Early imaging and molecular changes with neoadjuvant bevacizumab in stage ii/iii breast cancer

This prospective, phase II study evaluated novel biomarkers as predictors of response to bevacizumab in patients with breast cancer (BC), using serial imaging methods and gene expression analysis. Patients with primary stage II/III BC received bevacizumab 15 mg/kg (cycle 1; C1), then four cycles of neoadjuvant docetaxel doxorubicin, and bevacizumab every 3 weeks (C2–C5). Tumour proliferation and hypoxic status were evaluated using18F-fluoro-3'-deoxy-3'-L-fluorothymidine (FLT)-and18F-fluoromisonidazole (FMISO)-positron emission tomography (PET) at baseline, and during C1 and C5. Pre-and post-bevacizumab vascular changes were evaluated using dynamic contrastenhanced magnetic resonance imaging (DCE-MRI). Molecular biomarkers were assessed using microarray analysis. A total of 70 patients were assessed for treatment efficacy. Significant decreases from baseline in tumour proliferation (FLT-PET), vascularity, and perfusion (DCE-MRI) were observed during C1 (p = 0.001), independent of tumour subtype. Bevacizumab treatment did not affect hypoxic tumour status (FMISO-PET). Significant changes in the expression of 28 genes were observed after C1. Changes in vascular endothelial growth factor receptor (VEGFR)-2p levels were observed in 65 patients, with a > 20% decrease in VEGFR-2p observed in 13/65. Serial imaging techniques. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Chemical, Thermal and Spectroscopic Methods to Assess Biodegradation of Winery-Distillery Wastes during Composting

The objective of this work was to study the co-composting process of wastes from the winery and distillery industry with animal manures, using the classical chemical methods traditionally used in composting studies together with advanced instrumental methods (thermal analysis, FT-IR and CPMAS 13C NMR techniques), to evaluate the development of the process and the quality of the end-products obtained. For this, three piles were elaborated by the turning composting system, using as raw materials winery-distillery wastes (grape marc and exhausted grape marc) and animal manures (cattle manure and poultry manure). The classical analytical methods showed a suitable development of the process in all the piles, but these techniques were ineffective to study the humification process during the composting of this type of materials. However, their combination with the advanced instrumental techniques clearly provided more information regarding the turnover of the organic matter pools during the composting process of these materials. Thermal analysis allowed to estimate the degradability of the remaining material and to assess qualitatively the rate of OM stabilization and recalcitrant C in the compost samples, based on the energy required to achieve the same mass losses. FT-IR spectra mainly showed variations between piles and time of sampling in the bands associated to complex organic compounds (mainly at 1420 and 1540 cm-1) and to nitrate and inorganic components (at 875 and 1384 cm-1, respectively), indicating composted material stability and maturity; while CPMAS 13C NMR provided semi-quantitatively partition of C compounds and structures during the process, being especially interesting their variation to evaluate the biotransformation of each C pool, especially in the comparison of recalcitrant C vs labile C pools, such as Alkyl /O-Alkyl ratio.This work was supported by a contract to MABM, Spanish Ministry of Economy and Competitiveness (Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I+D+i) 2008-2011), co-funded by the EU through the Social Funds (contract reference PTQ-12-05655)

New constraints on the presence of debris disks around G 196-3 B and VHS J125601.92–125723.9 b

Context. The existence of warm (protoplanetary) disks around very young isolated planetary and brown dwarf mass objects is known based on near- and mid-infrared flux excesses and millimeter observations. These disks may later evolve into debris disks or rings, although none have been observed or confirmed so far. Little is known about circum(sub)stellar and debris disks around substellar objects. Aims. We aim to investigate the presence of debris disks around two of the closest (~20 pc), young substellar companions, namely G196-3 B and VHS J125601.92–125723.9 b (VHS J1256–1257 b), whose masses straddle the borderline between planets and brown dwarfs. Both are companions at wide orbits (≥100 au) of M-type dwarfs and their ages (50–100 Myr and 150–300 Myr, respectively) are thought to be adequate for the detection of second-generation disks. Methods. We obtained deep images of G196-3 B and VHS J1256–1257 b with the NOrthern Extended Millimeter Array (NOEMA) at 1.3 mm. These data were combined with recently published Atacama Large Millimeter Array (ALMA) and Very Large Array (VLA) data of VHS J1256–1257 b at 0.87 mm and 0.9 cm, respectively. Results. Neither G196-3 B nor VHS J1256–1257 b were detected in the NOEMA, ALMA, and VLA data. At 1.3 mm, we imposed flux upper limits of 0.108 mJy (G196-3 B) and 0.153 mJy (VHS J1256–1257 b) with a 3-σ confidence. Using the flux upper limits at the millimeter and radio wavelength regimes, we derived maximum values of 1.38×10−2 MEarth and 5.46 × 10−3 MEarth for the mass of any cold dust that might be surrounding G196-3 B and VHS J1256–1257 b, respectively. Conclusions. We put our results in the context of other deep millimeter observations of free-floating and companion objects with substellar masses smaller than 20 MJup and ages between approximately one and a few hundred million years. Only two very young (2–5.4 Myr) objects are detected out of a few tens of them. This implies that the disks around these very low-mass objects must have small masses, and possibly reduced sizes, in agreement with findings by other groups. If debris disks around substellar objects scale down (in mass and size) in a similar manner as protoplanetary disks do, millimeter observations of moderately young brown dwarfs and planets must be at least two orders of magnitude deeper to be able to detect and characterize their surrounding debris disks

