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Sulfide glasses, with high room-temperature Li-ion conductivities, are a promising class of solid-state electrolytes for all-solid-state batteries. Yet, when in contact with Li metal, our current understanding of important interfacial phenomena such as electrolyte reduction and Li-ion transport is still quite limited, especially at the atomic scale. Here, using first-principles molecular dynamics simulations, we tackle these open questions head-on and examine key interfacial properties of Li-argyrodite Li

This is a critical review of artificial intelligence/machine learning (AI/ML) methods applied to battery research. It aims at providing a comprehensive, authoritative, and critical, yet easily understandable, review of general interest to the battery community. It addresses the concepts, approaches, tools, outcomes, and challenges of using AI/ML as an accelerator for the design and optimization of the next generation of batteries - a current hot topic. It intends to create both accessibility of these tools to the chemistry and electrochemical energy sciences communities and completeness in terms of the different battery R&D aspects covered.

Triple-negative breast cancer (TNBC) is a heterogeneous group of breast cancer and is characterized by aggressiveness and poor prognosis. MicroRNA represents a new class of biomarkers, and accumulating evidence indicates that microRNAs contribute to tumorigenesis and cancer metastasis. It has been described that miR-210 is highly expressed in TNBC, and its overexpression had been linked to poor prognosis. In a previous work, we showed that in TNBC miR-210 is expressed in tumor cells and also in the tumor microenvironment (TME), particularly in inflammatory CD45-LCA positive cells. However, the exact identity of these cells remained unknown. In this study, we performed in situ hybridization and immunohistochemistry using validated antibodies for the different specific immune cell markers on adjacent sections of 23 TNBC infiltrated with immune cells. We found that miR-210 expressing cells in the TME were stained positive with CD79a, a B-cell lineage marker. These tumor-infiltrating cells were negative for CD20 and Ki-67 but positive for MUM1 and CD38 and also expressed immunoglobulins, indicating that they are immunoglobulin-producing plasma cells (PCs). To the best of our knowledge, this is the first study demonstrating miR-210 expression in tumor-infiltrating PCs.

This article reviews the research contributions along the past five years concerning to monolithic materials for the development of affinity-based sorbents in the field of microextraction techniques. The first part of this paper includes an introduction regarding monolithic affinity media and information of different binding agents (such as immunoglobulin-binding proteins, enzymes, lectins, antibodies, aptamers, dyes and immobilized metal ions and nanoparticles, among others) that can act as affinity ligands. Then, the preparation of monoliths and ligand immobilization strategies as well as the different available formats (syringes, pipette tips, spin columns, capillaries, disks and microfluidic devices) for their use in micro-solid phase extraction are mentioned. On the basis of the binding agents used to prepare affinity monolithic-based sorbents, the last part of manuscript includes several analytical and preparative applications of these monoliths for sample preparation covering different fields (analytical chemistry, biotechnology, proteomics, etc.). Current trends and possible future directions of these affinity-based sorbents in sample preparation are also given.

Desde que en 1987 se publicase el primer real decreto que regulaba las especialidades de enfermería hasta hoy mismo han transcurrido más de 30 años. Es el real decreto publicado en 2005 el que realmente permitió el desarrollo formativo de parte de las especialidades reconocidas en el mismo (enfermería familiar y comunitaria, enfermería pediátrica, enfermería geriátrica y enfermería del trabajo) ya que las enfermeras especialistas obstétrico-ginecológicas (matronas) y las especialistas de salud mental ya habían iniciado sus procesos formativos por vía de enfermero interno residente desde tiempo atrás. Hoy día, la formación de la especialidad de enfermería familiar y comunitaria ha logrado implementarse en todas las comunidades autónomas, pero no ha tenido idéntico desarrollo en cuanto a la incorporación de las especialistas en las instituciones sanitarias de los respectivos servicios de salud de las comunidades autónomas. Esta circunstancia está generando una gran desmotivación entre las enfermeras comunitarias, tanto las especialistas como quienes esperan poder obtener el título a través de la prueba excepcional. Muchos de los objetivos alcanzados hasta la fecha han sido posibles gracias al trabajo de las sociedades científicas de enfermería comunitaria (Asociación de Enfermería Comunitaria [AEC] y Federación de Asociaciones de Enfermería Comunitaria y Atención Primaria [FAECAP]), que han permitido avanzar y que el proceso no se paralizase, aunque aún son muchos los logros por alcanzar en los que las citadas sociedades científicas siguen trabajando. En una sociedad en la que el cuidado enfermero es cada vez más necesario y demandado, este debe tener una mayor consideración y posición en las políticas sanitarias, ya que ha demostrado su eficacia, y puede ser el modelo que permita hacer sostenible el sistema sanitario y, por tanto, las enfermeras especialistas en enfermería familiar y comunitaria deben dejar de ser una oportunidad para pasar a ser una realidad. More the 30 years have passed since the first Royal Decree that regulated nursing specialties was published in 1987. It is the Royal Decree published in 2005 that really allowed the training development of part of the specialties recognized in it (family and community nursing, paediatric nursing, geriatric nursing and occupational health nursing) since the obstetric-gynaecological specialist nurses (midwives) and mental health specialists had long since already started their training processes through the resident internal nurse model, today, training in the specialty of family and community nursing has been implemented in all the autonomous communities, but has not had the same development in terms of the incorporation of specialists in the health institutions of the respective health services of the autonomous communities This circumstance is generating a great lack of motivation among community nurses, both specialists and those who hope to obtain the qualification through a specialty exam. Many of the objectives achieved to date have been made possible thanks to the work of the scientific societies of community nursing (Association of Community Nursing [AEC] and Federation of Associations of Community Nursing and Primary Care [FAECAP]), which have allowed progress to be made and the process not to be halted, although there are still many achievements to be made on which the aforementioned scientific societies continue to work. In a society in which nursing care is increasingly necessary and demanded, it must have greater consideration and position in health policies, since it has demonstrated its effectiveness and can be the model that allows the health system to be sustainable. Therefore, nurses who specialize in family and community nursing must cease constituting an opportunity and become a reality.

