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Las metástasis óseas son frecuentes en el cáncer, apareciendo hasta en el 75% de las pacientes con cáncer de mama avanzado. Las complicaciones de las metástasis óseas incluyen dolor óseo, hipercalcemia y eventos relacionados con el esqueleto (EREs) como las fracturas, la necesidad de radioterapia o cirugía ósea y la compresión de la médula espinal. Presentamos a una paciente de 50 años diagnosticada de un cáncer de mama avanzado que sufrió múltiples eventos relacionados con el esqueleto y un empeoramiento de la calidad de vida.

Background: The appropriate selection criteria for breast-conserving surgery (BCS) or mastectomy after neoadjuvant chemotherapy (NAC) are poorly defined. The aim of this study is to analyse the incidence and prognostic factors for locoregional recurrence (LRR) in patients with breast cancer (BC) treated with NAC to develop a prognostic score to help with clinical decision-making. Materials and methods: Using our retrospective maintained BC database, we identified 730 patients treated with NAC (327 patients treated with BCS and 403 patients treated with mastectomy) between 1998 and 2014. To identify variables associated with an increased LRR rate, we performed firstly Kaplan-Meier curves, with comparisons among groups using log-rank test, and then, significant variables were included in a multivariate analysis using Cox proportional hazards. The prognostic index was developed by assigning score 0 (favourable) or score 1 (unfavourable) for each significant variable of multivariate analysis and was created separately for patients with BCS and mastectomy. Results: At a median follow-up of 72 months, the 6-year cumulative incidence of LRR was 7.2% ( ± 3%) for BCS and 7.9% ( ± 3%) for mastectomy. By univariate analysis, variables associated with an increased LRR were for BCS: HER2 positive, grade III, ductal carcinoma in situ (DCIS), No-pCR (ypTis, ypN0), and age < 40 years; and for mastectomy, HER2-positive, DCIS, No-pCR, and LVI. By multivariate analysis, variables associated with an increased LRR were for BCS: HER2 positive (HR: 11.1, p = 0.001), DCIS (HR: 3.1, p = 0.005), and age < 40 years (HR: 2.8, p = 0.02); and for mastectomy: HER2 positive (HR: 9.5, p = 0.03), DCIS (HR: 2.7, p = 0.01), No-pCR (HR: 11.4, p = 0.01), and age < 40 years (HR: 2.8, p = 0.006). The score stratified patients into three subsets with statistically different levels of risk for LRR. For BCS, the six-year LRR rates were 3%, 13%, and 33% for the low (score 0, n = 120), intermediate (score 1, n = 95) and high (score 2-3, n = 27) risk groups, respectively (p = 0.001). For mastectomy, the six-year LRR rates were 0%, 8%, and 27% for the low (score 0, n = 20), intermediate (score 1-2, n 191),and high (score 3-4, n = 30) risk groups, respectively (p = 0.001). Of note, 21 patients that had a LRR event were HER2 positive, all of them had received trastuzumab. Conclusions: Patients with a score of 0, which made up to 19% of the study population, had very low risk of LRR. The score enabled the identification of a small group (7%) of patients with very high risk of LRR, and who may benefit from alternative treatment. [ABSTRACT FROM AUTHOR]

New hybrid POM based on Lindqvist-type polyoxometalates [M6O19]8− (M = Nb, Ta) and organometallic fragment {Cp*Rh}2+ have been isolated and characterized. X-ray quality crystals of K4[(Cp*Rh)2Nb6O19]·20H2O (1) and Cs4[(Cp*Rh)2Ta6O19]·18H2O (2) were obtained from solutions with {Cp*Rh} : [M6O19]8− stoichiometry 2 : 1. The solution behavior of the hybrid polyoxoanions was studied with ESI-MS and 1H DOSY NMR. Amongst the poorly investigated chemistry of polyoxotantalates, complex 2 is the first complex bearing a grafted organometallic fragment. The formation of 1 : 1 complexes was detected by ESI-MS techniques. [ABSTRACT FROM AUTHOR]

Supported employment in many European countries is spreading somewhat slowly, with specific nationwide programs being required to enable significant progress in integrating people with disabilities and other limitations into the ordinary labor market. This article describes the Caja Madrid SE Program, deployed throughout every province in Spain, for people with disabilities and people who experience social exclusion. We set out the characteristics of the program, the profile of those taking part, and the results achieved in terms of employment between 2005 and 2007. Finally, we include the results of the research related to the participants' quality of life and self-determination. [ABSTRACT FROM AUTHOR]

