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Abstract Smart batteries, i.e., equipped with internal and external sensors, are emerging as promising solutions to enhance battery state of health and optimize operating conditions. However, for accurate correlations between the evolution of the cell parameters (e.g., temperature, strain) and physicochemical degradation mechanisms, it is crucial to know the reliability of sensors. To address this question, we perform a synchrotron operando X-ray diffraction experiment to investigate the local and global impact of the presence of internal sensors on a commercial prismatic Li-ion battery cell at various (dis)charge rates. We find that, while the overall electrochemical performance is unaffected, the sensors have a substantial impact on the local graphite lithiation kinetics, especially at high (dis)charge rates. These results show the importance of controlling local deformations induced by internal sensors and tailoring the dimensions of these sensors to obtain reliable battery performance indicators and optimize smart batteries.

Background A high density of resident memory T cells (TRM) in tumors correlates with improved clinical outcomes in immunotherapy-treated patients. In most clinical studies, TRM are defined by the CD103 marker. However, it is clearly established that not all TRM express CD103, but can be defined by other markers (CD49a, CD69, etc). The frequency of these subpopulations of TRM expressing or not CD103 varies according to the location of the cancer. Little is known about their functionality and their predictive impact on response to immunotherapy. In preclinical models, only some subpopulations of TRM are associated with cancer vaccine efficacy.Methods Multiparametric cytometry analyses were used to demonstrate the presence of TRM subpopulations in the lung in mice after vaccination and in fresh ex vivo human non-small cell lung cancer (NSCLC). An analysis of the T-cell repertoire of these TRM was conducted to search for their relationships. Multiplex immunofluorescence techniques were used to quantify intratumor infiltration of TRM subpopulations in two cohorts of patients with NSCLC. The impact on the clinical outcome of the TRM tumor infiltration was also investigated.Results We identified two main TRM subpopulations in tumor-infiltrating lymphocytes derived from patients with NSCLC: one co-expressing CD103 and CD49a (double positive (DP)), and the other expressing only CD49a (simple positive (SP)); both exhibiting additional TRM surface markers like CD69. Despite higher expression of inhibitory receptors, DP TRM exhibited greater functionality compared with SP TRM. Analysis of T-cell receptor (TCR) repertoire and expression of the stemness marker TCF1 revealed shared TCRs between populations, with the SP subset appearing more progenitor-like phenotype. In the training cohort, PD-L1 (Programmed Death-Ligand 1) and TCF1+CD8+T cells predict response to anti-PD-1. In patient with NSCLC validation cohorts, only DP TRM predicted PD-1 blockade response. Multivariate analysis, including various biomarkers associated with responses to anti-PD-(L)1, such as total CD8, TCF1+CD8+T cells, and PD-L1, showed that only intratumoral infiltration by DP TRM remained significant.Conclusions This study highlights the non-equivalence of TRM subpopulations. The population of TRM co-expressing CD103 and CD49a appears to be the most functional and has the most significant capacity for predicting response to immunotherapy in multivariate analysis in patients with NSCLC.

Abstract Background HER2 expression has a prognostic and predictive impact in early-stage breast cancer (BC). HER2 positive BC (immunohistochemistry (IHC) score 3 + or 2 + with in situ hybridization (ISH) amplification) are treated with HER2 targeted therapies. The concept of HER2-low BC (IHC score 1 + or 2 + without ISH amplification) is drawing attention as anti-HER2 treatment has recently shown efficacy in this subgroup. We aimed to explore the response to neoadjuvant chemotherapy (NAC) in HER2-low early BC according to the HER2 score (1 + or 2 + without amplification). Methods We conducted a retrospective study in two French comprehensive cancer centers. All patients with HER2-low BC treated with NAC from January 2014 to December 2020 were included. The primary objective was to analyze the pathological complete response (pCR) rate to NAC using the Sataloff or RCB system, according to the HER2 score. Secondary objectives were to assess disease free survival (DFS), overall survival (OS) and to explore the immune environment through the Neutrophil-to-Lymphocyte Ratio (NLR), according to HER2 expression. Univariate and multivariate analyses were performed. Results We included 237 tumors for 229 patients. Of these, 160 (67.5%) tumors were HER2 1 + , 77 (32.5%) were HER2 2 + , and 152 (64.1%) were hormone receptor (HR) positive. The median age was 53.9 years. No differences in tumor characteristics were observed between HER2 1 + and HER2 2 + subgroups. pCR was achieved in 38 tumors (17%), without any difference between HER2 1 + and HER2 2 + subgroups (p = 0.77). DFS and OS were significantly different between HER2 1 + and HER2 2 + patients (HR = 0.41,CI95%[0.17;0.97] p = 0.037 and HR = 0.31,CI95%[0.09;1.02] p = 0.042, respectively). HER2 status was still associated with DFS and OS after adjustment for age, HR status and NLR, with better outcomes in favor of HER2 score 2 + (HR = 0.35 [0.15–0.84] and HR = 0.24 [0.07–0.81], respectively). NLR was not associated with worse DFS or OS. Conclusion In HER2-low early BC, no differences in pCR were observed between HER2 1 + and HER2 2 + tumors, however patients with HER2 2 + tumors had a better DFS and OS than those with HER2 1 + . Further investigations are needed to describe the intrinsic differences in the spectrum of HER2-low BC.

