| 1. |
- Proletov, Ian, et al.
(författare)
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Primary and secondary glomerulonephritides 1.
- 2014
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Ingår i: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385. ; 29 Suppl 3:May, s. 186-200
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Ferrari, Raffaele, et al.
(författare)
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Frontotemporal dementia and its subtypes: a genome-wide association study.
- 2014
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Ingår i: Lancet Neurology. - 1474-4465. ; 13:7, s. 686-699
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72-have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder.
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| 3. |
- Chen, Qiao Sen, et al.
(författare)
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A machine learning based approach to identify carotid subclinical atherosclerosis endotypes
- 2023
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Ingår i: Cardiovascular Research. - : OXFORD UNIV PRESS. - 0008-6363 .- 1755-3245. ; 119:16, s. 2594-2606
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Tidskriftsartikel (refereegranskat)abstract
- Aims To define endotypes of carotid subclinical atherosclerosis. Methods and results We integrated demographic, clinical, and molecular data (n = 124) with ultrasonographic carotid measurements from study participants in the IMPROVE cohort (n = 3340). We applied a neural network algorithm and hierarchical clustering to identify carotid atherosclerosis endotypes. A measure of carotid subclinical atherosclerosis, the c-IMTmean-max, was used to extract atherosclerosis-related features and SHapley Additive exPlanations (SHAP) to reveal endotypes. The association of endotypes with carotid ultrasonographic measurements at baseline, after 30 months, and with the 3-year atherosclerotic cardiovascular disease (ASCVD) risk was estimated by linear (& beta;, SE) and Cox [hazard ratio (HR), 95% confidence interval (CI)] regression models. Crude estimates were adjusted by common cardiovascular risk factors, and baseline ultrasonographic measures. Improvement in ASCVD risk prediction was evaluated by C-statistic and by net reclassification improvement with reference to SCORE2, c-IMTmean-max, and presence of carotid plaques. An ensemble stacking model was used to predict endotypes in an independent validation cohort, the PIVUS (n = 1061). We identified four endotypes able to differentiate carotid atherosclerosis risk profiles from mild (endotype 1) to severe (endotype 4). SHAP identified endotype-shared variables (age, biological sex, and systolic blood pressure) and endotype-specific biomarkers. In the IMPROVE, as compared to endotype 1, endotype 4 associated with the thickest c-IMT at baseline (& beta;, SE) 0.36 (0.014), the highest number of plaques 1.65 (0.075), the fastest c-IMT progression 0.06 (0.013), and the highest ASCVD risk (HR, 95% CI) (1.95, 1.18-3.23). Baseline and progression measures of carotid subclinical atherosclerosis and ASCVD risk were associated with the predicted endotypes in the PIVUS. Endotypes consistently improved measures of ASCVD risk discrimination and reclassification in both study populations. Conclusions We report four replicable subclinical carotid atherosclerosis-endotypes associated with progression of atherosclerosis and ASCVD risk in two independent populations. Our approach based on endotypes can be applied for precision medicine in ASCVD prevention.
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| 4. |
- Chetaille, Philippe, et al.
(författare)
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Mutations in SGOL1 cause a novel cohesinopathy affecting heart and gut rhythm
- 2014
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46:11, s. 1245-1249
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Tidskriftsartikel (refereegranskat)abstract
- The pacemaking activity of specialized tissues in the heart and gut results in lifelong rhythmic contractions. Here we describe a new syndrome characterized by Chronic Atrial and Intestinal Dysrhythmia, termed CAID syndrome, in 16 French Canadians and 1 Swede. We show that a single shared homozygous founder mutation in SGOL1, a component of the cohesin complex, causes CAID syndrome. Cultured dermal fibroblasts from affected individuals showed accelerated cell cycle progression, a higher rate of senescence and enhanced activation of TGF-beta signaling. Karyotypes showed the typical railroad appearance of a centromeric cohesion defect. Tissues derived from affected individuals displayed pathological changes in both the enteric nervous system and smooth muscle. Morpholino-induced knockdown of sgol1 in zebrafish recapitulated the abnormalities seen in humans with CAID syndrome. Our findings identify CAID syndrome as a novel generalized dysrhythmia, suggesting a new role for SGOL1 and the cohesin complex in mediating the integrity of human cardiac and gut rhythm.