Due to their merits of high capacity, abundant resources and environmental benignity, Fe monosulfides are considered as attractive electrode materials for Li-ion batteries. However, inferior cyclability and rate performances resulted from inherent low conductivity limit their applications. Herein, we present novel 3D flower-like micro/nano-structure FeS/N-doped-C composites which are directly synthesized from low-cost organosulfur compounds through facile precipitation and subsequent calcination and for the first time applied as cathodes for lithium storage. The FeS nanoparticles are coated by highly conductive N-doped-C shells. Such a confinement of coating microstructures, especially outer N-doped-C, is highly beneficial for the conversion reactions (FeS+2Li++2e−↔Fe + Li2S), and could strengthen conductivity and simultaneously better protect FeS from electrolyte corrosions, ensuring stable conductive frameworks. Also, such N-doped-C anchor FeS, Fe, and Li2S effectively, as confirmed by density functional theory calculations. Thus, the FeS/N-doped-C cathodes exhibit remarkable cycling stability (621 mAh g−1 at 200th cycle at 1C, with a decay of 0.07%/cycle), and high rate performances (600 mAh g−1 even at 10C), delivering higher energy density than commercial LiCoO2 cathodes. This work discloses a novel and paramount route to exploit transition metal sulfides for lithium storage and helps us further understand the key role of N-doping in electrochemical energy storage.

This article reports for the first time a programmable-flow-based mesofluidic platform that accommodates electric-field-driven liquid phase microextraction (μ-EME) in a fully automated mode. The miniaturized system is composed of a computer-controlled microsyringe pump and a multiposition rotary valve for handling aqueous and organic solutions at a low microliter volume and acts as a front-end to online liquid chromatographic separation. The organic membrane is automatically renewed and disposed of in every analytical cycle, thus minimizing analyte carry-over effects while avoiding analyst intervention. The proof-of-concept applicability of the automated mesofluidic device is demonstrated by the liquid chromatographic determination of nonsteriodal anti-inflammatory drugs in μ-EME processed complex samples (such as urine and influent wastewater) using online heart-cut approaches. Using 5 μL of 1-octanol, 7.5 μL of untreated sample and 7.5 μL of acceptor solution (25 mM NaOH), and 250 V for only 10 min in a stopped-flow mode, the extraction recoveries for the μ-EME of ibuprofen, ketoprofen, naproxen, and diclofenac exceed 40% in real samples. The flow-through system features moderately selective extraction regardless of the sample matrix constituents with repeatability values better than 13%.

Summary With an extremely high theoretical energy density, solid-state lithium-sulfur (Li-S) batteries (SSLSBs) are emerging as one of the most feasible chemistries; however, their energy efficiency and long-term cyclability are severely hampered by the lithium metal (Li°) dendrite formation during repeated discharge/charge cycles and the shuttling of aggressive polysulfide intermediates between two electrodes. Herein, we report (difluoromethanesulfonyl) (trifluoromethanesulfonyl)imide anion [N(SO2CF2H)(SO2CF3)]−, hereafter DFTFSI−, as a designer anion for high-performance polymer-based SSLSBs. In contrast to the widely used bis(trifluoromethanesulfonyl)imide anion [N(SO2CF3)2]− (TFSI−), DFTFSI-based SSLSBs provide superior interfacial stability against Li°, extremely high discharge and areal capacities, very high Coulombic efficiency, and long-term cyclability, surpassing the reported literature values, in terms of gravimetric energy density. This work opens a new door for accelerating the practical deployment of SSLSBs in the future.

The anion chemistry of lithium salts plays a pivotal role in dictating the physicochemical and electrochemical performance of solid polymer electrolytes (SPEs), thus affecting the cyclability of all-solid-state lithium metal batteries (ASSLMBs). The bis(trifluoromethanesulfonyl)imide anion (TFSI- ) has long been studied as the most promising candidate for SPEs; however, the Li-ion conductivities of the TFSI-based SPEs still remain low (Li-ion transference number: ca. 0.2). In this work, we report new hydrogen-containing anions, conceived based on theoretical considerations, as an electrolyte salt for SPEs. SPEs comprising hydrogen-containing anions achieve higher Li-ion conductivities than TFSI-based ones, and those anions are electrochemically stable for various kinds of ASSLMBs (Li-LiFePO4 , Li-S, and Li-O2 batteries). This opens up a new avenue for designing safe and high-performance ASSLMBs in the future.

This article addresses the issue of information availability for decision-making at the subregional level. It proposes the construction of a territorial development index (TDI) based on administrative records and comprising 19 variables grouped into 6 dimensions: (i) cultural capital, (ii) social capital, (iii) human capital, (iv) institutional capital, (v) tangible capital and (vi) economic capital. The approach underlying the proposed model centres on territorial development and the structural factors determining it. The variables making up the TDI were selected in consultation with experts and with the use of multivariate statistical analyses. This paper sets out to document many of the phases, procedures and decisions leading to the TDI, as a way of opening up the discussion around this line of research. It concludes by presenting calculations of the TDI for the Chilean municipalities of Angol and Carahue.