Novel 2-amino bis(2-phosphonoacetic) acids were prepared by microwave irradiation of a mixture of amine, glyoxylic acid and phosphorous acid. The reaction takes place with various amines including primary and secondary amines and polyamines, but this reaction is more sensitive to steric hindrance of amine than the similar Kabachnik–Fields reaction. Amino acids can be also transformed into the expected bis(2-phosphonoacetic) acids, with the exception of tryptophan, which gives a β-carboline product.

Abstract Background Breast cancer is amongst the 10 first causes of death in women worldwide. Around 20% of patients are misdiagnosed leading to early metastasis, resistance to treatment and relapse. Many clinical and gene expression profiles have been successfully used to classify breast tumours into 5 major types with different prognosis and sensitivity to specific treatments. Unfortunately, these profiles have failed to subclassify breast tumours into more subtypes to improve diagnostics and survival rate. Alternative splicing is emerging as a new source of highly specific biomarkers to classify tumours in different grades. Taking advantage of extensive public transcriptomics datasets in breast cancer cell lines (CCLE) and breast cancer tumours (TCGA), we have addressed the capacity of alternative splice variants to subclassify highly aggressive breast cancers. Results Transcriptomics analysis of alternative splicing events between luminal, basal A and basal B breast cancer cell lines identified a unique splicing signature for a subtype of tumours, the basal B, whose classification is not in use in the clinic yet. Basal B cell lines, in contrast with luminal and basal A, are highly metastatic and express epithelial-to-mesenchymal (EMT) markers, which are hallmarks of cell invasion and resistance to drugs. By developing a semi-supervised machine learning approach, we transferred the molecular knowledge gained from these cell lines into patients to subclassify basal-like triple negative tumours into basal A- and basal B-like categories. Changes in splicing of 25 alternative exons, intimately related to EMT and cell invasion such as ENAH, CD44 and CTNND1, were sufficient to identify the basal-like patients with the worst prognosis. Moreover, patients expressing this basal B-specific splicing signature also expressed newly identified biomarkers of metastasis-initiating cells, like CD36, supporting a more invasive phenotype for this basal B-like breast cancer subtype. Conclusions Using a novel machine learning approach, we have identified an EMT-related splicing signature capable of subclassifying the most aggressive type of breast cancer, which are basal-like triple negative tumours. This proof-of-concept demonstrates that the biological knowledge acquired from cell lines can be transferred to patients data for further clinical investigation. More studies, particularly in 3D culture and organoids, will increase the accuracy of this transfer of knowledge, which will open new perspectives into the development of novel therapeutic strategies and the further identification of specific biomarkers for drug resistance and cancer relapse.

We previously demonstrated that F4 peptide (CNPEDCLYPVSHAHQR) from collagen XIX was able to inhibit melanoma cell migrationin vitro and cancer progression in a mouse melanoma model. The aim of the present work was to study the anti-angiogenic properties of F4 peptide. We demonstrated that F4 peptide inhibited VEGF-induced pseudo-tube formation on Matrigel by endothelial cells and endothelial sprouting in a rat aortic ring assay. By affinity chromatography, we identified αvβ3 and α5β1 integrins as potential receptors for F4 peptide on endothelial cell surface. Using solid phase assays, we proved the direct interaction between F4 and both integrins. Taken together, our results demonstrate that F4 peptide is a potent antitumor agent inhibiting both angiogenesis and tumor cell migration.

Hop, also known as Stip1 or Sti1, facilitates substrate transfer between the Hsp70 and Hsp90 molecular chaperones. Characterization of proteostasis-related pathways in STIP1 knock-out cell lines reveals that in eukaryotes Stip1 modulates the balance between protein folding and degradation.

