| 1. |
- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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| 2. |
- Kanai, M, et al.
(author)
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- 2023
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swepub:Mat__t
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| 3. |
- Alexander, Stephen P. H., et al.
(author)
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The Concise Guide to PHARMACOLOGY 2023/24: G protein-coupled receptors
- 2023
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In: BRITISH JOURNAL OF PHARMACOLOGY. - : British pharmacological society. - 0007-1188 .- 1476-5381. ; 180
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Journal article (peer-reviewed)abstract
- The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at . G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
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| 4. |
- Bergero, Roberta, et al.
(author)
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Meiosis and beyond - understanding the mechanistic and evolutionary processes shaping the germline genome
- 2021
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In: Biological Reviews. - : John Wiley & Sons. - 1464-7931 .- 1469-185X. ; 96:3, s. 822-841
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Research review (peer-reviewed)abstract
- The separation of germ cell populations from the soma is part of the evolutionary transition to multicellularity. Only genetic information present in the germ cells will be inherited by future generations, and any molecular processes affecting the germline genome are therefore likely to be passed on. Despite its prevalence across taxonomic kingdoms, we are only starting to understand details of the underlying micro-evolutionary processes occurring at the germline genome level. These include segregation, recombination, mutation and selection and can occur at any stage during germline differentiation and mitotic germline proliferation to meiosis and post-meiotic gamete maturation. Selection acting on germ cells at any stage from the diploid germ cell to the haploid gametes may cause significant deviations from Mendelian inheritance and may be more widespread than previously assumed. The mechanisms that affect and potentially alter the genomic sequence and allele frequencies in the germline are pivotal to our understanding of heritability. With the rise of new sequencing technologies, we are now able to address some of these unanswered questions. In this review, we comment on the most recent developments in this field and identify current gaps in our knowledge.
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| 5. |
- Diego, Jose M., et al.
(author)
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JWST's PEARLS : Mothra, a new kaiju star at z=2.091 extremely magnified by MACS0416, and implications for dark matter models
- 2023
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 679
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Journal article (peer-reviewed)abstract
- We report the discovery of Mothra, an extremely magnified monster star, likely a binary system of two supergiant stars, in one of the strongly lensed galaxies behind the galaxy cluster MACS J0416.1-2403. Mothra is in a galaxy with spectroscopic redshift z = 2.091 in a portion of the galaxy that is parsecs away from the cluster caustic. The binary star is observed only on the side of the critical curve with negative parity but has been detectable for at least eight years, implying the presence of a small lensing perturber. Microlenses alone cannot explain the earlier observations of this object made with the Hubble Space Telescope. A larger perturber with a mass of at least 10(4 )M(circle dot) offers a more satisfactory explanation. Based on the lack of perturbation on other nearby sources in the same arc, the maximum mass of the perturber is 2.5 x 10(6) M-circle dot, making this the smallest substructure constrained by lensing at z > 0.3. The existence of this millilens is fully consistent with expectations from standard cold dark matter cosmology. On the other hand, the existence of such a small substructure in a cluster environment has implications for other dark matter models. In particular, warm dark matter models with particle masses below 8.7 keV are excluded by our observations. Similarly, axion dark matter models are consistent with the observations only if the axion mass is in the range 0.5 x 10(-22) eV < m(a )< 5 x 10(-22) eV.
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| 6. |
- Grasselli, Giacomo, et al.
(author)
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ESICM guidelines on acute respiratory distress syndrome : definition, phenotyping and respiratory support strategies
- 2023
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In: Intensive Care Medicine. - : Springer Nature. - 0342-4642 .- 1432-1238. ; 49, s. 727-759
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Journal article (peer-reviewed)abstract
- The aim of these guidelines is to update the 2017 clinical practice guideline (CPG) of the European Society of Intensive Care Medicine (ESICM). The scope of this CPG is limited to adult patients and to non-pharmacological respiratory support strategies across different aspects of acute respiratory distress syndrome (ARDS), including ARDS due to coronavirus disease 2019 (COVID-19). These guidelines were formulated by an international panel of clinical experts, one methodologist and patients' representatives on behalf of the ESICM. The review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations. We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence and grade recommendations and the quality of reporting of each study based on the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network guidelines. The CPG addressed 21 questions and formulates 21 recommendations on the following domains: (1) definition; (2) phenotyping, and respiratory support strategies including (3) high-flow nasal cannula oxygen (HFNO); (4) non-invasive ventilation (NIV); (5) tidal volume setting; (6) positive end-expiratory pressure (PEEP) and recruitment maneuvers (RM); (7) prone positioning; (8) neuromuscular blockade, and (9) extracorporeal life support (ECLS). In addition, the CPG includes expert opinion on clinical practice and identifies the areas of future research.
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| 7. |
- Iyadurai, Lalitha, et al.
