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  • Olalde, I., et al. (author)
  • The Beaker phenomenon and the genomic transformation of northwest Europe
  • 2018
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 555:7695, s. 190-196
  • Journal article (peer-reviewed)abstract
    • From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain's gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries.
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  • Peripato, Vinicius, et al. (author)
  • More than 10,000 pre-Columbian earthworks are still hidden throughout Amazonia
  • 2023
  • In: Science (New York, N.Y.). - 1095-9203. ; 382:6666, s. 103-109
  • Journal article (peer-reviewed)abstract
    • Indigenous societies are known to have occupied the Amazon basin for more than 12,000 years, but the scale of their influence on Amazonian forests remains uncertain. We report the discovery, using LIDAR (light detection and ranging) information from across the basin, of 24 previously undetected pre-Columbian earthworks beneath the forest canopy. Modeled distribution and abundance of large-scale archaeological sites across Amazonia suggest that between 10,272 and 23,648 sites remain to be discovered and that most will be found in the southwest. We also identified 53 domesticated tree species significantly associated with earthwork occurrence probability, likely suggesting past management practices. Closed-canopy forests across Amazonia are likely to contain thousands of undiscovered archaeological sites around which pre-Columbian societies actively modified forests, a discovery that opens opportunities for better understanding the magnitude of ancient human influence on Amazonia and its current state.
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  • The Seventeenth Data Release of the Sloan Digital Sky Surveys : Complete Release of MaNGA, MaStar, and APOGEE-2 Data
  • 2022
  • In: Astrophysical Journal Supplement Series. - : Institute of Physics (IOP). - 0067-0049 .- 1538-4365. ; 259:2
  • Journal article (peer-reviewed)abstract
    • This paper documents the seventeenth data release (DR17) from the Sloan Digital Sky Surveys; the fifth and final release from the fourth phase (SDSS-IV). DR17 contains the complete release of the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, which reached its goal of surveying over 10,000 nearby galaxies. The complete release of the MaNGA Stellar Library accompanies this data, providing observations of almost 30,000 stars through the MaNGA instrument during bright time. DR17 also contains the complete release of the Apache Point Observatory Galactic Evolution Experiment 2 survey that publicly releases infrared spectra of over 650,000 stars. The main sample from the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), as well as the subsurvey Time Domain Spectroscopic Survey data were fully released in DR16. New single-fiber optical spectroscopy released in DR17 is from the SPectroscipic IDentification of ERosita Survey subsurvey and the eBOSS-RM program. Along with the primary data sets, DR17 includes 25 new or updated value-added catalogs. This paper concludes the release of SDSS-IV survey data. SDSS continues into its fifth phase with observations already underway for the Milky Way Mapper, Local Volume Mapper, and Black Hole Mapper surveys.
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  • Mohsen-Kanson, T., et al. (author)
  • Differentiation of Human Induced Pluripotent Stem Cells into Brown and White Adipocytes: Role of Pax3
  • 2014
  • In: Stem Cells. - : Oxford University Press (OUP). - 1066-5099 .- 1549-4918. ; 32:6, s. 1459-1467
  • Journal article (peer-reviewed)abstract
    • Identification of molecular mechanisms involved in generation of different types of adipocytes is progressing substantially in mice. However, much less is known regarding characterization of brown (BAP) and white adipocyte progenitors (WAPs) in humans, highlighting the need for an in vitro model of human adipocyte development. Here, we report a procedure to selectively derive BAP and WAPs from human-induced pluripotent stem cells. Molecular characterization of APs of both phenotypes revealed that BMP4, Hox8, Hoxc9, and HoxA5 genes were specifically expressed in WAPs, whereas expression of PRDM16, Dio2, and Pax3 marked BAPs. We focused on Pax3 and we showed that expression of this transcription factor was enriched in human perirenal white adipose tissue samples expressing UCP1 and in human classical brown fat. Finally, functional experiments indicated that Pax3 was a critical player of human AP fate as its ectopic expression led to convert WAPs into brown-like APs. Together, these data support a model in which Pax3 is a new marker of human BAPs and a molecular mediator of their fate. The findings of this study could lead to new anti-obesity therapies based on the recruitment of APs and constitute a platform for investigating in vitro the developmental origins of human white and brown adipocytes.