The Multicomponent Evaluation System of Supported Employment Programs "MESSEP", from the Spanish acronym Sistema de Evaluación Multicomponente de Programas de Empleo Con Apoyo "SEMECA", has been developed as a practical tool using qualitative and quantitative approaches to evaluate all the features of any supported employment initiative. This article shows all of its components, which has been originally developed or adapted to address relevant information from all the participants, comparing data with national and international references and standards. The MESSEP provides different reports from each toll and a final executive report integrating information of each tool. The final objective is to facilitate the decision making for managers and professionals in a supported employment service. The usability and capacity of the MESSEP has been checked in a real context. [ABSTRACT FROM AUTHOR]

The following adducts of cucurbit[6]uril and cucurbit[8]uril with triangular cluster chloroaquacomplexes have been prepared and characterized: {[Mo3S4(H2O)7Cl2]2(CB[6])}Cl4·13H2O ( I), (H3O)2{[Mo3Se4×(H2O)6Cl3](CB[6])}Cl3·3.5H2O ( II) and (H3O)2{[Mo3S4(H2O)4Cl5](CB[8])}Cl·14H2O ( III). It is shown that the formation of complementary hydrogen bonds in the systems cucurbit[6]uril/[M3Q4(H2O)9− x Clx](4− x)+ ( x = 1–3) results in a selective isolation of isomers containing chlorine atom in the trans-position to the capping μ3-ligand. For large x, a selective inclusion of one or another form into the supramolecular compound is also affected by other factors (a system of hydrogen bonds, S⋯S and S...Cl interactions between cluster complexes, packing effects etc.). [ABSTRACT FROM AUTHOR]

Reaction of [Nb6O19]8− with [Pt(OH)4(H2O)2] upon heating yielded first characterized platinum polyniobates. A dimeric complex [Nb6O19{Pt(OH)2}]212− (1) is produced in a 1 : 1 molar ratio. Increasing the Pt/Nb6 molar ratio to 1 : 2 yields a mixture of 1 and a sandwich-type complex [Pt(Nb6O19)2]12− (2). [ABSTRACT FROM AUTHOR]

Bone metastases are common in advanced cancer, occurring up to 75% of patients with advanced breast cancer. Complications of bone metastases include bone pain, hypercalcemia and skeletal-related events (SERs), such as fracture, need for radiation or surgery to bone, or spinal cord compression. A 50 year-old patient with advanced breast cancer, who has multiple skeletal-related events and poorer overall quality of life. [ABSTRACT FROM AUTHOR]

Bone metastases are common in advanced cancer, occurring up to 75% of patients with advanced breast cancer. Complications of bone metastases include bone pain, hypercalcemia and skeletal-related events (SERs), such as fracture, need for radiation or surgery to bone, or spinal cord compression. A 50 year-old patient with advanced breast cancer, who has multiple skeletal-related events and poorer overall quality of life. [ABSTRACT FROM AUTHOR]

Background: Low birth weight has been related to an increased risk for developing high blood pressure in adult life. The molecular and cellular analysis of umbilical cord artery and vein may provide information about the early vascular characteristics of an individual. We have assessed several phenotype characteristics of the four vascular cell types derived from human umbilical cords of newborns with different birth weight. Further follow-up studies could show the association of those vascular properties with infancy and adulthood blood pressure.Methods: Endothelial and smooth muscle cell cultures were obtained from umbilical cords from two groups of newborns of birth weight less than 2.8 kg or higher than 3.5 kg. The expression of specific endothelial cell markers (von Willebrand factor, CD31, and the binding and internalization of acetylated low-density lipoprotein) and the smooth muscle cell specific alpha-actin have been evaluated. Cell culture viability, proliferation kinetic, growth fraction (expression of Ki67) and percentage of senescent cells (detection of beta-galactosidase activity at pH 6.0) have been determined. Endothelial cell projection area was determined by morphometric analysis of cell cultures after CD31 immunodetection.Results: The highest variation was found in cell density at the confluence of endothelial cell cultures derived from umbilical cord arteries (66,789 +/- 5,093 cells/cm(2) vs. 45,630 +/- 11,927 cells/cm(2), p < 0.05). Morphometric analysis indicated that the projection area of the artery endothelial cells (1,161 +/- 198 and 1,544 +/- 472 microm(2), p < 0.05), but not those derived from the vein from individuals with a birth weight lower than 2.8 kg was lower than that of cells from individuals with a birth weight higher than 3.5 kg.Conclusion: The analysis of umbilical cord artery endothelial cells, which demonstrated differences in cell size related to birth weight, can provide hints about the cellular and molecular links between lower birth weight and increased adult high blood pressure risk. [ABSTRACT FROM AUTHOR]

