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This work was supported by grant PID2021-125858OB-100 and the Severo Ochoa Excellence Program CEX2021-001189-S, funded by MCIN/AEI/ 10.13039/501100011033 and by “ERDF, a way of making Europe.” C.R.P. and EM-G were recipients of predoctoral grants ACIF/2021/364 funded by Conselleria d’Educació (Generalitat Valenciana, Comunitat Valenciana, Spain) and FPU18/02019 funded by MCIN/AEI/10.13039/501100011033 and by “ESF Investing in your future”, respectively., With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX 2021-001189-S), Data for Figure 1; -- Data for Figure 2; -- Data for Figure 3; -- Data for Figure 6; -- Data for Figure 7; -- Data for Supplementary Figure 1; -- Data for Supplementary Figure 2; -- Data for Supplementary Figure 3; -- Data for Supplementary Figure 4, Peer reviewed

[Background] Managing the inflammatory response to SARS-Cov-2 could prevent respiratory insufficiency. Cytokine profiles could identify cases at risk of severe disease., [Methods] We designed a randomized phase II clinical trial to determine whether the combination of ruxolitinib (5 mg twice a day for 7 days followed by 10 mg BID for 7 days) plus simvastatin (40 mg once a day for 14 days), could reduce the incidence of respiratory insufficiency in COVID-19. 48 cytokines were correlated with clinical outcome., [Participants] Patients admitted due to COVID-19 infection with mild disease., [Results] Up to 92 were included. Mean age was 64 ± 17, and 28 (30%) were female. 11 (22%) patients in the control arm and 6 (12%) in the experimental arm reached an OSCI grade of 5 or higher (p = 0.29). Unsupervised analysis of cytokines detected two clusters (CL-1 and CL-2). CL-1 presented a higher risk of clinical deterioration vs CL-2 (13 [33%] vs 2 [6%] cases, p = 0.009) and death (5 [11%] vs 0 cases, p = 0.059). Supervised Machine Learning (ML) analysis led to a model that predicted patient deterioration 48h before occurrence with a 85% accuracy., [Conclusions] Ruxolitinib plus simvastatin did not impact the outcome of COVID-19. Cytokine profiling identified patients at risk of severe COVID-19 and predicted clinical deterioration., [Trial registration] https://clinicaltrials.gov/, identifier NCT04348695., Peer reviewed

[Background] Managing the inflammatory response to SARS-Cov-2 could prevent respiratory insufficiency. Cytokine profiles could identify cases at risk of severe disease., [Methods] We designed a randomized phase II clinical trial to determine whether the combination of ruxolitinib (5 mg twice a day for 7 days followed by 10 mg BID for 7 days) plus simvastatin (40 mg once a day for 14 days), could reduce the incidence of respiratory insufficiency in COVID-19. 48 cytokines were correlated with clinical outcome., [Participants] Patients admitted due to COVID-19 infection with mild disease., [Results] Up to 92 were included. Mean age was 64 ± 17, and 28 (30%) were female. 11 (22%) patients in the control arm and 6 (12%) in the experimental arm reached an OSCI grade of 5 or higher (p = 0.29). Unsupervised analysis of cytokines detected two clusters (CL-1 and CL-2). CL-1 presented a higher risk of clinical deterioration vs CL-2 (13 [33%] vs 2 [6%] cases, p = 0.009) and death (5 [11%] vs 0 cases, p = 0.059). Supervised Machine Learning (ML) analysis led to a model that predicted patient deterioration 48h before occurrence with a 85% accuracy., [Conclusions] Ruxolitinib plus simvastatin did not impact the outcome of COVID-19. Cytokine profiling identified patients at risk of severe COVID-19 and predicted clinical deterioration., [Trial registration] https://clinicaltrials.gov/, identifier NCT04348695., Peer reviewed