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  • Alexanderson, H, et al. (author)
  • Muscle Strength and Muscle Endurance During the First Year of Treatment of Polymyositis and Dermatomyositis: A Prospective Study
  • 2018
  • In: The Journal of rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 45:4, s. 538-546
  • Journal article (peer-reviewed)abstract
    • To investigate muscle impairment (isometric and dynamic) and disease activity during the first year after diagnosis of polymyositis (PM) and dermatomyositis (DM), and to study the relationship between muscle impairment, patient-reported health, and disease activity.Methods.Seventy-two patients enrolled in the Swedish Myositis Register, 2003–2010, were followed prospectively. The Manual Muscle test (MMT-8; isometric muscle strength), the Functional Index of myositis test (FI-2; dynamic, repetitive muscle function), and disease activity (6-item core set) were retrieved at the time of diagnosis, and after 6 and 12 months. Self-reported health (Medical Outcomes Study Short Form-36; SF-36) was retrieved at 12 months.Results.At the time of diagnosis, median (Q1–Q3) for the FI-2 was 27.2% (7.9–60.5%) of maximal score compared to 93.8% (92.5–98.8%) of maximal MMT-8. At 12 months, the FI-2 and the MMT-8 improved to 29.4% (16.5–60.7%; p < 0.05) and 96.1% (88.1–99.4%), respectively (p < 0.01). At 12 months, 45% of patients improved ≥ 20%, and 27% worsened ≥ 20% in FI-2 score, while 10% improved ≥ 20% in MMT-8. Physician’s global visual analog scale (VAS), Health Assessment Questionnaire, and creatine phosphokinase levels improved significantly at 12 months (p < 0.05–0.001) while patient’s global and extramuscular VAS remained unchanged. The SF-36 physical function correlated strongly with the FI-2 (rs = 0.74; CI 0.55–0.85) and moderately with the MMT (rs = 0.54; CI 0.27–0.73), with lower correlations between muscle function and other SF-36 domains.Conclusion.Patients with PM/DM were characterized by impaired dynamic repetitive muscle function (DRMF) that correlated well with patient-reported physical function. Assessment of DRMF adds information regarding muscle impairment in these patients.
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  • Beck, Dani, et al. (author)
  • Adipose tissue distribution from body MRI is associated with cross-sectional and longitudinal brain age in adults
  • 2022
  • In: NeuroImage. - : Elsevier Science Ltd. - 2213-1582. ; 33
  • Journal article (peer-reviewed)abstract
    • There is an intimate body-brain connection in ageing, and obesity is a key risk factor for poor cardiometabolic health and neurodegenerative conditions. Although research has demonstrated deleterious effects of obesity on brain structure and function, the majority of studies have used conventional measures such as waist-to-hip ratio, waist circumference, and body mass index. While sensitive to gross features of body composition, such global anthropometric features fail to describe regional differences in body fat distribution and composition. The sample consisted of baseline brain magnetic resonance imaging (MRI) acquired from 790 healthy participants aged 18-94 years (mean +/- standard deviation (SD) at baseline: 46.8 +/- 16.3), and follow-up brain MRI collected from 272 of those individuals (two time-points with 19.7 months interval, on average (min = 9.8, max = 35.6). Of the 790 included participants, cross-sectional body MRI data was available from a subgroup of 286 participants, with age range 19-86 (mean = 57.6, SD = 15.6). Adopting a mixed cross-sectional and longitudinal design, we investigated cross-sectional body magnetic resonance imaging measures of adipose tissue distribution in relation to longitudinal brain structure using MRI-based morphometry (T1) and diffusion tensor imaging (DTI). We estimated tissue-specific brain age at two time points and performed Bayesian multilevel modelling to investigate the associations between adipose measures at follow-up and brain age gap (BAG) - the difference between actual age and the prediction of the brains biological age - at baseline and follow-up. We also tested for interactions between BAG and both time and age on each adipose measure. The results showed credible associations between T1-based BAG and liver fat, muscle fat infiltration (MFI), and weight-to-muscle ratio (WMR), indicating older-appearing brains in people with higher measures of adipose tissue. Longitudinal evidence supported interaction effects between time and MFI and WMR on T1-based BAG, indicating accelerated ageing over the course of the study period in people with higher measures of adipose tissue. The results show that specific measures of fat distribution are associated with brain ageing and that different compartments of adipose tissue may be differentially linked with increased brain ageing, with potential to identify key processes involved in age-related transdiagnostic disease processes.