Abstract iMOKA (interactive multi-objective k-mer analysis) is a software that enables comprehensive analysis of sequencing data from large cohorts to generate robust classification models or explore specific genetic elements associated with disease etiology. iMOKA uses a fast and accurate feature reduction step that combines a Naïve Bayes classifier augmented by an adaptive entropy filter and a graph-based filter to rapidly reduce the search space. By using a flexible file format and distributed indexing, iMOKA can easily integrate data from multiple experiments and also reduces disk space requirements and identifies changes in transcript levels and single nucleotide variants. iMOKA is available at https://github.com/RitchieLabIGH/iMOKA and Zenodo https://doi.org/10.5281/zenodo.4008947 .

This study investigates the capacity of polyamide nanofiltration membrane (SNTE NF270-2540) to extract the lanthanum (La) (III) and its mixtures with the iron (Fe) (III). A three - level factorial design and response surface methodology was used to evaluate the effects of different parameters, such as: pH (3.0 – 9.0), concentration (10 – 100 ppm), pressure (6.0 – 13.5 bars). The results showed that the retention of La (III) varied from 29 % to 100 %, depending on the experimental condition it was possible to extract all of La (III) and Fe (III) from the same mixture. The results showed that the extraction of La (III) reaches 100 % for 10 and 55 ppm at pH = 3.0 and for 100 ppm at pH = 9.0, under the pressure of 13.5 bars. At pH = 3.0, the extraction of the mixtures La (III) / Fe (III) (50 ppm / 50 ppm) and (100 ppm / 100 ppm) whatever the pressure was all (100 %). The study confirmed a high lanthanum extraction using polyamide nanofiltration membrane.

L'étude des besoins en eau de Cenchrus ciliaris plante fourragère très bien appétée par le zébu malgache a été réalisée au cours de 2 campagnes à l'aide de la méthode neutronique de mesure de l'humidité des sols. On a défini un cofficient égal au rapport de l'évapotranspiration réelle maximale (ETRM) à l'évaporation d'un bac classe A (Ev. Bac), est égal à 0,40 pour les 10 premiers jours du cycle et à 0,80 pour les 30 jours suivants. Une culture de Cenchrus irriguée dans ces conditions pendant 4 années successives a donné une production de matière sèche égale à 18,7 kg par ha et par mm d'eau utile reçue

Hepatitis C virus (HCV) is a serious disease that threatens human health. Despite consistent efforts to inhibit the virus, it has infected more than 58 million people, with 300,000 deaths per year. The HCV nonstructural protein NS5A plays a critical role in the viral life cycle, as it is a major contributor to the viral replication and assembly processes. Therefore, its importance is evident in all currently approved HCV combination treatments. The present study identifies new potential compounds for possible medical use against HCV using the quantitative structure–activity relationship (QSAR). In this context, a set of 36 NS5A inhibitors was used to build QSAR models using genetic algorithm multiple linear regression (GA-MLR) and Monte Carlo optimization and were implemented in the software CORAL. The Monte Carlo method was used to build QSAR models using SMILES-based optimal descriptors. Four splits were performed and 24 QSAR models were developed and verified through internal and external validation. The model created for split 3 produced a higher value of the determination coefficients using the validation set (R2 = 0.991 and Q2 = 0.943). In addition, this model provides interesting information about the structural features responsible for the increase and decrease of inhibitory activity, which were used to develop eight novel NS5A inhibitors. The constructed GA-MLR model with satisfactory statistical parameters (R2 = 0.915 and Q2 = 0.941) confirmed the predicted inhibitory activity for these compounds. The Absorption, Distribution, Metabolism, Elimination, and Toxicity (ADMET) predictions showed that the newly designed compounds were nontoxic and exhibited acceptable pharmacological properties. These results could accelerate the process of discovering new drugs against HCV.

After the synthesis of polyethylenimine supported on silica, it has been used as a new and efficient catalyst in Knoevenagel and Michael condensations. The presence of the polyethylenimine in the catalytic system together with silica displays an acido-basic character allows a better catalytic activity in the condensations. Carried out under microwave irradiation, without organic solvent and during short time, the syntheses are respectful towards green chemistry. The solid catalyst can be easily reused. This catalyst has the acido-basic character at the same time.

Wastewater cleaning strategies based on the adsorption of materials are being increasingly considered, but the wide variety of organic pollutants at low concentrations still makes their removal a challenge. The hybrid material proposed here consists of a zwitterionic polyethylenimine polymer coating a magnetic core. Polyethylenimine is phosphonated at different percentages by a one-step process and used to coat maghemite nanoparticles. It selectively extracts high amounts of cationic and anionic contaminants over a wide range of pH values, depending on the adjustable number of phosphonate groups introduced on the polymer. After recovering the nanoparticles with a magnet, pollutants are quantitatively released by repeated washing with low amounts of pH-adjusted water. The material can be reused many times without noticeable loss of efficiency and is designed to resist high temperatures, oxidation and harsh conditions.

