In multivariate curve resolution (MCR) analysis, a range of feasible solutions is often encountered, because of the rotational ambiguities associated with the bilinear decomposition of data matrices. ...For quantitative purposes, the analysis is usually applied to a carefully designed set of calibration and test samples having uncalibrated interferents. Under the usual minimal constraints (non-negativity, unimodality, species correspondence, etc.), concentration and spectral profiles of the analyte in the test samples are not univocally recovered, unlike those in the calibration samples, especially when profile overlapping with the interferents is significant and selective regions do not exist for the analyte. In this report, a quantitative measure of the prediction errors due to rotational ambiguities is discussed, based on the calculation of the differences between the maximum and minimum area under the analyte concentration profiles calculated by the MCR-BANDS procedure. This methodology can be applied in different analytical scenarios with any number of analytes and interferents. Both absolute and relative quantitative errors due to rotation ambiguities are estimated and discussed in both simulated and experimental examples derived from liquid chromatography with diode array detection. The proposed procedure can be generalized to most of the analytical situations where every instrumentally measured sample produces a data table or data matrix.
For the first time, liquid chromatography-diode array detection (LC-DAD) and liquid-chromatography fluorescence detection (LC-FLD) second-order data, collected in a single chromatographic run, were ...fused and chemometrically processed for the quantitation of coeluting analytes. Two different experimental mixtures composed of fluorescent and nonfluorescent endocrine disruptors were analyzed. Adequate pretreatment of the matrices before their fusion was crucial to attain reliable results. Multivariate curve resolution-alternating least-squares (MCR-ALS) was applied to LC-DAD, LC-FLD, and fused LC-DAD-FLD data. Although different degrees of improvement are observed when comparing the fused matrix results in relation to those obtained using a single detector, clear benefits of data fusion are demonstrated through: (1) the obtained limits of detection in the ranges 2.1–24 ng mL–1 and 0.9–6.3 ng mL–1 for the two evaluated systems and (2) the low relative prediction errors, below 7% in all cases, indicating good recoveries and precision. The feasibility of fusing data and its advantages in the analysis of real samples was successfully assessed through the study of spiked tap, underground, and river water samples.
Multivariate curve resolution-alternating least-squares (MCR-ALS) is the model of choice when dealing with matrix data that cannot be arranged into a trilinear three-way array, that is, mostly from ...chromatographic origin with spectral detection. A range of feasible solutions may be found in MCR studies, due to the phenomenon of rotational ambiguity associated with bilinear decompositions of matrices. The application of chemically driven constraints is vital to achieving an adequate solution and minimizing the degree of rotational ambiguity present in the system. However, when studying complex samples, it may not be possible to recover unique solutions, even under the application of proper constraints. In such cases, it is important to be able to assess the propagation of rotation uncertainty to the estimated analyte concentrations, which stems from the existence of a finite range of feasible solutions. In this work, we present a new analytical parameter to estimate the potential uncertainty in analyte prediction brought about by rotational ambiguity, in the form of an associated root-mean-square error, named RMSERA. The proposed parameter comes in the form of a range of values, whose limits are δRA/(12)1/2 and δRA/(3)1/2, with δRA being defined as the difference between the maximum and minimum values of the analyte concentration that would be predicted by the MCR model from its concentration profiles lying in the range of feasible solutions, and corresponding to maximum and minimum area, respectively. We support our proposal on extensive simulations for systems of varying composition, and demonstrate its application on experimental data aimed at the determination of four pollutants in environmental water samples.
The partition coefficients,
P
IL/w
, of several compounds, some of them of biological and pharmacological interest, between water and room-temperature ionic liquids based on the imidazolium, ...pyridinium, and phosphonium cations, namely 1-octyl-3-methylimidazolium hexafluorophosphate,
N
-octylpyridinium tetrafluorophosphate, trihexyl(tetradecyl)phosphonium chloride, trihexyl(tetradecyl)phosphonium bromide, trihexyl(tetradecyl)phosphonium bis(trifluoromethylsulfonyl)imide, and trihexyl(tetradecyl)phosphonium dicyanamide, were accurately measured. In this way, we extended our database of partition coefficients in room-temperature ionic liquids previously reported. We employed the
solvation parameter model
with different probe molecules (the
training set
) to elucidate the chemical interactions involved in the partition process and discussed the most relevant differences among the three types of ionic liquids. The multiparametric equations obtained with the aforementioned model were used to predict the partition coefficients for compounds (the
test set
) not present in the training set, most being of biological and pharmacological interest. An excellent agreement between calculated and experimental log
P
IL/w
values was obtained. Thus, the obtained equations can be used to predict, a priori, the extraction efficiency for any compound using these ionic liquids as extraction solvents in liquid-liquid extractions.
Multivariate curve resolution-alternating least-squares (MCR-ALS) is the model of choice when dealing with some non-trilinear arrays, specifically when the data are of chromatographic origin. To ...drive the iterative procedure to chemically interpretable solutions, the use of constraints becomes essential. In this work, both simulated and experimental data have been analyzed by MCR-ALS, applying chemically reasonable constraints, and investigating the relationship between selectivity, analytical sensitivity (γ) and root mean square error of prediction (RMSEP). As the selectivity in the instrumental modes decreases, the estimated values for γ did not fully represent the predictive model capabilities, judged from the obtained RMSEP values. Since the available sensitivity expressions have been developed by error propagation theory in unconstrained systems, there is a need of developing new expressions or analytical indicators. They should not only consider the specific profiles retrieved by MCR-ALS, but also the constraints under which the latter ones have been obtained.