(author)
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Reducing intrusive memories after trauma via an imagery-competing task intervention in COVID-19 intensive care staff : a randomised controlled trial
- 2023
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In: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 13:1
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Journal article (peer-reviewed)abstract
- Intrusive memories (IMs) after traumatic events can be distressing and disrupt mental health and functioning. We evaluated the impact of a brief remotely-delivered digital imagery-competing task intervention on the number of IMs for intensive care unit (ICU) staff who faced repeated trauma exposure during the COVID-19 pandemic using a two-arm, parallel-group, single-blind randomised controlled trial, with the comparator arm receiving delayed access to active treatment (crossover). Eligible participants worked clinically in a UK NHS ICU during the pandemic and had at least 3 IMs of work-related traumatic events in the week before recruitment. Participants were randomly assigned (1:1) to immediate (weeks 1-4) or delayed (weeks 5-8) intervention access. Sequential Bayesian analyses to optimise the intervention and increase trial efficiency are reported elsewhere [1]. The primary endpoint for the pre-specified frequentist analysis of the final study population compared the number of IMs experienced in week 4 between the immediate and delayed access arms. Secondary outcomes included clinical symptoms, work functioning and wellbeing. Safety was assessed throughout the trial by scheduled questions and free report. All analyses were undertaken on an intention-to-treat basis (86 randomised participants). There were significantly fewer intrusive memories during week 4 in the immediate (median = 1, IQR = 0-3, n = 43), compared to the comparator delayed arm (median = 10, IQR = 6-17, n = 43), IRR 0.31, 95% CI: 0.20-0.48, p < 0.001. After crossover, the delayed arm also showed a significant reduction in IMs at week 8 compared to week 4. There were convergent findings for symptoms of PTSD, insomnia and anxiety, work engagement and burnout, general functioning and quality of life. The intervention was found safe and acceptable to participants. All adverse events were unrelated to the study. Our study provides the first evidence of a benefit on reducing IMs, improving other clinical symptoms, work functioning and wellbeing, as well as safety of a brief remotely-delivered digital imagery-competing task intervention. An efficacy trial with an active control and longer follow-up is warranted. The trial is registered at ClinicalTrials.gov (NCT04992390).
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| 8. |
- Nabizadeh, Armin, et al.
(author)
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A search for high-redshift direct-collapse black hole candidates in the PEARLS north ecliptic pole field
- 2024
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 683
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Journal article (peer-reviewed)abstract
- Direct-collapse black holes (DCBHs) of mass ∼ 104-105 M⊙ that form in HI-cooling halos in the early Universe are promising progenitors of the greater than or similar to 109 M⊙ supermassive black holes that fuel observed z greater than or similar to 7 quasars. Efficient accretion of the surrounding gas onto such DCBH seeds may render them sufficiently bright for detection with the JWST up to z ≈ 20. Additionally, the very steep and red spectral slope predicted across the ≈ 1-5 μm wavelength range of the JWST/NIRSpec instrument during their initial growth phase should make them photometrically identifiable up to very high redshifts. In this work, we present a search for such DCBH candidates across the 34 arcmin2 in the first two spokes of the JWST cycle-1 PEARLS survey of the north ecliptic pole time-domain field covering eight NIRCam filters down to a maximum depth of ∼ 29 AB mag. We identify two objects with spectral energy distributions consistent with the Pacucci et al. (2016) DCBH models. However, we also note that even with data in eight NIRCam filters, objects of this type remain degenerate with dusty galaxies and obscured active galactic nuclei over a wide range of redshifts. Follow-up spectroscopy would be required to pin down the nature of these objects. Based on our sample of DCBH candidates and assumptions on the typical duration of the DCBH steep-slope state, we set a conservative upper limit of less than or similar to 5x10-4 comoving Mpc-3 (cMpc-3) on the comoving density of host halos capable of hosting DCBHs with spectral energy distributions similar to the Pacucci et al. (2016) models at z ≈ 6-14.
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| 9. |
- Needham, E. J., et al.
(author)
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Brain injury in COVID-19 is associated with dysregulated innate and adaptive immune responses
- 2022
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In: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 145:11, s. 4097-4107
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Journal article (peer-reviewed)abstract
- COVID-19 is associated with neurological complications including stroke, delirium and encephalitis. Furthermore, a post-viral syndrome dominated by neuropsychiatric symptoms is common, and is seemingly unrelated to COVID-19 severity. The true frequency and underlying mechanisms of neurological injury are unknown, but exaggerated host inflammatory responses appear to be a key driver of COVID-19 severity. We investigated the dynamics of, and relationship between, serum markers of brain injury [neurofilament light (NfL), glial fibrillary acidic protein (GFAP) and total tau] and markers of dysregulated host response (autoantibody production and cytokine profiles) in 175 patients admitted with COVID-19 and 45 patients with influenza. During hospitalization, sera from patients with COVID-19 demonstrated elevations of NfL and GFAP in a severity-dependent manner, with evidence of ongoing active brain injury at follow-up 4 months later. These biomarkers were associated with elevations of pro-inflammatory cytokines and the presence of autoantibodies to a large number of different antigens. Autoantibodies were commonly seen against lung surfactant proteins but also brain proteins such as myelin associated glycoprotein. Commensurate findings were seen in the influenza cohort. A distinct process characterized by elevation of serum total tau was seen in patients at follow-up, which appeared to be independent of initial disease severity and was not associated with dysregulated immune responses unlike NfL and GFAP. These results demonstrate that brain injury is a common consequence of both COVID-19 and influenza, and is therefore likely to be a feature of severe viral infection more broadly. The brain injury occurs in the context of dysregulation of both innate and adaptive immune responses, with no single pathogenic mechanism clearly responsible. Needham et al. reveal elevations in blood biomarkers of brain injury in patients hospitalised with COVID-19. The changes, which were severity-dependent, were associated with dysregulated immune responses including increases in pro-inflammatory cytokines and autoantibodies. Ongoing active brain injury could still be seen months after infection.
