Electric Field Gradient in Chiral and Tetrahedral Molecules within High-Order LRESC Formalism.

In this work, we present the electric field gradient (EFG) given by the linear response elimination of the small component (LRESC) scheme up to the 1/c4 order (c is the speed of light in vacuum) in CHFClX (X = Br, I, At) chiral molecules, together with CHF2Br and CH2FX (X = Br, I, At) tetrahedral systems. The former could be good candidates for further parity violation studies, especially when heavy atoms are surrounding. In this context, the LRESC scheme demonstrates effective applicability to large tetrahedral and chiral molecules that incorporate heavy elements, with relativistic effects playing a crucial role. The LRESC results of EFG exhibit an excellent agreement with those calculated at the four-component level, giving differences of only hundredths order in a.u. (atomic units) for the bromine nucleus and less than 0.1 a.u. for the iodine nucleus. Regarding the other nuclei, for the chiral molecules, there is a heavy atom effect on the light atom (HALA) for chlorine and fluorine atoms as the substituent halogen atom becomes heavier. Furthermore, the electronic part of the EFG for the central carbon and the fluorine nuclei presents an important dependence with the environment in the molecules under study. With accurate calculations of the EFG and tabulated nuclear quadrupole moment, the nuclear quadrupole coupling constant is obtained within the LRESC scheme, including for the first time correlation effects on the spin-dependent corrections with this methodology, providing results close to the experimental ones for Cl, Br, and I atoms. At the Hartree-Fock level, the differences are around 6% for Br and I nuclei, and at the density functional theory level with the LDA and PBE0 functionals, the differences are no more than 2%.

DOCSIC: A Mean-Field Method for Orbital-by-Orbital Self-Interaction Correction.

We introduce a new method to remove the one-electron self-interaction error in approximate density functional calculations on an orbital-by-orbital basis, as originally proposed by Perdew and Zunger [Phys. Rev. B 1981, 23, 5048]. This method is motivated by a recent proposal by Pederson et al. [J. Chem. Phys. 2014, 140, 121103] to remove self-interaction that employs orbitals derived from the real-space density matrix, known as FLOSIC (Fermi Löwdin orbitals self-interaction correction). However, instead of Fermi Löwdin orbitals, our scheme utilizes columns of the density matrix to determine localized orbitals, like the localization procedure proposed by Fuemmeler et al. [J. Chem. Theory Comput. 2023, 19, 8572]. The new method, dubbed DOCSIC for density matrix as orbital coefficients self-interaction correction, contrasts with traditional Perdew-Zunger or FLOSIC in that it does not incorporate additional optimization parameters, and, unlike the average density self-interaction correction of Ciofini et al. [Chem. Phys. Lett. 2003, 380, 12], it makes use of localized orbitals. Another advantage of DOCSIC is that it can be implemented as a mean-field formalism. We show details of the self-consistent generalized Kohn-Sham implementation, some illustrative results, and we finally highlight its advantages and limitations.

Generalized Spin in the Variance-Based Wave Function Optimization Method within the Doubly Occupied Configuration Interaction Framework.

In this work, we implement a generalized spin formulation of the doubly occupied configuration interaction methodology using the energy variance of the N-electron Hamiltonian. We perform the optimization of the N-electron wave functions and calculate their corresponding energies, using a unified variational treatment for ground and excited states based on the energy variance, which allows us to describe the entire energy spectra on an equal footing. We analyze the effects produced by the breakdown of the S2 and Sz symmetries in the spectra of model hydrogenic clusters in terms of energies and spin-related quantities, arising from the restricted, unrestricted, and generalized spin methods. The results are compared with other related methods as well as full configuration interaction.

Density Matrix Implementation of the Fermi-Löwdin Orbital Self-Interaction Correction Method.

