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Einstein–Maxwell-scalar models allow for different classes of black hole solutions, depending on the non-minimal coupling function f(ϕ) employed, between the scalar field and the Maxwell invariant. Here, we address the linear mode stability of the black hole solutions obtained recently for a quartic coupling function, f(ϕ)=1+αϕ4 (Blázquez-Salcedo et al. in Phys. Lett. B 806:135493, 2020). Besides the bald Reissner–Nordström solutions, this coupling allows for two branches of scalarized black holes, termed cold and hot, respectively. For these three branches of black holes we calculate the spectrum of quasinormal modes. It consists of polar scalar-led modes, polar and axial electromagnetic-led modes, and polar and axial gravitational-led modes. We demonstrate that the only unstable mode present is the radial scalar-led mode of the cold branch. Consequently, the bald Reissner–Nordström branch and the hot scalarized branch are both mode-stable. The non-trivial scalar field in the scalarized background solutions leads to the breaking of the degeneracy between axial and polar modes present for Reissner–Nordström solutions. This isospectrality is only slightly broken on the cold branch, but it is strongly broken on the hot branch.

The general relativity vacuum black holes (BHs) can be scalarised in models where a scalar field non-minimally couples to the Gauss-Bonnet (GB) invariant. Such GB scalarisation comes in two flavours, depending on the GB sign that triggers the phenomenon. Hereafter these two cases are termed GB± scalarisation. For vacuum BHs, only GB+ scalarisation is possible in the static case, while GB− scalarisation is spin induced. But for electrovacuum BHs, GB− is also charged induced. We discuss the GB− scalarisation of Reissner-Nordström and Kerr-Newman BHs, discussing zero modes and constructing fully non-linear solutions. Some comparisons with GB+ scalarisation are given. To assess the generality of the observed features, we also briefly consider the GB± scalarisation of stringy dilatonic BHs and coloured BHs which provide qualitative differences with respect to the electrovacuum case, namely on the distribution and existence of regions triggering GB− scalarisation.

Background Cerebral cavernous malformations (CCM) are angiographically occult vascular anomalies of the brain, characterized by dilated capillaries, increased vascular permeability, and loss of endothelial junctional protein complexes. Loss-of-function mutations in one of the three genes, namely KRIT1/CCM1 , CCM2 , and PDCD10/CCM3, have been associated with the disease pathogenesis, although the contribution of other genetic determinants besides CCM genes has been recently identified. Despite recent advances in understanding the molecular mechanism of the disease, the current lack of therapies and its unpredictable clinical behavior represent a significant challenge in the identification of diagnostic biomarkers. ADGRL4/ETLD1 (epidermal growth factor, latrophilin and seven transmembrane domain-containing protein 1), a G-protein coupled receptor (GPCR) protein is a known biomarker of angiogenesis and inflammation, and it has been suggested to be a key therapeutic target for stroke and high-grade gliomas. However, the relevance of ELTD1 in CCM pathogenesis remains unexplored. Methods Through different analyses, including whole RNA transcriptome, immunohistochemistry, and real-time PCR, conducted in human CCM patients, cellular and animal models, herein we show the association between CCM disease and ELTD1. Results The whole RNA transcriptome approaches demonstrated ELTD1 is differentially expressed, and gene expression analysis revealed it is significantly upregulated in surgically resected tissue and plasma samples from CCMs, and clinical correlation analysis showed that increased ELTD1 associates with the presence of Focal Neurological Deficits in patients. Immuno-expression showed a strong ELTD1 immunoreactivity in endothelial cells lining affected lesions. According to these elevated levels of ELTD1 in human patients, we also showed a robust increase in the expression level of ELTD1 in cellular and animal models of CCM disease. Conclusions Taken together, our results demonstrate for the first time ELTD1 involvement in CCM pathogenesis, and its tight link with CCM genes. Thanks to this putative new prognostic biomarker, future clinical studies in larger patient cohorts will aim at improving the CCM disease management and risk stratification in patients, as well as placing the basis for targeted therapeutic strategies in CCM.

