Carcass and Meat Quality Traits in Female Lidia Cattle Slaughtered at Different Ages.

The aim of this study was to assess the carcass and meat quality of female Lidia cattle slaughtered at different ages, in order to deepen our understanding of the breed's unique characteristics. The effect of slaughter age on carcass traits and meat quality attributes of m. Longissimus was investigated in Lidia heifers (n = 200) and cows (n = 100) reared and finished in an extensive system. The animals were slaughtered at 24-36 months (Heifer I), 36-48 months (Heifer II) or >48 months (Cull cow). The carcasses (~120 kg) presented poor conformation (O, O+) and medium fatness (2, 2+). The dissection of the 6th rib yielded mean values of 58.6%, 14.3% and 24.8% for lean, fat and bone, respectively. The cows had a higher proportion of dissectible fat (p < 0.05). Subcutaneous fat was classified as dark and yellowish, and meat (aged for 21 days) as dark (L* = 25.5), reddish (a* = 14.4) and moderately yellowish (b* = 12.9), with acceptable water-holding capacity (TL = 5.34%; DL = 0.97%; PL = 8.9%; CL = 22.1%) and intermediate tenderness (WBSF = 4.6 kg/cm2). The b* value of meat was higher (p < 0.05) in cull cows. The meat of cull cows was more yellowish (p < 0.05) and obtained higher scores for flavor (p < 0.05), juiciness p < 0.01), overall tenderness (p < 0.001) and overall acceptance (p < 0.001).

Deconstructing neutrophil to lymphocyte ratio (NLR) in early breast cancer: lack of prognostic utility and biological correlates across tumor subtypes.

PURPOSE: The prognostic utility and biological correlates of neutrophil to lymphocyte ratio (NLR), a potential biomarker of the balance between immune response and the inflammatory status, are still uncertain in breast cancer (BC). METHODS: We analysed a cohort of 959 women with early breast cancer, mostly treated with neoadjuvant or adjuvant chemotherapy. Clinical and pathological data, survival, NLR (continuous and categorical) and stromal tumor infiltrating lymphocytes (sTIL) were evaluated. RESULTS: NLR was only weakly associated with Ki67, while no association was found for grade, histology, immunohistochemical subtype or stage. Lymphocyte infiltration of the tumor did not correlate with NLR (Rho: 0.05, p = 0.30). These results were similar in the whole group and across the different BC subtypes, with no differences in triple negative BC. Relapse free interval (RFI), breast cancer specific survival (BCSS) and overall survival (OS) changed according to pre-treatment NLR neither in the univariate nor in the multivariate Cox models (RFI: HR 0.948, p = 0.61; BCSS: HR 0.920, p = 0.57; OS: HR 0.96, p = 0.59). CONCLUSION: These results question the utility of NLR as a prognostic biomarker in early breast cancer and suggest the lack of correlation of NLR with tumor microenvironment immune response.

Fast quasi-null-filling of radiation patterns for multiple solutions generation.

Here we present an improved, rapid method for filling quasi-nulls in symmetrical radiation patterns synthesized by equispaced linear arrays, leading to the generation of multiple solutions. Considering the polynomial representation of the pattern, this null-filling is achieved by displacing the roots radially off the unit circle, keeping a constant displacement. This allows analyzing how the potential solutions vary with the quasi-uniform filling and the associated directivity loss. This method is based on the Cardano-Vieta relations, which link the coefficients of a complex Schelkunoff polynomial with its roots. As examples of application, we have considered a 20/100 element Dolph-Chebyshev pattern, with a spacing between the elements [Formula: see text], side lobe level of - 20/- 28 dB and three inner sidelobes at - 40/- 50 dB.

Tracking anthropogenic microparticles in wildlife of an alpine insular environment.