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[Ir1–xCoxO2 thin films were prepared by reactive magnetron co–sputtering deposition on Si substrates at room temperature (RT) from metallic Ir and Co targets. Crystal structures were characterized by powder X-ray diffraction (XRD) at room temperature in a Rigaku D-Max system using Cu Kalpha wavelength. The resistivity measurements were carried out in a PPMS-9T. The magnetic measurements were carried out in a SQUID magnetometer MPMS–XL (both from Quantum Design). Transmission electron microscopy images, HRTEM (High resolution transmission electron microscopy) and STEM-HAADF (scanning TEM with high angular annular dark field detector), were performed by Tecnai F30 and Titan G2 80-300 keV (with aberration corrected probe), respectively, operated at 300 keV. The compositional analysis profile was performed by energy dispersive spectroscopy (EDS) in an Oxford Aztec equipment in situ STEM-HAADF analysis. The lamellae for TEM analysis were prepared by focused ion beam in a commertial Helios 650 N dual beam equipment. X–ray absorption spectroscopy (XAS) measurements were carried out at the B18 beamline of the Diamond Light Source. Co K-edge and Ir L2,3-edge XAS spectra of the films were measured in fluorescence mode using Quick-EXAFS technique. A Si (111) double crystal monochromator was used to select the incident X-ray energy. Co K-edge (Ir L3-edge) measurements have been performed using collimating mirror with Pt (Cr) coating. The fluorescence measurements have been performed using Canberra 36-pixel Monolithic Segmented Hyper Pure Germanium Detector with the STFC Xspress4 Digital Pulse Processor.], Spanish MICINN Project No. PID2020-115159GBI00/AEI/10.13039/501100011033; Regional Government of Aragon (Grant No. E12-23R RASMIA); European Commission under the H2020-MSCA-RISE-2020 MELON project Nº 872631 and H2020-MSCA-RISE-2021 ULTIMATE-I project Nº 101007825., Peer reviewed

Contains: Figures S1-S2 and Table S1., The lack of effective first-line antibiotic treatments against Neisseria gonorrhoeae, and the worldwide dissemination of resistant strains, are the main drivers of a worsening global health crisis. β-lactam antibiotics have been the backbone of therapeutic armamentarium against gonococci. However, we are lacking critical insights to design rationally optimized therapies. In the present work, we generated the first PBP-binding data set on 18 currently available and clinically relevant β-lactams and 4 β-lactamase inhibitors in two N. gonorrhoeae ATCC type collection strains, 19424 and 49226 (PBP2 type XXII and A39T change in mtrR). PBP binding (IC50) was determined via the Bocillin FL binding assay in isolated membrane preparations. Three clusters of differential PBP IC50s were identified and were mostly consistent across both strains, but with quantitative differences. Carbapenems were coselective for PBP2 and PBP3 (0.01 to 0.03 mg/L). Third- and fourth-generation cephalosporins cefixime, cefotaxime, ceftazidime, cefepime, and ceftriaxone showed the lowest IC50 values for PBP2 (0.01 mg/L), whereas cefoxitin, ceftaroline, and ceftolozane required higher concentrations (0.04 to >2 mg/L). Aztreonam was selective for PBP2 in both strains (0.03 to 0.07 mg/L); amdinocillin bound this PBP at higher concentrations (1.33 to 2.94 mg/L). Penicillins specifically targeted PBP2 in strain ATCC 19424 (0.02 to 0.19 mg/L) and showed limited inhibition in strain ATCC 49226 (0.01 to >2 mg/L). Preferential PBP2 binding was observed by β-lactam-based β-lactamase inhibitors sulbactam and tazobactam (1.07 to 6.02 mg/L); meanwhile, diazabicyclooctane inhibitors relebactam and avibactam were selective for PBP3 (1.27 to 5.40 mg/L). This data set will set the bar for future studies that will help the rational use and translational development of antibiotics against multidrug-resistant (MDR) N. gonorrhoeae., B.M. received funds from a RADIX17/3-1 fellowship and RADIX17/3-2 grant, programs within the FUTURMed project IdISBa Research Institute of Health Sciences of the Balearic Islands, Hospital Universitario Son Espases, Palma, Spain. Call funded by the 2017 annual plan of the sustainable tourism tax. Govern de les Illes Balears, by the Miguel Servet Research Contract Program CP20/00138 from the National Institutes of Health Carlos III (ISCIII) and by the Agencia Estatal de Investigación (AEI - State Research Agency), Spain, through the Plan Estatal de Investigación Científica PROYECTOS DE I+D+i PID2020-112654RB-I00 / AEI / 10.13039/501100011033. The assay development part of this work was supported by the award R01AI136803 to B.M. from the National Institute of Allergy and Infectious Diseases (NIAID). The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health (NIH). A.O. received funds from the Ministerio de Economía y Competitividad of Spain, Instituto de Salud Carlos III, cofinanced by European Regional Development Fund “A Way to Achieve Europe” ERDF, through the Spanish Network for the Research in Infectious Diseases (RD16/0016). A.O. has received fees as speaker and/or research grants from MSD, Pfizer, and Wockhardt., Peer reviewed