Cloud point extraction (CPE) was used to extract uranium (VI) from an aqueous solution in acetate media. The methodology used is based on the formation of uranyl-ionic liquid (I) complexes and uranyl-D2EHPA soluble in a micellar phase of non-ionic surfactant (Triton X-100). The uranium (VI) complexes are then extracted into the surfactant-rich phase at ambient temperature. The ionic liquid (IL) used as a chelating agent was synthesized and characterized in this study. It is composed of N-butyl N’-triethoxy methyl imidazolium cation and diethylhexylphosphate (D2EHPA-H) as anion. The effect of the IL on the extraction efficiency was studied in presence and in absence of IL’s cation in acetate medium.

Research over the last few decades has shown that the characterization of microaggregates at the micrometer scale using Transmission Electron Microscopy (TEM) provides useful information on the influence of microorganisms on soil functioning. By taking soil heterogeneity into account, TEM provides qualitative information about the state of bacteria and fungi (e.g., intact state of living organisms, spores, residues) at the sampling date within organo-mineral associations, from the soil-root interface to the bulk soil, and in biogenic structures such as casts. The degree of degradation of organic matter can be related to the visualized enzymatic potential of microorganisms that degrade them, thus indicating organic matter dynamics within soil aggregates. In addition, analytical TEM characterization of microaggregates by EELS (Electron Energy Loss Spectroscopy) or EDX (Energy Dispersive X-rays spectroscopy) provides in situ identification of microbial involvement in the biogeochemical cycles of elements. Furthermore, micrometer characterization associated with other methodologies such as Nanoscale Secondary Ion Mass Spectrometry (NanoSIMS) or soil fractionation, enables monitoring both incorporation of biodegraded litter within soil aggregates and impacts of microbial dynamics on soil aggregation, particularly due to production of extracellular polymeric substances. The present focused review suggests that such an approach using micrometer characterization of soil microhabitats provides relevant qualitative and quantitative information when monitoring and modeling microbial processes in dynamics of organo-mineral associations.

Parmi les multiples dispositifs de formation à l’enseignement secondaire qui cohabitent au sein de la Confédération suisse, cet article présente et interroge celui nouvellement mis en place dans le canton de Genève qui donne aux didactiques disciplinaires une place centrale. Les raisons et les hypothèses qui sous-tendent ce « pari » des didactiques sont questionnées à partir de trois approches complémentaires: la première s’intéresse au contexte genevois, tentant de cerner l’effet du contexte local sur l’adaptation de mouvements de réformes d’envergure nationale et internationale. La deuxième analyse la nature des savoirs dispensés durant la formation en se focalisant sur l’articulation des didactiques disciplinaires avec les savoirs scientifiques, avec les savoirs issus des sciences de l’éducation et avec les savoirs issus de la pratique professionnelle. Enfin, la troisième porte sur l’inscription des didactiques dans un dispositif de formation universitaire interfacultaire qui articule recherche scientifique et formation à l’enseignement.

To investigate the influence of increasing age on clinical presentation, treatment and long-term outcome in patients with inducible paroxysmal supraventricular tachycardia (SVT) without pre-excitation syndromes.Clinical and electrophysiological study (EPS) data, as well as long-term clinical outcome (mean follow-up 2.4±4.0 years) were collected in patients referred for regular tachycardia with inducible SVT during EPS without pre-excitation.Among 1960 referred patients, 301 patients (15.4%) were aged ≥70 (70-97). In this subset, anticoagulants were prescribed in 49 patients following an erroneous diagnosis of atrial tachycardia and 14 were previously erroneously diagnosed with ventricular tachycardia because of wide QRS. Ablation was performed more frequently in patients ≥70 despite more frequent failure and complications. During follow-up, higher risks of AF, stroke, pacemaker implantation and death were observed in patients ≥70 whereas SVT recurrences were similar in both age groups. In multivariable analysis, age ≥70 was independently associated with higher risks of SVT-related adverse events prior to ablation (OR = 1.93, 1.41-2.62, p

Background: Accessory pathway (AP) ablation is not always easy. Our purpose was to assess the age-related prevalence of AP location, electrophysiological and prognostic data according to this location. Methods: Electrophysiologic study (EPS) was performed in 994 patients for a pre-excitation syndrome. AP location was determined on a 12 lead ECG during atrial pacing at maximal preexcitation and confirmed at intracardiac EPS in 494 patients. Results: AP location was classified as anteroseptal (AS)(96), right lateral (RL)(54), posteroseptal (PS)(459), left lateral (LL)(363), nodoventricular (NV)(22). Patients with ASAP or RLAP were younger than patients with another AP location. Poorly-tolerated arrhythmias were more frequent in patients with LLAP than in other patients (0.009 for ASAP, 0.0037 for RLAP,

