HOPE (SOLTI-1903) breast cancer study: real-world, patient-centric, clinical practice study to assess the impact of genomic data on next treatment decision-choice in patients with locally advanced or metastatic breast cancer

Background Metastatic breast cancer (mBC) causes nearly all BC-related deaths. Next-generation sequencing (NGS) technologies allow for the application of personalized medicine using targeted therapies that could improve patients' outcomes. However, NGS is not routinely used in the clinical practice and its cost induces access-inequity among patients. We hypothesized that promoting active patient participation in the management of their disease offering access to NGS testing and to the subsequent medical interpretation and recommendations provided by a multidisciplinary molecular advisory board (MAB) could contribute to progressively overcome this challenge. We designed HOPE (SOLTI-1903) breast cancer trial, a study where patients voluntarily lead their inclusion through a digital tool (DT). The main objectives of HOPE study are to empower mBC patients, gather real-world data on the use of molecular information in the management of mBC and to generate evidence to assess the clinical utility for healthcare systems.Trial design After self-registration through the DT, the study team validates eligibility criteria and assists patients with mBC in the subsequent steps. Patients get access to the information sheet and sign the informed consent form through an advanced digital signature. Afterwards, they provide the most recent (preferably) metastatic archival tumor sample for DNA-sequencing and a blood sample obtained at the time of disease progression for ctDNA analysis. Paired results are reviewed by the MAB, considering patient's medical history. The MAB provides a further interpretation of molecular results and potential treatment recommendations, including ongoing clinical trials and further (germline) genetic testing. Participants self-document their treatment and disease evolution for the next 2 years. Patients are encouraged to involve their physicians in the study. HOPE also includes a patient empowerment program with educational workshops and videos about mBC and precision medicine in oncology. The primary endpoint of the study was to describe the feasibility of a patient-centric precision oncology program in mBC patients when a comprehensive genomic profile is available to decide on a subsequent line of treatment

Towards precision medicine: defining and characterizing adipose tissue dysfunction to identify early immunometabolic risk in symptom-free adults from the GEMM family study

Interactions between macrophages and adipocytes are early molecular factors influencing adipose tissue (AT) dysfunction, resulting in high leptin, low adiponectin circulating levels and low-grade metaflammation, leading to insulin resistance (IR) with increased cardiovascular risk. We report the characterization of AT dysfunction through measurements of the adiponectin/leptin ratio (ALR), the adipo-insulin resistance index (Adipo-IRi), fasting/postprandial (F/P) immunometabolic phenotyping and direct F/P differential gene expression in AT biopsies obtained from symptom-free adults from the GEMM family study. AT dysfunction was evaluated through associations of the ALR with F/P insulin-glucose axis, lipid-lipoprotein metabolism, and inflammatory markers. A relevant pattern of negative associations between decreased ALR and markers of systemic low-grade metaflammation, HOMA, and postprandial cardiovascular risk hyperinsulinemic, triglyceride and GLP-1 curves was found. We also analysed their plasma non-coding microRNAs and shotgun lipidomics profiles finding trends that may reflect a pattern of adipose tissue dysfunction in the fed and fasted state. Direct gene differential expression data showed initial patterns of AT molecular signatures of key immunometabolic genes involved in AT expansion, angiogenic remodelling and immune cell migration. These data reinforce the central, early role of AT dysfunction at the molecular and systemic level in the pathogenesis of IR and immunometabolic disorders

Robust Iron Coordination Complexes with N‑Based Neutral Ligands As Efficient Fenton-Like Catalysts at Neutral pH

