Analysing the effect caused by increasing the molecular volume in M1-AChR receptor agonists and antagonists: a structural and computational study.

M1 muscarinic acetylcholine receptor (M1-AChR), a member of the G protein-coupled receptors (GPCR) family, plays a crucial role in learning and memory, making it an important drug target for Alzheimer's disease (AD) and schizophrenia. M1-AChR activation and deactivation have shown modifying effects in AD and PD preclinical models, respectively. However, understanding the pharmacology associated with M1-AChR activation or deactivation is complex, because of the low selectivity among muscarinic subtypes, hampering their therapeutic applications. In this regard, we constructed two quantitative structure-activity relationship (QSAR) models, one for M1-AChR agonists (total and partial), and the other for the antagonists. The binding mode of 59 structurally different compounds, including agonists and antagonists with experimental binding affinity values (pKi), were analyzed employing computational molecular docking over different structures of M1-AChR. Furthermore, we considered the interaction energy (Einter), the number of rotatable bonds (NRB), and lipophilicity (ilogP) for the construction of the QSAR model for agonists (R2 = 89.64, QLMO2 = 78, and Qext2 = 79.1). For the QSAR model of antagonists (R2 = 88.44, QLMO2 = 82, and Qext2 = 78.1) we considered the Einter, the fraction of sp3 carbons fCsp3, and lipophilicity (MlogP). Our results suggest that the ligand volume is a determinant to establish its biological activity (agonist or antagonist), causing changes in binding energy, and determining the affinity for M1-AChR.

Activity-Based Nitric Oxide-Responsive Porphyrin for Site-Selective and Nascent Cancer Ablation.

Nitric oxide (NO) generated within the tumor microenvironment is an established driver of cancer progression and metastasis. Recent efforts have focused on leveraging this feature to target cancer through the development of diagnostic imaging agents and activatable chemotherapeutics. In this context, porphyrins represent an extraordinarily promising class of molecules, owing to their demonstrated use within both modalities. However, the remodeling of a standard porphyrin to afford a responsive chemical that can distinguish elevated NO from physiological levels has remained a significant research challenge. In this study, we employed a photoinduced electron transfer strategy to develop a panel of NO-activatable porphyrin photosensitizers (NOxPorfins) augmented with real-time fluorescence monitoring capabilities. The lead compound, NOxPorfin-1, features an o-phenylenediamine trigger that can effectively capture NO (via N2O3) to yield a triazole product that exhibits a 7.5-fold enhancement and a 70-fold turn-on response in the singlet oxygen quantum yield and fluorescence signal, respectively. Beyond demonstrating excellent in vitro responsiveness and selectivity toward NO, we showcase the potent photodynamic therapy (PDT) effect of NOxPorfin-1 in murine breast cancer and human non-small cellular lung cancer cells. Further, to highlight the in vivo efficacy, two key studies were executed. First, we utilized NOxPorfin-1 to ablate murine breast tumors in a site-selective manner without causing substantial collateral damage to healthy tissue. Second, we established a nascent human lung cancer model to demonstrate the unprecedented ability of NOxPorfin-1 to halt tumor growth and progression completely. The results of the latter study have tremendous implications for applying PDT to target metastatic lesions.

Resultados de "Tomando Control de su Salud" online, en personas con enfermedades no transmisibles de México y Perú durante COVID-19 / Results of "Tomando Control de su Salud" online, in people with non-communicable diseases in Mexico and Peru during COVID-19