The Fermi-Löwdin orbital self-interaction correction (FLOSIC) method effectively provides a transformation from canonical orbitals to localized Fermi-Löwdin orbitals which are used to remove the self-interaction error in the Perdew-Zunger (PZ) framework. This transformation is solely determined by a set of points in space, called Fermi-Löwdin descriptors (FODs), and the occupied canonical orbitals or the density matrix. In this work, we provide a detailed workflow for the implementation of the FLOSIC method for removal of self-interaction error in DFT calculations in an orbital-by-orbital basis that takes advantage of the unitary invariant nature of the FLOSIC method. In this way, it is possible to cast the self-consistent energy minimization at fixed FODs in the same manner than standard Kohn-Sham with one additional term in the Kohn-Sham Hamiltonian that introduces the PZ self-interaction correction. Each energy minimization iteration is divided in two substeps, one for the density matrix and one for the FODs. Expressions for the effective Kohn-Sham matrix and FOD gradients are provided such that its implementation is suitable for most electronic structure codes. We analyze the convergence characteristics of the algorithm and present applications for the evaluation of NMR shielding constants and real-time time-dependent DFT simulations based on the Liouville-von Neumann equation to calculate excitation energies.

Generalized spin σ-SCF method.

We introduce a generalization of the σ-SCF method to approximate noncollinear spin ground and excited single-reference electronic states by minimizing the Hamiltonian variance. The new method is based on the σ-SCF method, originally proposed by Ye et al. [J. Chem. Phys. 147, 214104 (2017)], and provides a prescription to determine ground and excited noncollinear spin states on an equal footing. Our implementation was carried out utilizing an initial simulated annealing stage followed by a mean-field iterative self-consistent approach to simplify the cumbersome search introduced by generalizing the spin degrees of freedom. The simulated annealing stage ensures a broad exploration of the Hilbert space spanned by the generalized spin single-reference states with random complex element-wise rotations of the generalized density matrix elements in the simulated annealing stage. The mean-field iterative self-consistent stage employs an effective Fockian derived from the variance, which is utilized to converge tightly to the solutions. This process helps us to easily find complex spin structures, avoiding manipulating the initial guess. As proof-of-concept tests, we present results for Hn (n = 3-7) planar rings and polyhedral clusters with geometrical spin frustration. We show that most of these systems have noncollinear spin excited states that can be interpreted in terms of geometric spin frustration. These states are not directly targeted by energy minimization methods, which are meant to converge to the ground state. This stresses the capability of the σ-SCF methodology to find approximate noncollinear spin structures as mean-field excited states.

High order relativistic corrections on the electric field gradient within the LRESC formalism.

In this work, we present relativistic corrections to the electric field gradient (EFG) given by the Linear Response Elimination of the Small Component (LRESC) scheme at 1/c2 order and including for the first time spin-dependent (SD) corrections at 1/c4 order. We show that these new terms improve the performance of LRESC as results with this methodology are very close to those calculated at the four-component Dirac-Hartree-Fock (4c-DHF) level. We assess the new corrections in BrY and AtY di-halogen (Y = F, Cl, Br, I, and At) and XZY bi-linear molecules (Z = Zn, Cd, and Hg; X, Y = F, Cl, Br, I, and At). At the 4c-DHF level, we analyze the contributions coming from the large and small components of the relativistic 4c wave function to the electronic part of EFG and compare them with the LRESC corrections to find their electronic origin. For the HgX2 (X = Cl, Br, and I) subset, when the SD correcting terms are included, LRESC calculations match very well with 4c-DHF ones and those from the literature, with differences less than 1% for molecules containing up to three heavy atoms. We show that LRESC gives accurate values of EFG, allowing the analysis of the electronic origin of relativistic effects in terms of well-known nonrelativistic operators.

Antagonistic Activity of Lactic Acid Bacteria Against Phytopathogenic Fungi Isolated from Cherry Tomato (Solanum lycopersicum var. cerasiforme).

