Discordance of Biomarker Expression Profile between Primary Breast Cancer and Synchronous Axillary Lymph Node Metastasis in Preoperative Core Needle Biopsy.

Background: Breast cancer (BC) is a heterogeneous disease made up of clones with different metastatic potential. Intratumoral heterogeneity may cause metastases to show divergent biomarker expression, potentially affecting chemotherapy response. Methods: We investigated the immunohistochemical (IHC) and FISH profile of estrogen receptors (ER), progesterone (PR) receptors, Ki67, and HER2 in a series of BC-matched primary tumors (PTs) and axillary lymph node (ALN) metastases in pre-operative core needle biopsies (CNBs). Phenotypical findings were correlated to morphological features and their clinical implications. Results: Divergent expression between PTs and ALNs was found in 10% of the tumors, often involving multiple biomarkers (12/31, 39%). Most (52%) displayed significant differences in ER and PR staining. HER2 divergences were observed in almost three-quarters of the cases (23/31, 74%), with five (16%) switching from negativity to overexpression/amplification in ALNs. Roughly 90% of disparities reflected significant morphological differences between PTs and ALN metastases. Less than half of the discrepancies (12/31, 39%) modified pre/post-operative treatment options. Conclusions: We observed relevant discrepancies in biomarker expression between PTs and metastatic ALNs in a noteworthy proportion (10%) of preoperative BC CNBs, which were often able to influence therapies. Hence, our data suggest routine preoperative assessment of biomarkers in both PTs and ALNs in cases showing significant morphological differences.

Insights on the Anion Effect in N-heterocyclic Carbene Based Dinuclear Gold(I) Catalysts.

Dinuclear bisNHC (bis(N-heterocyclic carbene)) gold(I) complexes 3 a and 4 a of general formula [Au2 Br2 (bisNHC)] were tested as catalysts in the cycloisomerization of N-(prop-2-yn-1-yl)benzamide and in the hydromethoxylation of 3-hexyne in the presence of silver(I) activators bearing different counteranions. The catalytic performance of mononuclear NHC complexes (1 a, 2 a) in the same reactions was also studied. The results highlighted the fundamental role of both NHC ligand and counterion in the catalytic cycles and activation process: dinuclear catalysts exhibit higher initial activity even under milder conditions but suffer in terms of stability with respect to mono NHCs. Furthermore, a new dinuclear bisNHC gold(I) complex 4 b of general formula [Au2 (OTs)2 (bisNHC)] (OTs=p-toluenesulfonate) was successfully synthesized and characterized by means of NMR and ESI-MS analyses.

Bis(N-Heterocyclic Carbene) Manganese(I) Complexes in Catalytic N-Formylation/N-Methylation of Amines Using Carbon Dioxide and Phenylsilane.

A series of six Mn(I) complexes with general formula [MnBr(bisNHC)(CO)3 ], having a bidentate bis(N-heterocyclic carbene) ligand (bisNHC), has been developed by varying the bridging group between the NHC donors, the nitrogen wingtip substituents and the heterocyclic ring. The synthesis of the complexes has been accomplished by in situ transmetalation of the bisNHC from the corresponding silver(I) complexes. Removal of the bromide anion affords the corresponding solvento complexes [Mn(bisNHC)(CO)3 (CH3 CN)](BF4 ). The influence of the bisNHC structure on its electron donor ability has been evaluated by FTIR and 13 C NMR spectroscopy, both in the neutral and cationic complexes. Finally, the isolated Mn(I)-bisNHC complexes have been employed as homogeneous catalysts in the reductive N-formylation and N-methylation of amines with CO2 as C1 source and phenylsilane as reducing agent, showing a high selectivity for the N-methylated product. Preliminary mechanistic investigations suggest that, in the adopted reaction conditions, the formylated product can be formed via different reaction pathways, either metal-catalyzed or not, while the methylation reaction requires the use of the Mn(I) catalyst.

Copper and silver nanowires for CO2 electroreduction.

Copper and silver nanowires have been extensively investigated as the next generation of transparent conductive electrodes (TCEs) due to their ability to form percolating networks. Recently, they have been exploited as electrocatalysts for CO2 reduction. In this review, we present the most recent advances in this field summarizing different strategies used for the synthesis and functionalization/activation of copper and silver nanowires, as well as, the state of the art of their electrochemical performance with particular emphasis on the effect of the nanowire morphology. Novel perspectives for the development of highly efficient, selective, and stable electrocatalysts for CO2 reduction arise from the translation of NW-based TCEs in this challenging field.

