| 1. |
- Bender, Brian J., et al.
(författare)
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A practical guide to large-scale docking
- 2021
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Ingår i: Nature Protocols. - : Springer Nature. - 1754-2189 .- 1750-2799. ; 16:10, s. 4799-4832
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Tidskriftsartikel (refereegranskat)abstract
- Structure-based docking screens of large compound libraries have become common in early drug and probe discovery. As computer efficiency has improved and compound libraries have grown, the ability to screen hundreds of millions, and even billions, of compounds has become feasible for modest-sized computer clusters. This allows the rapid and cost-effective exploration and categorization of vast chemical space into a subset enriched with potential hits for a given target. To accomplish this goal at speed, approximations are used that result in undersampling of possible configurations and inaccurate predictions of absolute binding energies. Accordingly, it is important to establish controls, as are common in other fields, to enhance the likelihood of success in spite of these challenges. Here we outline best practices and control docking calculations that help evaluate docking parameters for a given target prior to undertaking a large-scale prospective screen, with exemplification in one particular target, the melatonin receptor, where following this procedure led to direct docking hits with activities in the subnanomolar range. Additional controls are suggested to ensure specific activity for experimentally validated hit compounds. These guidelines should be useful regardless of the docking software used. Docking software described in the outlined protocol (DOCK3.7) is made freely available for academic research to explore new hits for a range of targets. Structure-based docking screens of compound libraries are common in early drug and probe discovery. This protocol outlines best practices and control calculations to evaluate docking parameters prior to undertaking a large-scale prospective screen.
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| 2. |
- Buckland, Philip I., Dr. 1973-, et al.
(författare)
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Mid-Devensian climate and landscape in England : new data from Finningley, South Yorkshire
- 2019
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Ingår i: Royal Society Open Science. - : Royal Society Publishing. - 2054-5703. ; 6:7
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Tidskriftsartikel (refereegranskat)abstract
- While there is extensive evidence for the Late Devensian, less is known about Early and Middle Devensian (approx. 110-30 ka) climates and environments in the UK. The Greenland ice-core record suggests the UK should have endured multiple changes, but the terrestrial palaeo-record lacks sufficient detail for confirmation from sites in the British Isles. Data from deposits at Finningley, South Yorkshire, can help redress this. A channel with organic silts, dated 40 314-39 552 cal a BP, contained plant macrofossil and insect remains showing tundra with dwarf-shrub heath and bare ground. Soil moisture conditions varied from free draining to riparian, with ponds and wetter vegetated areas. The climate was probably low arctic with snow cover during the winter. Mutual climatic range (MCR), based on Coleoptera, shows the mean monthly winter temperatures of -22 to -2 degrees C and summer ones of 8-14 degrees C. Periglacial structures within the basal gravel deposits and beyond the glacial limits indicate cold-climate conditions, including permafrost. A compilation of MCR reconstructions for other Middle Devensian English sites shows that marine isotope stage 3-between 59 and 28 ka-experienced substantial variation in climate consistent with the Greenland ice-core record. The exact correlation is hampered by temporal resolution, but the Finningley site stadial at approximately 40 ka may correlate with the one of the Greenland stadials 7-11.
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| 3. |
- Kaufman, Darrell, et al.
(författare)
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A global database of Holocene paleotemperature records
- 2020
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- A comprehensive database of paleoclimate records is needed to place recent warming into the longer-term context of natural climate variability. We present a global compilation of quality-controlled, published, temperature-sensitive proxy records extending back 12,000 years through the Holocene. Data were compiled from 679 sites where time series cover at least 4000 years, are resolved at sub-millennial scale (median spacing of 400 years or finer) and have at least one age control point every 3000 years, with cut-off values slackened in data-sparse regions. The data derive from lake sediment (51%), marine sediment (31%), peat (11%), glacier ice (3%), and other natural archives. The database contains 1319 records, including 157 from the Southern Hemisphere. The multi-proxy database comprises paleotemperature time series based on ecological assemblages, as well as biophysical and geochemical indicators that reflect mean annual or seasonal temperatures, as encoded in the database. This database can be used to reconstruct the spatiotemporal evolution of Holocene temperature at global to regional scales, and is publicly available in Linked Paleo Data (LiPD) format.
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| 4. |
- Khatri, C, et al.
(författare)
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Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
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Tidskriftsartikel (refereegranskat)abstract
- Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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| 5. |
- Martins, Inês S., et al.
(författare)
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Widespread shifts in body size within populations and assemblages
- 2023
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Ingår i: Science. - 0036-8075 .- 1095-9203. ; 381:6662, s. 1067-1071
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Tidskriftsartikel (refereegranskat)abstract
- Biotic responses to global change include directional shifts in organismal traits. Body size, an integrative trait that determines demographic rates and ecosystem functions, is thought to be shrinking in the Anthropocene. Here, we assessed the prevalence of body size change in six taxon groups across 5025 assemblage time series spanning 1960 to 2020. Using the Price equation to partition this change into within-species body size versus compositional changes, we detected prevailing decreases in body size through time driven primarily by fish, with more variable patterns in other taxa. We found that change in assemblage composition contributes more to body size changes than within-species trends, but both components show substantial variation in magnitude and direction. The biomass of assemblages remains quite stable as decreases in body size trade off with increases in abundance.
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| 6. |
- Schnakers, Caroline, et al.
(författare)
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What names for covert awareness? : A systematic review
- 2022
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Ingår i: Frontiers in Human Neuroscience. - : Frontiers Media S.A.. - 1662-5161. ; 16
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Forskningsöversikt (refereegranskat)abstract
- Background: With the emergence of Brain Computer Interfaces (BCI), clinicians have been facing a new group of patients with severe acquired brain injury who are unable to show any behavioral sign of consciousness but respond to active neuroimaging or electrophysiological paradigms. However, even though well documented, there is still no consensus regarding the nomenclature for this clinical entity.Objectives: This systematic review aims to 1) identify the terms used to indicate the presence of this entity through the years, and 2) promote an informed discussion regarding the rationale for these names and the best candidates to name this fascinating disorder.Methods: The Disorders of Consciousness Special Interest Group (DoC SIG) of the International Brain Injury Association (IBIA) launched a search on Pubmed and Google scholar following PRISMA guidelines to collect peer-reviewed articles and reviews on human adults (>18 years) published in English between 2006 and 2021.Results: The search launched in January 2021 identified 4,089 potentially relevant titles. After screening, 1,126 abstracts were found relevant. Finally, 161 manuscripts were included in our analyses. Only 58% of the manuscripts used a specific name to discuss this clinical entity, among which 32% used several names interchangeably throughout the text. We found 25 different names given to this entity. The five following names were the ones the most frequently used: covert awareness, cognitive motor dissociation, functional locked-in, non-behavioral MCS (MCS*) and higher-order cortex motor dissociation.Conclusion: Since 2006, there has been no agreement regarding the taxonomy to use for unresponsive patients who are able to respond to active neuroimaging or electrophysiological paradigms. Developing a standard taxonomy is an important goal for future research studies and clinical translation. We recommend a Delphi study in order to build such a consensus.
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| 7. |
- Abbafati, Cristiana, et al.
(författare)
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- 2020
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Tidskriftsartikel (refereegranskat)
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| 8. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 9. |
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| 10. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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