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•Multivariate curve resolution figures of merit are analyzed.•Simulations and experimental data have been studied.•Prediction errors do not follow the trend expected from analytical sensitivities.•The effect is due to lack of consideration of constraints in the figures of merit.
The success of cancer immunotherapy with immune checkpoint blockade (ICB) has demonstrated the importance of targeting a preexisting immune response in a broad spectrum of tumors. This is ...particularly novel and relevant for less immunogenic tumors, such as breast cancer (BC), where the efficacy of ICB was more evident in the triple-negative (TNBC) subtype, in earlier stages, and in association with chemotherapy. Tumors harboring homologous recombination DNA repair (HRR) deficiency (HRD) are supposed to have a higher number of mutations, hence a higher tumor mutational burden, which could potentially make them more sensitive to immunotherapy. However, the mechanisms involved in ICB sensitivity and patient selection are still yet to be defined in BC: whether the innate system could play a role and how the adaptive immunity could be linked with HRR pathways are the two key points of debate that we will discuss in this article. The aim of this review was to close the loop between what was found in clinical trial results so far, go back to laboratory theory and preclinical results and point out what needs to be clarified from now on.
The aim of this study was to develop a novel analytical method for the determination of bisphenol A, nonylphenol, octylphenol, diethyl phthalate, dibutyl phthalate and diethylhexyl phthalate, ...compounds known for their endocrine-disruptor properties, based on liquid chromatography with simultaneous diode array and fluorescent detection. Following the principles of green analytical chemistry, solvent consumption and chromatographic run time were minimized. To deal with the resulting incomplete resolution in the chromatograms, a second-order calibration was proposed. Second-order data (elution time-absorbance wavelength and elution time-fluorescence emission wavelength matrices) were obtained and processed by multivariate curve resolution-alternating least-squares (MCR-ALS). Applying MCR-ALS allowed quantification of the analytes even in the presence of partially overlapped chromatographic and spectral bands among these compounds and the potential interferents. The obtained results from the analysis of beer, wine, soda, juice, water and distilled beverage samples were compared with gas chromatography-mass spectrometry (GC-MS). Limits of detection (LODs) in the range 0.04–0.38ngmL−1 were estimated in real samples after a very simple solid-phase extraction. All the samples were found to contain at least three EDs, in concentrations as high as 334ngmL−1.
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•A green chromatographic method for plastics-derived endocrine disruptors is developed.•Six endocrine disruptors of concern are determined in a wide type of beverages.•Diode array and fluorescence dual detection in a single run offers versatility.•Outstanding selectivity is attained with MCR-ALS second-order algorithm.•Chemometrics allows that compounds of different polarity are rapidly quantified.
HER2-positive breast cancers are rare amongst BRCA mutation carriers. No data exist regarding clinicopathological characteristics and prognosis of this subgroup of patients.
Using a retrospective ...matched cohort design, we collected data from 700 women who were diagnosed with operable invasive breast cancer from January 2006 to December 2016 and were screened for germline BRCA mutations. Clinicopathological features and survival rates were analyzed by BRCA and HER2 status.
One hundred and fifteen HER2-positive/BRCA mutated cases were evaluated in comparison to the three control groups: HER2-positive/BRCA wild type (n = 129), HER2-negative/BRCA mutated (n = 222), HER2-negative/BRCA wild type (n = 234). HER2-positive breast cancers were more likely to have high histologic grade and high proliferation rate than HER2-negative neoplasms, regardless of BRCA mutation status. An interaction between BRCA mutations and HER2-positive status was found to correlate with worse survival after adjusting for prognostic variables (HR = 3.4; 95% CI: 1.3–16.7).
Co-occurrence of BRCA mutations and HER2-positive status is a poor prognostic factor in patients with early or locally advanced breast cancer. This finding may be a proof of concept that a combined pharmacological intervention directed to these targets could be synergistic.
•Co-occurrence of BRCA mutations and HER2-positive status is a poor prognostic factor in patients with breast cancer.•Consider an actionable role for BRCA mutations in HER2-positive disease.•Combinations of PARPi plus anti-HER2 therapies are warranted in this setting.
The aim of this work was to quantify two relevant priority chemicals, bisphenol A (BPA) and 4-nonylphenol (NP), coupling the sensitivity of fluorescence in organized media and the selectivity of ...multivariate calibration, measuring excitation–emission fluorescence matrices in an aqueous methyl-β-cyclodextrin solution. The studied priority pollutants are two of the most frequently found xenoestrogens in the environment, and are therefore of public health concern.The data were successfully processed by applying unfolded partial least-squares coupled to residual bilinearization (U-PLS/RBL), which provided the required selectivity for overcoming the severe spectral overlapping among the analyte spectra and also those for the interferents present in real samples. A rigorous International Union of Pure and Applied Chemistry (IUPAC)-consistent approach was applied for the calculation of the limits of detection. Values in the ranges of 1–2 and 4–14ngmL−1 were obtained in validation samples for BPA and NP, respectively. On the other hand, low relative prediction errors between 3% and 8% were achieved. The proposed method was successfully applied to the determination of BPA and NP in different plastics. In positive samples, after an easy treatment with a small volume of ethanol at 35°C, concentrations were found to range from 26 to 199ngg−1 for BPA, and from 95 to 30,000ngg−1 for NP.
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•A green non-separative method for two very high concern xenoestrogens is proposed.•Cyclodextrin enhanced fluorescence is exploited for sensitivity increase.•Low detection limits are attained without preconcentration steps.•Outstanding selectivity is attained with a proper second-order algorithm.
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