Dinuclear gold(I) Complexes with Bidentate NHC Ligands as Precursors for Alkynyl Complexes via Mechanochemistry.

The use of alkynyl gold(I) complexes covers different research fields, such as bioinorganic chemistry, catalysis, and material science, considering the luminescent properties of the complexes. Regarding this last application, we report here the synthesis of three novel dinuclear gold(I) complexes of the general formula [(diNHC)(Au-C≡CPh)2]: two Au-C≡CPh units are connected by a bridging di(N-heterocyclic carbene) ligand, which should favor the establishment of semi-supported aurophilic interactions. The complexes can be easily synthesized through mechanochemistry upon reacting the pristine dibromido complexes [(diNHC)(AuBr)2] with phenylacetylene and KOH. Interestingly, we were also able to isolate the monosubstituted complex [(diNHC)(Au-C≡CPh)(AuBr)]. The gold(I) species were fully characterized by multinuclear NMR spectroscopy and mass spectrometry. The emission properties were also evaluated, and the salient data are comparable to those of analogous compounds reported in the literature.

Aplicación de redes neuronales convolucionales para la detección del tizón tardío Phytophthora infestans en papa Solanum tuberosum / Application of convolutional neural networks for detection of the late blight Phytophthora infestans in potato Solanum tuberosum

RESUMEN La presencia del tizón tardío o gota en el cultivo de papa afecta directamente el crecimiento de la planta y el desarrollo del tubérculo, por ello, es importante la detección temprana de la enfermedad. Actualmente, la aplicación de redes neuronales convolucionales es una oportunidad orientada a la identificación de patrones en la agricultura de precisión, incluyendo el estudio del tizón tardío, en el cultivo de papa. Este estudio describe un modelo de aprendizaje profundo capaz de reconocer el tizón tardío en el cultivo de papa, por medio de la clasificación de imágenes de las hojas. Se utilizó, en la aplicación de este modelo, el conjunto de datos aumentado de PlantVillage, para entrenamiento. El modelo propuesto ha sido evaluado a partir de métricas de rendimiento, como precisión, sensibilidad, puntaje F1 y exactitud. Para verificar la efectividad del modelo en la identificación y la clasificación del tizón tardío y comparado en rendimiento con arquitecturas. como AlexNet, ZFNet, VGG16 y VGG19. Los resultados experimentales obtenidos con el conjunto de datos seleccionado mostraron que el modelo propuesto alcanza una exactitud del 90 % y un puntaje F1, del 91 %. Por lo anterior, se concluye que el modelo propuesto es una herramienta útil para los agricultores en la identificación del tizón tardío y escalable a plataformas móviles, por la cantidad de parámetros que lo comprenden.

ABSTRACT The presence of late blight in potato crops directly affects plant growth and tuber development; therefore, early detection of the disease is important. Currently, the application of convolutional neural networks is an opportunity oriented to the identification of patterns in precision agriculture, including the study of late blight in potato crops. This study describes a deep learning model capable of recognizing late blight in potato crops by means of leaf image classification. The PlantVillage augmented dataset was used in the application of this model for training. The proposed model has been evaluated from performance metrics such as precision, sensitivity, F1 score, and accuracy; to verify the effectiveness of the model in the identification and classification of late blight and compared in performance with architectures such as AlexNet, ZFNet, VGG16, and VGG19. The experimental results obtained with the selected data set showed that the proposed model achieves an accuracy of 90 % and an F1 score of 91 %. Therefore, it is concluded that the proposed model is a useful tool for farmers in the identification of late blight and scalable to mobile platforms due to the number of parameters that comprise it.

Synthesis and Biological Studies on Dinuclear Gold(I) Complexes with Di-(N-Heterocyclic Carbene) Ligands Functionalized with Carbohydrates.

The design of novel metal complexes with N-heterocyclic carbene (NHC) ligands that display biological activity is an active research field in organometallic chemistry. One of the possible approaches consists of the use of NHC ligands functionalized with a carbohydrate moiety. Two novel Au(I)-Au(I) dinuclear complexes were synthesized; they present a neutral structure with one bridging diNHC ligand, having one or both heterocyclic rings decorated with a carbohydrate functionality. With the symmetric diNHC ligand, the dicationic dinuclear complex bearing two bridging diNHC ligands was also synthesized. The study was completed by analyzing the antiproliferative properties of these complexes, which were compared to the activity displayed by similar mononuclear Au(I) complexes and by the analogous bimetallic Au(I)-Au(I) complex not functionalized with carbohydrates.