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| 10. |
- Ramineni, Varsha, et al.
(author)
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Treating intrusive memories after trauma in healthcare workers: a Bayesian adaptive randomised trial developing an imagery-competing task intervention
- 2023
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In: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 28:7, s. 2985-2994
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Journal article (peer-reviewed)abstract
- Intensive care unit (ICU) staff continue to face recurrent work-related traumatic events throughout the COVID-19 pandemic. Intrusive memories (IMs) of such traumatic events comprise sensory image-based memories. Harnessing research on preventing IMs with a novel behavioural intervention on the day of trauma, here we take critical next steps in developing this approach as a treatment for ICU staff who are already experiencing IMs days, weeks, or months post-trauma. To address the urgent need to develop novel mental health interventions, we used Bayesian statistical approaches to optimise a brief imagery-competing task intervention to reduce the number of IMs. We evaluated a digitised version of the intervention for remote, scalable delivery. We conducted a two-arm, parallel-group, randomised, adaptive Bayesian optimisation trial. Eligible participants worked clinically in a UK NHS ICU during the pandemic, experienced at least one work-related traumatic event, and at least three IMs in the week prior to recruitment. Participants were randomised to receive immediate or delayed (after 4 weeks) access to the intervention. Primary outcome was the number of IMs of trauma during week 4, controlling for baseline week. Analyses were conducted on an intention-to-treat basis as a between-group comparison. Prior to final analysis, sequential Bayesian analyses were conducted (n = 20, 23, 29, 37, 41, 45) to inform early stopping of the trial prior to the planned maximum recruitment (n = 150). Final analysis (n = 75) showed strong evidence for a positive treatment effect (Bayes factor, BF = 1.25 × 106): the immediate arm reported fewer IMs (median = 1, IQR = 0–3) than the delayed arm (median = 10, IQR = 6–16.5). With further digital enhancements, the intervention (n = 28) also showed a positive treatment effect (BF = 7.31). Sequential Bayesian analyses provided evidence for reducing IMs of work-related trauma for healthcare workers. This methodology also allowed us to rule out negative effects early, reduced the planned maximum sample size, and allowed evaluation of enhancements. Trial Registration NCT04992390 (www.clinicaltrials.gov).
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| 11. |
- Windhorst, Rogier A., et al.
(author)
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JWST PEARLS. Prime extragalactic areas for reionization and lensing science : project overview and first results
- 2023
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In: Astronomical Journal. - : Institute of Physics (IOP). - 0004-6256 .- 1538-3881. ; 165:1
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Journal article (peer-reviewed)abstract
- We give an overview and describe the rationale, methods, and first results from NIRCam images of the JWST “Prime Extragalactic Areas for Reionization and Lensing Science” (PEARLS) project. PEARLS uses up to eight NIRCam filters to survey several prime extragalactic survey areas: two fields at the North Ecliptic Pole (NEP); seven gravitationally lensing clusters; two high redshift protoclusters; and the iconic backlit VV 191 galaxy system to map its dust attenuation. PEARLS also includes NIRISS spectra for one of the NEP fields and NIRSpec spectra of two high-redshift quasars. The main goal of PEARLS is to study the epoch of galaxy assembly, active galactic nucleus (AGN) growth, and First Light. Five fields—the JWST NEP Time-Domain Field (TDF), IRAC Dark Field, and three lensing clusters—will be observed in up to four epochs over a year. The cadence and sensitivity of the imaging data are ideally suited to find faint variable objects such as weak AGN, high-redshift supernovae, and cluster caustic transits. Both NEP fields have sightlines through our Galaxy, providing significant numbers of very faint brown dwarfs whose proper motions can be studied. Observations from the first spoke in the NEP TDF are public. This paper presents our first PEARLS observations, their NIRCam data reduction and analysis, our first object catalogs, the 0.9–4.5 μm galaxy counts and Integrated Galaxy Light. We assess the JWST sky brightness in 13 NIRCam filters, yielding our first constraints to diffuse light at 0.9–4.5 μm. PEARLS is designed to be of lasting benefit to the community.
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