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| 5. |
- Cristina Baglio, Maria, et al.
(författare)
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A Wildly Flickering Jet in the Black Hole X-Ray Binary MAXI J1535-571
- 2018
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 867:2
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Tidskriftsartikel (refereegranskat)abstract
- We report on the results of optical, near-infrared (NIR), and mid-infrared observations of the black hole X-ray binary candidate (BHB) MAXI J1535-571 during its 2017/2018 outburst. During the first part of the outburst (MJD 58004-58012), the source shows an optical-NIR spectrum that is consistent with an optically thin synchrotron power law from a jet. After MJD 58015, however, the source faded considerably, the drop in flux being much more evident at lower frequencies. Before the fading, we measure a dereddened flux density of 100 mJy in the mid-infrared, making MAXI J1535-571 one of the brightest mid-infrared BHBs known so far. A significant softening of the X-ray spectrum is evident contemporaneous with the infrared fade. We interpret it as being due to the suppression of the jet emission, similar to the accretion-ejection coupling seen in other BHBs. However, MAXI J1535-571 did not transition smoothly to the soft state, instead showing X-ray hardness deviations associated with infrared flaring. We also present the first mid-IR variability study of a BHB on minute timescales, with a fractional rms variability of the light curves of ∼15%-22%, which is similar to that expected from the internal shock jet model, and much higher than the optical fractional rms (≲7%). These results represent an excellent case of multiwavelength jet spectral timing and demonstrate how rich, multiwavelength time-resolved data of X-ray binaries over accretion state transitions can help in refining models of the disk-jet connection and jet launching in these systems.
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| 6. |
- Dittenber, Benjamin, et al.
(författare)
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Accretion-driven Sources in Spatially Resolved Lyα Emitters
- 2020
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 890:1
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Tidskriftsartikel (refereegranskat)abstract
- Lyα emission is a standard tracer of starburst galaxies at high redshift. However, a number of local Lyα emitters (LAEs) are X-ray sources, suggesting a possible origin of Lyα photons other than young, hot stars, and which may be active at much later ages relative to the parent starburst. Resolved, nearby LAEs offer the opportunity to discriminate between diffuse X-ray emission arising from supernova-heated gas, high-mass X-ray binaries (HMXBs), or low-luminosity active galactic nuclei (LLAGN). We examine archival X-ray imaging from Chandra and XMM-Newton for 11 galaxies with spatially resolved Lyα imaging to determine the luminosity, morphology, and spectral hardness of the X-ray sources. The data are consistent with 9 of the 12, bright Lyα sources being driven by luminous, >10(40) erg s(-1) X-ray sources. Half of the eight Chandra sources are unresolved. The data suggest that nuclear activity, whether from LLAGN or nuclear starbursts, may play an important role in Lyα emission. Our results also suggest a significant link between Lyα emission and HMXBs, ultraluminous X-ray sources, and/or LLAGN, which would imply that Lyα may be generated over timescales 1-2 orders of magnitude longer than produced by photoionization from OB stars. This highlights a critical need to quantify the relative contributions of different sources across cosmic time, to interpret Lyα observations and the resulting properties of distant galaxies.
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| 7. |
- Echiburu-Trujillo, Constanza, et al.
(författare)
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Chasing the Break: Tracing the Full Evolution of a Black Hole X-Ray Binary Jet with Multiwavelength Spectral Modeling
- 2024
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Ingår i: Astrophysical Journal. - 1538-4357 .- 0004-637X. ; 962:2
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Tidskriftsartikel (refereegranskat)abstract
- Black hole (BH) X-ray binaries (XRBs) are ideal targets to study the connection between accretion inflow and jet outflow. Here we present quasi-simultaneous, multiwavelength observations of the Galactic BH system MAXI J1820+070, throughout its 2018-2019 outburst. Our data set includes coverage from the radio through X-ray bands from 17 different instruments/telescopes, and encompasses 19 epochs over a 7 month period, resulting in one of the most well-sampled multiwavelength data sets of a BH XRB outburst to date. With our data, we compile and model the broadband spectra of this source using a phenomenological model that includes emission from the jet, a companion star, and an accretion flow. This modeling allows us to track the evolution of the spectral break in the jet spectrum, a key observable that samples the jet launching region. We find that the spectral break location changes over at least approximate to 3 orders of magnitude in electromagnetic frequency over this period. Using these spectral break measurements, we link the full cycle of jet behavior, including the rising, quenching, and reignition, to the changing accretion flow properties as the source evolves through its different accretion states. Our analysis shows consistent jet behavior with other sources in similar phases of their outbursts, reinforcing the idea that jet quenching and recovery may be a global feature of BH XRB systems in outburst. Our results also provide valuable evidence supporting a close connection between the geometry of the inner accretion flow and the base of the jet.