Structural and Luminescent Properties of Homoleptic Silver(I), Gold(I), and Palladium(II) Complexes with nNHC-tzNHC Heteroditopic Carbene Ligands.

Novel silver(I), gold(I), and palladium(II) complexes were synthesized with bidentate heteroditopic carbene ligands that combine an imidazol-2-ylidene (nNHC) with a 1,2,3-triazol-5-ylidene (tzNHC) connected by a propylene bridge. The silver(I) and gold(I) complexes were dinuclear species, [M2(nNHC-tzNHC)2](PF6)2 (M = Ag or Au), with the two bidentate ligands bridging the metal centers, whereas in the palladium(II) complex [Pd(nNHC-tzNHC)2](PF6)2, the two ligands were chelated on the same metal center. Because of the presence of two different carbene units, isomers were observed for the gold(I) and palladium(II) complexes. The molecular structures of the head-to-tail isomer for gold(I) complexes, with a twisted or folded-syn conformation of the bridge between the carbene units, were determined by X-ray diffraction analysis. The study was completed with a systematic structural investigation through density functional theory (DFT) calculations. For palladium(II) species, the head-to-head form was structurally characterized. The dinuclear gold(I) complexes were emissive in the solid state in the blue region (PLQY up to 8%); time-dependent density functional theory (abbreviated as TD-DFT) calculations disclosed that the absorption bands have metal-to-ligand-charge-transfer character and evidenced that the emission occurs from the T1 level (phosphorescence).

Possible Synthetic Approaches for Heterobimetallic Complexes by Using nNHC/tzNHC Heteroditopic Carbene Ligands.

The synthesis of heterobimetallic complexes remains a synthetic challenge in the field of organometallic chemistry. A possible approach in this regard might be the use of a bidentate heteroditopic bis(carbene) ligand that combines an imidazol-2-ylidene (nNHC) with a 1,2,3-triazol-5-ylidene (tzNHC) connected by an organic spacer. The optimized strategy to heterobimetallic complexes with this type of ligand involves a 3-step procedure: (i) Coordination of the nNHC, functionalized with a 1,2,3-triazole ring, to a metal center; (ii) formation of the triazolium ring by alkylation of the triazole N-3; (iii) deprotonation of the tzNHC precursor and coordination of the second metal center. Following this procedure, a novel Au(I)-Ag(I) dinuclear complex was isolated and its properties were compared to the analogous homobimetallic Ag(I)-Ag(I) and Au(I)-Au(I) complexes. The study was completed by the determination of the molecular structures of some synthetic intermediates.

A square planar gold(iii) bis-(1,1'-dimethyl-3,3'-methylene-diimidazol-2,2'-diylidene) trication as an efficient and selective receptor towards halogen anions: the cooperative effect of AuX and XHC interactions.

Treatment of the tricationic gold(iii) [Au(MeImCH2ImMe)2](PF6)3 complex 1-3PF6 (Im = imidazol-2-ylidene) with excess halides affords complexes 1-3X (X = Cl, Br, and I), resulting from counter anion PF6-/X- exchange. The 1H chemical shift of the CH3 groups and particularly that of the CH2 linker in DMSO-d6 are different in the three complexes, thus suggesting selective XHC interactions. Complex 13+ can therefore be used as a halide sensor in DMSO and water. The host-guest interaction between the tricationic gold(iii) complex and the halides Cl-, Br- and I- in solution and in the solid state has been investigated by means of NMR titration experiments, DFT calculations and X-ray structure analysis. The electrostatic interaction between the halides and the triple formal positive charge on the metal centre, together with the CHX hydrogen bonding between the NHC ligand and halides, contributes to the formation of stable supramolecular aggregates in solution and in the solid state. The complexing properties of 13+ are strongly influenced by the nature of the solvent. Formation of the 1 : 1 and 1 : 2 species (1X2+ and 1X2+) is observed in DMSO-d6, while that of only the 1 : 1 aggregates (1X2+) is observed in D2O (X = Cl, Br, and I). Moreover, the selectivity towards the various halides is reversed in the two solvents, being in the order Cl- > Br- > I- in DMSO-d6 and I- > Br- > Cl- in D2O. The formation constants of the species 1X2+ and 1X2+ in DMSO and 1X2+ in water have been determined by fitting the NMR titration curves.

Insights into the Halogen Oxidative Addition Reaction to Dinuclear Gold(I) Di(NHC) Complexes.