[EN] In designing low enthalpy geothermal systems, the ideal location and length of the boreholes in the well-field is the key to improve the performance and reduce the costs of the installation. The correct assessment of the heat conductivity of the ground (λ) plays also a very important role in estimating the amount of energy that we are going to be able to obtain from the subsoil and the ideal pace of the process. In low enthalpy geothermal installations based on granite type environments is especially important to improve the information we have from the subsoil at a small scale. This is due to the great horizontal variation we can find on this kind of terrain. Electrical conductivity (C = 1/ρ, ρ = resistivity in ohm meters) can be related to thermal conductivity (λ) of many rock types (Directive (EU), 2019) (see Robertson, 1988). We show that a 3D electrical resistivity survey can be used as a proxy for λ in terrain with weathered and solid granitic rock. Knowledge of λ is essential for the design of efficient ground source heat pump systems that use vertical wells for closed-loop systems. Shorter well lengths are accomplished if wells are in solid granite with high λ. Furthermore the electrical resistivity survey identifies low density, clayey subsurface materials that may require specialized drilling methods. Project cost savings can result from shorter borehole lengths, number of holes, and correct drilling methods.

Among high-capacity, low-cost cathode contenders for Na-ion batteries, layered transition-metal oxides are particularly promising materials. Yet there is a strong need to improve their long-term st...

Este articulo aborda la problematica de la disponibilidad de informacion para la toma de decisiones a nivel subregional. Se propone construir un indice de desarrollo territorial (IDT) sobre la base de registros administrativos, que se compone de 19 variables, agrupadas en 6 dimensiones: i) capital cultural; ii) capital social; iii) capital humano; iv) capital institucional; v) capital fisico, y vi) capital economico. El modelo propuesto se basa en el enfoque del desarrollo territorial y los factores estructurales que lo definen. La definicion de las variables que componen el IDT se basa en la consulta a expertos y en analisis estadisticos multivariantes. Se intenta documentar gran parte de las fases, los procedimientos y las decisiones que dieron lugar al IDT, como una forma de abrir la discusion en torno a esta linea de investigacion. Para finalizar se presenta el calculo del IDT de los municipios chilenos de Angol y Carahue.

Electrolytes with high ionic conductivity and intrinsic safety are key to achieving practical high-performance batteries and supercapacitors. Water-in-salt electrolytes (WiSEs) make the performance of an aqueous lithium-ion battery well comparable to that of non-aqueous systems owing to their wide electrochemical windows and non-flammability. Critically, a WiSE is practically limited by the issues of high viscosity and inevitable leakage, restricting its rate performance and safety. Here, we report an approach to achieve ultra-high salt loading of hydrogels by implanting hydrogel 3D ion channels in a WiSE, endowing the WiSE-based electrolyte with versatility and high ionic conductivity. Our polyacrylamide–chitosan-based WiSE (HiSE) affords high ionic conductivity (51.3 mS cm−1) and operating voltage (2.6 V) and excellent flexibility and self-healing ability. These properties are benefitted by polar corona, which is formed by immobilizing water molecules on abundant hydroxyl and amino groups inside the HiSE. The core–corona configuration offers a unique 3D channel to allow Li+ to fast transport at an unsaturated coordination state, as evidenced though differential scanning calorimetry, Raman spectroscopy and first-principles calculations. As expected, these merits impart unprecedented flexibility, reversibility and stability to HiSE-based supercapacitors and lithium-ion batteries. The former delivers a specific energy of 23.54 W h kg−1, while 110.7 W h kg−1 can be reached for the latter, both of which maintain high rate performance and long-term stability.

The search for sodium ion battery cathodes has led to considerable interest in sodium layered oxides due to their attractive properties – e.g. flexibility, versatility, and intrinsically fast Na ion structural diffusion (leading to enhanced rate capability). Based upon our rational approach to material selection (i.e. doping a Mn-rich structure with small quantities of elements carefully selected to enhance performance properties), we present here two high performance materials synthesised via solid-state reaction: P2-Na2/3Mn0.9−xNixTi0.05Fe0.05O2 (x = 0.10 and 0.20, designated Ni 10% and Ni 20% respectively). Electrochemical characterisation demonstrated that, while both materials compare favourably with the literature, the energy density and cyclability of the Ni 10% material was superior to that of Ni 20%. Detailed examination of the two materials using a range of techniques (including in situ and ex situ X-ray and neutron diffraction, scanning and transmission electron microscopy, solid state NMR, and DFT simulations) provides a good understanding of their relative physiochemical nature and electrochemical behaviour, and demonstrates the power of our stoichiometric selection strategy. In this way this work provides details of both new, high-performance materials, and validates our rational design approach.

Interaction between groundwaters with different salinities and lakes show seasonal variations driven by changes in precipitation and evapotranspiration. In the vicinity of Villafáfila lakes, local fresh and brackish regional groundwaters feeds the lakes, forming a brine in the lake sediments aquitard. Two TDEM surveys (summer 2019 and winter 2020) were carried out. Five TDEM soundings were acquired at the same location for each survey, forming a profile from the hills to the lake-shore. Simultaneously to the TDEM surveys, electric conductivity of lake water and groundwater was measured. The resistivity boundary between the local fresh (10–35 Ohm/m) and regional brackish groundwater (2–5 Ohm/m) is well marked at 600 m above sea level (masl) below the hills, and at 650 masl below the lowlands surrounding the lakes. During the summer, fresh-brackish groundwater interphase rises due to evaporative pumping occurring in the lowlands. This increases groundwater salinity close to the terrain surface favoring precipitation of halite efflorescences. Annual record of EC in a piezometer confirms the summer ascendant of the brine contained in the lake aquitard. TDEM sounding is fast and simple technique to monitor seasonal variations in fresh-brackish groundwater interphase and to detect possible salinization of consumption wells and environmental changes.