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  • Brunet-Ratnasingham, Elsa, et al. (author)
  • Sustained IFN signaling is associated with delayed development of SARS-CoV-2-specific immunity.
  • 2024
  • In: Nature Communications. - 2041-1723. ; 15:1, s. 4177-
  • Journal article (peer-reviewed)abstract
    • Plasma RNAemia, delayed antibody responses and inflammation predict COVID-19 outcomes, but the mechanisms underlying these immunovirological patterns are poorly understood. We profile 782 longitudinal plasma samples from 318 hospitalized patients with COVID-19. Integrated analysis using k-means reveals four patient clusters in a discovery cohort: mechanically ventilated critically-ill cases are subdivided into good prognosis and high-fatality clusters (reproduced in a validation cohort), while non-critical survivors segregate into high and low early antibody responders. Only the high-fatality cluster is enriched for transcriptomic signatures associated with COVID-19 severity, and each cluster has distinct RBD-specific antibody elicitation kinetics. Both critical and non-critical clusters with delayed antibody responses exhibit sustained IFN signatures, which negatively correlate with contemporaneous RBD-specific IgG levels and absolute SARS-CoV-2-specific B and CD4+ T cell frequencies. These data suggest that the "Interferon paradox" previously described in murine LCMV models is operative in COVID-19, with excessive IFN signaling delaying development of adaptive virus-specific immunity.
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  • Dehnavi, Gholamali Z., et al. (author)
  • Fractionation of the main components of barley spent grains from a microbrewery
  • 2011
  • In: Cellulose Chemistry and Technology. - 0576-9787. ; 45:5-6, s. 339-345
  • Journal article (peer-reviewed)abstract
    • The chemical composition of barley spent grains generated in a microbrewery and their fractionation by acid hydrolysis and delignification were investigated. The material contained high amount of carbohydrates (60%), while its lignin content was lower than that reported for other sorts of barley spent grains. Different dilute-acid hydrolysis methods were evaluated for separating the main components of the spent grains, without affecting the sugars generated by starch hydrolysis. The utilization of a two-step dilute-acid hydrolysis approach allowed to hydrolyse starch in a first step, at 100 ºC, and hemicelluloses in a second step, at 121 ºC. Acetosolv and alkaline delignification were used for solubilising the lignin fraction. A higher lignin solubilisation (95% of the lignin contained in the raw material) was achieved after alkaline delignification, whereas only 34% of the initial lignin was removed by direct acetosolv. When the acetosolv treatment was combined with acid hydrolysis, lignin solubilisation increased to 74%. Lignin was precipitated from the liquors at recovery rates from 40 to 93%, as depending on the hydrolysis/delignification method used.
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  • Deshpande, Prasannakumar, et al. (author)
  • Protein synthesis is suppressed in sporadic and familial Parkinson’s disease by LRRK2
  • 2020
  • In: FASEB Journal. - 0892-6638. ; 34:11, s. 14217-14233
  • Journal article (peer-reviewed)abstract
    • Gain of function LRRK2-G2019S is the most frequent mutation found in familial and sporadic Parkinson's disease. It is expected therefore that understanding the cellular function of LRRK2 will provide insight on the pathological mechanism not only of inherited Parkinson's, but also of sporadic Parkinson's, the more common form. Here, we show that constitutive LRRK2 activity controls nascent protein synthesis in rodent neurons. Specifically, pharmacological inhibition of LRRK2, Lrrk2 knockdown or Lrrk2 knockout, all lead to increased translation. In the rotenone model for sporadic Parkinson's, LRRK2 activity increases, dopaminergic neuron translation decreases, and the neurites atrophy. All are prevented by LRRK2 inhibitors. Moreover, in striatum and substantia nigra of rotenone treated rats, phosphorylation changes are observed on eIF2α-S52(↑), eIF2s2-S2(↓), and eEF2-T57(↑) in directions that signify protein synthesis arrest. Significantly, translation is reduced by 40% in fibroblasts from Parkinson's patients (G2019S and sporadic cases alike) and this is reversed upon LRRK2 inhibitor treatment. In cells from multiple system atrophy patients, translation is unchanged suggesting that repression of translation is specific to Parkinson's disease. These findings indicate that repression of translation is a proximal function of LRRK2 in Parkinson's pathology.
