Explore the vast range of titles available.

Thousands of loci in the human and mouse genomes give rise to circular RNA transcripts; at many of these loci, the predominant RNA isoform is a circle. Using an improved computational approach for circular RNA identification, we found widespread circular RNA expression in Drosophila melanogaster and estimate that in humans, circular RNA may account for 1% as many molecules as poly(A) RNA. Analysis of data from the ENCODE consortium revealed that the repertoire of genes expressing circular RNA, the ratio of circular to linear transcripts for each gene, and even the pattern of splice isoforms of circular RNAs from each gene were cell-type specific. These results suggest that biogenesis of circular RNA is an integral, conserved, and regulated feature of the gene expression program.

An unexpectedly large fraction of genes in metazoans (human, mouse, zebrafish, worm, fruit fly) express high levels of circularized RNAs containing canonical exons. Here we report that circular RNA isoforms are found in diverse species whose most recent common ancestor existed more than one billion years ago: fungi (Schizosaccharomyces pombe and Saccharomyces cerevisiae), a plant (Arabidopsis thaliana), and protists (Plasmodium falciparum and Dictyostelium discoideum). For all species studied to date, including those in this report, only a small fraction of the theoretically possible circular RNA isoforms from a given gene are actually observed. Unlike metazoans, Arabidopsis, D. discoideum, P. falciparum, S. cerevisiae, and S. pombe have very short introns (∼ 100 nucleotides or shorter), yet they still produce circular RNAs. A minority of genes in S. pombe and P. falciparum have documented examples of canonical alternative splicing, making it unlikely that all circular RNAs are by-products of alternative splicing or 'piggyback' on signals used in alternative RNA processing. In S. pombe, the relative abundance of circular to linear transcript isoforms changed in a gene-specific pattern during nitrogen starvation. Circular RNA may be an ancient, conserved feature of eukaryotic gene expression programs.

The ESA Swarm mission to identify and measure very accurately the different magnetic signals that arise in the Earth’s core, mantle, crust, oceans, ionosphere and magnetosphere, which together form the magnetic field around the Earth, has increased interest in magnetic data collected on the surface of the Earth at observatories. The scientific use of Swarm data and Swarm-derived products is greatly enhanced by combination with observatory data and indices. As part of the Swarm Level-2 data activities plans are in place to distribute such ground-based data along with the Swarm data as auxiliary data products. We describe here the preparation of the data set of ground observatory hourly mean values, including procedures to check and select observatory data spanning the modern magnetic survey satellite era. We discuss other possible combined uses of satellite and observatory data, in particular those that may use higher cadence 1-second and 1-minute data from observatories.

We present CHAOS-8, an extension of the CHAOS field model series that describes the time-dependent near-Earth geomagnetic field, valid from 1999 to 2025. It is estimated from magnetic measurements collected by multiple low-earth-orbit satellites, such as CHAMP and Swarm , and ground observatories. An initial version of this model, CHAOS-8.1, served as the parent model for constructing DTU’s candidate models for the 14th generation International Geomagnetic Reference Field. CHAOS-8 comprises a time-dependent internal field up to spherical harmonic degree 20, a static internal field that merges with the LCS-1 lithospheric field model above degree 25, a model of the magnetospheric field and its induced counterpart, and estimates of alignment parameters for satellite vector magnetometers, along with calibration parameters for platform magnetometers. It also includes a co-estimated climatological model of the ionospheric field previously ignored within the CHAOS framework. The climatological model describes magnetic fields produced by polar ionospheric E-layer currents, which can be significant even under dark conditions. A new temporal regularization of the internal field is implemented, based on a priori statistics of the secular acceleration extracted from numerical geodynamo simulations. This enables rapid internal field changes to be better captured at small length scales. Magnetic measurements from the MSS-1 and CSES satellite missions were included for the first time in a CHAOS model. Model parameters were estimated using regularized iteratively reweighted least squares. The fit to the data was generally comparable to earlier versions of the CHAOS model. Co-estimation of an ionospheric field resulted in an improved fit in the polar regions. The new temporal regularization allowed stronger and more rapid temporal variations of the internal field at high spherical harmonic degrees. Analyzing sub-decadal variations of the internal field at the core–mantle boundary, we find westward-moving features and tentative evidence for eastward-moving features at low latitudes. The latter are of small length scales (apparent azimuthal wavenumber 13), moving at a speed of 200km/yr at the equator between 0 ∘ and 90 ∘ E after 2012. There are also indications of features moving across the geographic equator. These propagating features provide further evidence of traveling hydromagnetic waves at the core–mantle boundary. Graphical Abstract