A new class of dicationic ionic liquids (ILs) were synthesized for electrochemical applications at high temperatures. The syntheses are based on a dialkylation reaction of N-alkylpiperidine followed by anion exchange. The structures of ILs, based on piperidinium combined with hexafluorophosphate anion, were identified by using 1H, 13C, 19F, 31P NMR and FT-IR spectroscopy. ILs’ thermal properties were investigated in the temperature range from −50 to 350 °C by using differential scanning calorimetry (DSC). In the frequency of 10−2–106 Hz range, dielectric measurements were performed on ILs’ samples at various temperatures from −80 to 20 °C, i.e. around the glass transition temperature. The peak relaxation was observed near to this temperature. Also, the conductivity was investigated and the energy activation determined. The temperature dependence of the relaxation times was shown to be governed by the Arrhenius equation.

New host-guest materials have been prepared by incorporation of a home-made organic probe displaying a pyrene motif and a phosphonate function into a regular amphiphilic copolymer. Using powder X-Ray diffraction, photoluminescence and FT-IR spectroscopy, we have been able to study the non-covalent interactions between the host matrix and the guest molecule in the solid state. Interestingly, we have shown that the matrix directs the guest spatial localization and alters its properties. Thanks to the comparison of pyrene vs. N-pyrenylmaleimide derivatives, the influence of the chemical nature of the guest molecules on the non-covalent interactions with the host have been studied. In addition, using polyethylene glycol as a reference host, we have been able to evidence a true matrix effect within our new insertion materials. The phosphonated guest molecule appears to be a novel probe targeting the hydrophilic domain of the host copolymer.

The inhibitive effect of the piperidin-1-yl-phosphonic acid (PPA) on the corrosion of iron in 1 M H2SO4 solution has been investigated by weight loss measurement, potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) techniques. The presence of (PPA) reduces remarkably the corrosion rate of iron in acidic solution. The effect of temperature on the corrosion behavior of iron was studied in the range of 298–328 K. Results clearly reveal that the (PPA) behaves as a mixed type corrosion inhibitor with the highest inhibition at 5 × 10−3 M. The adsorption of PPA on the iron surface obeys the Langmuir's adsorption isotherm.

The inhibitive effect of the hexamethylenediamine tetra(methylene phosphonic acid) (HMDTMPA) on the corrosion of carbon steel in 1.0 M HCl solution has been investigated by weight loss measurement, potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) techniques. The presence of (HMDTMPA) reduces remarkably the corrosion rate of carbon steel in acidic solution. The effect of temperature on the corrosion behavior of carbon steel was studied in the range of 298–328 K. Results clearly reveal that the (HMDTMPA) behaves as a mixed type corrosion inhibitor with the highest inhibition at 4 × 10−3 M. The adsorption of HMDTMPA on the carbon steel surface obeys to the Langmuir’s adsorption isotherm. Surface analysis via scanning electron microscope (SEM) shows a significant improvement on the surface morphology of the carbon steel plate.

Diaminododecyltetramethylenetetraphosphonic acid (DADTMTPA) has been investigated in liquid - liquid extraction of Zn (II) and Cu (II) in acetate media. The extraction of both cations was carried out in different media with the addition of CH3COONa, CH3COOH, HCl and H2SO4 at different pH values. The maximum extraction yield for copper is 70% after addition of 10 mg of sodium acetate and for zinc is 30% after addition of acetic acid at pHi = 5.5, in one step.

The 2-aminopyridines constitute a very large class of nitrogen heterocycles, which have a great biological activity, such as the antibacterial, anti-inflammatory and analgesics activity, as well as the 2-amino-4-(4-chlorophenyl)-5-oxo-5,6,7,8-tetrahydroquinoline-3-carbonitrile has a antifungal activity. A new approach of synthesis of 2 amino-3-cyanopyridines was developed in our laboratory, based on the condensation of the intermediary of enaminonitrile with different primary amines in solvent-free environments.