Radio emission in a nearby, ultra-cool dwarf binary: A multifrequency study

Context. The substellar triple system VHS J125601.92−125723.9 (hereafter VHS 1256−1257) is composed of an equal-mass M7.5 brown dwarf binary and an L7 low-mass substellar object. In Guirado et al. (2018, A&A, 610, A23) we published the detection of radio emission at 8.4 GHz coming from the central binary and making it an excellent target for further observations. Aims. We aim to identify the origin of the radio emission occurring in the central binary of VHS 1256−1257 while discussing the expected mechanisms involved in the radio emission of ultra-cool dwarfs. Methods. We observed this system with the Karl G. Jansky Very Large Array, the European very-long-baseline interferometry (VLBI) Network, the enhanced Multi-Element Remotely Linked Interferometer Network, the NOrthern Extended Millimeter Array, and the Atacama Large Millimetre Array at frequencies ranging from 5 GHz up to 345 GHz in several epochs during 2017, 2018, and 2019. Results. We found radio emission at 6 GHz and 33 GHz coincident with the expected position of the central binary of VHS 1256−1257. The Stokes I density fluxes detected were 73 ± 4 μJy and 83 ± 13 μJy, respectively, with no detectable circular polarisation or pulses. No emission is detected at higher frequencies (230 GHz and 345 GHz), nor at 5 GHz with VLBI arrays. The emission appears to be stable over almost three years at 6 GHz. To explain the constraints obtained both from the detections and non-detections, we considered multiple scenarios including thermal and nonthermal emission, and different contributions from each component of the binary. Conclusions. Our results can be well explained by nonthermal gyrosynchrotron emission originating at radiation belts with a low plasma density (ne = 300−700 cm−3), a moderate magnetic field strength (B ≈ 140 G), and an energy distribution of electrons following a power-law (dN/dE ∝ E−δ) with δ fixed at 1.36. These radiation belts would need to be present in both components and also be viewed equatorially. © ESO 2022.We sincerely thank the anonymous referee for his/her very useful and constructive criticisms and suggestions. This paper is based on observations carried out with the IRAM NOEMA interferometer and the IRAM 30-m telescope. IRAM is supported by INSU/CNRS (France), MPG (Germany), and IGN (Spain). JBC and JCG were partially supported by the Spanish MINECO projects AYA2015-63939-C2-2-P, PGC2018-098915-B-C22 and by the Generalitat Valenciana project GVPROMETEO2020−080. MPT acknowledges financial support from the State Agency for Research of the Spanish MCIU through the “Center of Excellence Severo Ochoa” award to the Instituto de Astrofísica de Andalucía (SEV-2017-0709) and through grants PGC2018-098915-B-C21 and PID2020-117404GB-C21 (MCI/AEI/FEDER, UE). RA was supported by the Generalitat Valenciana postdoctoral grant APOSTD/2018/177. BG acknowledges support from the UK Science and Technology Facilities Council (STFC) via the Consolidated Grant ST/R000905/1. MRZO and VJSB acknowledge the financial support from PID2019-109522GB-C51 and PID2019-109522GB-C53, respectively.Peer reviewe

A Novel Framework for Phenotyping Children With Suspected or Confirmed Infection for Future Biomarker Studies