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  • Gershtein, Eli Crater, et al. (author)
  • High-resolution mapping and analysis of shiny grooved rock surfaces: The case study of the Skiles Shelter, Lower Pecos, Texas
  • 2017
  • In: Quaternary International. - 1040-6182. ; 439, s. 69-82
  • Research review (peer-reviewed)abstract
    • Shiny grooved rock surfaces found in archaeological sites are common across west Texas and the Southwest (U.S.). In most cases they are cursorily described, with very little in terms of detailed characterization and analysis. Interpretations regarding the meaning of the grooves include fertility rituals and functional use (e.g., bone tool or axe polishing), while the formation of the shiny surface has been attributed to lichen, foot or hand traffic, and hide or plant processing. In the Lower Pecos region (Texas), such remains are common in rockshelters. In several cases, there is only one such surface at a prominent location within the site, commonly associated with bedrock features (mortars, slicks, etc.). We used Structure from Motion (SfM) to document, characterize and analyze more than 700 elongated grooves and incisions concentrated on one shiny surface, at Skiles Shelter. All were mapped, and the larger grooves were also measured and studied using macro-lens and microscope photos. The direction and sequence of engraving were reconstructed, with evidence for most grooves and incisions being earlier than the shiny cover. The incorporation of small pits with the engravings was established. Although organic residues were retrieved from several bedrock features at the site, no distinct chemical signature was identified from the shiny surface. We could not ascertain the origin of the shiny crust, and based on other works and our observations we suggest that hand or foot traffic, hide working and plant fiber processing are the most likely explanations.
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  • Hong, Ye, et al. (author)
  • PhosPiR : an automated phosphoproteomic pipeline in R
  • 2022
  • In: Briefings in Bioinformatics. - : Oxford University Press (OUP). - 1467-5463 .- 1477-4054. ; 23:1
  • Journal article (peer-reviewed)abstract
    • Large-scale phosphoproteome profiling using mass spectrometry (MS) provides functional insight that is crucial for disease biology and drug discovery. However, extracting biological understanding from these data is an arduous task requiring multiple analysis platforms that are not adapted for automated high-dimensional data analysis. Here, we introduce an integrated pipeline that combines several R packages to extract high-level biological understanding from large-scale phosphoproteomic data by seamless integration with existing databases and knowledge resources. In a single run, PhosPiR provides data clean-up, fast data overview, multiple statistical testing, differential expression analysis, phosphosite annotation and translation across species, multilevel enrichment analyses, proteome-wide kinase activity and substrate mapping and network hub analysis. Data output includes graphical formats such as heatmap, box-, volcano- and circos-plots. This resource is designed to assist proteome-wide data mining of pathophysiological mechanism without a need for programming knowledge.
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  • Junker, Robert R., et al. (author)
  • Covariation and phenotypic integration in chemical communication displays : Biosynthetic constraints and eco-evolutionary implications
  • 2018
  • In: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 220:3, s. 739-749
  • Journal article (peer-reviewed)abstract
    • Chemical communication is ubiquitous. The identification of conserved structural elements in visual and acoustic communication is well established, but comparable information on chemical communication displays (CCDs) is lacking. We assessed the phenotypic integration of CCDs in a meta-analysis to characterize patterns of covariation in CCDs and identified functional or biosynthetically constrained modules. Poorly integrated plant CCDs (i.e. low covariation between scent compounds) support the notion that plants often utilize one or few key compounds to repel antagonists or to attract pollinators and enemies of herbivores. Animal CCDs (mostly insect pheromones) were usually more integrated than those of plants (i.e. stronger covariation), suggesting that animals communicate via fixed proportions among compounds. Both plant and animal CCDs were composed of modules, which are groups of strongly covarying compounds. Biosynthetic similarity of compounds revealed biosynthetic constraints in the covariation patterns of plant CCDs. We provide a novel perspective on chemical communication and a basis for future investigations on structural properties of CCDs. This will facilitate identifying modules and biosynthetic constraints that may affect the outcome of selection and thus provide a predictive framework for evolutionary trajectories of CCDs in plants and animals.