In the context of chameleon gravity, we present a semi-analytical solution of the chameleon field profile in an accurately modelled galaxy cluster’s mass components, namely the stellar mass of the Brightest Cluster Galaxy (BCG), the baryonic mass in galaxies other than the BCG, the mass of the Intra-Cluster Medium (ICM) and the diffuse cold dark matter (CDM). The obtained semi-analytic profile is validated against the numerical solution of the chameleon field equation and implemented in the MG-MAMPOSSt code for kinematic analyses of galaxy clusters in modified gravity scenarios. By means of mock halos, simulated both in GR and in modified gravity, we show that the combination of the velocities and positions of cluster member galaxies, along with the data of the stellar velocity dispersion profile of the BCG, can impose constraints on the parameter space of the chameleon model; for a cluster generated in GR, these constraints are at the same level as a joint lensing+kinematics analysis of a cluster modelled with a single mass profile, without the BCG data.

Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here we present the data obtained from 2345 acute leukemia patients. Genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and 11 novel TPGs were identified. Thus, a total of 135 different MLL rearrangements have been identified so far, of which 94 TPGs are now characterized at the molecular level. In all, 35 out of these 94 TPGs occur recurrently, but only 9 specific gene fusions account for more than 90% of all illegitimate recombinations of the MLL gene. We observed an age-dependent breakpoint shift with breakpoints localizing within MLL intron 11 associated with acute lymphoblastic leukemia and younger patients, while breakpoints in MLL intron 9 predominate in AML or older patients. The molecular characterization of MLL breakpoints suggests different etiologies in the different age groups and allows the correlation of functional domains of the MLL gene with clinical outcome. This study provides a comprehensive analysis of the MLL recombinome in acute leukemia and demonstrates that the establishment of patient-specific chromosomal fusion sites allows the design of specific PCR primers for minimal residual disease analyses for all patients.

The flavonoid izalpinin was isolated from the aerial parts of Chromolaena leivensis. Its structural determination was carried out using MS and NMR spectroscopic techniques (1H, 13C). This compound was evaluated for its anti-inflammatory effect in a rat model on λ-carrageenan-induced plantar edema. Paw inflammation was measured at one-hour intervals for seven hours following the administration of λ-carrageenan. Serum creatine kinase (CK) levels were evaluated, obtaining statistically significant results with the treatments at doses of 10 mg/kg (* p < 0.01) and 20 mg/kg (** p < 0.005). The anti-inflammatory effect of the compound was evaluated by using plethysmography, and the results showed significant differences at the three concentrations (10 mg/kg, 20 mg/kg, 40 mg/kg) in the first and third hours after treatment. * p < 0.05; ** p < 0.001; *** p < 0.0001 vs. the negative control group treated with vehicle (DMSO). Lastly, molecular docking analyses reveal that izalpinin has a strong binding affinity with five target proteins involved in the inflammatory process. The analysis using molecular dynamics allowed demonstrating that the ligand–protein complexes present acceptable stability, with RMSD values within the allowed range.