Despite the isolation of remote natural regions, it has been discovered that they are experiencing the accumulation of anthropogenic microparticles (i.e., microplastics or natural or semisynthetic cellulosic particles). Teide National Park (Canary Islands, Spain) is a high-mountain protected area known for its rich biodiversity. This study aims to assess the occurrence of coloured anthropogenic particles in the faecal matter of wild mammals, specifically rabbits and mouflons, residing in the park. With this purpose, faeces were collected from 68 systematically distributed sampling points. A stereomicroscopy-guided grinding process allowed a chemical-free and quick visual inspection of 616 individual excreta, revealing that 96% were particle-free. However, 37 anthropogenic particles were found, which correspond to 0.79 ± 0.20 items per gram of dry faecal matter. The archetypical particle was a cellulosic blue microfibre of 2721 ± 407 µm, though poly(ethylene-vinyl acetate) and polypropylene were also identified via micro Fourier-transform infrared spectroscopic analysis. Atmospheric deposition and touristic pressure may be the sources of the anthropogenic particles, as they were randomly found in 36% of the sampling points. These findings represent the first evidence of anthropogenic particle ingestion by wild rabbits and mouflons, signifying the introduction of microplastics into terrestrial food chains in a remote high-mountain environment.

Beneath the water column: Uncovering microplastic pollution in the sublittoral coastal sediments of the Canary Islands, Spain.

Marine ecosystems pollution by microplastics (MPs) is a global problem of special concern. The present study examines the prevalence and distribution of MPs and cellulosic particles in sublittoral coastal sediments of the Canary Islands archipelago (Spain). At twenty-six different locations alongside seven islands, three samples were taken parallel to the shoreline between 1 and 10 m depth (n = 78). Sediment samples were primarily digested with a H2O2 solution followed by four flotations in a saturated NaCl solution. The mean concentration obtained was 3.9 ± 1.6 items/g of dry weight. A similar distribution pattern was observed across all islands concerning particles morphology, color, size and composition: mainly colorless/translucent and blue fibers (60.0%). Additionally, fragments were also found, and to a much lesser extent microbeads, films and tangled messes. MicroFourier Transform Infrared spectroscopy analysis of 12.5% of the fibers, showed that they were mainly cellulosic (54.5%) -either natural or semisynthetic- followed by polyester (22.7%) and acrylic (4.5%). The potential correlation between particle distribution in nearshore sediments and wave intensity was also explored. This work provides the first comprehensive report on the current MPs content of the seabed of the region.

Recurrent genetic variants and prioritization of variants of uncertain clinical significance associated with hereditary breast and ovarian cancer in families from the Region of Murcia.

Objectives: Hereditary breast and ovarian cancer (HBOC) follows an autosomal dominant inheritance pattern of cancer susceptibility genes. The risk of developing this disease is primarily associated with germline mutations in the BRCA1 and BRCA2 genes. The advent of massive genetic sequencing technologies has expanded the mutational spectrum of this hereditary syndrome, thereby increasing the number of variants of uncertain clinical significance (VUS) detected by genetic testing. Methods: A prevalence study of HBOC was performed within 2,928 families from the Region of Murcia, in southeastern Spain. Genetic testing enabled the identification of recurrent pathogenic variants and founder mutations, which were mainly related to the BRCA1 and BRCA2 genes. VUS testing was performed using a prioritization algorithm designed by our working group. Results: Variants c.68_69del, c.212+1G>A, and c.5123C>A were detected in 30 % of BRCA1 carriers, whereas exon 2 deletion concurrent with c.3264dupT, c.3455T>G and c.9117G>A variants were found in 30 % of BRCA2 carriers. A total of 16 VUS (15 %) were prioritized. Conclusions: The genotype-phenotype correlation observed in our study is consistent with the scientific literature. Furthermore, the founder effect of c.1918C>T (BRCA1) and c.8251_8254del (ATM) was verified in the Murcian population, whereas exon 2 deletion (BRCA2) was proven to be a Spanish founder mutation. Our algorithm enabled us to prioritize potentially pathogenic VUS that required further testing to determine their clinical significance and potential role in HBOC.

A Review on the Effects of Thermal Inversions and Electromagnetic Fields on Cell Cultures and Wireless Communications.

Thermal inversions, typical in the winter season, consist of cold air at the Earth's surface being trapped under a layer of warmer air. Such an effect keeps normal convective overturning of the atmosphere from penetrating through. This phenomenon highly increases the toxicity of the atmosphere, while modifying its dielectric constant, resulting in major implications in terms of public health and wireless communications. Indeed, air pollution in large cities (related, in most cases, to particulate matter that consists of different chemical components, which can have warming or cooling effects) is primarily caused by chemical and photochemical reactions in the atmosphere. Appropriate usage of array antennas allows the effective tracking of changes in humidity (e.g., coated Yagi-Uda antennas, which do not interfere with 5G) and in the dielectric constant (e.g., optimized quasi-Yagi-Uda antennas, yielding to accurate measurements of sulfides and black carbon concentration). Remarkably, important health effects come from the combined action of electromagnetic fields with fine and coarse black carbon particles. The appearance of ducts, which are caused by thermal inversions, provokes the creation of super-refractive regions in the troposphere as well, which result in the anomalous propagation of wireless communications.

