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The 4D (four-dimensional) eigenvector 1 (E1) sequence has proven to be a highly effective tool for organizing observational and physical properties of type-1 active galactic nuclei (AGNs). In this paper, we present multiple measurements of metallicity for the broad line region gas, from new and previously-published data. We demonstrate a consistent trend along the optical plane of the E1 (also known as the quasar main sequence), defined by the line width of Balmer hydrogen Hβ profile and by a parameter measuring the prominence of singly-ionized iron emission. The trend involves an increase from sub-solar metallicity in correspondence with extreme Population B (weak Feii emission, large Hβ FWHM (full width at half maximum)) to metallicity several tens the solar value in correspondence with extreme Population A (strongest Feii optical emission, narrower Hβ profiles). The data establish the metallicity as a correlate of the 4DE1/main sequence. If the considerably high metallicity (Z≳10Z⊙, solar metallicity) gas is expelled from the sphere of influence of the central black hole, as indicated by the widespread evidence of nuclear outflows and disk wind in the case of sources radiating at a high Eddington ratio, then it is possible that the outflows from quasars played a role in chemically enriching the host galaxy.

Objective: To evaluate sleep disorders and associated factors in patients with rheumatoid-arthritis-associated interstitial lung disease (RA-ILD). Methods: We performed an observational study of 35 patients with RA-ILD (cases) and 35 age- and sex-matched RA patients without ILD (controls). We evaluated sleep disorders (Oviedo Sleep Questionnaire), positive psychological factors (resilience using the Wagnild and Young Resilience Scale, emotional intelligence using the 24-item Trait Meta-Mood Scale), anxiety and depression (Hospital Anxiety and Depression Scale), quality of life (36-item short-form survey), and fatigue (Functional Assessment of Chronic Illness Therapy Questionnaire). Other variables studied included the Charlson Comorbidity Index (CCI) and RA activity according to the DAS28-ESR. Results: Compared to the controls, the cases were characterized by poorer sleep quality with a higher prevalence of insomnia (42% vs. 20%; p = 0.039), greater severity of insomnia (p = 0.001), and lower sleep satisfaction (p = 0.033). They also had poorer resilience and emotional recovery and more severe anxiety and depression. A diagnosis of ILD was the only factor independently associated with the three dimensions of sleep quality. The predictors of poorer sleep satisfaction in patients with RA-ILD were age (β = −0.379), DAS28-ESR (β = −0.331), and usual interstitial pneumonia pattern (β = −0.438). The predictors of insomnia were DAS28-ESR (β = 0.294), resilience (β = −0.352), and CCI (β = 0.377). Conclusions: RA-ILD is associated with significant sleep disorders. RA-ILD seems to be an independent risk factor for sleep alterations, with a greater impact on insomnia. Age, disease activity, and comorbidity also play a role in sleep disorders in patients with RA-ILD.

Hexapod robots have gained significant attention due to their potential applications in complex terrains and dynamic environments. However, traditional inverse kinematics approaches often face challenges in meeting the precision required for adaptive omnidirectional movement. This work introduces a novel approach to addressing these challenges through the Directed Angular Restitution (DAR) method. The DAR method offers significant innovation by simplifying the calculation of rotational transformations necessary for aligning vectors across different planes, thus enhancing control, stability, and accuracy in robotic applications. Unlike conventional methods, the DAR method extends the range of trigonometric functions and incorporates spin functions to ensure continuous and smooth trajectory tracking. This innovative approach has been rigorously tested on a hexapod robot model, demonstrating superior performance in movement precision and stability. The results confirm that the DAR method provides a robust and scalable solution for the inverse kinematics of hexapod robots, making it a critical advancement for applications in robotics and automation where precise control and adaptability are paramount.