The postharvest deterioration of cherry tomatoes due to diseases caused by fungi is one of the main causes of the loss of this product. The objective of this study was to determine the antagonistic capacity by evaluating the antifungal power of nine strains of lactic acid bacteria (LAB) in vitro against the phytopathogenic fungi Aspergillus niger, Fusarium sp., and Rhizopus stolonifer isolated from cherry tomatoes (Solanum lycopersicum var. cerasiforme) and to measure the biosurfactant production capacity, its antagonism in vivo, and the production of organic acids. The results showed that seven of the nine strains were able to inhibit at least one of the three fungi isolated in the in vitro assay. In eight of nine strains, biosurfactant production was identified, and the strains Weissella confusa and Lactiplantibacillus plantarum A6 showed the highest antifungal activity in vitro and in vivo against the fungi evaluated, with the identification of organic acid production in both strains. LAB demonstrated the ability to inhibit cherry tomato fungi, thus emerging as an alternative to the use of chemical preservatives in the production of this fruit and being projected as a preservation technology for this type of product through the use of strains or their metabolites.

Study of the sRNA RsmY involved in the genetic regulation of the synthesis of alginate and alkyl resorcinols in Azotobacter vinelandii.

Azotobacter vineladii is a Gram-negative bacterium that produces alginate and poly-hydroxybutyrate (PHB), two polymers of biotechnological interest. This bacterium has the ability to form desiccation-resistant cysts. In the cyst the membrane phospholipids are replaced with a family of phenolic lipids called alkylresorcinols (ARs). The alginate, PHB, and ARs are controlled by the GacS/A two-component system and the small regulatory RNA (sRNA) RsmZ1, belonging to the Rsm (Csr) regulatory system. The Rsm (Csr) systems usually possess two or more sRNAs, in this regard A. vinelandii is the bacterium with the highest number of rsm-sRNAs. Originally, the presence of two sRNAs of the RsmY family (RsmY1 and RsmY2) was reported, but in a subsequent work it was suggested that they conformed to a single sRNA. In this work we provide genetic evidence confirming that rsmY1 and rsmY2 constitute a single gene. Also, it was established that rsmY mutation decreased alginate and ARs production, but did not affect the PHB synthesis. Transcriptional studies showed that rsmY has its higher expression during the stationary growth phase, and in the absence of RsmZ1, rsmY increases its transcription. Interestingly, rsmY expression was influenced by the carbon source, but its expression did not correlate with alginate production.

Performance of the LRESC Model on top of DFT Functionals for Relativistic NMR Shielding Calculations.

The linear response within the elimination of the small component model (LRESC) is an insightful and computationally efficient method for including relativistic effects on molecular properties like the nuclear magnetic shielding constants, spin-rotation constant, g-tensor, and electric field gradient of heavy atom containing molecules with atoms belonging up to the sixth row of the periodic table. One of its main advantages is its capacity to analyze the electronic origin of the different relativistic correcting terms. Until now, it was always applied on top of Hartree-Fock ground-state wave functions (LRESC/HF) to calculate and analyze NMR shieldings. In this work, we show the performance of the LRESC formalism on top of some density functional theory (DFT) functionals to compute tin shielding constants in SnX4 (X = H, F, Cl, Br, I) molecular systems. We analyze the performance of each LRESC/DFT scheme on reproducing the electronic mechanisms of the shieldings, taking as a benchmark the results of relativistic calculations at the RPA level of approach (4c/RPA). As in previous works, we divide the LRESC relativistic correcting terms into two groups: core-dependent and ligand-dependent contributions. It is shown here that core-dependent corrections are well-reproduced for the selected DFT functionals, but some differences arise in the ligand-dependent ones. We focus on the performance of different functionals, including the same electron correlation part but containing different amounts of HF exchange. The best results are obtained for the BHandHLYP functional (50% of HF exchange) and the worst for BLYP (0%). When the percentage of HF exchange increases, ligand-dependent contributions are better described, and the final LRESC/DFT results are closer to those obtained with LRESC/HF and 4c/RPA methods. The spin-orbit correction to the shielding constant is one of the main ligand-dependent contributions (there are two more) with total value depending on the amount of HF exchange included in the functional. When the amount of HF exchange decreases, the spin-orbit contribution becomes larger, overestimating the shielding constant even when nonrelativisitc DFT values are much smaller than the nonrelativistic HF ones, as it happens for the heaviest molecular system studied here (SnI4).