Las enfermedades no transmisibles (ENT) son una creciente preocupación global que afecta tanto a la atención médica como a la calidad de vida. Los programas de automanejo de enfermedades crónicas como el denominado "Tomando Control de su Salud" (TCS), se han vuelto estrategias efectivas para abordar este problema. OBJETIVO: Evaluar el resultado del programa TCS, versión en línea, en las variables automanejo y autoeficacia, en muestras de personas con ENT de México y Perú, durante la pandemia por COVID-19. METODOLOGÍA: El diseño del estudio fue cuasiexperimental con mediciones independientes (intervenidos y controles) y mediciones en línea, al inicio y término de la intervención; evaluadas con Partners in Health Scale y la Escala de Autoeficacia. Los cambios en el tiempo se examinaron mediante la prueba de Wilcoxon. RESULTADOS: De los 114 participantes, la mayoría eran mujeres (83.3%) con una edad promedio de 58.8 años. Antes de la intervención, los grupos fueron iguales en las variables de estudio. No se encontró ningún aumento significativo en las variables de estudio en el grupo control, sin embargo, hubo un aumento estadísticamente significativo en la autoeficacia y automanejo en el grupo intervenido. CONCLUSIONES: El programa TCS en línea contribuyó al aumento de la autoeficacia, el automanejo, el conocimiento de la enfermedad, la adherencia al tratamiento y el manejo de síntomas en participantes con ENT de México y Perú durante la pandemia de COVID-19. Esto respalda la evidencia de que el programa mejora la salud y la calidad de vida de quienes viven con estas enfermedades.

Non-communicable diseases (NCD) are a growing global concern that affects both healthcare and quality of life. Chronic disease self-management programs, such as "Tomando Control de su Salud" (TCS), have become effective strategies to address this problem. PURPOSE: To evaluate the results of the TCS program, online version, in the self-management and self-efficacy variables, in samples of people with NCD from Mexico and Peru, during the COVID-19 pandemic. METHODOLOGY: The study design was quasi-experimental with independent measurements (interventions and controls) and online measurements, at the beginning and end of the intervention; evaluated with the Partners in Health Scale and the Self-Efficacy Scale. Changes over time were examined using the Wilcoxon test. RESULTS: Out of the 114 participants, most were women (83.3%) with an average age of 58.8 years. Before the intervention, the groups were equal in the study variables. No significant increase in the study variables was found in the control group; however, there was a statistically significant increase in self-efficacy and self-management in the intervention group. CONCLUSIONS: The online TCS program contributed to increased self-efficacy, self-management, disease knowledge, treatment adherence, and symptom management in participants with NCD from Mexico and Peru during the COVID-19 pandemic. This supports evidence that the program improves the health and quality of life of those living with these illnesses.

Ligand-Based Drug Design of Genipin Derivatives with Cytotoxic Activity against HeLa Cell Line: A Structural and Theoretical Study.

Cervical cancer is a malignant neoplastic disease, mainly associated to HPV infection, with high mortality rates. Among natural products, iridoids have shown different biological activities, including cytotoxic and antitumor effects, in different cancer cell types. Geniposide and its aglycone Genipin have been assessed against different types of cancer. In this work, both iridoids were evaluated against HeLa and three different cervical cancer cell lines. Furthermore, we performed a SAR analysis incorporating 13 iridoids with a high structural similarity to Geniposide and Genipin, also tested in the HeLa cell line and at the same treatment time. Derived from this analysis, we found that the dipole moment (magnitude and direction) is key for their cytotoxic activity in the HeLa cell line. Then, we proceeded to the ligand-based design of new Genipin derivatives through a QSAR model (R2 = 87.95 and Q2 = 62.33) that incorporates different quantum mechanic molecular descriptor types (ρ, ΔPSA, ∆Polarizability2, and logS). Derived from the ligand-based design, we observed that the presence of an aldehyde or a hydroxymethyl in C4, hydroxyls in C1, C6, and C8, and the lack of the double bond in C7-C8 increased the predicted biological activity of the iridoids. Finally, ten simple iridoids (D9, D107, D35, D36, D55, D56, D58, D60, D61, and D62) are proposed as potential cytotoxic agents against the HeLa cell line based on their predicted IC50 value and electrostatic features.

A Computational Method for the Binding Mode Prediction of COX-1 and COX-2 Inhibitors: Analyzing the Union of Coxibs, Oxicams, Propionic and Acetic Acids.

