Activity of osimeRTInib in non-small-cell lung Cancer with UNcommon epidermal growth factor receptor mutations: retrospective Observational multicenter study (ARTICUNO).

BACKGROUND: Osimertinib represents the standard of care for the treatment of advanced non-small-cell lung cancer (NSCLC) harboring classical epidermal growth factor receptor (EGFR) mutations, constituting 80%-90% of all EGFR alterations. In the remaining cases, an assorted group of uncommon alterations of EGFR (uEGFR) can be detected, which confer variable sensitivity to previous generations of EGFR inhibitors, overall with lower therapeutic activity. Data on osimertinib in this setting are limited and strongly warranted. PATIENTS AND METHODS: The ARTICUNO study retrospectively evaluated data on osimertinib activity from patients with advanced NSCLC harboring uEGFR treated in 21 clinical centers between August 2017 and March 2023. Data analysis was carried out with a descriptive aim. Investigators collected response data according to RECIST version 1.1 criteria. The median duration of response, progression-free survival (mPFS), and overall survival were estimated by the Kaplan-Meier method. RESULTS: Eighty-six patients harboring uEGFR and treated with osimertinib were identified. Patients with 'major' uEGFR, that is, G719X, L861X, and S768I mutations (n = 51), had an overall response rate (ORR) and mPFS of 50% and 9 months, respectively. Variable outcomes were registered in cases with rarer 'minor' mutations (n = 27), with ORR and mPFS of 31% and 4 months, respectively. Among seven patients with exon 20 insertions, ORR was 14%, while the best outcome was registered among patients with compound mutations including at least one classical EGFR mutation (n = 13). Thirty patients presented brain metastases (BMs) and intracranial ORR and mPFS were 58% and 9 months, respectively. Amplification of EGFR or MET, TP53 mutations, and EGFR E709K emerged after osimertinib failure in a dataset of 18 patients with available rebiopsy. CONCLUSION: The ARTICUNO study confirms the activity of osimertinib in patients with uEGFR, especially in those with compound uncommon-common mutations, or major uEGFR, even in the presence of BMs. Alterations at the E709 residue of EGFR are associated with resistance to osimertinib.

Artificial intelligence for predictive biomarker discovery in immuno-oncology: a systematic review.

BACKGROUND: The widespread use of immune checkpoint inhibitors (ICIs) has revolutionised treatment of multiple cancer types. However, selecting patients who may benefit from ICI remains challenging. Artificial intelligence (AI) approaches allow exploitation of high-dimension oncological data in research and development of precision immuno-oncology. MATERIALS AND METHODS: We conducted a systematic literature review of peer-reviewed original articles studying the ICI efficacy prediction in cancer patients across five data modalities: genomics (including genomics, transcriptomics, and epigenomics), radiomics, digital pathology (pathomics), and real-world and multimodality data. RESULTS: A total of 90 studies were included in this systematic review, with 80% published in 2021-2022. Among them, 37 studies included genomic, 20 radiomic, 8 pathomic, 20 real-world, and 5 multimodal data. Standard machine learning (ML) methods were used in 72% of studies, deep learning (DL) methods in 22%, and both in 6%. The most frequently studied cancer type was non-small-cell lung cancer (36%), followed by melanoma (16%), while 25% included pan-cancer studies. No prospective study design incorporated AI-based methodologies from the outset; rather, all implemented AI as a post hoc analysis. Novel biomarkers for ICI in radiomics and pathomics were identified using AI approaches, and molecular biomarkers have expanded past genomics into transcriptomics and epigenomics. Finally, complex algorithms and new types of AI-based markers, such as meta-biomarkers, are emerging by integrating multimodal/multi-omics data. CONCLUSION: AI-based methods have expanded the horizon for biomarker discovery, demonstrating the power of integrating multimodal data from existing datasets to discover new meta-biomarkers. While most of the included studies showed promise for AI-based prediction of benefit from immunotherapy, none provided high-level evidence for immediate practice change. A priori planned prospective trial designs are needed to cover all lifecycle steps of these software biomarkers, from development and validation to integration into clinical practice.