Routes of phosphoryl group transfer during signal transmission and signal decay in the dimeric sensor histidine kinase ArcB.

The Arc (anoxic redox control) two-component system of Escherichia coli, comprising ArcA as the response regulator and ArcB as the sensor histidine kinase, modulates the expression of numerous genes in response to respiratory growth conditions. Under reducing growth conditions, ArcB autophosphorylates at the expense of ATP, and transphosphorylates ArcA via a His292 → Asp576 → His717 → Asp54 phosphorelay, whereas under oxidizing growth conditions, ArcB catalyzes the dephosphorylation of ArcA-P by a reverse Asp54 → His717 → Asp576 → Pi phosphorelay. However, the exact phosphoryl group transfer routes and the molecular mechanisms determining their directions are unclear. Here, we show that, during signal propagation, the His292 → Asp576 and Asp576 → His717 phosphoryl group transfers within ArcB dimers occur intra- and intermolecularly, respectively. Moreover, we report that, during signal decay, the phosphoryl group transfer from His717 to Asp576 takes place intramolecularly. In conclusion, we present a mechanism that dictates the direction of the phosphoryl group transfer within ArcB dimers and that enables the discrimination of the kinase and phosphatase activities of ArcB.

Magnetic Properties of Co(II) Complexes with Polyhedral Carborane Ligands.

In this work we present a computational analysis of a new family of magnetic Co(II) single-ion complexes with large magnetic anisotropy based on icosahedral and octahedral carborane ligands. In particular, we extend our previous computational work on mononuclear Co(II) complexes with 1,2-(HS)2-1,2-C2B10H10 and 9,12-(HS)2-1,2-C2B10H10 icosahedral o-carborane ligands to a larger set of complexes where the Co(II) ion is doubly chelated by those ligands and by other two positional isomers belonging to the 1,2-dicarba- closo-dodecaborane family. We also describe Co(II) complexes with octahedral ligands derived from 1,2-dicarba- closo-hexaborane and study the effects of replacing a thiol group by a hydroxy group in both polyhedral geometries, as well as the influence of the position of the carbon atoms. On analysis of the results for a total of 20 complexes, our results show that carborane-based Co(II) single-ion compounds present a distorted-tetrahedral geometry, high-spin ground states, and high values for the magnetic anisotropy parameters. We point out which of these would be suitable candidates to be synthesized and used as molecular magnets.

Magnetic Properties of Mononuclear Co(II) Complexes with Carborane Ligands.

We analyze the magnetic properties of three mononuclear Co(II) coordination complexes using quantum chemical complete active space self-consistent field and N-electron valence perturbation theory approaches. The complexes are characterized by a distorted tetrahedral geometry in which the central ion is doubly chelated by the icosahedral ligands derived from 1,2-(HS)2-1,2-C2B10H10 (complex I), from 1,2-(HS)2-1,2-C2B10H10 and 9,12-(HS)2-1,2-C2B10H10 (complex II), and from 9,12-(HS)2-1,2-C2B10H10 (complex III), which are two positional isomers of dithiolated 1,2-dicarba- closo-dodecaborane (complex I). Complex I was realized experimentally recently (Tu, D.; Shao, D.; Yan, H.; Lu, C. Chem. Commun. 2016, 52, 14326) and served to validate the computational protocol employed in this work, while the remaining two proposed complexes can be considered positional isomers of I. Our calculations show that these complexes present different axial and rhombic zero-field splitting anisotropy parameters and different values of the most significant components of the g tensor. The predicted axial anisotropy D = -147.2 cm-1 for complex II is twice that observed experimentally for complex I, D = -72.8 cm-1, suggesting that this complex may be of interest for practical applications. We also analyze the temperature dependence of the magnetic susceptibility and molar magnetization for these complexes when subject to an external magnetic field. Overall, our results suggest that o-carborane-incorporated Co(II) complexes are worthwhile candidates for experimental exploration as single-ion molecular magnets.

Theoretical analysis of NMR shieldings of group-11 metal halides on MX (M = Cu, Ag, Au; X = H, F, Cl, Br, I) molecular systems, and the appearance of quasi instabilities on AuF.