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[Description of methods used for collection/generation of data] Morhological studies and microphotographs were carried out with the Hayear 5130 ocular camera and E3ISPM 20000 camera coupled to Euromex SB. 1903-P stereomicroscope., We present the description of a new species of Solifugae from the Iberian Peninsula, Gluvia brunnea sp. nov., which has been found so far in southeast Spain. The morphological description is accompanied by molecular and multiple factor analyses, jointly giving full support to the specific status of the taxon. Finally, we discuss the intraspecific variability of both species, G. dorsalis and G. brunnea sp. nov., and the recent history of the genus. We also discuss the usefulness of multiple factor analysis to quantitatively separate species, and also stress that some specimens of this new species were found in Mesovoid Shallow Substratum stations, being the very first time that Solifugae are captured in this type of traps., This research was funded by MCIN/AEI /10.13039/501100011033, grant number PID2019-103863RB-I00, and by Museum of Natural History at the University of Almeria (CECOUAL) grant number 001592, and some support by the Institute for Almeria Studies and the Berja City Council” and “The APC was funded by the Spanish National Research Council (CSIC) and by MCIN/AEI /10.13039/501100011033, grant number PID2019-103863RB-I00., Peer reviewed

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This file contains: Supplementary Figure 1 and 2 and Supplementary Table 1 to 4., Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors demonstrated activity in terms of progression-free survival (PFS) in advanced dedifferentiated liposarcoma (DD-LPS), a sarcoma with CDK4 amplification. CDK4 overexpression is by far more common than amplification in sarcomas and it might be a rational target for CDK inhibitors. Preclinical investigators of this study found that CDK4 overexpression, while not of CDKN2A, was the most consistent predictive factor for palbociclib efficacy in sarcomas. Advanced adult-type soft-tissue sarcoma, excluding DD-LPS, or bone sarcoma patients, progressing after at least one systemic line, whose tumors overexpressed CDK4, but not CDKN2A at baseline biopsy, were accrued in this single-arm phase II trial (EudraCT number: 2016-004039-19). With the main endpoint of a 6-month PFS rate, 40% was considered promising in this population. Palbociclib was administered orally at 125 mg/day for 21 days in 28-day cycles. A total of 214 patients with 236 CDK4/CDKN2A determinations were assessed for prescreening, archival material (141), and screening, baseline biopsy (95). There were 28 (29%) with favorable mRNA profiles from 95 screened patients at baseline. From 23 enrolled patients, 21 evaluable, the 6-month PFS rate was 29% (95% CI 9–48), and there were 6 patients out of 21 with a PFS longer than 6 months. The median PFS and overall survival were 4.2 (95% CI 3.6–4.8) and 12 (95% CI 8.7–15.4) months, respectively. Translational research showed a significant correlation between CDK4 mRNA and protein expression. Palbociclib was active in a variety of sarcoma subtypes, selected by CDK4/CDKN2A, and deserves further investigation in the sarcoma context., The authors also thank the donors and all the hospitals for participating in patient screening/pre-screening. The authors would like to thank the Spanish Group for Research on Sarcomas (GEIS) for supporting the study Pfizer for providing drug supply and funding for patient screening, and the International Accelerator Award funded by Cancer Research UK [C56167/A29363], Associazione Italiana per la Ricerca sul Cancro [AIRC-24297] and Fundacion Científica—Asociacion Espanola Contra el Cancer [Foundation AECC-GEACC19007MA] for funding translational research. The authors would like to thank Patricio Ledesma, Araceli Rodriguez Morales, and Gabriela Golab for Data Management, Helen Wright for the English edition, and Paloma Sanchez-Bustos and Angela Gavilan for helping with patient screening. David S. Moura is a recipient of a Sara Borrell postdoctoral fellowship funded by the National Institute of Health Carlos III (ISCIII) (CD20/00155). The authors would also like to thank the SELNET project. SELNET has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 825806. The authors would like to give special thanks to all the patients who participated in the study and their relatives., Peer reviewed