Among the biological targets extensively investigated to improve inflammation and chronic inflammatory conditions, cyclooxygenase enzymes (COXs) occupy a prominent position. The inhibition of these enzymes, essential for mitigating inflammatory processes, is chiefly achieved through Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). In this work, we introduce a novel method-based on computational molecular docking-that could aid in the structure-based design of new compounds or the description of the anti-inflammatory activity of already-tested compounds. For this, we used eight crystal complexes (four COX-1 and COX-2 each), and each pair had a specific NSAID: Celecoxib, Meloxicam, Ibuprofen, and Indomethacin. This selection was based on the ligand selectivity towards COX-1 or COX-2 and their binding mode. An interaction profile of each NSAID was compiled to detect the residues that are key for their binding mode, highlighting the interaction made by the Me group. Furthermore, we rigorously validated our models based on structural accuracy (RMSD < 1) and (R2 > 70) using eight NSAIDs and thirteen compounds with IC50 values for each enzyme. Therefore, this model can be used for the binding mode prediction of small and structurally rigid compounds that work as COX inhibitors or the prediction of new compounds that are designed by means of a structure-based approach.

Development and refinement of a corner-based injury prevention programme for Latino day labourers.

Objective: Latino day labourers (LDLs) in the USA are at increased risk for non-fatal and fatal occupational injuries, which are compounded by stressors that include wage theft, job insecurity and discrimination. This paper describes the development and refinement of Vales+Tú (You are Worthy of More), an injury prevention programme currently being evaluated as part of a cluster randomised trial in which health promotion is taken directly to the 'corners' (e.g. street corners, home improvement store parking lots, and public parks) where workers gather to seek employment. Design: Vales+Tú comprises two corner-based intervention approaches, group problem-solving (small group discussions) and brief motivational interviewing (one-on-one dialogue), that aim to activate LDL agency to control their safety and that of their peers. Setting: Corners in Houston, Texas, where LDLs seek employment. Method: Intervention Mapping informed the refinement of Vales+Tú for the current trial. We provide a narrative review of the development process based on needs assessment and formative development activities (surveys, focus group discussions and pilot tests). Results: In addition to documenting the need for LDL injury prevention, with 20.2%-41.6% of Houston-based LDLs surveyed between 2013-2014 and 2019 reporting a severe work-related injury in the past year, we describe key facets of the Vales+Tú corner-based intervention approaches - including their theoretical basis and LDL-centred activities, as well as enhancements made informed by formative evaluation. Conclusion: The community-engaged development process of Vales+Tú resulted in two practical intervention approaches that can be adopted by worker centres and other organisations to promote LDL worker safety.

Finding a Novel Chalcone-Cinnamic Acid Chimeric Compound with Antiproliferative Activity against MCF-7 Cell Line Using a Free-Wilson Type Approach.