Quantitative Structure Activity Relationships (QSAR or SAR) have helped scientists to establish mathematical relationships between molecular structures and their biological activities. In the present article, SAR studies have been carried out on 89 tetrahydroimidazo[4,5,1-jk][1,4]benzodiazepine (TIBO) derivatives using different classifiers, such as support vector machines, artificial neural networks, random forests, and decision trees. The goal is to propose classification models that will be able to classify TIBO compounds into two groups: high and low inhibitors of HIV-1 reverse transcriptase. Each molecular structure was encoded by 10 descriptors. To check the validity of the established models, all of them were subjected to various validation tests: internal validation, Y-randomization, and external validation. The established classification models have been successful. The correct classification rates reached 100% and 90% in the learning and test sets, respectively. Finally, molecular docking analysis was carried out to understand the interactions between reverse transcriptase enzyme and the TIBO compounds studied. Hydrophobic and hydrogen bond interactions led to the identification of active binding sites. The established models could help scientists to predict the inhibition activity of untested compounds or of novel molecules prior to their synthesis. Therefore, they could reduce the trial and error process in the design of human immunodeficiency virus (HIV) inhibitors.

The chemical and physical properties of imidazolium-based ionic liquids are determined by the interactions between the counter-ions. The C(2) position plays an important role in these interactions, as it represents the predominant site for interionic hydrogen bonding. This study shows that the directional hydrogen bonds between highly symmetrical anions (iodide, tetrafluoroborate, hexafluorophosphate) and the C(2)-H group of the 1-methyl-3-propylimidazolium cation determine the molecular and macroscopic behavior in terms of the thermal properties. Upon replacing the C(2) proton by a methyl group, the anion repositions itself at the C(4)/(5) moiety, where it forms a new hydrogen bond, apparently with only one of the two CH groups. In addition, the larger the anion is in diameter, the more likely it will establish further interactions with other parts of the cation, such as the propyl chain.

The design of various experiments in order to assess and simulate the effects of the acid activation of an Algerian bentonite on the bleaching capacity of Colza oil is described. Three key parameters of the acidic activation, namely acid concentration, contact time and temperature, were considered. The calculations made indicated that all variables display advantageous effects up to a certain level on the effectiveness of bleaching, regarded as the responsefunction. The acid concentration exerts a predominant individual effect as compared to the other parameters. Some small interactions between parameters were considered. High bleaching capacity reached 99% as optimal activation. Under accurate statistical measurements, synergy phenomena could be observed. Excessive activation is discussed in terms of loss in both porosity and acid strength.

Purpose of the researchTo study the influence of age on the clinical presentation and long-term outcome of patients referred for atrial flutter (AFL) ablation. Age-related differences have been reported regarding the prognosis of arrhythmias.MethodsA total of 1187 patients with a mean age 65±12 years consecutively referred for AFL ablation were retrospectively analyzed in the study.Results445 (37.5%) patients were aged ≥70 (range 70 to 93) among which 345 were aged 70 to 79 years (29.1%) and 100 were aged ≥80 (8.4%). In multivariable analysis, AFL-related rhythmic cardiomyopathy and presentation with 1/1 AFL were less frequent (respectively adjusted OR = 0.44, 0.27-0.74, p = 0.002 and adjusted OR = 0.29, 0.16-0.52, pConclusionsOlder patients represent 37.5% of patients referred for AFL ablation and displayed a

Metallophthalocyanine complexes are obtained quickly and efficiently by the reaction of phthalodinitrile with hydrated metallic salts without solvent and under microwave irradiation. The use of a modified commercial microwave oven to perform this type of reactions under dry conditions is described. Metallophthalocyanines and metallododecachlorophthalocyanines of some divalent metals can be also obtained from phthalic or tetrachlorophthalic anhydrides with hydrated metallic salt and urea under microwave irradiation and without solvent.

3(2)-Naphthofuranone (1) was condensed in the presence of Al2O3-KF with aromatic aldehydes (4) to give arylidenenaphthofuranones (5a-f) without solvent under focused microwave irradiation.

A new chelating polymeric sorbent has been developed using polystyrene resin grafted with phosphonic acid. After characterization by FTIR and elementary analysis, the new resin has been investigated in liquid-solid extraction of cadmium(II). The results indicated that phosphonic resin could adsorb Cd(II) ion effectively from aqueous solution. The adsorption was strongly dependent on the pH of the medium and the optimum pH value level for better sorption was between 3.2 and 5.2. The influence of other analytical parameters including contact time, amount of resin, metal ion concentration, and the presence of some electrolytes was investigated. The maximum uptake capacity of Cd(II) ions was 37,9 mg·g−1 grafted resin at ambient temperature, at an initial pH value of 5.0. The overall adsorption process was best described by pseudo second-order kinetic. When Freundlich and Langmuir isotherms were tested, the latter had a better fit with the experimental data. Furthermore, more than 92% of Cd(II) could be eluted by using 1.0 mol·L−1 HCl in one cycle.