A new ruthenium black dye design with improved optical properties for transparent dye sensitized solar devices.

We report here on the preparation and on the electronic properties of a panchromatic Ru(ii) sensitizer based on a new ligand which allows for higher molar extinction coefficients in the visible and better performances (32% efficiency improvement) over conventional "black dye" in transparent DSSC.

Is it possible to study the kinetic parameters of interaction between PNA and parallel and antiparallel DNA by stopped-flow fluorescence?

Peptide nucleic acids (PNAs) are among the most interesting and versatile artificial structural mimics of nucleic acids and exhibit peculiar and important properties (i.e. high chemical stability, and a high resistance to cellular enzymes and nucleases). Despite their unnatural structure, they are able to recognize and bind DNA and RNA in a very high, specific and selective manner. One of the most popular, easy and reliable method to measure the stability of PNA-DNA hybrid systems is the melting temperature but the thermodynamic data are obtained using a big quantity of materials failing to provide information on the kinetics of the interaction. In the present work, the PNA decamer 6, with the TCACTAGATG sequence of nucleobases, and the corresponding fluorescent PNA-FITU (fluorescein isothiourea) decamer 8 were synthesized with standard manual Boc-based chemistry. The interaction of the PNA-FITU with parallel and antiparallel DNA has been studied by stopped-flow fluorescence, which is proposed as an alternative technique to obtain the kinetic parameters of the binding. The great advantage of using the stopped-flow technique is the possibility of studying the kinetics of the PNA-DNA duplex formation in a physiological environment. In particular, fluorescence stopped-flow technique has been exploited to compare the affinity of two PNA-DNA duplexes since it can discriminate between parallel and antiparallel DNA binding.

Unveiling iodine-based electrolytes chemistry in aqueous dye-sensitized solar cells.

Aqueous dye-sensitized solar cells (DSSCs) have recently emerged as promising systems, which can combine low cost and environmental compatibility with appreciable efficiency, long-term durability and enhanced safety. In the present study, we thoroughly investigate the chemistry behind the iodide/triiodide-based redox mediator, which presents - in a completely aqueous environment - several differences when compared to the behavior observed in the conventionally used organic solvents. The speciation of ions, the effect of the concentration of the redox mediator and the type of counter-ion are characterized from the electrochemical, spectroscopic, photovoltaic and analytical viewpoints. Furthermore, we demonstrate that aqueous DSSCs, often assumed as unstable, hold the potential to assure unparalleled stability after five months of aging without any addition of stabilizers or gelling agents, thus envisaging the construction of eco-friendly photovoltaic devices free of expensive, flammable and toxic solvents.

[Severe poisoning by plants used for traditional medicine in Mayotte]. / Intoxications graves lors de traitements traditionnels par les plantes à Mayotte.

The authors describe three cases of severe accidental poisoning by plants used as part of a traditional treatment in Mayotte. The established, or suspected, toxicity of Thevetia peruviana (Yellow oleander), Cinchona pubescens (Red quinine-tree), Melia azaderach (Persian lilac, also called china berry) and Azadirachta indica (Neem), is discussed. The clinical presentation is cardiac (atrioventricular block) and well known for Thevetia and Cinchona intoxications. Neurological signs and multi-organ failure are found for Azadirachta and Melia. The identification of the plants is never easy, nor is the evidence of their accountability. In the three cases reported, no other cause than the traditional treatment has been found to explain the clinical presentation. The outcome was favorable in all cases. The authors emphasize the difficulties to investigate these accidents, the poor medical knowledge of these practices in tropical areas, and in Mayotte particularly. The need for cooperation with local botanists, familiar with traditional medicine, is also underlined.

Panchromatic symmetrical squaraines: a step forward in the molecular engineering of low cost blue-greenish sensitizers for dye-sensitized solar cells.