In this work, we carried out the design and synthesis of new chimeric compounds from the natural cytotoxic chalcone 2',4'-dihydroxychalcone (2',4'-DHC, A) in combination with cinnamic acids. For this purpose, a descriptive and predictive quantitative structure-activity relationship (QSAR) model was developed to study the chimeric compounds' anti-cancer activities against human breast cancer MCF-7, relying on the presence or absence of structural motifs in the chalcone structure, like in a Free-Wilson approach. For this, we used 207 chalcone derivatives with a great variety of structural modifications over the α and ß rings, such as halogens (F, Cl, and Br), heterocyclic rings (piperazine, piperidine, pyridine, etc.), and hydroxyl and methoxy groups. The multilinear equation was obtained by the genetic algorithm technique, using logIC50 as a dependent variable and molecular descriptors (constitutional, topological, functional group count, atom-centered fragments, and molecular properties) as independent variables, with acceptable statistical parameter values (R2 = 86.93, Q2LMO = 82.578, Q2BOOT = 80.436, and Q2EXT = 80.226), which supports the predictive ability of the model. Considering the aromatic and planar nature of the chalcone and cinnamic acid cores, a structural-specific QSAR model was developed by incorporating geometrical descriptors into the previous general QSAR model, again, with acceptable parameters (R2 = 85.554, Q2LMO = 80.534, Q2BOOT = 78.186, and Q2EXT = 79.41). Employing this new QSAR model over the natural parent chalcone 2',4'-DHC (A) and the chimeric compound 2'-hydroxy,4'-cinnamate chalcone (B), the predicted cytotoxic activity was achieved with values of 55.95 and 17.86 µM, respectively. Therefore, to corroborate the predicted cytotoxic activity compounds A and B were synthesized by two- and three-step reactions. The structures were confirmed by 1H and 13C NMR and ESI+MS analysis and further evaluated in vitro against HepG2, Hep3B (liver), A-549 (lung), MCF-7 (breast), and CasKi (cervical) human cancer cell lines. The results showed IC50 values of 11.89, 10.27, 56.75, 14.86, and 29.72 µM, respectively, for the chimeric cinnamate chalcone B. Finally, we employed B as a molecular scaffold for the generation of cinnamate candidates (C-K), which incorporated structural motifs that enhance the cytotoxic activity (pyridine ring, halogens, and methoxy groups) according to our QSAR model. ADME/tox in silico analysis showed that the synthesized compounds A and B, as well as the proposed chalcones C and G, are the best candidates with adequate drug-likeness properties. From all these results, we propose B (as a molecular scaffold) and our two QSAR models as reliable tools for the generation of anti-cancer compounds over the MCF-7 cell line.

Identification of a Family of Glycoside Derivatives Biologically Active against Acinetobacter baumannii and Other MDR Bacteria Using a QSPR Model.

As the rate of discovery of new antibacterial compounds for multidrug-resistant bacteria is declining, there is an urge for the search for molecules that could revert this tendency. Acinetobacter baumannii has emerged as a highly virulent Gram-negative bacterium that has acquired multiple resistance mechanisms against antibiotics and is considered of critical priority. In this work, we developed a quantitative structure-property relationship (QSPR) model with 592 compounds for the identification of structural parameters related to their property as antibacterial agents against A. baumannii. QSPR mathematical validation (R2 = 70.27, RN = -0.008, a(R2) = 0.014, and δK = 0.021) and its prediction ability (Q2LMO= 67.89, Q2EXT = 67.75, a(Q2) = -0.068, δQ = 0.0, rm2¯ = 0.229, and Δrm2 = 0.522) were obtained with different statistical parameters; additional validation was done using three sets of external molecules (R2 = 72.89, 71.64 and 71.56). We used the QSPR model to perform a virtual screening on the BIOFACQUIM natural product database. From this screening, our model showed that molecules 32 to 35 and 54 to 68, isolated from different extracts of plants of the Ipomoea sp., are potential antibacterials against A. baumannii. Furthermore, biological assays showed that molecules 56 and 60 to 64 have a wide antibacterial activity against clinically isolated strains of A. baumannii, as well as other multidrug-resistant bacteria, including Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia, and Pseudomonas aeruginosa. Finally, we propose 60 as a potential lead compound due to its broad-spectrum activity and its structural simplicity. Therefore, our QSPR model can be used as a tool for the investigation and search for new antibacterial compounds against A. baumannii.

Study EDEN-12: Analysis of access to intensive care units of patients older than 65 years requiring emergency hospitalization.