Reaction of [(C6H6)RuCl2]2 and Na8[Ta6O19] gives two new hybrid organometallic POM complexes, Na10[{(C6H6)RuTa6O18}2(µ-O)]·39.4H2O (Na10-1) and Na4(trans-[{(C6H6)Ru}2Ta6O19]·20H2O (Na4-2). In both cases the half-sandwich fragments {(C6H6)Ru}2+ are coordinated as additional vertices to the {Ta3(µ2-O)3} triangles of the hexatantalate. According to NMR and ESI-MS data, the dimeric complex [{(C6H6)RuTa6O18}2(µ-O)]10- dissociates in water with the formation of monomeric [(C6H6)RuTa6O19]6- species (1a). X-ray structural characterization and aqueous speciation of the complexes by 13C, ¹H, and DOSY NMR; ESI-MS; and capillary electrophoresis (CE) have been carried out. [ABSTRACT FROM AUTHOR]

Abstract: New cluster complex [Mo3SeO3(acac)3(py)3]+ was obtained by ligand substitution in the aqua complex [Mo3SeO3(H2O)9]4+. Crystal structure was determined for [Mo3SeO3(acac)3(py)3]PF6·C6H5CH3. The complex was characterized by 77Se NMR, electrospray mass-spectrometry, and cyclic voltammetry. DFT calculations were used to confirm the assignment of chemical shift and to study Mo–Mo bonding in the cluster core. [Copyright &y& Elsevier]

Carboxylate-assisted Pd-catalyzed C-H bond activation constitutes a mild and versatile synthetic tool to efficiently and selectively cleave inert C-H bonds. Herein, we demonstrate a simple method to experimentally evaluate both reactivity and selectivity in such systems using mass spectrometry (MS) methods. The N-heterocyclic carbene (NHC) cations [(NHC)PdX] + , bearing as X - ligand bases commonly used to promote the C-H activation (carboxylates and bicarbonate), are generated in the gas-phase by ESI-MS. Their C-H bond activation at the N-bound groups of the NHC is then studied using Collision Induced Dissociation (CID) experiments. Ion Mobility Spectrometry (IM)-MS is exploited to identify a number of regioisomers associated with the distinctive site selective C-H activations. It is demonstrated that such C-H activation concomitant with acetic acid release occurs from a mixture of activated [(NHC-H)Pd(CH 3 CO 2 H)] + and non-activated [(NHC)Pd(CH 3 CO 2 )] + complexes. The identity of the X-type ligands (X = Cl - , carboxylates and bicarbonate) has a significant impact on the regioisomer branching ratio upon CID conditions. IM-MS in conjunction with a DFT mechanistic study is presented for the acetate-assisted C-H activation of the [(NHC)Pd(CH 3 CO 2 )] + cation featuring butyl and aryl as N-donor groups.

Purpose: Tamoxifen is a drug used for hormone receptor-positive breast cancers, primarily metabolised by the CYP2D6 enzyme into active metabolites such as endoxifen. CYP2D6 displays varying degrees of activity depending on its genotype. This study aims to analyse the effect of an early increase in tamoxifen dose in poor metabolisers (PM) on survival., Methods: We enrolled 220 patients diagnosed with breast cancer who were treated with tamoxifen. CYP2D6 polymorphisms were determined, and the phenotype was estimated according to the Clinical Pharmacogenetics Implementation Consortium. Disease-free survival (DFS) and overall survival (OS) were analysed considering the entire patient group, and a subgroup of 110 patients selected by Propensity Score Matching (PSM). All women were treated with 20 mg/day of tamoxifen for 5 years, except PM, who initially received 20 mg/day for 4 months, followed by 40 mg/day for 4 months and 60 mg/day for 4 months before returning to the standard dose of 20 mg/day until completing 5 years of treatment., Results: The analysis of the influence of CYP2D6 polymorphisms in the complete group and in the PSM subgroup revealed no significant differences for DFS or OS. Furthermore, DFS and OS were analysed in relation to various covariates such as age, histological grade, nodal status, tumour size, HER-2, Ki-67, chemotherapy, and radiotherapy. Only age, histological grade, nodal status, and chemotherapy treatment demonstrated statistical significance., Conclusion: An early increase in tamoxifen dose in PM patients is not associated with survival differences among CYP2D6 phenotypes., Competing Interests: Declaration of competing interest Isabel Blancas received grants and support by Roche., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The activation of C-H bonds in a selective manner still constitutes a major challenge from a synthetic point of view; thus, it remains an active area of fundamental and applied research. Herein, we introduce ion mobility spectrometry mass spectrometry-based (IM-MS) approaches to uncover site-selective C-H bond activation in a series of metal complexes of general formula [(NHC)LMCl] + (NHC = N-heterocyclic carbene; L = pentamethylcyclopentadiene (Cp*) or p -cymene; M = Pd, Ru, and Ir). The C-H bond activation at the N-bound groups of the NHC ligand is promoted upon collision induced dissociation (CID). The identification of the resulting [(NHC-H)LM] + isomers relies on the distinctive topology that such cyclometalated isomers adopt upon site-selective C-H bond activation. Such topological differences can be reliably evidenced as different mobility peaks in their respective CID-IM mass spectra. Alternative isomers are also identified via dehydrogenation at the Cp*/ p -cymene (L) ligands to afford [(NHC)(L-H)M] + . The fragmentation of the ion mobility-resolved peaks is also investigated by CID-IM-CID. It enables the assignment of mobility peaks to the specific isomers formed from C(sp 2 )-H or C(sp 3 )-H bond activation and distinguishes them from the Cp*/ p -cymene (L) dehydrogenation isomers. The conformational change of the NHC ligands upon C-H bond activation, concomitant with cyclometalation, is also discussed on the basis of the estimated collision cross section (CCS). A unique conformation change of the pyrene-tagged NHC members is identified that involves the reorientation of the NHC ring accompanied by a folding of the pyrene moiety.