The homogeneous Fenton-like oxidation of organic substrates in water with hydrogen peroxide, catalyzed by six different metal coordination complexes with N-based neutral ligands, was studied at ambient conditions and initial pH 7, employing hydrogen peroxide as the terminal oxidant. At low catalyst concentration, the catalytic oxidative depletion of toluene achieved by selected catalysts was much more efficient than that obtained by the Fenton reagent at pH 3. The influence of pH, the water matrix and the catalyst/hydrogen peroxide concentration were investigated for the oxidation of toluene employing [FeCl₂(bpmcn)] (<b>1</b>, bpmcn = <i>N</i>,<i>N</i>′-bis­(2-pyridylmethyl)-<i>N</i>,<i>N</i>′-dimethyl-<i>trans</i>-1,2-diaminocyclohexane), the most efficient catalyst of the series. Moreover, the evolution of catalysts [FeCl₂(bpmcn)] (<b>1</b>) and [Fe­(OTf)₂(Pytacn)] (<b>3</b>, Pytacn = 1-(2-pyridylmethyl)-4,7-dimethyl-1,4,7-triazacyclononane, OTf = trifluoromethanesulfonate anion) during the course of the reaction was also studied by electrospray ionization mass spectrometry (ESI-MS). The oxidation products derived from toluene oxidation were also analyzed. A plausible mechanism of toluene degradation using [FeCl₂(bpmcn)] (<b>1</b>) and [Fe­(OTf)₂(Pytacn)] (<b>3</b>) as catalysts was proposed, which involves the coexistence of a metal-based path, analogous to that operating in organic media where substrate oxidation is executed by an iron­(V)-oxo-hydroxo species, in parallel to a Fenton-type process where hydroxyl radicals are formed

Metoprolol and metoprolol acid degradation in UV/H2O2 treated wastewaters: An integrated screening approach for the identification of hazardous transformation products

Advancements on analytical strategies to determine the chemicals present in treated wastewater are necessary to clearly link their occurrence with the ecotoxicity of such effluents. This study describes the development of an integrated screening approach to determine the highest number of pharmaceutical transformation products (TPs) in a single run. The identification of TPs was based on the comparison of detected features with literature sources, compound prediction tools, in-house libraries and reference standards using high-resolution mass spectrometry (HRMS). This integrated approach allowed a better estimation (in silico) of the ecotoxicological contribution of the individual TPs identified. As a proof of concept, this methodology was applied for identification of the TPs generated from metoprolol and its main human metabolite (metoprolol acid) in pure water, hospital wastewater and industrial wastewater treated by UV/H2O2. Twenty-four TPs with potential ecotoxicological implications were identified and their presence was pinpointed as a function of the treated wastewater. An integrated screening approach has been developed using four different screening methodologies in the same run. Additionally, the metabolite MTPA has been considered as a target pollutant in UV/H2O2 experiments. © 2019 Elsevier B.V.This work has been funded by the Spanish Ministry of Economy and Competitiveness (projects CTM 2013 48545-C2-1-R and CTM2017-85385-C2-1-R) and partly supported by the Generalitat de Catalunya (Consolidated Research Groups 2017-SGR-14, 2017-SGR-1404, 2017-SGR-1124, 2017-SGR-1318 and 2017-SGR-1016). S.R.M and R.G.O acknowledge the “Redes de Excelencia 2015″ program (CTM2015-71054-REDT). S.R.M and G.B. acknowledge the Ramon y Cajal research fellowships (RYC-2014-16707 and RYC-2014-16754) from the Spanish Ministry of Economy and Competitiveness. A.J.G. acknowledges the predoctoral grant from AGAUR (2018FI_B1_00212). R.G.O thanks to “Obra Social La Caixa” for receiving funding to carry out this research through the Intensification Research Fellowship 2017-URL-IR2Q-023. We would like to thank Sant Joan de Déu Hospital staff for their collaboration during the sampling campaign. We also thank to Thermo Scientific and Marie-Pierre Pavageau for providing us the technical support using Compound Discoverer 2.0 software.Peer reviewe

Hydrophobic Fe-Zeolites for Removal of MTBE from Water by Combination of Adsorption and Oxidation

Several zeolites were evaluated as adsorbents for the removal of MTBE from water in a screening process. It was observed that the SiO₂/Al₂O₃ molar ratio is a decisive factor for the adsorption properties, at least in the case of ZSM5 zeolites. ZSM5 zeolites with SiO₂/Al₂O₃ ratios >200 were found to provide the best sorption properties for MTBE. To design a combined sorption/reaction method, regeneration of the loaded zeolites by selected advanced oxidation processes (AOP) was studied: (1) Fenton treatment using H₂O₂ with dissolved iron salts and (2) heterogeneous Fenton-like oxidation with Fe immobilized on the zeolites. The first was ineffective in regenerating loaded zeolites. However, heterogeneous catalysis using Fe species immobilized on the zeolite by liquid ion exchange was markedly more effective. Although these hydrophobic zeolites have a low ion exchange capacity, resulting in iron loadings of ≤0.09 wt %, it was possible to obtain sufficiently active catalysts. Hydrophobic Fe-zeolites can therefore be regarded as promising materials for the removal of MTBE from water, since they allow the combination of efficient adsorption and oxidative degradation of MTBE by H₂O₂. In contrast to the homogeneous catalysis by dissolved iron ions, these heterogeneous catalysts work at near-neutral pH and can be easily reused. Fe-zeolites as adsorbents/catalysts showed a good stability in both batch and column experiments