Accurate calculations of nuclear magnetic shieldings of group-11 metal halides, σ(M; MX) (M = Cu, Ag, Au; X = H, F, Cl, Br, I), were performed with relativistic and nonrelativistic theoretical schemes in order to learn more about the importance of the involved electronic mechanisms that underlie such shieldings. We applied state of the art schemes: polarization propagators at a random phase level of approach (PP-RPA); spin-free Hamiltonian (SF); linear response elimination of small component (LRESC) and density functional theory (DFT) with two different functionals: B3LYP and PBE0. The results from DFT calculations are not close to those from the relativistic polarization propagator calculations at the RPA level of approach (RelPP-RPA), in line with previous results. The spin-orbit (SO) contribution to a shielding constant is important only for MF molecules (M = Cu, Ag, Au). Different electronic mechanisms are considered within the LRESC method, bunched into two groups: core- and ligand-dependent. For the analysed shieldings the core-dependent electronic mechanisms are the most important ones; the ligand-dependent being only important for MF molecules. An out of range value for σ(Au) is found in AuF. It was previously reported in the literature, either originated in the large fluorine electronegativity together with large spin-orbit coupling contributions; or, due to Fermi-contact contributions. We argue here that such an unexpected large value is an artifact originated in the appearance of quasi instabilities, and show how to handle this apparent problem.

Theoretical study of the nuclear spin-molecular rotation coupling for relativistic electrons and non-relativistic nuclei. II. Quantitative results in HX (X = H,F,Cl,Br,I) compounds.

In the present work, numerical results of the nuclear spin-rotation (SR) tensor in the series of compounds HX (X = H,F,Cl,Br,I) within relativistic 4-component expressions obtained by Aucar et al. [J. Chem. Phys. 136, 204119 (2012)] are presented. The SR tensors of both the H and X nuclei are discussed. Calculations were carried out within the relativistic Linear Response formalism at the Random Phase Approximation with the DIRAC program. For the halogen nucleus X, correlation effects on the non-relativistic values are shown to be of similar magnitude and opposite sign to relativistic effects. For the light H nucleus, by means of the linear response within the elimination of the small component approach it is shown that the whole relativistic effect is given by the spin-orbit operator combined with the Fermi contact operator. Comparison of "best estimate" calculated values with experimental results yield differences smaller than 2%-3% in all cases. The validity of "Flygare's relation" linking the SR tensor and the NMR nuclear magnetic shielding tensor in the present series of compounds is analyzed.

Experimental Composite Resin with Myristyltrimethylammonium Bromide (MYTAB) and Alpha-Tricalcium Phosphate (α-TCP): Antibacterial and Remineralizing Effect.

The aim of this study was to develop an experimental composite resin with the addition of myristyltrimethylammonium bromide (MYTAB) and α -tricalcium phosphate (α-TCP) as an antibacterial and remineralizing material. Experimental composite resins composed of 75 wt% Bisphenol A-Glycidyl Methacrylate (BisGMA) and 25 wt% Triethylene Glycol Dimethacrylate (TEGDMA) were produced. Some 1 mol% Trimethyl benzoyl-diphenylphosphine oxide (TPO) was used as a photoinitiator, and butylated hydroxytoluene (BTH) was added as a polymerization inhibitor. Silica (1.5 wt%) and barium glass (65 wt%) particles were added as inorganic fillers. For remineralizing and antibacterial effect, α-TCP (10 wt%) and MYTAB (5 wt%) were incorporated into the resin matrix (α-TCP/MYTAB group). A group without the addition of α-TCP/MYTAB was used as a control. Resins were evaluated for their degree of conversion (n = 3) by Fourier Transform Infrared Spectroscopy (FTIR). The flexural strength (n = 5) was assessed based on ISO 4049:2019 requirements. Microhardness was assessed to calculate softening in solvent (n = 3) after ethanol immersion. The mineral deposition (n = 3) was evaluated after immersion in SBF, while cytotoxicity was tested with HaCaT cells (n = 5). Antimicrobial activity (n = 3) was analyzed against S. mutans. The degree of conversion was not influenced by the antibacterial and remineralizing compounds, and all groups reached values > 60%. The α-TCP/MYTAB addition promoted increased softening of polymers after immersion in ethanol and reduced their flexural strength and the viability of cells in vitro. A reduction in S. mutans viability was observed for the α-TCP/MYTAB group in biofilm formation and planktonic bacteria, with an antibacterial effect > 3log10 for the developed materials. Higher intensity of phosphate compounds on the sample's surface was detected in the α-TCP/MYTAB group. The addition of α-TCP and MYTAB promoted remineralizing and antibacterial effects on the developed resins and may be a strategy for bioactive composites.