Chitosan is a biodegradable polymer derived from chitin, which is a versatile material for various biological applications due to its attractive properties such as biocompatibility, biodegradability, and non-toxicity. Furthermore, chitosan possesses Second Harmonic Generation (SHG) properties that are useful for biosensing applications. In this work, we explored the possibility of exploiting chitosan-based nanospheres as SHG-based biosensors, and also as carriers of 89Sr radionuclide, an Active Pharmaceutical Ingredient (API) for radiopharmaceutical treatments in cancer therapy. To opportunely load the Sr ion on the nanospheres, we used a fructose-based Metal–Organic Framework, with the formula [Sr(C6H12O6)2(H2O)2]Cl2·H2O, because the sugar was able to drive the Sr ions on the chitosan matrix. Sr-loaded chitosan nanospheres were synthesized, characterized, and their SHG response was measured. The results encouraged us to propose the nanospheres for theranostic purposes, i.e., valuable for both therapeutic and diagnostic applications at the same time.

This work describes a mathematical model for handwriting devices without a specific reference surface (SRS). The research was carried out on two hypotheses: the first considers possible circular segments that could be made during execution for the reconstruction of the trace, and the second is the combination of lines and circles. The proposed system has no flat reference surface, since the sensor is inside the pencil that describes the trace, not on the surface as in tablets or cell phones. An inertial sensor was used for the measurements, in this case, a commercial Micro-Electro Mechanical sensor of linear acceleration. The tracking device is an IMU sensor and a processing card that allows inertial measurements of the pen during on-the-fly tracing. It is essential to highlight that the system has a non-inertial reference frame. Comparing the two proposed models shows that it is possible to construct shapes from curved lines and that the patterns obtained are similar to what is recognized; this method provides an alternative to quaternion calculus for poorly specified orientation problems.

Beauveria bassiana is an entomopathogenic fungus that parasitizes and kills insects. The role of volatile organic compounds (VOCs) emitted by B. bassiana acting as semiochemicals during its interaction with lepidopterans is poorly explored. Here, we studied the effect of VOCs from B. bassiana and 3-methylbutanol (as a single compound) on the feeding behavior of L2 larvae of Spodoptera frugiperda in sorghum plants. Additionally, we assessed whether fungal VOCs induce chemical modifications in the plants that affect larval food preferences. Metabolomic profiling of plant tissues was performed by mass spectrometry and bioassays in a dual-choice olfactometer. The results showed that the larval feeding behavior was affected by the B. bassiana strain AI2, showing that the insect response is strain-specific. Furthermore, 80 µg of 3-methylbutanol affected the number of bites. The larval feeding choice was dependent on the background context. Fragment spectra and a matching precursor ion mass of 165.882 m/z enabled the putative identification of 4-coumaric acid in sorghum leaves exposed to fungal VOCs, which may be associated with larval deterrent responses. These results provide valuable insights into the bipartite interaction of B. bassiana with lepidopterans through VOC emission, with the plant as a mediator of the interaction.

For most patients admitted to a hospital, it is a requirement to continuously monitor their vital signs. Among these are the waveforms from ECG and the pulmonary arterial pulse. At present, there are several electronic devices that can measure the arterial pulse waveform. However, they can be affected by electromagnetic wave radiation, and the fabrication of electronic sensors is complicated and contributes to the e-waste, among other problems. In this paper, we propose an optical method to measure arterial pulse based on a Fabry-Perot interferometer composed of two mirrors. A pulse sensor formed by an acrylic cell with a thin membrane is used to gather the vasodilatation of the wrist, forming an air pulse that is enacted by means of a tube to a metallic cell containing a mirror that is glued to a thin silicone membrane. When the air pulse arrives, a displacement of the mirror takes place and produces a shift of the interference pattern fringes given by the Fabry-Perot. A detector samples the fringe intensity. With this method, an arterial pulse waveform is obtained. We characterize this optical device as a test of concept, and its application to measuring artery pulse is presented. The optical device is compared to other electronic devices.