Two novel symmetrical blue squaraine sensitizers were synthesized, which exhibit panchromatic light harvesting and a record efficiency over 6% with Jsc exceeding 14 mA cm(-2), and Voc over 620 mV under 1 sun. Their color, low cost, easiness of synthesis, and relatively high photo- and thermal stability open up the way for commercial applications.

Silver oxide ointment wound dressing in venous ulcerations: home, self-management.

AIM: Venous ulcers are a common, chronic medical and social problem. These ulcers are difficult to heal in most patients with sustained venous hypertension. This pilot product evaluation registry study has evaluated the efficacy and safety of an antimicrobial silver oxide wound dressing ointment ("Silver Oxide Ointment") as part of the treatment of 'difficult' venous ulcerations. METHODS: The study was conducted measuring the variations in the area of the ulceration and microcirculatory parameters. RESULTS: After four weeks, treatment with the Silver Oxide Ointment proved more effective than the 'best management' used in controls. Transcutaneous PO2 was increased (improved); Laser Doppler skin flux and transcutaneous PCO2 were improved (decreased). Also in the silver oxide group a significantly higher number of venous ulcers were completely healed at four weeks. The silver oxide ointment improved both the microcirculation and the healing rate of their ulcers. No significant tolerability problems were observed. CONCLUSION: In difficult venous ulcerations, local treatment with this Silver Oxide Ointment, as one component of the total wound dressing, improved microcirculation measurements and healing rate. Most of the treatments were done at home by the patients or by their tutors. This study indicates the important role of this type of treatment and indicates the need to plan larger and more prolonged studies.

Synthesis, characterization, and DFT-TDDFT computational study of a ruthenium complex containing a functionalized tetradentate ligand.

A ruthenium complex trans-[Ru(L)(NCS)2], L = 4,4' ''-di-tert-butyl-4',4' '-bis(carboxylic acid)-2,2':6',2' ':6' ',2' ''-quaterpyridine (N886), was synthesized and characterized by spectroscopic and electrochemical methods. The absorption spectrum of the N886 complex shows metal-to-ligand charge-transfer transitions in the entire visible region and quasi-reversible oxidation and reduction potentials at E(1/2) = +0.38 and -1.92 V vs ferrocene, respectively. The electronic spectra of the N886 complex were calculated by density functional theory (DFT)-time-dependent DFT, which qualitatively reproduces the experimental absorption spectra for both the protonated and deprotonated species. From the analysis of the computed optical transitions of N886, we assign its absorption bands as mixed Ru/SCN-to-quaterpyridine charge-transfer transitions, which extend from the near-IR to the UV regions. The panchromatic response of the N886 complex renders it as a suitable sensitizer for solar energy conversion applications based on titanium dioxide mesoporous electrodes. The preliminary results using the N886 complex as a sensitizer in a dye-sensitized solar cell, with an electrolyte containing 0.60 M butylmethylimidazolium iodide, 0.03 M I2, and 0.50 M tert-butylpyridine in a mixture of acetonitrile and valeronitrile (volume ratio 1:1), show 40% incident photon-to-current efficiencies, yielding under standard AM 1.5 sunlight a short-circuit photocurrent density of 11.8 +/- 0.2 mA/cm(2), an open-circuit voltage of 680 +/- 30 mV, and a fill factor of 0.73 +/- 0.03, corresponding to an overall conversion efficiency of 5.85%.

An immunohistochemical study of adenohypophyseal cells in the viviparous reptile Chalcides chalcides.