Bioavailability and systemic transport of oleanolic acid in humans, formulated as a functional olive oil.

Evidence of the pharmacological activity of oleanolic acid (OA) suggests its potential therapeutic application. However, its use in functional foods, dietary supplements, or nutraceuticals is hindered by limited human bioavailability studies. The BIO-OLTRAD trial is a double-blind, randomized controlled study with 22 participants that received a single dose of 30 mg OA formulated as a functional olive oil. The study revealed that the maximum serum concentration of OA ranged from 500 to 600 ng mL-1, with an AUC0-∞ value of 2862.50 ± 174.50 ng h mL-1. Furthermore, we discovered a physiological association of OA with serum albumin and triglyceride-rich lipoproteins (TRL). UV absorption spectra showed conformational changes in serum albumin due to the formation of an adduct with OA. Additionally, we demonstrated that TRL incorporate OA, reaching a maximum concentration of 140 ng mL-1 after 2-4 hours. We conjecture that both are efficient carriers to reach target tissues and to yield high bioavailability.

Relativistic effects on nuclear magnetic shieldings of CH(n)X(4-n) and CHXYZ (X, Y, Z = H, F, Cl, Br, I).

Nuclear magnetic shieldings of both carbon and hydrogen atoms of haluro methyl molecules are highly influenced by the substitution of one or more hydrogen by halogen heavy atoms. We applied the linear response elimination of small components, LRESC, formalism to calculate such shieldings and learn whether including only few terms is enough for getting quantitative reproduction of the total shieldings or not. First, we discuss the contribution of all leading relativistic corrections to σ(C), in CHX(2)I molecular models with X = H, F, and Cl, and show that spin-orbit (SO) effects are the main ones. After adding the SO effects to the non-relativistic (NR) results, we obtain ~ 97% (93%) of the total LRESC values for σ(C) (σ(H)). The magnitude of SO terms increases when the halogen atom becomes heavier. In this case, such contributions to σ(C) can be extrapolated as a function of Z, the halogen atomic number. Furthermore, when paramagnetic spin-orbit (PSO) contributions are also considered, we obtain results that are within 1% of the total LRESC value. Then we study in detail the main electronic mechanisms involved to contribute C and H shieldings on CH(n)X(4 - n) (n = 1, 3), and CHXYZ (X, Y, Z = F, Cl, Br, I) model compounds. The pattern of σ(C) for all series of compounds follows a normal halogen dependence (NHD), though with different rate of increase. A special family of compounds is that of CHF(2)X for which σ(nr)(C) follows an inverse halogen dependence though the total shielding have a NHD due to the SO contributions. For the series CH(3)X (X = F, Cl, Br and I), we found that σ(SO) ~ Z(X) (2.53). Another important finding of this work is the logarithmic dependence of σ(SO)(C) with the substituent atomic number: ln σ(SO)(C) = A(X) + a(X) Z(Y) for both family of compounds CH(2)XY and CHX(2)Y. We also performed four-component calculations using the spin-free Hamiltonian to obtain SO contributions within a four-component framework.

A conservative approach for restoring anterior guidance: a case report.