Seismic hazard assessment of present-day tectonic faults may be improved by studying their structure and kinematics. These features have been mainly determined by surface geological studies of exposed fault traces, structural lateral segmentation or paleoseismic trenches. All these approaches rely mainly on two-dimensional analyses of surface outcrops, while knowledge of the faults at depth remain largely inaccessible. To improve on such limitations, geophysical methods can be applied to establish detailed information on fault morphology and segmentation at depth. This work analyzes new results of a deep electrical resistivity tomography survey acquired across the Baza Fault, a present-day tectonic fault that controls the geometry of the Neogene intra-mountainous Baza Basin (Betic Cordillera, Spain). Interpretation of our preferred resistivity model reveals its detailed structure down to approximately 1000 m depth. The survey shows a minimum 2 km wide complex normal fault system, with rotational tilting blocks bounded by potentially listric normal faults. This study presents subsurface evidence of the Baza fault (F3), coincident the main topographic scarps. However, the geophysical model and geomorphic evidence also support a fault branch (F1) that might be an additional active seismogenic source. The geophysical survey technique presented in this study provides essential data to improve assessment of the seismogenic potential of the Baza Fault., The project was funded by GEOLAND SERVICES SL and Técnicas Geofísicas SL. The authors appreciate the assistance of anonymous reviewers for their comments and support on this paper, especially professor D. Pedro Carrasco Morillo. Without his vision this work would not have been possible. This manuscript has been edited by Guido Jones, currently funded by the Cabildo de Tenerife, under the TFinnova Programme supported by MEDI and FDCAN funds. PJG's contribution was supported by the Spanish Ministerio de Ciencia e Innovación research project COMPACT (proyecto PID2019-104571RA-I00 de investigación financiado por MCIN/AEI/10.13039/501100011033) and a 2020 Leonardo Fellowship Grant for Researchers and Cultural Creators, BBVA Foundation (IN[20]_CMA_CCT_0015).

Unlocking the full potential of solid-state electrolytes (SSEs) is key to enabling safer and more-energy dense technologies than today's Li-ion batteries. In particular, composite materials comprising a conductive, flexible polymer matrix embedding ceramic filler particles are emerging as a good strategy to provide the combination of conductivity and mechanical and chemical stability demanded from SSEs. However, the electrochemical activity of these materials strongly depends on their polymer/ceramic interfacial Li-ion dynamics at the molecular scale, whose fundamental understanding remains elusive. While this interface has been explored for nonconductive ceramic fillers, atomistic modeling of interfaces involving a potentially more promising conductive ceramic filler is still lacking. We address this shortfall by employing molecular dynamics and enhanced Monte Carlo techniques to gain unprecedented insights into the interfacial Li-ion dynamics in a composite polymer-ceramic electrolyte, which integrates polyethylene oxide plus LiN(CF

Resumen de la publicación de una participación en formato µVídeo en en el congreso Divulga NextGen (1ª edición) que se celebrará online, de manera gratuita y en las redes sociales los días 26, 27 y 28 de mayo de 2021., Proyecto CTM2017-84763-C3-3-R Contrato postdoctoral VALi+D (APOSTD/2019/141), {"references":["K. Zhu et al., Long-term phototransformation of microplastics under simulated sunlight irradiation in aquatic environments: Roles of reactive oxygen species. Water Research. 173 (2020), 115564.","A. Milne, M. S. Davey, P. J. Worsfold, E. P. Achterberg, A. R. Taylor, Real-time detection of reactive oxygen species generation by marine phytoplankton using flow injection-chemiluminescence. Limnology and Oceanography: Methods. 7 (2009) 706-715."]}

Resumen de la publicación de una participación en formato µVídeo en en el congreso Divulga NextGen (1ª edición) que se celebrará online, de manera gratuita y en las redes sociales los días 26, 27 y 28 de mayo de 2021., {"references":["O. M. Rodriguez-Narvaez, J. M. Peralta-Hernandez, A. Goonetilleke, E. R. Bandala, Treatment technologies for emerging contaminants in water: A review. Chemical Engineering Journal. 323 (2017), pp. 361–380.","C. Sophia A., E. C. Lima, Removal of emerging contaminants from the environment by adsorption. Ecotoxicology and Environmental Safety. 150, 1–17 (2018)."]}

Using first-principles simulations, we focus on the study of Co

Predictive factors for adverse events in metastatic colorectal cancer patients treated with regorafenib are currently lacking. In this safety analysis of a prospective phase II clinical trial, we assess the association between several clinical, laboratory, and imaging parameters and the occurrence of adverse events. Our results show that female sex is an independent risk factor for increased toxicity. Background: Regorafenib is a standard treatment for refractory metastatic colorectal cancer (mCRC). In view of the toxicity burden, significant research efforts have been made to increase the therapeutic ratio of this multikinase inhibitor. Predictive factors for treatment-related adverse events (TRAEs), however, are still lacking. Materials and Methods: We assessed the association between a number of baseline clinical, laboratory and imaging parameters and the occurrence of TRAEs in 136 patients who had received regorafenib (160 mg/day, 3-weeks-on/1-week-off) in a prospective phase II clinical trial. Results: Grade >= 2 TRAEs during the first cycle of treatment (84% vs. 60%, P=.002) and grade >= 3 TRAEs throughout the whole treatment (71% vs. 53%, P=.035) occurred more frequently in females, with sex being the only independent predictive factor of early and any-time toxicity (OR 3.4; 95% CI: 1.2-11.1, P=.02 and OR 2.1; 95% CI: 1.0-4.4, P=.045, respectively). Fatigue, anorexia, hypertension, and rash were reported significantly more frequently by females than males (P