Fucoidans are widespread cost-effective sulfated marine polysaccharides which have raised interest in the scientific community over last decades for their wide spectrum of bioactivities. Unsurprisingly, nanomedicine has grasped these compounds to develop innovative therapeutic and diagnostic nanosystems. The applications of fucoidans in nanomedicine as imaging agents, drug carriers or for their intrinsic properties are reviewed here after a short presentation of the main structural data and biological properties of fucoidans. The origin and the physicochemical specifications of fucoidans are summarized in order to discuss the strategy of fucoidan-containing nanosystems in Human health. Currently, there is a need for reproducible, well characterized fucoidan fractions to ensure significant progress.

Abstract Drug-tolerance has emerged as one of the major non-genetic adaptive processes driving resistance to targeted therapy (TT) in non-small cell lung cancer (NSCLC). However, the kinetics and sequence of molecular events governing this adaptive response remain poorly understood. Here, we combine real-time monitoring of the cell-cycle dynamics and single-cell RNA sequencing in a broad panel of oncogenic addiction such as EGFR-, ALK-, BRAF- and KRAS-mutant NSCLC, treated with their corresponding TT. We identify a common path of drug adaptation, which invariably involves alveolar type 1 (AT1) differentiation and Rho-associated protein kinase (ROCK)-mediated cytoskeletal remodeling. We also isolate and characterize a rare population of early escapers, which represent the earliest resistance-initiating cells that emerge in the first hours of treatment from the AT1-like population. A phenotypic drug screen identify farnesyltransferase inhibitors (FTI) such as tipifarnib as the most effective drugs in preventing relapse to TT in vitro and in vivo in several models of oncogenic addiction, which is confirmed by genetic depletion of the farnesyltransferase. These findings pave the way for the development of treatments combining TT and FTI to effectively prevent tumor relapse in oncogene-addicted NSCLC patients.

This qualitative study investigated the effectiveness of blended learning using MOOCs (massive open online courses) for capacity-building in knowledge translation (KT). The evaluation followed Kirkpatrick's updated model. A total of 23 semi-directed interviews were conducted with participants working at a research centre in Côte d'Ivoire, with a first wave of interviews immediately post-training and a second wave after five months. Results showed that the training met learners' needs, with both the content and teaching format being deemed appropriate. Learners reacted positively to face-to-face activities and affirmed the importance of coaching for putting learning into practice. Specific KT skills and principles appeared to have been acquired, such as a procedure for structuring the KT process and improved skills for communicating and presenting scientific knowledge. Five months after the training, encouraging changes were reported, but the sustainability of the new KT practices remained uncertain. KT capacity-building initiatives in low- and middle-income countries struggle to meet demand. Little is known about effective KT training in that context, and even less in non-anglophone countries. The study presented here contributes to the understanding of success factors from the learners' standpoint.

ABSTRACTThis study aimed to evaluate the anti-inflammatory and analgesic properties of the methanolic extract of Opuntia ficus indica L. in small animal (rats and mice model). The current treatment for febrile conditions often involves the use of non-steroidal anti-inflammatory drugs (NSAIDs), which can have adverse effects, particularly gastrointestinal ulcers. Therefore, there is a growing need to explore natural alternatives with fewer side effects. The study utilized various experimental models to assess the effects of the extract. The results demonstrated a significant analgesic effect of the extract, as evidenced by a reduction in pain induced by acetic acid and hot plate tests. Additionally, the extract exhibited anti-inflammatory effects, as indicated by a decrease in carrageenan-induced paw edema and dextran-induced inflammation. To gain insights into the chemical composition of the extract, HPLC analysis was conducted. The analysis successfully identified and quantified 20 compounds, including luteolin, galangin, catechin, thymol, methylated quercetin, quercetin, rutin, acacetin, hesperidin, apigenin, kaempferol, pinocembrin, chrysin, gallic acid, caffeic acid, ascorbic acid, ferulic acid, m-coumaric acid, rosmarinic acid, and trans-cinnamic acid.The findings suggest that Opuntia ficus indica L. extract holds promise as an effective and reasonably priced natural remedy for pain and inflammation in rats and mice model. The comprehensive chemical composition analysis provided valuable insights into the presence of various bioactive compounds, which may contribute to the observed therapeutic effects. Further research and exploration of the extract’s mechanisms of action are warranted to fully understand its potential in small animal healthcare.