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| 8. |
- El Bairi, Khalid, et al.
(författare)
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The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group
- 2021
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Ingår i: npj Breast Cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 7:1
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Forskningsöversikt (refereegranskat)abstract
- The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC.
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| 9. |
- Gallo, Valentina, et al.
(författare)
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Parkinson's Disease Case Ascertainment in the EPIC Cohort : The NeuroEPIC4PD Study
- 2015
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Ingår i: Neurodegenerative Diseases. - : S. Karger. - 1660-2854 .- 1660-2862. ; 15:6, s. 331-338
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Large epidemiological prospective studies represent an important opportunity for investigating risk factors for rare diseases such as Parkinson's disease (PD). Here we describe the procedures we used for ascertaining PD cases in the EPIC (European Prospective Investigation into Cancer and Nutrition) study. Methods: The following three-phase procedure was used: (1) elaboration of a NeuroEPIC4PD template for clinical data collection, (2) identification of all potential PD cases via record linkage and (3) validation of the diagnosis through clinical record revision, in a population of 220,494 subjects recruited in 7 European countries. All cases were labelled with the NeuroEPIC4PD diagnoses of 'definite', 'very likely', 'probable', or 'possible' PD. Results: A total of 881 PD cases were identified, with over 2,741,780 person-years of follow-up (199 definite, 275 very likely, 146 probable, and 261 possible). Of these, 734 were incident cases. The mean age at diagnosis was 67.9 years (SD 9.2) and 458 patients (52.0%) were men. Bradykinesia was the most frequent presenting motor sign (76.5%). Tremor-dominant and akinetic rigid forms of PD were the most common types of PD. A total of 289 patients (32.8%) were dead at the time of the last follow-up. Conclusions: This exercise proved that it is feasible to ascertain PD in large population-based cohort studies and offers a potential framework to be replicated in similar studies.
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| 10. |
- Hadfield, James, et al.
(författare)
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Comprehensive global genome dynamics of Chlamydia trachomatis show ancient diversification followed by contemporary mixing and recent lineage expansion
- 2017
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory Press. - 1088-9051 .- 1549-5469. ; 27:7, s. 1220-1229
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Tidskriftsartikel (refereegranskat)abstract
- Chlamydia trachomatis is the world's most prevalent bacterial sexually transmitted infection and leading infectious cause of blindness, yet it is one of the least understood human pathogens, in part due to the difficulties of in vitro culturing and the lack of available tools for genetic manipulation. Genome sequencing has reinvigorated this field, shedding light on the contemporary history of this pathogen. Here, we analyze 563 full genomes, 455 of which are novel, to show that the history of the species comprises two phases, and conclude that the currently circulating lineages are the result of evolution in different genomic ecotypes. Temporal analysis indicates these lineages have recently expanded in the space of thousands of years, rather than the millions of years as previously thought, a finding that dramatically changes our understanding of this pathogen's history. Finally, at a time when almost every pathogen is becoming increasingly resistant to antimicrobials, we show that there is no evidence of circulating genomic resistance in C. trachomatis.
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| 11. |
- Hoeber, Jan, et al.