Gold(I) dicarbene complexes [Au2 (MeIm-Y-ImMe)2 ](PF6 )2 (Y=CH2 (1), (CH2 )2 (2), (CH2 )4 (4), MeIm=1-methylimidazol-2-ylidene) react with iodine to give the mixed-valence complex [Au(MeIm-CH2 -ImMe)2 AuI2 ](PF6 )2 (1 a(I) ) and the gold(III) complexes [Au2 I4 (MeIm-Y-ImMe)2 ](PF6 )2 (2 c(I) and 4 c(I) ). Reaction of complexes 1 and 2 with an excess of ICl allows the isolation of the tetrachloro gold(III) complexes [Au2 Cl4 (MeIm-CH2 -ImMe)2 ](PF6 )2 (1 c(Cl) ) and [Au2 Cl4 (MeIm-(CH2 )2 -ImMe)2 ](Cl)2 (2 c(Cl) -Cl) (as main product); remarkably in the case of complex 2, the X-ray molecular structure of the crystals also shows the presence of I-Au-Cl mixed-sphere coordination. The same type of coordination has been observed in the main product of the reaction of complexes 3 or 4 with ICl. The study of the reactivity towards the oxidative addition of halogens to a large series of dinuclear bis(dicarbene) gold(I) complexes has been extended and reviewed. The complexes react with Cl2 , Br2 and I2 to give the successive formation of the mixed-valence gold(I)/gold(III) n a(X) and gold(III) n c(X) (excluding compound 1 c(I) ) complexes. However, complex 3 affords with Cl2 and Br2 the gold(II) complex 3 b(X) [Au2 X2 (MeIm-(CH2 )3 -ImMe)2 ](PF6 )2 (X=Cl, Br), which is the predominant species over compound 3 c(X) even in the presence of free halogen. The observed different relative stabilities of the oxidised complexes of compounds 1 and 3 have also been confirmed by DFT calculations.

Advances in Transition-Metal-Catalysed Alkyne Hydroarylations.

We present herein a personal account of our achievements in the development of novel catalytic systems based on late-transition-metal complexes for the hydroarylation of alkynes. In particular, our targets were intermolecular hydroarylation reactions with arene or heteroarene substrates devoid of directing groups. We have shown that complexes of palladium, platinum or gold with N-heterocyclic carbene (NHC) ligands can be particularly useful catalysts for this reaction; the NHC ligand imparts greater stability to the complex and renders the catalytic system more productive. Furthermore, we have identified promoters and reaction media that allow to significantly improve the catalytic activity under mild conditions, to control the reaction chemoselectivity and to steer it towards more complex products; thus making this reaction considerably more attractive for the synthetic chemist.

Metal complexes with di(N-heterocyclic carbene) ligands bearing a rigid ortho-, meta or para-phenylene bridge.

Three novel dinuclear bis-dicarbene silver(i) complexes of general formula [Ag2(MeIm-phenylene-MeIm)2](PF6)2 (Im = imidazol-2-ylidene) were synthesized. The corresponding copper(i) and gold(i) complexes were obtained by transmetalation of the di(N-heterocyclic carbene) ligand from the silver(i) species, and both coordination geometry and stoichiometry are maintained for all three group 11 metals as expected. The photophysical properties of the Ag(i) and Au(i) complexes were also investigated and discussed; in particular the most strongly emitting complex was also studied via DFT calculations. In addition, the ruthenium(ii) and iridium(iii) complexes [RuCl(MeIm-(o-phenylene)-MeIm)(p-cym)](PF6) and [IrClCp*(MeIm-(o-phenylene)-MeIm)](PF6) were prepared and shown to present in these cases a chelating coordination of the di(N-heterocyclic carbene) ligand.

Synthesis and biological assays on cancer cells of dinuclear gold complexes with novel functionalised di(N-heterocyclic carbene) ligands.

New dinuclear di(N-heterocyclic carbene) silver(I), gold(I) and gold(III) complexes have been synthesised and their antiproliferative effects towards various cancer cell lines have been screened. The di(N-heterocyclic carbene) ligands have a propylene linker between the carbene moieties and the imidazole backbone has been functionalised with a 1-benzyl- or 1-PEG-1,2,3-triazole ring (PEG=poly(ethylene glycol)) via a CuAAC (copper azido alkyne cycloaddition) reaction. The resulting gold(I) and gold(III) complexes display an antiproliferative activity superior to that of the unfunctionalised pristine complexes together with a higher selectivity towards cancerous cells with respect to healthy cells.