UNLABELLED: One of the most common dental problems in today's clinics is tooth wear, specifically when related to bruxism. In such cases, the esthetics of anterior teeth may be compromised when excessive wear to the incisal surfaces occurs. Anterior tooth wear resulting from parafunctional bruxism can be conservatively treated with the use of direct resin composite restorations. This restorative approach has the advantages of presenting good predictability, load resistance, acceptable longevity, preservation of healthy dental tissues, and lower cost when compared with indirect restorations. The use of resin composites to solve esthetic problems, however, requires skill and practice. Thus, the present article demonstrates a conservative approach for restoring the esthetics and function of worn anterior teeth with the aid of direct resin composite restorations and selective occlusal adjustment. CLINICAL SIGNIFICANCE: A conservative approach to restore anterior teeth with excessive wear is possible with direct resin composites.

First-line cisplatin, docetaxel, and cetuximab for patients with recurrent or metastatic head and neck cancer: A multicenter cohort study.

BACKGROUND: The targeted therapy cetuximab [directed at the epidermal growth factor receptor (EGFR)] in combination with 5-fluorouracil and platinum-based chemotherapy (the EXTREME regimen) has shown substantial efficacy for patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). Thus, this scheme has been established as the preferred first-line option for these patients. However, more recently, a new strategy combining platinum, taxanes, and cetuximab (the TPEx regimen) has demonstrated similar efficacy with a more favorable toxicity profile in clinical trials. AIM: To evaluate the safety and efficacy of the TPEx scheme as first-line therapy in advanced SCCHN in a multicenter cohort study. METHODS: This retrospective multicenter cohort study included patients with histologically confirmed recurrent or metastatic SCCHN treated with first-line TPEx at five medical centers in Argentina between January 1, 2017 and April 31, 2020. Chemotherapy consisted of four cycles of docetaxel, cisplatin, and cetuximab followed by cetuximab maintenance therapy. Clinical outcomes and toxicity profiles were collected from medical charts. Treatment response was assessed by the investigator in accordance with Response Evaluation Criteria in Solid Tumors (version 1.1). Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0). RESULTS: Twenty-four patients were included. The median age at diagnosis was 58 years (range: 36-77 years). The majority of patients (83.3%) received at least four chemotherapy cycles in the initial phase. In the included group, the overall response rate was 62.5%, and 3 patients achieved a complete response (12.5%). The median time to response was 2.4 mo [95% confidence interval (CI): 1.3-3.5]. With a median follow-up of 12.7 mo (95%CI: 8.8-16.6), the median progression-free survival (PFS) was 6.9 mo (95%CI: 6.5-7.3), and the overall survival rate at 12 mo was 82.4%. Patients with documented tumor response showed a better PFS than those with disease stabilization or progression [8.5 mo (95%CI: 5.5-11.5) and 4.5 mo (95%CI: 2.5-6.6), respectively; P = 0.042]. Regarding the safety analysis, two-thirds of patients reported at least one treatment-related adverse event, and 25% presented grade 3 toxicities. Of note, no patient experienced grade 4 adverse events. CONCLUSION: TPEx was an adequately tolerated regimen in our population, with low incidence of grade 3-4 adverse events. The median PFS were consistent with those in recent reports of clinical trials evaluating this treatment combination. This regimen may be considered an attractive therapeutic strategy due to its simplified administration, decreased total number of chemotherapy cycles, and treatment tolerability.

NMR nuclear magnetic shielding anisotropy of linear molecules within the linear response within the elimination of the small component approach.

The influence of the spin-Zeeman (SZ) operator in the evaluation of the spin-orbit effect on the nuclear magnetic shielding tensor in the context of the linear response within the elimination of the small component approach is critically discussed. It is shown that such term yields no contribution to the isotropic nuclear magnetic shielding constant, but it may be of great importance in the determination of individual tensor components, and particularly of the tensor anisotropy. In particular, an interesting relation between the SZ and orbital Zeeman contributions to the spin-orbit effect for the case of linear molecules is shown to hold. Numerical examples for the BrH, IH, and XeF(2) molecules are presented which show that, provided the SZ term is taken into account, results of the individual shielding tensor components and the tensor anisotropy are in good agreement with those obtained by other theoretical methods, and particularly by the Dirac-Hartree-Fock approach.