(CoxMn1-x)3O4 is a promising candidate material for solar thermochemical energy storage. A high-temperature model for this system would provide a valuable tool for evaluating its potential. However, predicting phase diagrams of complex systems with ab initio calculations is challenging due to the varied sources affecting the free energy, and with the prohibitive amount of configurations needed in the configurational entropy calculation. In this work, we compare three different machine learning (ML) approaches for sampling the configuration space of (CoxMn1-x)3O4, including a simpler ML approach, which would be suitable for application in high-throughput studies. We use experimental data for a feature of the phase diagram to assess the accuracy of model predictions. We find that with some methods, data pre-treatment is needed to obtain accurate predictions due to inherently composition-imbalanced training data for a mixed phase. We highlight that the important entropy contributions depend on the physical regimes of the system under investigation and that energy predictions with ML models are more challenging at compositions where there are energetically competing ground state crystal structures. Similar methods to those outlined here can be used to screen other candidate materials for thermochemical energy storage

This article reports on the first attempt towards investigating the leaching rates in the human gastrointestinal (GI) tract of plastic-borne contaminants that can be ingested accidentally using physiologically relevant body fluids. Oral bioaccessibility under fasted and fed states was determined in dynamic mode exploiting an automatic flow setup. The flow system is able to mimic the fast uptake of the released species from the polymeric matrix by absorption in the human digestive system by the in-line removal of the leached species. Complex GI extractants based on the Unified Bioaccessibility Method (UBM, fasted state) and Versantvoort test (fed-state) were brought through a microplastic-loaded metal microcolumn for semi-continuous leaching of plasticizers (phthalic acid ester congeners) and monomer/antioxidant species (bisphenol A, BPA) followed by in-line solid-phase extraction and clean-up of GI extracts prior to liquid chromatography analysis. The temporal extraction profiles were fitted to a first-order kinetic model for the estimation of maximum bioaccessibility pools and apparent leaching rates. Among all studied contaminants, only BPA, dimethylphthalate and diethylphthalate were appreciably released under dynamic GI conditions from high-density polyethylene pellets (average size of 110 μm), with average bioaccessibility values spanning from 51 to 84% and 48 to 87% for UBM and Versantvoort methods, respectively. No statistically significant differences in oral bioaccessibility pools were found under fed- and fasted-state dynamic extractions. The apparent kinetic constants under the fed state were greater by ≥30% as a consequence of the effect of the larger amounts of bile salts and digestive enzymes in the Versantvoort test on the leaching rates. The estimated average daily intake, in which bioaccessibility data are contemplated, indicated that plastic materials exceeding 0.3% (w/w) BPA might pose real risks to human health.

SCOPUS: le.j, info:eu-repo/semantics/published

Background Despite recent improvements, management of locally advanced rectal cancer (LARC) remains challenging, and many patients (pts) still experience recurrence. In preclinical models, combining Rego with an anti-PD-1 inhibitor led to superior tumour growth suppression as compared with either treatment alone. In a phase I clinical trial, remarkable results were reported for the combination of Rego and Nivo in advanced MSS colorectal cancer. This synergistic effect is thought to be secondary to the anti-angiogenic effects of Rego and its potential to reduce TAMs, promote M1 macrophage conversion, and downregulate expression of immunosuppressive factors. Building on these data, we designed a trial of Rego-Nivo with standard SCRT in the neoadjuvant setting of RC. Trial design REGINA is an academic, multicentre, single-arm, phase II trial sponsored by Institut Jules Bordet. Eligible patients are treated according to the following plan: induction phase (Nivo 240 mg IV D1&15, and Rego 80 mg PO D1-14), SCRT (D22-26), consolidation phase (Nivo 240 mg IV D29,43&57, and Rego 80 mg PO D29-49), and surgery (7-8 weeks after SCRT). Key eligibility criteria include age ≥18 years, ECOG PS ≤1, adenocarcinomas below the peritoneal reflection, intermediate-risk, stage II-III tumour (ie, cT3/T4aNany or cT1-2N+, no involvement/threatening of the mesorectal fascia, no involvement of lateral pelvic lymph nodes). The primary endpoint is pathological complete response (pCR). Secondary endpoints include, among others, toxicity, compliance to treatment, pTRG, event-free survival, and overall survival. The study follows a Simon’s two-stage design (null hypothesis pCR=12%, alternative hypothesis pCR=24%; α=5%, β=20%) with a maximum of 60 pts to be enrolled. A safety interim analysis is planned after the first 6 pts have completed treatment. Serial collection of tumour, blood, and stool samples is mandatory at pre-specified time points for exploratory correlative biomarker analyses. The trial is planned to be run at 8-10 centres across Belgium. Study recruitment started in Q1 2021 and is anticipated to complete in Q3 2023. Clinical trial information: NCT04503694.