Tropical coastal freshwater forested wetlands in coastal regions are rapidly disappearing as a result of various disturbance agents, mainly wildfires caused by high accumulations of forest fuels. The objective of this study was to characterize the structure and composition of fuel beds in tropical coastal freshwater forested wetlands with three levels of disturbance at El Castaño, La Encrucijada Biosphere Reserve. Seventeen sampling units were used to describe the structure of the forest’s fuel beds (canopy, sub-canopy, and understory). Fallen woody material and litter (surface and fermented) were characterized using the planar intersection technique. Diversity comprised eight species of trees, two shrubs, five lianas, and two herbaceous species. The vertical strata were dominated by trees between 2 and 22 m in height. The horizontal structure had a higher percentage of trees with normal diameter between 2.5 and 7.5 cm (61.4%) of the total. Sites with low disturbance had the highest arboreal density (2686 ind. ha−1). Diversity of species showed that the Fisher, Margalef, Shannon, and Simpson α indices were higher in the low disturbance sites. The Berger–Parker index exhibited greater dominance in the sites with high disturbance. Pachira aquatica Aubl. Showed the highest importance value index and was the largest contributor to fuel beds. Sites with the highest disturbance had the highest dead fuel load (222.18 ± 33.62 Mg ha−1), with woody fuels of classes 1, 10, and 1000 h (rotten) being the most representative. This study contributes to defining areas prone to fire in these ecosystems and designing prevention strategies.

The life cycle assessment (LCA) methodology is becoming increasingly prevalent in the quantification of the environmental status in the building sector following new legislative frameworks. Countries need to quantify and assess their environmental impacts as a previous step to regulation and decision-making. In this context, based on a consensus with manufacturers, standardized national data sets are being developed, referred to as sectoral environmental product declarations (EPDs). This study assesses these EPDs with the aim of providing relevant information for global decision-making, focusing on their consistency and shortcomings. An assessment was carried out at both the national level, considering all sectoral EPDs and declared products, and at the international level, with three common building materials (brick, steel, and concrete). The results highlight the lack of traceability in the development and assessment of uncertainty, resulting in substantial discrepancies in reported impacts, especially in the later stages of the life cycle (up to 90% difference). Meanwhile, impacts such as global warming potential or total renewable and non-renewable primary energy use show homogeneous values in the cradle-to-gate stages, with differences generally being under 10%. The analysis of sectoral EPDs should act as a guideline for designing buildings with environmental sustainability criteria, as the last section of this study attempts to highlight.

Canine distemper virus (CDV) affects a huge diversity of domestic and wild carnivores, with increasing numbers of mortality events worldwide. The local cell-mediated immune response elicited against a natural infection is an important factor in determining the outcome of CDV infection. Therefore, the purposes of this study were to describe the local immune response within the central nervous systems (CNSs) of seven badgers naturally infected with CDV in Asturias (Atlantic Spain) and to determine the phenotype and distribution of microglial cells, T and B lymphocytes, and astrocytes in the foci of gliosis located in the thalamus and cerebellum using immunohistochemistry. The immunohistochemical assessment demonstrated the presence of Iba1-positive microglia and GFAP-positive astrocytes in the foci of gliosis, whereas T (CD3-negative) or B (CD20-negative) lymphocytes in those same lesions were absent. Our results also revealed that the badgers with natural CDV encephalitis presented lesions mostly located in the white matter of the thalamus and cerebellum, suggesting a CDV-specific tropism for the white matter of badger brains in those locations. The knowledge gained in the field of the immunopathogenesis of distemper disease affecting the CNSs of badgers could help to clarify CDV disease patterns in this species.

Wine is a temperature, light, and oxygen-sensitive product, so its physicochemical characteristics can be modified by variations in temperature and time when samples are either sampled, transported, and/or analyzed. These changes can alter its metabolomic fingerprinting, impacting further classification tasks and quality/quantitative analyses. For these reasons, the aim of this work is to compare and analyze the information obtained by different chemometric methods used in a complementary form (PCA, ASCA, and PARAFAC) to study 1H-NMR spectra variations of four red wine samples kept at different temperatures and time lapses. In conjunction, distinctive changes in the spectra are satisfactorily tracked with each chemometric method. The chemometric analyses reveal variations related to the wine sample, temperature, and time, as well as the interactions among these factors. Moreover, the magnitude and statistical significance of the effects are satisfactorily accounted for by ASCA, while the time-related effects variations are encountered by PARAFAC modeling. Acetaldehyde, formic acid, polyphenols, carbohydrates, lactic acid, ethyl lactate, methanol, choline, succinic acid, proline, acetoin, acetic acid, 1,3-propanediol, isopentanol, and some amino acids are identified as some of the metabolites which present the most important variations.