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  • Kujawska, Agnieszka, et al. (author)
  • Prospective association of occupational and leisure-time physical activity with orthostatic blood pressure changes in older adults
  • 2023
  • In: Scientific Reports. - : Springer. - 2045-2322. ; 13:1
  • Journal article (peer-reviewed)abstract
    • Orthostatic hypotension (OH) is common in older people. We examined the influence of self-reported occupational-related physical activity (PA) and leisure-time physical exercise (PE) on orthostatic response in a sample of older people over a 2 year period. Supine and orthostatic systolic blood pressure (sBP), diastolic blood pressure (dBP), and mean blood pressure (mBP) were assessed in response to Active Stand (AS) test in 205 older subjects (> 60 years old) at baseline and 2-year follow-up. OH was found in 24 subjects (11.71%) at baseline and 20 subjects (9.76%) after 2 years, with a significant degree of variability in the occurrence of OH after 2 years. Twenty-two subjects who had OH at baseline were free of it after 2 years, two subjects had persistent OH at baseline and after 2 years. After 2 years, adults with occupational PA showed no significant decrease of blood pressure in response to AS test, while lack of undertaking an occupation-related PA was significantly related with a greater decrease in sBP and mBP in response to AS testing in the 1st min. Occupation-related PA and leisure-time-related PE were related to an increase in the response of BP on AS in change between baseline and after 2 years. High between-subjects variance in OH over 2 years was noted. Occupations that involved continuous physical activity and leisure-time physical exercise in middle age were both protective for BP decline on orthostatic stress test within 2 years.
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  • Lloyd-Hughes, J., et al. (author)
  • The 2021 ultrafast spectroscopic probes of condensed matter roadmap
  • 2021
  • In: Journal of Physics. - : Institute of Physics Publishing (IOPP). - 0953-8984 .- 1361-648X. ; 33:35
  • Research review (peer-reviewed)abstract
    • In the 60 years since the invention of the laser, the scientific community has developed numerous fields of research based on these bright, coherent light sources, including the areas of imaging, spectroscopy, materials processing and communications. Ultrafast spectroscopy and imaging techniques are at the forefront of research into the light-matter interaction at the shortest times accessible to experiments, ranging from a few attoseconds to nanoseconds. Light pulses provide a crucial probe of the dynamical motion of charges, spins, and atoms on picosecond, femtosecond, and down to attosecond timescales, none of which are accessible even with the fastest electronic devices. Furthermore, strong light pulses can drive materials into unusual phases, with exotic properties. In this roadmap we describe the current state-of-the-art in experimental and theoretical studies of condensed matter using ultrafast probes. In each contribution, the authors also use their extensive knowledge to highlight challenges and predict future trends.