BackgroundThe skills of performing joint/periarticular injections by rheumatology fellows are learned during training but achieving the necessary level of expertise can be challenging if the rotations lack dedicated skills teaching. There is also a paucity of literature reporting how injection proficiency evolves and how the type and number of procedures can affect performance.ObjectivesTo combat these issues and enhance fellow training and patient outcomes, we started an exclusive fellows’ monthly injection clinic and assessed the learners’ progress by analyzing their proficiency scores (PS) over time, and asking if these differ between size of joints and number of procedures done. We selected 10 or more procedures as the number needed to achieve higher expertise and determined the patient response (efficacy) and side effects as secondary outcomes.MethodsThe clinic is led by a single attending rheumatologist who demonstrates the proper technique prior to the encounter, supervises the procedure and provides feedback. Outcome measures include the procedure type classified as small/medium or large joint/periarticular structures. The PS was measured by the same teacher throughout and used a numerical scale of 1-3 defined as 1 – early, 2 – progressing, or 3 - advanced. Factors affecting proficiency score included preparation, technique, and cleanup. Efficacy was measured by successful aspiration and for steroid injections, by patient report of >50% improvement in joint pain at the next follow-up visit. Patients were advised to call the clinic to report any adverse events.ResultsThirteen clinics took place between December 2020-August 2022. Fellows performed an average of 4 procedures per clinic for a total of 52 procedures. PS were compared at initial (n=15) and last clinic encounter (n=17), and between large (n= 32) and small/medium joints/periarticular procedures (n=20). PS steadily increased over time with higher proficiency achieved by the 3rd or 4th clinic compared to the initial clinic [2(1-3) vs 1(1-2), p=0.018]. Fellows tended to achieve higher PS for large joint/periarticular procedures (hip and knee) compared to the more technically difficult small/medium joint/periarticular procedures (shoulder, feet and hands) [2[1-3) vs 1(1-2), p < 0.0001]. We arbitrarily selected 10 or more procedures as the number needed to achieve higher expertise but found no difference in PS between performing <10 versus > 10 injections [2(1-3) vs 2(1-3), p= 0.35]. The procedures were highly effective and safe with favorable responses seen in 94.0% (49/52 procedures) with no reported side effects.ConclusionThe longitudinal injection clinic demonstrated a steady improvement in proficiency among fellows while minimum number of procedures needed to attain expertise needs further studies. Our data can provide a useful template for designing a skills-based curriculum for rheumatology training programs.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsWhitney Martin: None declared, Shirley Albano-Aluquin: None declared, Sharon Banks: None declared, Nancy Olsen Grant/research support from: Research grants from Amgen and UCB.

In December 2019, the 13th revision of the International Geomagnetic Reference Field (IGRF) was released by the International Association of Geomagnetism and Aeronomy (IAGA) Division V Working Group V-MOD. This revision comprises two new spherical harmonic main field models for epochs 2015.0 (DGRF-2015) and 2020.0 (IGRF-2020) and a model of the predicted secular variation for the interval 2020.0 to 2025.0 (SV-2020-2025). The models were produced from candidates submitted by fifteen international teams. These teams were led by the British Geological Survey (UK), China Earthquake Administration (China), Universidad Complutense de Madrid (Spain), University of Colorado Boulder (USA), Technical University of Denmark (Denmark), GFZ German Research Centre for Geosciences (Germany), Institut de physique du globe de Paris (France), Institut des Sciences de la Terre (France), Pushkov Institute of Terrestrial Magnetism, Ionosphere and Radio Wave Propagation (Russia), Kyoto University (Japan), University of Leeds (UK), Max Planck Institute for Solar System Research (Germany), NASA Goddard Space Flight Center (USA), University of Potsdam (Germany), and Université de Strasbourg (France). The candidate models were evaluated individually and compared to all other candidates as well to the mean, median and a robust Huber-weighted model of all candidates. These analyses were used to identify, for example, the variation between the Gauss coefficients or the geographical regions where the candidate models strongly differed. The majority of candidates were sufficiently close that the differences can be explained primarily by individual modeling methodologies and data selection strategies. None of the candidates were so different as to warrant their exclusion from the final IGRF-13. The IAGA V-MOD task force thus voted for two approaches: the median of the Gauss coefficients of the candidates for the DGRF-2015 and IGRF-2020 models and the robust Huber-weighted model for the predictive SV-2020-2025. In this paper, we document the evaluation of the candidate models and provide details of the approach used to derive the final IGRF-13 products. We also perform a retrospective analysis of the IGRF-12 SV candidates over their performance period (2015–2020). Our findings suggest that forecasting secular variation can benefit from combining physics-based core modeling with satellite observations.