OBJECTIVE: To investigate the relationship between the age of an urgently hospitalized patient and his or her probability of admission to an intensive care unit (ICU). DESIGN: Observational, retrospective, multicenter study. SETTING: 42 Emergency Departments from Spain. TIME-PERIOD: April 1-7, 2019. PATIENTS: Patients aged ≥65 years hospitalized from Spanish emergency departments. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: ICU admission, age sex, comorbidity, functional dependence and cognitive impairment. RESULTS: 6120 patients were analyzed (median age: 76 years; males: 52%. 309 (5%) were admitted to ICU (186 from ED, 123 from hospitalization). Patients admitted to the ICU were younger, male, and with less comorbidity, dependence and cognitive impairment, but there were no differences between those admitted from the ED and from hospitalization. The OR for ICU-admission adjusted by sex, comorbidity, dependence and dementia reached statistical significance >83 years (OR: 0.67; 95%CI: 0.45-0.49). In patients admitted to the ICU from ED, the OR did not begin to decrease until 79 years, and was significant >85 years (OR: 0.56, 95%CI: 0.34-0.92); while in those admitted to ICU from hospitalization, the decrease began 65 years of age, and were significant from 85 years (OR: 0.55, 95%CI: 0.30-0.99). Sex, comorbidity, dependency and cognitive deterioration of the patient did not modify the association between age and ICU-admission (overall, from the ED or hospitalization). CONCLUSIONS: After taking into account other factors that influence admission to the ICU (comorbidity, dependence, dementia), the chances of admission to the ICU of older patients hospitalized on an emergency basis begin to decrease significantly after 83 years of age. There may be differences in the probability of admission to the ICU from the ED or from hospitalization according to age.

Self-Injurious Behavior and Its Characteristics in a Sample of Mexican Adolescent Students.

Adolescence is a difficult stage, a period of risk for developing disorders, including depression and self-injurious behavior. A non-random sample was drawn (n = 563) from first-year high school students (32.8%) 185 males and 378 females (67.14%) from public schools in Mexico. The age range was 15 and 19 years, with a mean age of 15.63 (SD = 0.78). According to the results, the sample was divided into n1 = 414 (73.3%) adolescents without self-injury (S.I.) and n2 = 149 (26.4%) S.I. adolescents. In addition, results were obtained on methods, motives, time, and frequency of S.I., and a model was generated in which depression and first sexual experience obtained the highest Odd Ratio and d values in their relationship with S.I. Finally, we contrasted the results with earlier reports and concluded that depression is an important variable in S.I. behavior. Early S.I. detection will prevent the aggravation of S.I. and suicide attempts.

Psychosocial Factors Associated with Self-Management in Patients with Diabetes.

Despite the significant advances in research on diabetes, relatively few researchers have examined the theoretical and empirical usefulness of explanatory models that contribute to self-management of the disease. In response to the theoretical and empirical approaches related to this topic, the objective of this research was to assess a hypothetical model to explain self-management behavior in patients with type II diabetes through structural equation modeling in a population of users of the services of the State Health Department of Tamaulipas, Mexico. The study used a cross-sectional and explanatory design. The sample was intentional. A total of 183 patients with a diabetes diagnosis completed a sociodemographic data questionnaire, the Partners in Health Scale, the Duke-UNC-11, the Family Apgar, the Self-Efficacy Scale, the Personal Health Questionnaire and the Physical Activity Scale. The results indicated that the hypothetical model was improved by excluding the exercise variable. The appropriate model was used to determine the effects of depression, social support, self-efficacy, family functioning, years of formal education and years with a diagnosis on self-management. The goodness-of-fit indices (GFIs) were good, i.e., χ2/gl = 0.89 (p = 0.529), root mean square error of approximation (RMSEA) = 0.000, and comparative fit index (CFI) = 1.000, with an acceptable degree of parsimony (PNFI = 0.409 and PGFI = 317). The model explained 33.6% of the variance. Therefore, this model represents an important advance in knowledge concerning self-management and provides empirical and theoretical evidence, particularly for the Mexican or Latino population.

Application of AlDeSense to Stratify Ovarian Cancer Cells Based on Aldehyde Dehydrogenase 1A1 Activity.