Ethnobotanical, Phytochemical, and Pharmacological Properties of the Subfamily Nepetoideae (Lamiaceae) in Inflammatory Diseases.

Nepetoideae is the most diverse subfamily of Lamiaceae, and some species are well known for their culinary and medicinal uses. In recent years, there has been growing interest in the therapeutic properties of the species of this group regarding inflammatory illnesses. This study aims to collect information on traditional uses through ethnobotanical, pharmacological, and phytochemical information of the subfamily Nepetoideae related to inflammatory diseases. UNAM electronic resources were used to obtain the information. The analysis of the most relevant literature was compiled and organised in tables. From this, about 106 species of the subfamily are traditionally recognised to alleviate chronic pain associated with inflammation. Pharmacological studies have been carried out in vitro and in vivo on approximately 308 species belonging to the genera Salvia, Ocimum, Thymus, Mentha, Origanum, Lavandula, and Melissa. Phytochemical and pharmacological evaluations have been performed and mostly prepared as essential oil or high polarity extracts, whose secondary metabolites are mainly of a phenolic nature. Other interesting and explored metabolites are diterpenes from the abietane, clerodane, and kaurane type; however, they have only been described in some species of the genera Salvia and Isodon. This review reveals that the Nepetoideae subfamily is an important source for therapeutics of the inflammatory process.

Stabilizing vimentin phosphorylation inhibits stem-like cell properties and metastasis of hybrid epithelial/mesenchymal carcinomas.

Epithelial-mesenchymal transition (EMT) empowers epithelial cells with mesenchymal and stem-like attributes, facilitating metastasis, a leading cause of cancer-related mortality. Hybrid epithelial-mesenchymal (E/M) cells, retaining both epithelial and mesenchymal traits, exhibit heightened metastatic potential and stemness. The mesenchymal intermediate filament, vimentin, is upregulated during EMT, enhancing the resilience and invasiveness of carcinoma cells. The phosphorylation of vimentin is critical to its structure and function. Here, we identify that stabilizing vimentin phosphorylation at serine 56 induces multinucleation, specifically in hybrid E/M cells with stemness properties but not epithelial or mesenchymal cells. Cancer stem-like cells are especially susceptible to vimentin-induced multinucleation relative to differentiated cells, leading to a reduction in self-renewal and stemness. As a result, vimentin-induced multinucleation leads to sustained inhibition of stemness properties, tumor initiation, and metastasis. These observations indicate that a single, targetable phosphorylation event in vimentin is critical for stemness and metastasis in carcinomas with hybrid E/M properties.

General aspects of the use of mixed methods for health research. / Aspectos generales del uso de métodos mixtos para investigación en salud.

Traditionally, research has been divided according to its methodology into quantitative and qualitative. Mixed research methodology combines both methods and has established itself as a third approach, allowing to comprehensively address high-complexity research problems. Although there are various definitions of mixed methods research, they all share aspects such as the collection and analysis of both quantitative and qualitative data and the integrated interpretation of the results within the same research. This type of research is an important tool to address the complexity of health sciences, allowing the understanding and integration of quantitative data with experience-based aspects. In this way, a broad and deep perspective of health problems is achieved, providing a solution to sanitary policies and services. During the development of mixed methods research, there are key stages where both approaches can be integrated depending on the objectives set by the investigators. Although mixed methods studies may differ widely, general models have been identified to guide the development of a single specific design. These models are classified according to the priority of each approach, the sequence in which each approach will be executed, the level and timing of data integration, and the purpose of integrating the data for the study.