Humans perceive a range of basic emotional connotations from music, such as joy, sadness, and fear, which can be decoded from structural characteristics of music, such as rhythm, harmony, and timbre. However, despite theory and evidence that music has multiple social functions, little research has examined whether music conveys emotions specifically associated with social status and social connection. This investigation aimed to determine whether the social emotions of dominance and affiliation are perceived in music and whether structural features of music predict social emotions, just as they predict basic emotions. Participants ( N  = 1513) listened to subsets of 750 music excerpts and provided ratings of energy arousal, tension arousal, valence, dominance, and affiliation. Ratings were modelled based on ten structural features of music. Dominance and affiliation were readily perceived in music and predicted by structural features including rhythm, harmony, dynamics, and timbre. In turn, energy arousal, tension arousal and valence were also predicted by musical structure. We discuss the results in view of current models of music and emotion and propose research to illuminate the significance of social emotions in music.

Background:The manifestations of giant cell arteritis(GCA) are mediated by macrophages thru T-cell activation, interferon-gamma(IG), interleukin-12(IL12) production and vascular remodeling but there are no diagnostic or therapeutic modalities directed at these macrophages. CD163-macrophages are pathogenic in ANCA-vasculitis and lupus nephritis but their role in GCA is unknown. The folate-receptor beta (FRB) is a membrane glycoprotein selectively expressed in GCA macrophages and can be a druggable target for folate/antifolate/folate-conjugated therapeutics. We hypothesized that FRB and CD163 macrophages play key roles in GCA and explored their expression in the vascular microenvironment of early and chronic disease.Objectives:To compare the immune microenvironment and novel FRB and CD163 macrophage expression in GCA and controls and between early and chronic disease.Methods:Temporal artery biopsies (TABs) from GCA-positive (n=9) and negative controls (n=5) were analyzed for FRB, CD163, CD2, IG and IL12 expression/distribution by immunohistochemistry (IHC). Formalin-fixed paraffin-embedded blocks were processed by standard protocol and incubated with the following primary antibodies: FRB (1:800; placenta for control), CD163 (1:25; placenta for control); CD3 (1:75; spleen for control), IG (1:400; Hodgkin lymphoma for control) and IL-12 (1:75; lung cancer for control). We counted the average number of cells per high-power-field for FRB, CD163 and CD3 and semi-quantitatively assessed IG and IL12 as the percentage of inflammatory cells (1=<25%,2=26 to 50%,3= 51-75%,4=>75%). Values were calculated and compared between (1) GCA (n=9) and controls (n=5) and (2) early and late GCA. The correlation between FRB and CD163 macrophages were determined. Statistical analyses were performed using SAS (SAS Institute, Cary, NC) -Wilcoxon rank-sum test and Spearman rank correlation-with significance set at p <0.05Results:The early GCA group (n=6;1 male;5 females) had TABs within 2-3 weeks of symptoms which included vision loss and tongue gangrene and were on high-dose prednisone. Late GCA (n=3; all females) presented with vision loss and chronic relapsing disease that prompted a second TAB done 2.5 years post-diagnosis and were on low dose prednisone. In GCA, FRB and CD163 expression were restricted to activated macrophages in vascular adventitia/media and in close proximity to T cells. IG was noted in T-cells and macrophages while IL-12 was in endothelial cells/macrophages (Figure 1). As expected, the expression of each component was significantly higher in GCA than controls: FRB (14.0 vs 2.3; p=0.006), CD163 (14.7 vs 1.5; p=0.023), CD3 (79 vs 0; p=0.004), IG (3.0 vs1.0; p=0.005) and IL12 (1.5 vs 0; p=0.003). There was no correlation between FRB and CD163 (r=0.52; p=0.17). FRB macrophages persisted in late GCA (13.3 vs 12.5; p=0.52) along with CD3(113.2 vs 72.5; p=0.16), IG (3 vs 3.2; p=0.9) and IL12 (1.5 vs 1.5; p=0.22) with no statistical difference between the first and second biopsies. In contrast, CD163 expression was significantly reduced in late GCA (18.8 vs 9.5; p=0.038) suggesting that these macrophage biomarker responds to chronic steroid therapy.Conclusion:Chronic GCA demonstrated persistent FRB macrophages which can predict a relapsing trajectory and serve as novel targets for selective drug therapy.Figure 1.Macrophage, T-cell and cytokine expression in temporal arteries of patients with giant cell arteritis (GCA) Representative photomicrographs showing sections of biopsy specimens obtained from patients with GCA stained for A. folate receptor beta in activated macrophages(arrows) distributed in adventitia at 40x (scale bar, 2 mm),B. CD163+ in activated macrophages (arrows) distributed in adventitia at 40x (scale bar, 2mm), C. CD3+ in T cells (arrows) distributed in adventitia at 40x magnification (scale bar, 50 micrometer), D. interferon-gamma in T cells (small arrows) and macrophages (big arrows) at 60X (scale bar, 20 micrometer), E. interleukin-12 in macrophages (arrow) in adventitia at 40X (scale bar, 50 micrometer),F. folate receptor-beta in multinucleated giant cell (arrow) at 60x (scale bar, 2 mm).REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.