Dinuclear gold(I) complexes with propylene bridged N-heterocyclic dicarbene ligands: synthesis, structures, and trends in reactivities and properties.

Four novel dinuclear N-heterocyclic dicarbene gold(I) complexes with a propylene linker between the carbene moieties have been synthesized and their luminescence and electrochemical properties, together with their reactivity towards bromine oxidative addition, have been screened. All the complexes emit in the solid state in the blue-green spectral range (400-500 nm) with appreciable intensities (Φ(em) up to ≈10%). In cyclic voltammetry, the Au(I)/Au(0) peak splits at low temperature into two separate peaks relative to the couples Au(I)-Au(I)/Au(I)-Au(0) and Au(I)-Au(0)/Au(0)-Au(0), thus indicating the presence of an Au···Au interaction in the dinuclear complex. Oxidative addition of bromine affords as a major or unique product Au(II)-Au(II) complexes most likely as a consequence of the interaction between the two gold centres favoured by the propylene linker.

Within-day and between-day repeatability of measurements with an electronic nose in patients with COPD.

Electronic noses (e-noses), artificial sensor systems generally consisting of chemical sensor arrays for the detection of volatile compound profiles, have potential applications in respiratory medicine. We assessed within-day and between-day repeatability of an e-nose made from 32 sensors in patients with stable chronic obstructive pulmonary disease (COPD). We also compared between-day repeatability of an e-nose, fraction of exhaled nitric oxide (FENO) and pulmonary function testing. Within-day and between-day repeatability for the e-nose was assessed in two breath samples collected 30 min and seven days apart, respectively. Repeatability was expressed as an intraclass correlation coefficient (ICC). All sensors had ICC above 0.5, a value that is considered acceptable for repeatability. Regarding within-day repeatability, ICC ranged from 0.75 to 0.84 (mean = 0.80 ± 0.004). Sensors 6 and 19 were the most reproducible sensors (both, ICC = 0.84). Regarding between-day repeatability, ICC ranged from 0.57 to 0.76 (mean = 0.68 ± 0.01). Sensor 19 was the most reproducible sensor (ICC = 0.76). Within-day e-nose repeatability was greater than between-day repeatability (P < 0.0001). Between-day repeatability of FENO (ICC = 0.91) and spirometry (ICC range = 0.94-0.98) was greater than that of e-nose (mean ICC = 0.68). In patients with stable COPD, the e-nose used in this study has acceptable within-day and between-day repeatability which varies between different sensors.

Alkyne hydroarylation with Au N-heterocyclic carbene catalysts.

Mono- and dinuclear gold complexes with N-heterocyclic carbene (NHC) ligands have been employed as catalysts in the intermolecular hydroarylation of alkynes with simple unfunctionalised arenes. Both mono- and dinuclear gold(III) complexes were able to catalyze the reaction; however, the best results were obtained with the mononuclear gold(I) complex IPrAuCl. This complex, activated with one equivalent of silver tetrafluoroborate, exhibited under acidic conditions at room temperature much higher catalytic activity and selectivity compared to more commonly employed palladium(II) catalysts. Moreover, the complex was active, albeit to a minor extent, even under neutral conditions, and exhibited lower activity but higher selectivity compared to the previously published complex AuCl(PPh(3)). Preliminary results on intramolecular hydroarylations using this catalytic system indicate, however, that alkyne hydration by traces of water may become a serious competing reaction.

Blue-emitting dinuclear N-heterocyclic dicarbene gold(I) complex featuring a nearly unit quantum yield.

Dinuclear N-heterocyclic dicarbene gold(I) complexes of general formula [Au(2)(RIm-Y-ImR)(2)](PF(6))(2) (R = Me, Cy; Y = (CH(2))(1-4), o-xylylene, m-xylylene) have been synthesized and screened for their luminescence properties. All the complexes are weakly emissive in solution whereas in the solid state some of them show significant luminescence intensities. In particular, crystals or powders of the complex with R = Me, Y = (CH(2))(3) exhibit an intense blue emission (λ(max) = 450 nm) with a high quantum yield (Φ(em) = 0.96). The X-ray crystal structure of this complex is characterized by a rather short intramolecular Au···Au distance (3.272 Ǻ). Time dependent density functional theory (TDDFT) calculations have been used to calculate the UV/vis properties of the ground state as well as of the first excited state of the complex, the latter featuring a significantly shorter Au···Au distance.