Tradicionalmente la investigación se ha dividido según su metodología en cuantitativa y cualitativa. La metodología mixta de investigación, que combina ambos métodos, se ha consolidado como una tercera vía, permitiendo abordar de forma integral problemas de investigación de alta complejidad. Aunque existen diversas definiciones sobre la investigación con métodos mixtos, todas ellas comparten aspectos como la recolección y análisis de datos tanto cuantitativos como cualitativos, y la interpretación integrada de los resultados dentro de una misma investigación. Este tipo de investigación es una herramienta importante para abordar la complejidad propia del campo de la salud, permitiendo comprender e integrar los datos cuantitativos con aspectos vivenciales y experienciales. Con ello se logra una perspectiva amplia y profunda de los problemas de salud, dando respuesta a las políticas y servicios sanitarios. Durante el desarrollo de una investigación con métodos mixtos, existen etapas clave donde ambos enfoques pueden integrarse dependiendo de los objetivos planteados por los equipos de investigación. Aunque los estudios con métodos mixtos pueden ser muy diferentes, se han identificado modelos generales que guían el desarrollo de un diseño específico a utilizar. Estos modelos se clasifican según la prioridad de cada enfoque, la secuencia en la que se ejecutará cada enfoque, el nivel y momento de integración de los datos y el propósito de esta integración para el estudio en particular.

Modulation of vagal activity may help reduce neurodevelopmental damage in the offspring of mothers with pre-eclampsia.

Maternal Immune Activation (MIA) has been linked to the pathogenesis of pre-eclampsia and adverse neurodevelopmental outcomes in the offspring, such as cognitive deficits, behavioral abnormalities, and mental disorders. Pre-eclampsia is associated with an activation of the immune system characterized by persistently elevated levels of proinflammatory cytokines, as well as a decrease in immunoregulatory factors. The Cholinergic Anti-inflammatory Pathway (CAP) may play a relevant role in regulating the maternal inflammatory response during pre-eclampsia and protecting the developing fetus from inflammation-induced damage. Dysregulation in the CAP has been associated with the clinical evolution of pre-eclampsia. Some studies suggest that therapeutic stimulation of this pathway may improve maternal and fetal outcomes in preclinical models of pre-eclampsia. Modulation of vagal activity influences the CAP, improving maternal hemodynamics, limiting the inflammatory response, and promoting the growth of new neurons, which enhances synaptic plasticity and improves fetal neurodevelopment. Therefore, we postulate that modulation of vagal activity may improve maternal and fetal outcomes in pre-eclampsia by targeting underlying immune dysregulation and promoting better fetal neurodevelopment. In this perspective, we explore the clinical and experimental evidence of electrical, pharmacological, physical, and biological stimulation mechanisms capable of inducing therapeutical CAP, which may be applied in pre-eclampsia to improve the mother's and offspring's quality of life.

Aspectos generales del uso de métodos mixtos para investigación en salud / General aspects of the use of mixed methods for health research

Tradicionalmente la investigación se ha dividido según su metodología en cuantitativa y cualitativa. La metodología mixta de investigación, que combina ambos métodos, se ha consolidado como una tercera vía, permitiendo abordar de forma integral problemas de investigación de alta complejidad. Aunque existen diversas definiciones sobre la investigación con métodos mixtos, todas ellas comparten aspectos como la recolección y análisis de datos tanto cuantitativos como cualitativos, y la interpretación integrada de los resultados dentro de una misma investigación. Este tipo de investigación es una herramienta importante para abordar la complejidad propia del campo de la salud, permitiendo comprender e integrar los datos cuantitativos con aspectos vivenciales y experienciales. Con ello se logra una perspectiva amplia y profunda de los problemas de salud, dando respuesta a las políticas y servicios sanitarios. Durante el desarrollo de una investigación con métodos mixtos, existen etapas clave donde ambos enfoques pueden integrarse dependiendo de los objetivos planteados por los equipos de investigación. Aunque los estudios con métodos mixtos pueden ser muy diferentes, se han identificado modelos generales que guían el desarrollo de un diseño específico a utilizar. Estos modelos se clasifican según la prioridad de cada enfoque, la secuencia en la que se ejecutará cada enfoque, el nivel y momento de integración de los datos y el propósito de esta integración para el estudio en particular.

Traditionally, research has been divided according to its methodology into quantitative and qualitative. Mixed research methodology combines both methods and has established itself as a third approach, allowing to comprehensively address high-complexity research problems. Although there are various definitions of mixed methods research, they all share aspects such as the collection and analysis of both quantitative and qualitative data and the integrated interpretation of the results within the same research. This type of research is an important tool to address the complexity of health sciences, allowing the understanding and integration of quantitative data with experience-based aspects. In this way, a broad and deep perspective of health problems is achieved, providing a solution to sanitary policies and services. During the development of mixed methods research, there are key stages where both approaches can be integrated depending on the objectives set by the investigators. Although mixed methods studies may differ widely, general models have been identified to guide the development of a single specific design. These models are classified according to the priority of each approach, the sequence in which each approach will be executed, the level and timing of data integration, and the purpose of integrating the data for the study.