Sulfide glasses, with high room-temperature Li-ion conductivities, are a promising class of solid-state electrolytes for all-solid-state batteries. Yet, when in contact with Li metal, our current understanding of important interfacial phenomena such as electrolyte reduction and Li-ion transport is still quite limited, especially at the atomic scale. Here, using first-principles molecular dynamics simulations, we tackle these open questions head-on and examine key interfacial properties of Li-argyrodite Li6PS5Cl electrolyte at bare and coated Li-metal anodes. Specifically, we investigate the role of the interfacial composition and morphology in a number of Li-metal surfaces, including surfaces coated with thin films of Li2Sn5, MoS2, LiF, and Li3P. Our materials models are designed to gain insights into the early stages of interface formation and structural evolution. In addition, by employing a novel topological analysis of procrystal electron density distribution as applied to interfacial solid-state ionics, we thoroughly assess Li-ion conductivity through the investigated interfaces. Our results provide evidence of progressive breaking of P-S bonds in PS43- groups and eventual P-P recombination of intermediate species as the main reaction mechanisms of Li6PS5Cl reduction by Li metal. We also predict Li2Sn5 as the most suitable coating to partially prevent the electrolyte degradation while keeping a relatively low interfacial resistance. These findings shed light on the interface chemistry of sulfide-based electrolytes in contact with Li metal and pave the way for rationalizing further computational and experimental studies in the field.

3596 Background: Surgical resection of CRLM aims to maximize patient survival. However, recurrence rates remain high post-surgery. We previously reported the prognostic relevance of tumor regression grading (TRG) and HGP of resected CRLM. Several studies reported the association of tumoral heterogeneity with anti-cancer drug resistance and prognosis. This study aims to explore tumoral heterogeneity for TRG and HGP in patients resected for CRLM and its prognostic implication. Methods: Tumor homogeneity for PR and HGP was evaluated in 2 independent cohorts. Cohort 1 included 57 patients (159 CRLMs) resected after chemotherapy/bevacizumab (prospective BEV-ONCO trial). Cohort 2 included 221 patients (582 CRLMs) operated after preoperative treatment or not. TRG (1 to 5 according complete to no response), HGP (desmoplastic, pushing, replacement or mixed) were evaluated for each CRLM. Max-TRG (higher TRG among all the CRLM) was used to define PR. Homogenous TRG (TRG-h) and HGP (HGP-h) was defined when all CRLMs had the same TRG or HGP pattern. HGP homogeneous desmoplastic (HGP-hd) was defined when all CRLM had a desmoplastic HGP. TRG-h, HGP-h and HGP-hd were combined into a homogeneity score (H-score: 0 to 3, 1 point given for each parameter and summed-up). Overall survival (OS for both cohorts), progression-free survival (PFS for cohort 1) and time to relapse (TTR for cohort 2) were estimated using the Kaplan–Meier method and compared by log-rank tests. Cox proportional hazard models were used for univariate and multivariate analyses. Results: Patient and disease characteristics were comparable in both cohorts excepted for preoperative treatment. In cohort 1, TRG-h and HGP-h were significantly associated with a longer PFS (HR = 0.21; 95CI:0.10-0.43, p < 0.001; HR = 0.27; 95CI = 0.14-0.54, p < 0.001) and better OS (HR = 0.23; 95CI = 0.07-0.70, p = 0.010; HR = 0.32; 95CI = 0.10-0.93, p = 0.037). Interestingly, the same significant results were observed in cohort 2 for TTR (TRG-h: HR = 0.60; 95CI = 0.43-0.85, p = 0.004; HGP-h: HR = 0.68; 95CI = 0.49-0.94, p = 0.017) and OS (TRG-h: HR = 0.51;95CI = 0.33-0.80, p = 0.003; HGP-h: HR = 0.63; 95CI = 0.41-0.97, p = 0.034). HGP-h reported a significant association with TRG-h, a Max-TRG < = 3, the absence of HGP replacement and mixed, a desmoplastic pattern, and the absence of sinusoidal obstruction syndrome in both cohorts. H-score was significantly associated with TTR (score 1-2: HR = 0.57; 95CI = 0.38-0.85, p = 0.004; score 3: HR = 0.4; 95CI = 0.24-0.64, p < 0.001) and OS (score 3: HR = 0.31; 95CI = 0.15-0.64, p < 0.001) in univariate analysis and with OS (HR = 0.74; 95CI = 0.59-0.94, p = 0.011) in multivariate analysis (cohort 2). Conclusions: TRG-h and HGP-h are strongly associated with patient’s survival. H-score could be an easy morphological and prognostic score to assess. Validation studies are needed.

3595 Background: Immune checkpoint inhibitors demonstrated poor efficacy in MSS mCRC. Cetuximab (anti-EGFR inhibitor) could initiate, independently from RAS mutation, an immunogenic tumor cell death and mediate antitumor immune response. In this trial, we aim to explore the clinical efficacy and safety of avelumab (anti-PDL1) combined with cetuximab and irinotecan for treatment refractory MSS mCRC and to understand its mechanisms of action through associated translational research. Methods: AVETUXIRI trial (NCT03608046) enrols MSS, chemorefractory (fluoropyrimidine, oxaliplatin, irinotecan and anti-EGFR treatment if RAS wt tumor) mCRC patients in 2 cohorts (A: RAS-wt, n = 10 – B: RAS-mut, n = 13). Primary endpoints are safety and tumor response rate ((i)RECIST1.1). Secondary endpoints include disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). According to a Simon 2-stage design, 23 patients have been included in the first stage of the trial. Multiplex immunofluorescence and RNA sequencing were realized on metastasis biopsies performed before, during and after the treatment. Densities of CD3+ (T cells) and CD8+ (cytotoxic) were quantified and analyzed with to generate an immunoscore (IS). RNA-seq data was used to perform differential expression analysis (DESeq2), gene set enrichment analysis (GSEA), deconvolution analysis (ConsensusTME) and gene ontology analysis (GO). Results:: No unexpected safety signals were observed. 3/10 tumor responses were observed in cohort A, 0/13 in cohort B. DCR was 60.0% and 61.5% in cohort A and B, respectively. 6-months PFS and 12-months OS rates were respectively 40.0% and 50.0% (cohort A) and 38.5% and 46.2% (cohort B). Independently of RAS mutation, patients with a high IS (metastasis biopsy, baseline) had significantly higher tumor shrinkage (OR = 18.67 p = 0.019), median PFS (6.9 vs 3.4 months; HR = 0.16, p = 0.002) and median OS (13.7 vs 7.9 months, HR = 0.26, p = 0.009). Similarly, tumor shrinkage and survival outcome (PFS > 6 months, OS > 12 months) were associated with upregulation of an adaptive immune response signature (including Th1, chemokine, adhesion molecules, immune checkpoints and T-cell activation genes, p. adj = 0.009) and the GSEA hallmark of epithelial to mesenchymal transition (p. adj = 0.045). Few modifications of IS and gene expression profiles were observed on the different metastasis biopsies performed overtime in the included patients. Conclusions: AVETUXIRI met its preliminary primary efficacy endpoint for RAS-wt mCRC pts, justifying its current continuation. Encouraging survival data observed in RAS-mut cohort allow the opening of a new cohort (PFS as primary endpoint). IS and adaptive immune response signature evaluated on metastases biopsies were associated with treatment efficacy and survival. Clinical trial information: NCT03608046.