Complexation of the glutamic-tyrosine-glutamic tripeptide (EYE) with a series of pseudopeptidic cages has been thoroughly investigated using different analytical techniques. The stoichiometry and affinities of the supramolecular host : guest complexes both in aqueous solution and in the gas-phase were obtained from a suitable combination of fluorescence spectroscopy, NMR, and mass spectrometry (MS) methods. The cages bearing basic groups (lysine, ornitine and histidine) display the tightest EYE binding in aqueous media following the order CyHis > CyLys > CyOrn, thus suggesting that Tyr side chain encapsulation is additionally modulated by the identity of the cage side chains and their ability to be engaged in polar interactions with the EYE peptide. Similarly, binding affinities estimated by MS methods clearly point towards a reduced affinity for the Cy cages with acidic pendant groups and a higher affinity of the CyHis cage over CyLys and CyOrn. Ion mobility spectrometry (IMS)-MS, assisted by molecular modelling, has been used to uncover the structural and conformational characteristics of the pseudopeptidic hosts and their supramolecular adducts with the EYE peptide. The cages display a collisional cross-section increase upon EYE inclusion that is associated with the expansion of the binding pocket of the cage cavity, thus constituting a unique example of conformational pseudopeptidic host adaptation to accommodate the inclusion of the guest.

Background: Most breast cancer (BC) patients fail to achieve pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). The aim of this study was to evaluate whether imaging features (perfusion/diffusion imaging biomarkers + radiomic features) extracted from pre-treatment multiparametric (mp)MRIs were able to predict, alone or in combination with clinical data, pCR to NAC., Methods: Patients with stage II-III BC receiving NAC and undergoing breast mpMRI were retrospectively evaluated. Imaging features were extracted from mpMRIs performed before NAC. Three different machine learning models based on imaging features, clinical data or imaging features + clinical data were trained to predict pCR. Confusion matrices and performance metrics were obtained to assess model performance. Statistical analyses were conducted to evaluate differences between responders and non-responders., Results: Fifty-eight patients (median [range] age, 52 [45-58] years) were included, of whom 12 showed pCR. The combined model improved pCR prediction compared to clinical and imaging models, yielding 91.5% of accuracy with no false positive cases and only 17% false negative results. Changes in different parameters between responders and non-responders suggested a possible increase in vascularity and reduced tumour heterogeneity in patients with pCR, with the percentile 25th of time-to-peak (TTP), a classical perfusion parameter, being able to discriminate both groups in a 75% of the cases., Conclusions: A combination of mpMRI-derived imaging features and clinical variables was able to successfully predict pCR to NAC. Specific patient profiles according to tumour vascularity and heterogeneity might explain pCR differences, where TTP could emerge as a putative surrogate marker for pCR.

In this study we report the preparation of a new mechanically interlocked molecule formed by the self-aggregation of two metallotweezers composed by two pyrene-imidazolylidene gold(I) arms and a pyridine-centered pentacyclic bis-alkynyl linker. The mechanically interlocked nature of this molecule arises from the presence of the bulky tert-butyl groups attached to the sides of the pyrene moieties of the arms of the tweezer, which act as stoppers avoiding the dissociation of the self-aggregated metallotweezer dimer once it is formed. By combining experimental techniques, we were able to confirm the mechanically interlocked nature of this molecule in solution, in the gas phase and in the solid state. The behavior of the tert-butyl substituted tweezer differs greatly form that shown by the tweezer lacking of these bulky groups, whose dimeric structure is in equilibrium with the monomeric structure, therefore not showing any mechanical coercion that avoids the disassembly of the self-aggregated structure., (© 2021 Wiley-VCH GmbH.)