Relapse after cancer treatment is often attributed to the persistence of a subpopulation of tumor cells known as cancer stem cells (CSCs), which are characterized by their remarkable tumor-initiating and self-renewal capacity. Depending on the origin of the tumor (e.g., ovaries), the CSC surface biomarker profile can vary dramatically, making the identification of such cells via immunohistochemical staining a challenging endeavor. On the contrary, aldehyde dehydrogenase 1A1 (ALDH1A1) has emerged as an excellent marker to identify CSCs, owing to its conserved expression profile in nearly all progenitor cells including CSCs. The ALDH1A1 isoform belongs to a superfamily of 19 enzymes that are responsible for the oxidation of various endogenous and xenobiotic aldehydes to the corresponding carboxylic acid products. Chan et al. recently developed AlDeSense, an isoform-selective "turn-on" probe for the detection of ALDH1A1 activity, as well as a non-reactive matching control reagent (Ctrl-AlDeSense) to account for off-target staining. This isoform-selective tool has already been demonstrated to be a versatile chemical tool through the detection of ALDH1A1 activity in K562 myelogenous leukemia cells, mammospheres, and melanoma-derived CSC xenografts. In this article, the utility of the probe was showcased through additional fluorimetry, confocal microscopy, and flow cytometry experiments where the relative ALDH1A1 activity was determined in a panel of five ovarian cancer cell lines.

Inverse molecular design and parameter optimization with Hückel theory using automatic differentiation.

Semiempirical quantum chemistry has recently seen a renaissance with applications in high-throughput virtual screening and machine learning. The simplest semiempirical model still in widespread use in chemistry is Hückel's π-electron molecular orbital theory. In this work, we implemented a Hückel program using differentiable programming with the JAX framework based on limited modifications of a pre-existing NumPy version. The auto-differentiable Hückel code enabled efficient gradient-based optimization of model parameters tuned for excitation energies and molecular polarizabilities, respectively, based on as few as 100 data points from density functional theory simulations. In particular, the facile computation of the polarizability, a second-order derivative, via auto-differentiation shows the potential of differentiable programming to bypass the need for numeric differentiation or derivation of analytical expressions. Finally, we employ gradient-based optimization of atom identity for inverse design of organic electronic materials with targeted orbital energy gaps and polarizabilities. Optimized structures are obtained after as little as 15 iterations using standard gradient-based optimization algorithms.

In silico Study on the Binding Interactions of SSTA and 18F-SSTA Towards Somatostatin Receptor Subtype 2.

BACKGROUND: Somatostatin analogs (SSTAs) are versatile drugs that target a group of proteins known as somatostatin receptors. SSTAs are used for the treatment and PET-molecular imaging of Neuro Endocrine Tumors (NET), for they are labeled with the radionuclide 18F, a positron emitter radionuclide. OBJECTIVE: The aim of this work was to theoretically study the binding interactions of SSTA labeled with 18F (half-life of 109.7 min) and somatostatin receptor subtype 2. As the labeling of SSTA with 18F required the use of a prosthetic group, a hydrophilicity enhancer, and a linker, the influence of these traits on the interactions of 18F-SSTA with the SSTR-2 binding site was studied. METHODS: The binding modes of 18F-labeled analogues with SSTR-2 were studied by using protein homology modelling, non-equilibrium molecular dynamics, and molecular docking calculations, by means of three docking software: MVD, MOE, and VINA. RESULTS: The results showed the main role of Asp122, Asn276, Phe272 and Phe294 from the SSTR-2 binding site, which form interactions with residues Lys, Trp, Tyr, and Thr from 18F-labeled somatostatin analogues. CONCLUSION: The interaction between Lys (from 18F-SSTA) and Asp122 (from SSTR-2) was identified as the most energetic and considered the one that drives the binding between 18F-SSTA and SSTR-2 (the anchor interaction). Despite the presence of prosthetic groups, linkers, and hydrophilicity enhancers, all the studied 18F-SSTA formed the anchor interaction. The trend in the results agreed with the experimental reports, identifying the main role of Asp122 in the binding of somatostatin-14 to SSTR-2.

Novel ciprofloxacin and norfloxacin-tetrazole hybrids as potential antibacterial and antiviral agents: Targeting S. aureus topoisomerase and SARS-CoV-2-MPro.