TPS3641 Background: Colorectal cancer (CRC) is one of the most commonly occurring cancers with high recurrence and mortality rate. Circulating tumor DNA (ctDNA) can be used as a marker of minimal residual disease after completion of surgical resection of stage II/III CRC, where detectable ctDNA levels (positive) post-AdCTx are associated with an increased risk of disease recurrence and novel therapies are needed. Autogene cevumeran is an investigational individualized neoantigen-specific immunotherapy that is designed to harness an immune response against patient-specific, tumor neoantigens. This clinical trial is in progress in patients with Stage II (high risk) / Stage III colorectal cancer who are ctDNA positive following resection. Methods: Autogene cevumeran is being evaluated in an open-label, Phase 2, randomized, controlled trial in patients with Stage II / III CRC patients who are ctDNA positive following resection. Patients are randomized to adjuvant therapy followed by autogene cevumeran compared to adjuvant therapy followed by watchful waiting. The primary endpoint is disease-free survival (DFS). The trial has a Biomarker Cohort of 15 patients who will receive autogene cevumeran irrespective of the ctDNA status to pursue exploratory objectives. The main study of the phase 2 trial consists of a randomized (1:1) design comparing the experimental arm (autogene cevumeran) with the observational arm (watchful waiting) in ctDNA positive CRC patients. A third Exploratory Cohort explores the efficacy and safety of autogene cevumeran in ctDNA positive CRC patients with early recurrence/relapse during or after completion of AdCTx. Patients enrolled onto the experimental group, the biomarker and exploratory cohorts will receive autogene cevumeran 6x q1w, followed by 2x q2w, followed by 7 “booster” doses q6w, to receive a total of 15 doses (dosed at 25μg). AEs are assessed according to CTCAE v5. DFS will be determined by an independent central radiology assessment. Key eligibility criteria include 1) Patients must have stage II/III rectal cancer or stage II (high risk)/III colon cancer that has been surgically resected (R0 confirmed by pathology report); 2) patients must be ctDNA positive following resection; and 3) at least 5 tumor neoantigens must be identified in the provided tumor sample for autogene cevumeran manufacturing (RNA lipoplex, RNA-LPX). ClinicalTrials.gov identifier: NCT04486378.

Development of efficient strategies for the rational design of materials involved in the production and storage of renewable energy is essential for accelerating the transition to a low-carbon economy. To contribute to this goal, we propose a novel workflow for the assessment and optimization of battery materials. The approach effectively combines quantum and atomistic modelling/simulations, enhanced by efficient sampling, Bayesian parameterization, and experimental information. It is implemented to study prospective materials for lithium and sodium batteries.

Heart failure (HF) and diabetes are 2 strongly associated diseases. The main objective of this work was to analyze changes in the prognosis of patients with diabetes who were admitted for heart failure in 2 time periods.This work is a prospective study comparing prognosis at one year of follow-up among patients with diabetes who were hospitalized for HF in either 2008-2011 or 2018. The patients are from the Spanish Society of Internal Medicine's National Heart Failure Registry (RICA, for its initials in Spanish). The primary endpoint was to analyze the composite outcome of total mortality and/or readmission due to HF in 12 months. A multivariate Cox regression model was used to evaluate the strength of association (hazard ratio [HR]) between diabetes and the outcomes between both periods.A total of 936 patients were included in the 2018 cohort, of which 446 (48%) had diabetes. The baseline characteristics of the populations from the 2 periods were similar. In patients with diabetes, the composite outcome was observed in 233 (47.5%) in the 2008-2011 cohort and 162 (36%) in the 2018 cohort [HR 1.48; 95% confidence interval (95%CI) 1.18-1.85; p .001]. The proportion of readmissions (HR 1.39; 95%CI 1.07-1.80; p = .015) and total mortality (HR 1.60; 95%CI 1.20-2.14; p .001) were also significantly higher in patients with diabetes from the 2008-2011 cohort compared to the 2018 cohort.In 2018, an improvement was observed in the prognosis for all-cause mortality and readmissions over one year of follow-up in patients with diabetes hospitalized for HF compared to the 2008-2011 period.