Copyright © 2021 Nijman, Oostenbrink, Moll, Casals-Pascual, von Both, Cunnington, De, Eleftheriou, Emonts, Fink, van der Flier, de Groot, Kaforou, Kohlmaier, Kuijpers, Lim, Maconochie, Paulus, Martinon-Torres, Pokorn, Romaine, Calle, Schlapbach, Smit, Tsolia, Usuf, Wright, Yeung, Zavadska, Zenz, Levin, Herberg, Carrol and the PERFORM consortium (Personalized Risk assessment in febrile children to optimize Real-life Management across the European Union).Background: The limited diagnostic accuracy of biomarkers in children at risk of a serious bacterial infection (SBI) might be due to the imperfect reference standard of SBI. We aimed to evaluate the diagnostic performance of a new classification algorithm for biomarker discovery in children at risk of SBI. Methods: We used data from five previously published, prospective observational biomarker discovery studies, which included patients aged 0– <16 years: the Alder Hey emergency department (n = 1,120), Alder Hey pediatric intensive care unit (n = 355), Erasmus emergency department (n = 1,993), Maasstad emergency department (n = 714) and St. Mary's hospital (n = 200) cohorts. Biomarkers including procalcitonin (PCT) (4 cohorts), neutrophil gelatinase-associated lipocalin-2 (NGAL) (3 cohorts) and resistin (2 cohorts) were compared for their ability to classify patients according to current standards (dichotomous classification of SBI vs. non-SBI), vs. a proposed PERFORM classification algorithm that assign patients to one of eleven categories. These categories were based on clinical phenotype, test outcomes and C-reactive protein level and accounted for the uncertainty of final diagnosis in many febrile children. The success of the biomarkers was measured by the Area under the receiver operating Curves (AUCs) when they were used individually or in combination. Results: Using the new PERFORM classification system, patients with clinically confident bacterial diagnosis (“definite bacterial” category) had significantly higher levels of PCT, NGAL and resistin compared with those with a clinically confident viral diagnosis (“definite viral” category). Patients with diagnostic uncertainty had biomarker concentrations that varied across the spectrum. AUCs were higher for classification of “definite bacterial” vs. “definite viral” following the PERFORM algorithm than using the “SBI” vs. “non-SBI” classification; summary AUC for PCT was 0.77 (95% CI 0.72–0.82) vs. 0.70 (95% CI 0.65–0.75); for NGAL this was 0.80 (95% CI 0.69–0.91) vs. 0.70 (95% CI 0.58–0.81); for resistin this was 0.68 (95% CI 0.61–0.75) vs. 0.64 (0.58–0.69) The three biomarkers combined had summary AUC of 0.83 (0.77–0.89) for “definite bacterial” vs. “definite viral” infections and 0.71 (0.67–0.74) for “SBI” vs. “non-SBI.” Conclusion: Biomarkers of bacterial infection were strongly associated with the diagnostic categories using the PERFORM classification system in five independent cohorts. Our proposed algorithm provides a novel framework for phenotyping children with suspected or confirmed infection for future biomarker studies.publishersversionPeer reviewe

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A multi-platform approach to identify a blood-based host protein signature for distinguishing between bacterial and viral infections in febrile children (PERFORM): a multi-cohort machine learning study.

BACKGROUND Differentiating between self-resolving viral infections and bacterial infections in children who are febrile is a common challenge, causing difficulties in identifying which individuals require antibiotics. Studying the host response to infection can provide useful insights and can lead to the identification of biomarkers of infection with diagnostic potential. This study aimed to identify host protein biomarkers for future development into an accurate, rapid point-of-care test that can distinguish between bacterial and viral infections, by recruiting children presenting to health-care settings with fever or a history of fever in the previous 72 h. METHODS In this multi-cohort machine learning study, patient data were taken from EUCLIDS, the Swiss Pediatric Sepsis study, the GENDRES study, and the PERFORM study, which were all based in Europe. We generated three high-dimensional proteomic datasets (SomaScan and two via liquid chromatography tandem mass spectrometry, referred to as MS-A and MS-B) using targeted and untargeted platforms (SomaScan and liquid chromatography mass spectrometry). Protein biomarkers were then shortlisted using differential abundance analysis, feature selection using forward selection-partial least squares (FS-PLS; 100 iterations), along with a literature search. Identified proteins were tested with Luminex and ELISA and iterative FS-PLS was done again (25 iterations) on the Luminex results alone, and the Luminex and ELISA results together. A sparse protein signature for distinguishing between bacterial and viral infections was identified from the selected proteins. The performance of this signature was finally tested using Luminex assays and by calculating disease risk scores. FINDINGS 376 children provided serum or plasma samples for use in the discovery of protein biomarkers. 79 serum samples were collected for the generation of the SomaScan dataset, 147 plasma samples for the MS-A dataset, and 150 plasma samples for the MS-B dataset. Differential abundance analysis, and the first round of feature selection using FS-PLS identified 35 protein biomarker candidates, of which 13 had commercial ELISA or Luminex tests available. 16 proteins with ELISA or Luminex tests available were identified by literature review. Further evaluation via Luminex and ELISA and the second round of feature selection using FS-PLS revealed a six-protein signature: three of the included proteins are elevated in bacterial infections (SELE, NGAL, and IFN-γ), and three are elevated in viral infections (IL18, NCAM1, and LG3BP). Performance testing of the signature using Luminex assays revealed area under the receiver operating characteristic curve values between 89·4% and 93·6%. INTERPRETATION This study has led to the identification of a protein signature that could be ultimately developed into a blood-based point-of-care diagnostic test for rapidly diagnosing bacterial and viral infections in febrile children. Such a test has the potential to greatly improve care of children who are febrile, ensuring that the correct individuals receive antibiotics. FUNDING European Union's Horizon 2020 research and innovation programme, the European Union's Seventh Framework Programme (EUCLIDS), Imperial Biomedical Research Centre of the National Institute for Health Research, the Wellcome Trust and Medical Research Foundation, Instituto de Salud Carlos III, Consorcio Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Grupos de Refeencia Competitiva, Swiss State Secretariat for Education, Research and Innovation

Heterogeneous catalysis for sustainable biodiesel production via esterification and transesterification

Concern over the economics of accessing fossil fuel reserves, and widespread acceptance of the anthropogenic origin of rising CO2 emissions and associated climate change from combusting such carbon sources, is driving academic and commercial research into new routes to sustainable fuels to meet the demands of a rapidly rising global population. Here we discuss catalytic esterification and transesterification solutions to the clean synthesis of biodiesel, the most readily implemented and low cost, alternative source of transportation fuels to meet future societal demands

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group