The oxyfuel combustion of a model MSW (municipal solid waste) under various conditions was carried out in a lab-scale reactor. The aim was to study the behavior of MSW and identify challenges and opportunities associated with the development of this technology in the context of integration with CCS (carbon capture and storage). The experimental results show the effects of the oxidizer composition on the combustion process. Complete combustion can be attained under a variety of oxyfuel conditions, and the differences highlighted with O2/CO2 as an oxidizer compared with O2/N2 do not constitute showstoppers. MSW oxyfuel combustion hence offers a great potential for the combined (1) treatment of waste (contaminants’ destruction, volume, and weight reduction), (2) production of heat/power, and (3) CCS with negative CO2 emissions.

BackgroundThe diagnosis of giant cell arteritis (GCA) is confirmed by temporal artery (TA) biopsy findings of internal elastic lamina disruption, activated macrophages and T-lymphocytes infiltrating the arterial layers. The immune microenvironment in GCA becomes T helper-1 polarized after steroid therapy and consists of potential anti-tumor cytokines including interferon-gamma (IFG) and interleukin-12 (IL-12) which can be protective against the development of cancer. We have previously identified folate receptor beta positive macrophages in GCA, which can serve as a target for hacking this immune microenvironment.ObjectivesTo compare the tumor outcomes in our cohort of GCA vs controls who had TA biopsies.To select a line-up of CD3, IFG, IL12 and FRB as potential anti-tumor proteins and compare their expression in GCA+ TA tissue that did not develop tumors versus GCA -negative tissues that developed tumors.To assess the persistence of this line-up over time.MethodsWe performed a retrospective chart review of GCA subjects and controls to assess development of tumors over long-term follow up.Formalin-fixed paraffin embedded tissue sections were obtained from both groups and immunohistochemical stains were performed using CD3, IFG, IL12 and FRB antibodies.Results40 GCA and 40 controls demonstrated similar follow-up durations (76.9 vs 70.1 years; NS), time-to-incident cancer (21 vs 62 mos; NS) and deaths from cancer (5% vs 17.5%;NS). GCA subjects were older than controls (77.2 vs 69.7 years; p= 0.004). Cancer incidence is lower in GCA than controls (25% vs.47.5%; p=0.036). The incident cancers in GCA include 8 basal or squamous cell skin cancer(BCC/SCC) and 1 each of chronic lymphocytic leukemia, thyroid, esophageal and angiosarcoma. The controls had 6 BCC/SCC, 2 each of breast, skin melanoma and lymphoma, and 1 each of tonsil, parotid, colon, lung, renal, prostate, myelodysplastic syndrome and metastatic disease of unknown primary.Histopathology/IHC Findings: FRB was selectively expressed in macrophages and correlated with IFG, IL12 and CD3 expression. FRB, IFG, IL12 and CD3 expression were higher in GCA without incident cancer compared to controls with cancer: FRB (14 vs 2.3;p=0.006), IFG (3 vs 1;p=0.005), IL12 (1.5 vs 0;p=0.003), CD3 (79 vs 0;p=0.004). This multi- protein expression persisted for years in 3 repeat biopsies.ConclusionGCA has a lower risk of cancer which was associated with a chronic FRB+-macrophage and Th1-polarized anti-tumor autoimmunity.References[1]Deng J, Younge BR, Olshen RA, et al. Th17 and Th1 T-cell responses in giant cell arteritis. Circulation. 2010;121:906-915.[2]Bruni D, Angell HK, Galon J. et al. The immune contexture and immunoscore in cancer prognosis and therapeutic efficacy. Nat Rev Cancer 2020;20:662-680.[3]Fridman WH, Pagès F, Sautès-Fridman C, et al. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer. 2012;12:298-306.[4]Smyth MJ, Taniguchi M, Street SE The anti-tumor activity of IL-12: mechanisms of innate immunity that are model and dose dependent. J Immunol 2000;165:2665-70.[5]Albano-Aluquin S, Malysz J, Aluquin VR, et al. An immunohistochemical analysis of folate receptor beta expression and distribution in giant cell arteritis: a pilot study. Am J Clin Exp Immunol. 2017;6:107-114.[6]Xia W, Hilgenbrink W, Matteson L, et al. A functional folate receptor is induced during macrophage activation can be used to target drugs to activated macrophages. Blood 2009;113:438-446Acknowledgements:NIL.Disclosure of InterestsNone Declared.