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  • Moss, Brian D., et al. (author)
  • Climate change and the future of freshwater biodiversity in Europe : a primer for policy-makers
  • 2009
  • In: Freshwater Reviews. - : Freshwater Biological Association. - 1755-084X. ; 2:2, s. 103-130
  • Journal article (peer-reviewed)abstract
    • Earth's climate is changing, and by the end of the 21st century in Europe, average temperatures are likely to have risen by at least 2 °C, and more likely 4 °C with associated effects on patterns of precipitation and the frequency of extreme weather events. Attention among policy-makers is divided about how to minimise the change, how to mitigate its effects, how to maintain the natural resources on which societies depend and how to adapt human societies to the changes. Natural systems are still seen, through a long tradition of conservation management that is largely species-based, as amenable to adaptive management, and biodiversity, mostly perceived as the richness of plant and vertebrate communities, often forms a focus for planning. We argue that prediction of particular species changes will be possible only in a minority of cases but that prediction of trends in general structure and operation of four generic freshwater ecosystems (erosive rivers, depositional floodplain rivers, shallow lakes and deep lakes) in three broad zones of Europe (Mediterranean, Central and Arctic-Boreal) is practicable. Maintenance and rehabilitation of ecological structures and operations will inevitably and incidentally embrace restoration of appropriate levels of species biodiversity. Using expert judgement, based on an extensive literature, we have outlined, primarily for lay policy makers, the pristine features of these systems, their states under current human impacts, how these states are likely to alter with a warming of 2 °C to 4 °C and what might be done to mitigate this. We have avoided technical terms in the interests of communication, and although we have included full referencing as in academic papers, we have eliminated degrees of detail that could confuse broad policy-making 
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  • Schindler, Louise S., et al. (author)
  • Associations between abdominal adipose tissue, reproductive span, and brain characteristics in post-menopausal women
  • 2022
  • In: NeuroImage. - : ELSEVIER SCI LTD. - 2213-1582. ; 36
  • Journal article (peer-reviewed)abstract
    • The menopause transition involves changes in oestrogens and adipose tissue distribution, which may influence female brain health post-menopause. Although increased central fat accumulation is linked to risk of cardiometabolic diseases, adipose tissue also serves as the primary biosynthesis site of oestrogens post-menopause. It is unclear whether different types of adipose tissue play diverging roles in female brain health post-menopause, and whether this depends on lifetime oestrogen exposure, which can have lasting effects on the brain and body even after menopause. Using the UK Biobank sample, we investigated associations between brain characteristics and visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (ASAT) in 10,251 post-menopausal females, and assessed whether the relationships varied depending on length of reproductive span (age at menarche to age at menopause). To parse the effects of common genetic variation, we computed polygenic scores for reproductive span. The results showed that higher VAT and ASAT were both associated with higher grey and white matter brain age, and greater white matter hyperintensity load. The associations varied positively with reproductive span, indicating more prominent associations between adipose tissue and brain measures in females with a longer reproductive span. The effects were in general small, but could not be fully explained by genetic variation or relevant confounders. Our findings indicate that associations between abdominal adipose tissue and brain health post-menopause may partly depend on individual differences in cumulative oestrogen exposure during reproductive years, emphasising the complexity of neural and endocrine ageing processes in females.
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  • Voss, Erica A, et al. (author)
  • Contextualising adverse events of special interest to characterise the baseline incidence rates in 24 million patients with COVID-19 across 26 databases: a multinational retrospective cohort study.
  • 2023
  • In: EClinicalMedicine. - 2589-5370. ; 58
  • Journal article (peer-reviewed)abstract
    • Adverse events of special interest (AESIs) were pre-specified to be monitored for the COVID-19 vaccines. Some AESIs are not only associated with the vaccines, but with COVID-19. Our aim was to characterise the incidence rates of AESIs following SARS-CoV-2 infection in patients and compare these to historical rates in the general population.A multi-national cohort study with data from primary care, electronic health records, and insurance claims mapped to a common data model. This study's evidence was collected between Jan 1, 2017 and the conclusion of each database (which ranged from Jul 2020 to May 2022). The 16 pre-specified prevalent AESIs were: acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, deep vein thrombosis, disseminated intravascular coagulation, encephalomyelitis, Guillain- Barré syndrome, haemorrhagic stroke, non-haemorrhagic stroke, immune thrombocytopenia, myocarditis/pericarditis, narcolepsy, pulmonary embolism, transverse myelitis, and thrombosis with thrombocytopenia. Age-sex standardised incidence rate ratios (SIR) were estimated to compare post-COVID-19 to pre-pandemic rates in each of the databases.Substantial heterogeneity by age was seen for AESI rates, with some clearly increasing with age but others following the opposite trend. Similarly, differences were also observed across databases for same health outcome and age-sex strata. All studied AESIs appeared consistently more common in the post-COVID-19 compared to the historical cohorts, with related meta-analytic SIRs ranging from 1.32 (1.05 to 1.66) for narcolepsy to 11.70 (10.10 to 13.70) for pulmonary embolism.Our findings suggest all AESIs are more common after COVID-19 than in the general population. Thromboembolic events were particularly common, and over 10-fold more so. More research is needed to contextualise post-COVID-19 complications in the longer term.None.
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