Asbestosis is a prevalent worldwide problem, but scarce data sourced from developing countries are available. We describe the sociodemographic characteristics and patterns in the occurrence of care provided for asbestosis in Colombia during the periods 2010-2014 and 2015-2019 to establish the behavior, trends, and variables associated with concentrations among people attended by asbestosis. A retrospective descriptive study was carried out with data from the Integrated Social Protection Information System (SISPRO) for two 5-year periods. People attended by asbestosis (ICD-10: J61) were identified; the frequency of patient visits, sociodemographic characteristics, case distribution patterns, and trends in both five-year periods were described, as was the crude frequency (cFr, 95% CI) of asbestosis (1,000,000 people/year) in both five-year periods (cFr ratio, 95% CI). During the period 2010-2019, 765 people attended by asbestosis were identified; there were 308 people attended by asbestosis between 2010-2014 (cFr: 2.20, 1.96-2.47), and ther were 457 people attended by asbestos between 2015-2019 (cFr: 3.14, 2.92-3.50). In both periods, the estimated cFr in men was nine times the estimated cFr in women. The cFr increased in the 2015-2019 period (cFr_ratio: 1.23, 1.06-1.43). Compared with the 2010-2014 period, the cFr of asbestosis increased in women (cFr_ratio: 1.44, 1.03-2.01), in the Andean (cFr_ratio: 1.61, 1.35-1.95) and Caribbean regions (cFr_ratio: 1. 66, 1.21-2.30), in the urban area (cFr_ratio: 1.24, 1.05-1.48), and in the age groups 45-59 years (cFr_ratio: 1.34, 1.001-1.79) and ≥60 years (cFr_ratio: 1.43, 1.13-1.83). During two five-year periods, the cFr of asbestosis was higher in men; between the first and second five-year periods, it increased significantly, especially in urbanized geographic areas and in populations aged ≥45 years. The estimates possibly reflect the effect of disease latency or the expected impact of public health policies to monitor asbestos exposure and complications.

Background:Respiratory tract infections are among the leading causes of hospitalization in rheumatoid arthritis (RA) and Streptococcus Pneumoniae (Sp) is one of the most frequent pathogens involved. For these patients, the CDC recommends a combined vaccination scheme (CVS) using two types of Sp vaccines but evidence on its effectiveness remains insufficient.1Objectives:To assess the impact of the combined vaccination scheme on the incidence of Sp infections in patients with RA treated with DMARD.Methods:A cohort was nested in a register including patients with RA who were prescribed a bDMARD or tsDMARD -either naïve or switch- from 2000 to March 2019.The target outcomes were invasive pneumococcal disease (IPD) and all-cause community-acquired pneumonia (CAP), as defined by relevant MedDRA codes. Demographic and clinical features were also retrieved. Each participant centre informed about the date when they implemented a systematic Sp vaccination protocol and whether they were using the CVS. Those not adopting this practice were excluded from the analysis.Crude incidence rates (IRs) were calculated for each outcome as well as for its combination (combined variable defined as “Sp infections”). Exposure was split into two periods, considering the date when the CVS was officially recommended in Spain (May 2015). The incidence rate ratio (IRR) comparing pre and post implementation periods was estimated with a Poisson regression model adjusted for sex, age and comorbidities (Charlson Index).Results:1704 patients were included, their characteristics are shown in table 1. One centre was excluded for not using any Sp vaccination protocol while the remaining ones reported using the CVS. Crude IRs by periods (pre and post CVS implementation) and age groups are shown in table 2. The IRR of the post-vaccination period after adjusting for age, sex and comorbidities (Charlson index) was 0.40 (95% CI: 0.29 - 0.56), p<0.001.Table 1.Baseline features