Phosphonated polyethylenimine grafted on iron oxide nanoparticles was used as a magnetic support for loading palladium. This cheap and accessible heterogeneous catalyst demonstrated good efficiency in Suzuki-Miyaura, Mizoroki-Heck, and Tsuji-Trost couplings. The nanocomposite is resistant to harsh conditions and can therefore be recycled up to 10 cycles with high catalyst efficiency.

BackgroundCyclin dependent kinase inhibitors (CdK4/6i) changed the course of hormone receptor positive (HR+) HER2 negative (HER2-) metastatic breast cancer (mBC). To date, no factors have been shown to predict response to CdK4/6i. Neutrophil-to-lymphocyte ratio (NLR), an indicator of the host systemic inflammatory response, is an independent prognostic factor for survival in cancers. We conducted this study to evaluate the impact of NLR on survival in mBC patients treated with first line CdK4/6i.MethodsAll mBC patients treated with first line CdK4/6i between November 2015 and December 2019 were retrospectively included. The biomarker threshold was defined using ROC curves. We analyzed progression free survival (PFS), overall survival (OS), 12-month PFS and response rate according to NLR in univariable and multivariable analysis.ResultsA total of 126 patients treated with palbociclib (n=101), ribociclib (n=18) or abemaciclib (n=7) were included, with a median follow-up of 33 months [range: 2.9–57]. Median age was 65 years [29-86], 40% patients had good performance status (ECOG-PS 0). Most patients (71%) were included at the metastatic relapse stage and 29% had only bone metastases. Median PFS and median OS were 27 and 51 months, respectively. High NLR (≥ 2.53) was significantly associated with worse PFS (Hazard Ratio (HR)=0.50, CI95% = [0.32–0.79]) and worse OS (HR=0.45, [CI95%: 0.23–0.87]). In multivariable analysis, NLR and ECOG PS were independently factors associated with PFS (p=0.016 and p=0.001, respectively).ConclusionHigh NLR was associated with worse PFS and OS in HR+ HER2- mBC patients treated with first line CdK4/6i. NLR is a reliable and inexpensive prognostic marker, easily accessible in routine clinical practice, which could help optimize the therapeutic strategy. These results need to be confirmed in larger prospective studies.

Ricinine is an alkaloid of Ricinus communis that displays numerous biological properties. Ricinine (4-methoxy-1-methyl-2-oxo-dihydropyridine-3-carbonitrile)) and new N-analogues of Ricinine were obtained by the reaction of ethyl α-ethoxyethylidenecyanoacetate with various amines. Earlier, ethyl α-ethoxyethylidenecyanoacetate was easily prepared from ethyl cyanoacetate. Biologically, amines such as tryptamine and histamine were used in order to introduce a second pharmacophore on the target molecule.

In the present work, the synthesis and biological activities of substituted 2-aminopyridine δ-lactone derivatives were achieved. 4,6,6-trimethyl-2-oxo-5,6-dihydro-2H-pyran-3-carbonitrile was synthesised from 4-hydroxy-4-methylpentan-2-one, followed by its transformation in enaminonitrile with DMFDMA. The antioxidant effects of substituted 2-aminopyridine δ-lactone derivatives were evaluated through DPPH assay and revealed a great antioxidant capacity. The antifungal and antibacterial activities were investigated by disc diffusion method against clinical Gram-negative bacteria and against clinical fungi. The study shows moderate to very good antibacterial and antifungal activities for the new substituted 2-aminopyridine δ-lactone derivatives.

Purpurogallin or (6E,8Z)-2,3,4,6-tetrahydroxy-5H-benzo[7]annulen-5-one is a benzotropolone possessing a dienic system and known to inhibit the TLR1/TLR2 activation pathway. We have recently described the easy green synthesis of purpurogallin from pyrogallol catalyzed by a copper complex or by vegetable oxidases. The purpurogallin was acetylated and the tetra-acetate derivative thus obtained was engaged in a Diels–Alder reaction with various dienophiles (benzoquinone, maleic anhydride, ethylmaleimide, phenylmaleimide, etc.). The results obtained are presented and discussed.

This article explores a training need common to every stage of a teacher’s career : the need to be accompanied. It takes an integrative perspective on the process of the situated learning of teaching, throughout the career, from the pre-service practicums to the period of entrance in the profession then to the in-service training. Providing a reflexive accompaniment of the teachers’ practical experiences is here presented as a central factor for linking the training and the work environments. The first part of the article exposes our conception of a reflexive accompaniment and justifies its importance for the evolution of the teaching practices. Then, we describe how we were convinced of that importance through our role as directors of two teacher training devices, one in Switzerland, one in Quebec. Finally, the third part of the article is devoted to the training of the persons that practice such an accompaniment.