The morphology of the hypophysis and the immunocharacteristics of the adenohypophyseal cells in the viviparous reptile Chalcides chalcides were studied by light microscopy, using conventional staining methods and an indirect antibody technique (ABC method), respectively. The general morphology of the C. chalcides hypophysis was comparable to that of other reptiles, showing three main regions: the pars distalis, the pars intermedia and the pars nervosa. The gland appeared as an elongated body in a cephalic-caudal direction and was almost completely enclosed in the sella turcica. For this reason, the hypophysis was studied in toto with the brain in decalcified specimens. The pars distalis accounted for most of the whole organ. The pars intermedia surrounded the pars nervosa as a goblet. The pars tuberalis was lacking. The immunohistochemical identification of the adenohypophyseal cells was performed using rabbit antisera against mammalian/synthetic hypophyseal hormones. Prolactin cells were clustered in small cellular cordons in the rostral pars distalis and in the medial pars distalis in both male and female specimens. Somatotropic cells were found in the caudal pars distalis. Corticotropic cells were observed in the medio-rostral pars distalis, as well as in the pars intermedia, where melanotropic cells were also present. Melanotropic cells were confined to the pars intermedia. Gonadotropic cells were mostly distributed in the ventral and lateral portions of the pars distalis, where they were found isolated or in small clusters. Thyrotropic cells were detected in the pars distalis with a distribution similar to that of the gonadotropic cells; however, atypically, they were also found in the pars intermedia. Therefore, the cytological characteristics of the adenohypophyseal cells appeared mostly conserved.

Synthesis and surface and antimicrobial properties of novel cationic surfactants.

A series of surfactants with tuned polarity were prepared, including a new class of compounds: gluco-pyridinium surfactants. Pure anomers were obtained by chromatographic separation. The conductivity and surface tension of surfactant solutions in water were measured, and provided interesting information regarding their aggregation behavior. Peculiarities were observed in the premicellar range. Tensidic parameters correlated with antimicrobial activity. A few parameters, mainly the hydrophobicity of the headgroup, may play a role in finding more efficient antimicrobial structures.

Effect of the Counterion on Thermodynamic Properties of Aqueous Micellar Solutions of 1-(3,3,4,4,5,5,6,6,6-Nonafluorohexyl) Pyridinium Halides

We report a thermodynamic study of the aqueous solutions of 1-(3,3,4,4,5,5,6,6,6-nonafluorohexyl) pyridinium chloride, bromide, and iodide and N-octyl pyridinium iodide. Dilution enthalpies and osmotic coefficients of the aqueous solutions of these cationic surfactants have been measured at 313 K as a function of the concentration. The experimental data are expressed in terms of apparent and partial molar quantities. The changes in thermodynamic properties upon micellization have been obtained from the experimental data by using a pseudo phase transition approach. The cmc at 313 K have been evaluated from the plot of the milliosmolality, the measured quantity, vs molality. From the comparison with the trends of the enthalpies at 298 K of the same set of compounds, the effect of temperature on the energetics of their solutions can be derived. The trends of thermodynamic properties vs molality and the micellization parameters confirm that the effect of the counterions, however strong and inversely proportional to the radius of the hydrated counterion, seems to be reduced with respect to the hydrogenated analogs. The curves of the apparent and partial molar enthalpies vs m for the bromide and the iodide are lowered, with respect to the curve of the chloride, by an amount comparable to that at 298 K. This observation suggests that the changes in the absolute trends of the curves and in the micellization enthalpies are due to the modification of the more mobile hydrophobic hydration shell of the perfluoroalkyl chain, whereas the hydration sphere of the counterions is practically unaffected. The heat capacity data and the comparison with the behaviour of hydrogenated analogs is in agreement with the above observation. The trends of the free energies confirm that the degree of counterion binding, beta, and the aggregation number, n, increase with the increasing of the radius of the hydrated counterion.

Preconcentration and selective metal ion separation using chelating micelles.

Chelating aggregates consisting of Triton X100 host micelles and hydrophobic derivatives of PAN have been examined as suitable candidates for preconcentration and selective separation of transition metal ions through micellar-enhanced ultrafiltration. The effective accumulation in the surfactant-rich retentate of nickel(II), copper(II), cobalt(II), manganese(II) and zinc(II), present at trace levels in aqueous samples, has been achieved by operating at pH ca. 6 with a ligand having a binding constant to the host micelles higher than 2000 l./mol. The efficient separation of micelle-bound metal chelates from unreactive ions has been assessed, together with the feasibility of selective enrichment and purification of the investigated metal ions present in mixtures through a multistage process.