing autoimmunity. Compared to wild-type T(regs), PTPN22(-/-) T(regs) produced increased amounts of the immunosuppressive cytokine interleukin-10 and had enhanced adhesive properties mediated by the integrin lymphocyte function-associated antigen-1, processes that are critical for T(reg) function. This previously undiscovered role of PTPN22 in regulating integrin signaling and T(reg) function suggests that PTPN22 may be a useful therapeutic target for manipulating T(reg) function in human disease.
Alzheimer's disease (AD) is a neurodegenerative disorder that develops over decades. Glial cells, including astrocytes are tightly connected to the AD pathogenesis, but their impact on disease ...progression is still unclear. Our previous data show that astrocytes take up large amounts of aggregated amyloid-beta (Aβ) but are unable to successfully degrade the material, which is instead stored intracellularly. The aim of the present study was to analyze the astrocytic Aβ deposits composition in detail in order to understand their role in AD propagation. For this purpose, human induced pluripotent cell (hiPSC)-derived astrocytes were exposed to sonicated Aβ42 fibrils and magnetic beads. Live cell imaging and immunocytochemistry confirmed that the ingested Aβ aggregates and beads were transported to the same lysosomal compartments in the perinuclear region, which allowed us to successfully isolate the Aβ deposits from the astrocytes. Using a battery of experimental techniques, including mass spectrometry, western blot, ELISA and electron microscopy we demonstrate that human astrocytes truncate and pack the Aβ aggregates in a way that makes them highly resistant. Moreover, the astrocytes release specifically truncated forms of Aβ via different routes and thereby expose neighboring cells to pathogenic proteins. Taken together, our study establishes a role for astrocytes in mediating Aβ pathology, which could be of relevance for identifying novel treatment targets for AD.
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•Human iPSC-derived astrocytes engulf large amounts of aggregated Aβ, but do not effectively degrade the ingested material.•Using magnetic beads, we could successfully isolate the intracellular Aβ inclusions and analyze their content.•The astrocytes process, pack and truncate the Aβ aggregates in a way that makes them highly resistant.•The Aβ-containing astrocytes release modified Aβ species via direct secretion and via extracellular vesicles.
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