Background Hyperglycaemia has emerged as an important risk factor for death in coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the association between blood glucose (BG) levels and in-hospital mortality in non-critically patients hospitalized with COVID-19. Methods This is a retrospective multi-centre study involving patients hospitalized in Spain. Patients were categorized into three groups according to admission BG levels: 180 mg/dL. The primary endpoint was all-cause in-hospital mortality. Results Of the 11,312 patients, only 2128 (18.9%) had diabetes and 2289 (20.4%) died during hospitalization. The in-hospital mortality rates were 15.7% (180 mg/dL), p.001. The cumulative probability of mortality was significantly higher in patients with hyperglycaemia compared to patients with normoglycaemia (log rank, p.001), independently of pre-existing diabetes. Hyperglycaemia (after adjusting for age, diabetes, hypertension and other confounding factors) was an independent risk factor of mortality (BG >180 mg/dL: HR 1.50; 95% confidence interval (CI): 1.31-1.73) (BG 140-180 mg/dL; HR 1.48; 95%CI: 1.29-1.70). Hyperglycaemia was also associated with requirement for mechanical ventilation, intensive care unit (ICU) admission and mortality. Conclusions Admission hyperglycaemia is a strong predictor of all-cause mortality in non-critically hospitalized COVID-19 patients regardless of prior history of diabetes. KEY MESSAGE Admission hyperglycaemia is a stronger and independent risk factor for mortality in COVID-19. Screening for hyperglycaemia, in patients without diabetes, and early treatment of hyperglycaemia should be mandatory in the management of patients hospitalized with COVID-19. Admission hyperglycaemia should not be overlooked in all patients regardless prior history of diabetes., The study was completely support by the Spanish Federation of Internal Medicine.

We propose laconic classification as a novel way to understand and compare the performance of diverse image classifiers. The goal in this setting is to minimise the amount of information (aka. entropy) required in individual test images to maintain correct classification. Given a classifier and a test image, we compute an approximate minimal-entropy positive image for which the classifier provides a correct classification, becoming incorrect upon any further reduction. The notion of entropy offers a unifying metric that allows to combine and compare the effects of various types of reductions (e.g., crop, colour reduction, resolution reduction) on classification performance, in turn generalising similar methods explored in previous works. Proposing two complementary frameworks for computing the minimal-entropy positive images of both human and machine classifiers, in experiments over the ILSVRC test-set, we find that machine classifiers are more sensitive entropy-wise to reduced resolution (versus cropping or reduced colour for machines, as well as reduced resolution for humans), supporting recent results suggesting a texture bias in the ILSVRC-trained models used. We also find, in the evaluated setting, that humans classify the minimal-entropy positive images of machine models with higher precision than machines classify those of humans.

It is unclear to which extent the higher mortality associated with hypertension in the coronavirus disease (COVID-19) is due to its increased prevalence among older patients or to specific mechanisms. Cross-sectional, observational, retrospective multicenter study, analyzing 12226 patients who required hospital admission in 150 Spanish centers included in the nationwide SEMI-COVID-19 Network. We compared the clinical characteristics of survivors versus non-survivors. The mean age of the study population was 67.5 &plusmn, 16.1 years, 42.6% were women. Overall, 2630 (21.5%) subjects died. The most common comorbidity was hypertension (50.9%) followed by diabetes (19.1%), and atrial fibrillation (11.2%). Multivariate analysis showed that after adjusting for gender (males, OR: 1.5, p = 0.0001), age tertiles (second and third tertiles, OR: 2.0 and 4.7, p = 0.0001), and Charlson Comorbidity Index scores (second and third tertiles, OR: 4.7 and 8.1, p = 0.0001), hypertension was significantly predictive of all-cause mortality when this comorbidity was treated with angiotensin-converting enzyme inhibitors (ACEIs) (OR: 1.6, p = 0.002) or other than renin-angiotensin-aldosterone blockers (OR: 1.3, p = 0.001) or angiotensin II receptor blockers (ARBs) (OR: 1.2, p = 0.035). The preexisting condition of hypertension had an independent prognostic value for all-cause mortality in patients with COVID-19 who required hospitalization. ARBs showed a lower risk of lethality in hypertensive patients than other antihypertensive drugs.

Background: Spain has been one of the countries most affected by the COVID-19 pandemic. Objective: To create a registry of patients with COVID-19 hospitalized in Spain, in order to improve our knowledge of the clinical, diagnostic, therapeutic, and prognostic aspects of this disease. Methods: A multicentre retrospective cohort study, including consecutive patients hospitalized with confirmed COVID-19 throughout Spain. Epidemiological and clinical data, additional tests at admission and at seven days, treatments administered, and progress at 30 days of hospitalization were collected from electronic medical records. Results: Up to June 30th 2020, 15,111 patients from 150 hospitals were included. Their median age was 69.4 years (range: 18-102 years) and 57.2% were male. Prevalences of hypertension, dyslipidemia, and diabetes mellitus were 50.9%, 39.7%, and 19.4%, respectively. The most frequent symptoms were fever (84.2%) and cough (73.5%). High values of ferritin (73.5%), lactate dehydrogenase (73.9%), and D-dimer (63.8%), as welt as lymphopenia (52.8%), were frequent. The most used antiviral drugs were hydroxychloroquine (85.6%) and lopinavir/ritonavir (61.4%); 33.1% developed respiratory distress. Overall mortality rate was 21.0%, with a marked increase with age (50-59 years: 4.7%, 60-69 years: 10.5%, 70-79 years: 26.9%, >= 80 years: 46.0%). Conclusions: The SEMI-COVID-19 Network provides data on the clinical characteristics of patients with COVID-19 hospitalized in Spain. Patients with COVID-19 hospitalized in Spain are mostly severe cases, as one in three patients developed respiratory distress and one in five patients died. These findings confirm a close relationship between advanced age and mortality. (C) 2020 The Authors. Published by Elsevier Espana, S.L.U.