Automotive Electrification Challenges Shown by Real-World Driving Data and Lifecycle Assessment

Electric mobility is considered a solution to reduce carbon emissions. We expanded a lifecycle assessment with data on technical limitations and driving habits (based on real-world data) in order to identify the environmentally optimal drivetrain for each individual driving behavior with current and projected technologies, focusing on CO2 emissions. By combining all data, an environmentally optimal European drivetrain mix is calculated, which is dominated by fuel-cell electric vehicles (50% in 2020, 47% in 2030), followed by plug-in hybrid-electric vehicles (37%, 40%), battery-electric vehicles (BEV) (5%, 12%), and Diesel vehicles (2%, 1%). Driving behavior defines the most environmental drivetrain and the coexistence of different drivetrains is currently still necessary. Such information is crucial to identify limitations and unmet technological needs for full electrification. If range is not considered a limitation, the environmentally optimal drivetrain mix is dominated by BEVs (71%, 75%), followed by fuel cell electric vehicles (25%, 19%) and plug-in electric vehicles (4%, 6%). This confirms the potential environmental benefits of BEVs for current and future transportation. Developments in battery energy density, charging, and sustainable production, as well as a change in driving behavior, will be crucial to make BEVs the environmentally optimal drivetrain choice

Forecasting the Global Battery Material Flow: Analyzing the Break-Even Points at Which Secondary Battery Raw Materials Can Substitute Primary Materials in the Battery Production

Growing numbers of electric vehicles (EVs) as well as controversial discussions on cost, scarcity and the environmental and social sustainability of primary raw materials that are needed for battery production together emphasize the necessity for battery recycling in the future. Nonetheless, the market for battery recycling is not fully understood and captured in data today. The underlying reasons are found in both market size and various parameters such as the battery-technology mix, the resulting material demand and expected battery lifetime. In consequence, the question of when secondary-material availability from battery recycling is sufficient to satisfy the global cobalt demand for EV applications has not yet been clarified. To address this question, this study estimates the global battery raw-material demand together with the expected amount of the recycled materials by 2035, taking into account a number of parameters affecting future battery material flows. While focusing on cobalt, nickel, lithium, and manganese, the results indicate that the global cobalt demand can be satisfied from secondary sources by the early 2030s in three out of four different technology forecast scenarios. Furthermore, a sensitivity analysis highlights the amount of waste occurring during battery production and battery lifetime as the main drivers for secondary-material availability by 2035

Forecasting the Global Battery Material Flow:Analyzing the Break-Even Points at Which Secondary Battery Raw Materials Can Substitute Primary Materials in the Battery Production

Growing numbers of electric vehicles (EVs) as well as controversial discussions on cost, scarcity and the environmental and social sustainability of primary raw materials that are needed for battery production together emphasize the necessity for battery recycling in the future. Nonetheless, the market for battery recycling is not fully understood and captured in data today. The underlying reasons are found in both market size and various parameters such as the battery-technology mix, the resulting material demand and expected battery lifetime. In consequence, the question of when secondary-material availability from battery recycling is sufficient to satisfy the global cobalt demand for EV applications has not yet been clarified. To address this question, this study estimates the global battery raw-material demand together with the expected amount of the recycled materials by 2035, taking into account a number of parameters affecting future battery material flows. While focusing on cobalt, nickel, lithium, and manganese, the results indicate that the global cobalt demand can be satisfied from secondary sources by the early 2030s in three out of four different technology forecast scenarios. Furthermore, a sensitivity analysis highlights the amount of waste occurring during battery production and battery lifetime as the main drivers for secondary-material availability by 2035