This study was designed to synthesize hybridizing molecules from ciprofloxacin and norfloxacin by enhancing their biological activity with tetrazoles. The synthesized compounds were investigated in the interaction with the target enzyme of fluoroquinolones (DNA gyrase) and COVID-19 main protease using molecular similarity, molecular docking, and QSAR studies. A QSAR study was carried out to explore the antibacterial activity of our compounds over Staphylococcus aureus a QSAR study, using descriptors obtained from the docking with DNA gyrase, in combination with steric type descriptors, was done obtaining suitable statistical parameters ( R 2 = 87.00 , Q L M O 2 = 71.67 , and Q E X T 2 = 73.49 ) to support our results. The binding interaction of our compounds with CoV-2-Mpro was done by molecular docking and were compared with different covalent and non-covalent inhibitors of this enzyme. For the docking studies we used several crystallographic structures of the CoV-2-Mpro. The interaction energy values and binding mode with several key residues, by our compounds, support the capability of them to be CoV-2-Mpro inhibitors. The characterization of the compounds was completed using FT-IR, 1H-NMR, 13C-NMR, 19F-NMR and HRMS spectroscopic methods. The results showed that compounds 1, 4, 5, 10 and 12 had the potential to be further studied as new antibacterial and antiviral compounds.

Exploring the Gallic and Cinnamic Acids Chimeric Derivatives as Anticancer Agents over HeLa Cell Line: An in silico and in†vitro Study.

Cervical cancer is one of the most aggressive and important cancer types in the female population, due to its low survival rate. Actually, the search for new bioactive compounds, like gallic and cinnamic acid, is one of the most employed options to finding a treatment. In the present study, 134 phenolic compounds with cytotoxic activity over HeLa cell line were used to generate a descriptive ( R 2 ${{R}^{2}}$ =0.76) and predictive ( Q 2 ${{Q}^{2}}$ =0.69 and Q e x t 2 ${{Q}_{{\rm e}{\rm x}{\rm t}}^{2}}$ =0.62) QSAR model. Structural, electronic, steric, and hydrophobic features are represented as different molecular descriptors in our QSAR model. From this model, nine gallate-cinnamate ester derivatives (N1-N9) were designed and synthesized. Furthermore, in vitro cytotoxic activity was evaluated against HeLa and non-tumorigenic cells. Derivatives N6, N5, N1, and N9 were the most active molecules with IC50ExpHeLa values from 7.26 to 11.95 µM. Finally, the binding of the synthesized compounds to the colchicine binding site on tubulin was evaluated by molecular docking as a possible action mechanism. N1, N5 and N6 can be considered as templates for the design of new cervical anticancer compounds.

Fast evaluation of the adsorption energy of organic molecules on metals via graph neural networks.

Modeling in heterogeneous catalysis requires the extensive evaluation of the energy of molecules adsorbed on surfaces. This is done via density functional theory but for large organic molecules it requires enormous computational time, compromising the viability of the approach. Here we present GAME-Net, a graph neural network to quickly evaluate the adsorption energy. GAME-Net is trained on a well-balanced chemically diverse dataset with C1-4 molecules with functional groups including N, O, S and C6-10 aromatic rings. The model yields a mean absolute error of 0.18 eV on the test set and is 6 orders of magnitude faster than density functional theory. Applied to biomass and plastics (up to 30 heteroatoms), adsorption energies are predicted with a mean absolute error of 0.016 eV per atom. The framework represents a tool for the fast screening of catalytic materials, particularly for systems that cannot be simulated by traditional methods.

Extension of the bright high-harmonic photon energy range via nonadiabatic critical phase matching.

The concept of critical ionization fraction has been essential for high-harmonic generation, because it dictates the maximum driving laser intensity while preserving the phase matching of harmonics. In this work, we reveal a second, nonadiabatic critical ionization fraction, which substantially extends the phase-matched harmonic energy, arising because of the strong reshaping of the intense laser field in a gas plasma. We validate this understanding through a systematic comparison between experiment and theory for a wide range of laser conditions. In particular, the properties of the high-harmonic spectrum versus the laser intensity undergoes three distinctive scenarios: (i) coincidence with the single-atom cutoff, (ii) strong spectral extension, and (iii) spectral energy saturation. We present an analytical model that predicts the spectral extension and reveals the increasing importance of the nonadiabatic effects for mid-infrared lasers. These findings are important for the development of high-brightness soft x-ray sources for applications in spectroscopy and imaging.