of the cohort.DemographicsAge, years *60.6 (12.5)Female1356 (79.6%)Current smoking287 (16.8%)RA clinical characteristicsDisease duration, years*9.1 (7.9)RF positive875 (74%)ACPA positive831 (71%)DAS28*4.6 (1.4)Other clinical characteristicsBody Mass Index*27.5 (5.2)Charlson index*2.3 (1.5)Chronic pulmonary Disease125 (9.3%)Diabetes mellitus147 (9%)*Data presented as mean (standard deviation).Table 1Characteristics of patients with RA at time of RA diagnosis and patients with SAB with/without RA at time of SAB diagnosisCharacteristic, n (%)At RA diagnosisAt first-time SABRA (n=34,627)RA (n=228)Non-RA (n=25,268)Age, years (IQR)59.8 (48.8-70.3)71.8 (62.3-79.2)69.7 (57.7-79.7)Female, %69%59%38%Diabetes mellitus2,467 (7.1%)51 (22.4%)5,678 (22.5%)Heart failure1,018 (2.9%)42 (18.4%)4,718 (18.7%)Liver disease454 (1.3%)12 (5.3%)2,189 (8.7%)Chronic obstructive pulmonary disease1,677 (4.8%)36 (15.8%)3,412 (13.5%)Cancer2,124 (6.1%)60 (26.3%)6,742 (26.7%)HIV11 (0.0%)0 (0%)127 (0.5%)Solid organ transplant8 (0.0%)0 (0%)357 (1.4%)Alcohol abuse642 (1.9%)12 (5.3%)3,356 (13.3%)Chronic dialysis29 (0.1%)11 (4.8%)2,256 (8.9%)Orthopedic implant3,807 (11.0%)89 (39.0%)5,422 (21.5%)Cardiac or vascular implant731 (2.1%)18 (7.9%)1,940 (7.7%)Glucocorticoid (0-90 days prior)7,062 (20.4%)99 (43.4 %)2,911 (11.5%)Invasive surgery (0-30 days prior)1,962 (5.7%)62 (27.2%)8,451 (33.5%)Table 2.Crude IRs (95% CI) of the outcomes of interest split by age.Overall<65≥65PrePostPrePostPrePostSP-Infections33 (27.4-39.9)12.7 (9.8-16.4)28 (22.4-35)11.8 (8.9-15.6)60.3 (42.4-85.8)19.5 (10.8-35.2)IPD–0.4 (0.1-1.6)–0.4 (0.1-1.8)––All cause CAP23.6 (19.0-29.3)11.5 (8.8-15)18.7 (14.4-24.4)10.4 (7.7-14)50.8 (34.8-74)19.5 (10.8-35.2)Conclusion:The incidence of Sp infections experienced a decrease in RA patients taking bDMARD or tsDMARD after the introduction of the stepwise combined vaccination scheme that is not related to age, sex or comorbidities.References:[1] Furer V, et al. Ann Rheum Dis 2019;0:1–14Disclosure of Interests:Sebastian C Rodriguez-García Speakers bureau: Novartis Farmaceutica, S.A., Merck Sharp & Dohme España, S.A., Sanofi Aventis, UCB Pharma, Carlos Sánchez-Piedra: None declared, Raul Castellanos-Moreira Speakers bureau: Lilly, MSD, Sanofi, UCB, Dolores Ruiz-Montesinos: None declared, Victoria Hernandez: None declared, Manuel Pombo: None declared, Fernando Sánchez-Alonso: None declared, Loreto Carmona Grant/research support from: Novartis Farmaceutica, SA, Pfizer, S.L.U., Merck Sharp & Dohme España, S.A., Roche Farma, S.A, Sanofi Aventis, AbbVie Spain, S.L.U., and Laboratorios Gebro Pharma, SA (All trhough institution), Juan Jesús Gómez-Reino: None declared

IntroductionAsymptomatic carriers (AC) of the new SARS-CoV-2 represent an important source of spread for COVID-19. Early diagnosis of these cases is a powerful tool to control the pandemic. Our objective was to characterise patients with AC status and identify associated sociodemographic factors.MethodsUsing a cross-sectional design and the national database of daily occurrence of COVID-19, we characterised both socially and demographically all ACs. Additional correspondence analysis and logistic regression model were performed to identify characteristics associated with AC state (OR, 95% CI).Results76.162 ACs (12.1%; 95% CI 12.0% to 12.2%) were identified, mainly before epidemiological week 35. Age≤26 years (1.18; 1.09 to 1.28), male sex (1.51; 1.40 to 1.62), cases imported from Venezuela, Argentina, Brazil, Germany, Puerto Rico, Spain, USA or Mexico (12.6; 3.03 to 52.5) and autochthonous cases (22.6; 5.62 to 91.4) increased the risk of identifying ACs. We also identified groups of departments with moderate (1.23; 1.13 to 1.34) and strong (19.8; 18.6 to 21.0) association with ACs.ConclusionSociodemographic characteristics strongly associated with AC were identified, which may explain its epidemiological relevance and usefulness to optimise mass screening strategies and prevent person-to-person transmission.