RECOVER identifies synergistic drug combinations in vitro through sequential model optimization.

For large libraries of small molecules, exhaustive combinatorial chemical screens become infeasible to perform when considering a range of disease models, assay conditions, and dose ranges. Deep learning models have achieved state-of-the-art results in silico for the prediction of synergy scores. However, databases of drug combinations are biased toward synergistic agents and results do not generalize out of distribution. During 5 rounds of experimentation, we employ sequential model optimization with a deep learning model to select drug combinations increasingly enriched for synergism and active against a cancer cell line-evaluating only ∼5% of the total search space. Moreover, we find that learned drug embeddings (using structural information) begin to reflect biological mechanisms. In silico benchmarking suggests search queries are ∼5-10× enriched for highly synergistic drug combinations by using sequential rounds of evaluation when compared with random selection or ∼3× when using a pretrained model.

Caloric Effect Due to the Aharonov-Bohm Flux in an Antidot.

In this work, we report the caloric effect for an electronic system of the antidot type, modeled by combining a repulsive and attractive potential (parabolic confinement). In this system, we consider the action of a perpendicular external magnetic field and the possibility of having an Aharonov-Bohm flux (AB-flux) generated by a current passing through a solenoid placed inside the forbidden zone for the electron. The energy levels are obtained analytically, and the model is known as the Bogachek and Landman model. We propose to control the caloric response of the system by varying only the AB-flux, finding that, in the absence of an external magnetic field, the maximization of the effect always occurs at the same AB-flux intensity, independently of the temperature, while fixing the external magnetic field at a non-zero value breaks this symmetry and changes the point where the caloric phenomenon is maximized and is different depending on the temperature to which the process is carried. Our calculations indicate that using an effective electron mass of GaAs heterostructures and a trap intensity of the order of 2.896 meV, the modification of the AB-flux achieves a variation in temperature of the order of 1 K. Our analysis suggests that increasing the parabolic confinement twofold increases the effect threefold, while increasing the antidot size generates the reverse effect, i.e., a strong decrease in the caloric phenomenon under study. Due to the great diversity in technological applications that have antidots in electronics, the possibility of controlling their thermal response simply by varying the intensity of the internal current inside the solenoid (i.e., the intensity of AB-flux) can be a platform of interest for experimental studies.

Synthesis of portimines reveals the basis of their anti-cancer activity.

Marine-derived cyclic imine toxins, portimine A and portimine B, have attracted attention because of their chemical structure and notable anti-cancer therapeutic potential1-4. However, access to large quantities of these toxins is currently not feasible, and the molecular mechanism underlying their potent activity remains unknown until now. To address this, a scalable and concise synthesis of portimines is presented, which benefits from the logic used in the two-phase terpenoid synthesis5,6 along with other tactics such as exploiting ring-chain tautomerization and skeletal reorganization to minimize protecting group chemistry through self-protection. Notably, this total synthesis enabled a structural reassignment of portimine B and an in-depth functional evaluation of portimine A, revealing that it induces apoptosis selectively in human cancer cell lines with high potency and is efficacious in vivo in tumour-clearance models. Finally, practical access to the portimines and their analogues simplified the development of photoaffinity analogues, which were used in chemical proteomic experiments to identify a primary target of portimine A as the 60S ribosomal export protein NMD3.

SEOM-GEICAM-SOLTI clinical guidelines for early-stage breast cancer (2022)

Breast cancer is the leading cause of cancer in women in Spain and its annual incidence is rapidly increasing. Thanks to the screening programs in place, nearly 90% of breast cancer cases are detected in early and potentially curable stages, despite the COVID-19 pandemic possibly having impacted these numbers (not yet quantified). In recent years, locoregional and systemic therapies are increasingly being directed by new diagnostic tools that have improved the balance between toxicity and clinical benefit. New therapeutic strategies, such as immunotherapy, targeted drugs, and antibody–drug conjugates have also improved outcomes in some patient subgroups. This clinical practice guideline is based on a systematic review of relevant studies and on the consensus of experts from GEICAM, SOLTI, and SEOM (AU)