COVID-19: una revisión radiológica en medio de la pandemia / COVID-19: a radiological review in the middle of the pandemic

Resumen La actual pandemia SARS-CoV-2 ha cambiado nuestra manera de trabajar y relacionarnos. Fue notificada en Wuhan, provincia de Hubei, en China, en diciembre de 2019. Habían existido dos brotes previos importantes de Coronavirus: el SARS, en 2002-2003 y el MERS, en 2012. Este artículo pretende ser una breve revisión acerca de algunos aspectos de la infección COVID-19 desde los aspectos fisiopatológicos, hallazgos por imagen y de las principales indicaciones de las pruebas de imagen, si bien estas siempre serán individualizadas. Tampoco podemos dejar de lado la posibilidad de que algunos de estos pacientes presente una evolución a fibrosis pulmonar. Finalmente, mencionaremos algunas recomendaciones para protegernos en nuestro puesto de trabajo.

Abstract The current SARS-CoV-2 pandemic has changed the way we work and interact. It was notified in Wuhan, Hubei province, China, in December 2019. There had been two previous major outbreaks of Coronavirus: SARS in 2002-2003 and MERS in 2012. This article aims to be a brief review of some aspects of the COVID-19 infection from the pathophysiological aspects, imaging findings, as well as the main indications for the imaging, although these will always be individualized. We cannot ignore the possibility that some of these patients may present evolution to pulmonary fibrosis. Finally, we will mention some recommendations to protect ourselves in our workplace.

Vales+Tú: a cluster-randomized pilot study to reduce workplace injuries among US Latino day laborers.

Latino day laborers (LDL) are a vulnerable population of workers facing considerable risk for occupational injury. Under the guidance of our Community Advisory Board, we developed and tested the feasibility, acceptability and preliminary effects of Vales+Tú (You Are Worth More), a workplace injury risk-reduction program implemented by promotores on street-corners where LDL seek employment. The program was informed by theoretical perspectives emphasizing individual and group agency and self-determination. A pilot three-arm cluster-randomized community trial was conducted among 75 LDL. The intervention arms consisted of an individualized Brief Motivational Interview, a Group Problem Solving activity and a standard of care control (OSHA safety cards). We met our study goal of 25 LDL per intervention arm, and contacted 88% of participants post intervention. Participants evaluated the interventions favorably. At post-test, the Brief Motivational Interview group reported significant reductions in exposure to workplace hazards and increases in risk-reduction practices. The Group Problem Solving participants showed significant reductions in exposure to hazards (t-test -4.16, p < 0.001). Both intervention groups increased their reliance on corner peers, a measure of social support. Standard of care participants increased in self-efficacy to work safely. Overall, the only significant different between the three study conditions was in self-efficacy. These findings provide evidence of the feasibility and acceptability of Vales+Tú and show preliminary program efficacy. A large-scale replication trial will permit a more formal modeling of the study findings. Clinical Trial Registration (ClinicalTrials.gov): NCT04378348.

This pilot-randomized trial tested the feasibility and initial efficacy of an injury risk-reduction program among Latino day laborers (LDL). The study tested two alternative interventions consisting of a Brief Motivational Interview (Individual) and a Group Problem Solving (Group) conditions that were compared with a Standard-of-Care control group receiving safety cards. We then tested the extent to which the study conditions reduced exposure to workplace hazards and increased safety practices at work. Results indicate that intervening at day labor corners is a feasible intervention strategy acceptable to these immigrant workers. Initial results also indicate that there were multiple within-group significant differences in risk reduction, mostly in the individual condition, and that there was one significant between-group difference in safety self-efficacy at post-test. A larger more rigorous trial can further test the stability of these results and determine the extent to which these intervention approaches can reduce the risk for injury that LDL confront at work.