(författare)
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Human Embryonic Stem Cell-Derived Progenitors Assist Functional Sensory Axon Regeneration after Dorsal Root Avulsion Injury
- 2015
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Dorsal root avulsion results in permanent impairment of sensory functions due to disconnection between the peripheral and central nervous system. Improved strategies are therefore needed to reconnect injured sensory neurons with their spinal cord targets in order to achieve functional repair after brachial and lumbosacral plexus avulsion injuries. Here, we show that sensory functions can be restored in the adult mouse if avulsed sensory fibers are bridged with the spinal cord by human neural progenitor (hNP) transplants. Responses to peripheral mechanical sensory stimulation were significantly improved in transplanted animals. Transganglionic tracing showed host sensory axons only in the spinal cord dorsal horn of treated animals. Immunohistochemical analysis confirmed that sensory fibers had grown through the bridge and showed robust survival and differentiation of the transplants. Section of the repaired dorsal roots distal to the transplant completely abolished the behavioral improvement. This demonstrates that hNP transplants promote recovery of sensorimotor functions after dorsal root avulsion, and that these effects are mediated by spinal ingrowth of host sensory axons. These results provide a rationale for the development of novel stem cell-based strategies for functionally useful bridging of the peripheral and central nervous system.
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| 12. |
- Saikia, Payaswini, et al.
(författare)
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A Multiwavelength Study of GRS 1716-249 in Outburst: Constraints on Its System Parameters
- 2022
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 932:1
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Tidskriftsartikel (refereegranskat)abstract
- We present a detailed study of the evolution of the Galactic black hole transient GRS 1716-249 during its 2016-2017 outburst at optical (Las Cumbres Observatory), mid-infrared (Very Large Telescope), near-infrared (Rapid Eye Mount telescope), and ultraviolet (the Neil Gehrels Swift Observatory Ultraviolet/Optical Telescope) wavelengths, along with archival radio and X-ray data. We show that the optical/near-infrared and UV emission of the source mainly originates from a multi-temperature accretion disk, while the mid-infrared and radio emission are dominated by synchrotron emission from a compact jet. The optical/UV flux density is correlated with the X-ray emission when the source is in the hard state, consistent with an X-ray irradiated accretion disk with an additional contribution from the viscous disk during the outburst fade. We find evidence for a weak, but highly variable jet component at mid-infrared wavelengths. We also report the long-term optical light curve of the source and find that the quiescent i'-band magnitude is 21.39 +/- 0.15 mag. Furthermore, we discuss how previous estimates of the system parameters of the source are based on various incorrect assumptions, and so are likely to be inaccurate. By comparing our GRS 1716-249 data set to those of other outbursting black hole X-ray binaries, we find that while GRS 1716-249 shows similar X-ray behavior, it is noticeably optically fainter, if the literature distance of 2.4 kpc is adopted. Using several lines of reasoning, we argue that the source distance is further than previously assumed in the literature, likely within 4-17 kpc, with a most likely range of similar to 4-8 kpc.
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| 13. |
- van Daalen, Kim R., et al.
(författare)
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The 2024 Europe report of the lancet countdown on health and climate change : unprecedented warming demands unprecedented action
- 2024
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Ingår i: The Lancet Public Health. - : Elsevier. - 2468-2667. ; 9:7, s. e495-e522
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Forskningsöversikt (refereegranskat)abstract
- Record-breaking temperatures were recorded across the globe in 2023. Without climate action, adverse climate-related health impacts are expected to worsen worldwide, affecting billions of people. Temperatures in Europe are warming at twice the rate of the global average, threatening the health of populations across the continent and leading to unnecessary loss of life. The Lancet Countdown in Europe was established in 2021, to assess the health profile of climate change aiming to stimulate European social and political will to implement rapid health-responsive climate mitigation and adaptation actions. In 2022, the collaboration published its indicator report, tracking progress on health and climate change via 33 indicators and across five domains.This new report tracks 42 indicators highlighting the negative impacts of climate change on human health, the delayed climate action of European countries, and the missed opportunities to protect or improve health with health-responsive climate action. The methods behind indicators presented in the 2022 report have been improved, and nine new indicators have been added, covering leishmaniasis, ticks, food security, health-care emissions, production and consumption-based emissions, clean energy investment, and scientific, political, and media engagement with climate and health. Considering that negative climate-related health impacts and the responsibility for climate change are not equal at the regional and global levels, this report also endeavours to reflect on aspects of inequality and justice by highlighting at-risk groups within Europe and Europe's responsibility for the climate crisis.
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| 14. |
- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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| 15. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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