To successfully implement additive manufacturing (AM) techniques for custom medical device (MD) production with low-cost resources, it is imperative to understand the effect of common and affordable sterilization processes, such as formaldehyde or steam sterilization, on pieces manufactured by AM. In this way, the performance of low-risk MDs, such as biomodels and surgical guides, could be assessed for complying with safety, precision, and MD delivery requirements. In this context, the aim of the present work was to evaluate the effect of formaldehyde and steam sterilization on the dimensional and mechanical stability of standard polylactic acid (PLA) test pieces produced by fused deposition modeling (FDM). To achieve this, PLA samples were sterilized according to the sterilization protocol of a public hospital in the city of Bucaramanga, Colombia. Significant changes regarding mechanical and dimensional properties were found as a function of manufacturing parameters. This research attempts to contribute to the development of affordable approaches for the fabrication of functional and customized medical devices through AM technologies, an issue of particular interest for low- and middle-income countries.

The focus of this work is to analyze the sintering kinetics of Ti12.5Ta12.5Nb alloy by dilatometry. The mixture of powders was achieved by mixing individual powders of Ti, Ta and Nb, which were then axially pressed. Sintering was performed at 1260 °C using different heating rates. The microstructure was determined by X-ray diffraction and scanning electron microscopy. Results show that densification is achieved by solid state diffusion and that the relative density increased as the heating rate was slow. Due to the full solubility of Ta and Nb in Ti, the relative density reached was up to 93% for all samples. Activation energy was estimated from the densification rate and it was determined that two main diffusion mechanisms were predominant: grain boundary and lattice self-diffusion. This suggests that Ta and Nb diffusion did not affect the atomic diffusion to form the necks between particles. The microstructure shows a combination of α, β and α′, and α″ martensitic phases as a result of the diffusion of Ta and Nb into the Ti unit cell. It was concluded that the heating rate plays a major role in the diffusion of Ta and Nb during sintering, which affects the resulting microstructure.

Opuntia Ficus-indica, or nopal, is traditionally used for its medicinal properties in Mexico. This study aims to decellularize and characterize nopal (Opuntia Ficus-indica) scaffolds, assess their degradation and the proliferation of hDPSC, and determine potential pro-inflammatory effects by assessing the expression of cyclooxygenase 1 and 2 (COX-1 and 2). The scaffolds were decellularized using a 0.5% sodium dodecyl sulfate (SDS) solution and confirmed by color, optical microscopy, and SEM. The degradation rates and mechanical properties of the scaffolds were determined by weight and solution absorbances using trypsin and PBS and tensile strength testing. Human dental pulp stem cells (hDPSCs) primary cells were used for scaffold–cell interaction and proliferation assays, as well as an MTT assay to determine proliferation. Proinflammatory protein expression of COX-I and -II was discovered by Western blot assay, and the cultures were induced into a pro-inflammatory state with interleukin 1-β. The nopal scaffolds exhibited a porous structure with an average pore size of 252 ± 77 μm. The decellularized scaffolds showed a 57% reduction in weight loss during hydrolytic degradation and a 70% reduction during enzymatic degradation. There was no difference in tensile strengths between native and decellularized scaffolds (12.5 ± 1 and 11.8 ± 0.5 MPa). Furthermore, hDPSCs showed a significant increase in cell viability of 95% and 106% at 168 h for native and decellularized scaffolds, respectively. The combination of the scaffold and hDPSCs did not cause an increase in the expression of COX-1 and COX-2 proteins. However, when the combination was exposed to IL-1β, there was an increase in the expression of COX-2. This study demonstrates the potential application of nopal scaffolds in tissue engineering and regenerative medicine or dentistry, owing to their structural characteristics, degradation properties, mechanical properties, ability to induce cell proliferation, and lack of enhancement of pro-inflammatory cytokines.

Nanocarriers, and especially nanostructured lipid carriers (NLC), represent one of the most effective systems for topical drug administration. NLCs are biodegradable, biocompatible and provide a prolonged drug release. The glutamate release inhibitor Riluzole (RLZ) is a drug currently used for amyotrophic lateral sclerosis (ALS), with anti-proliferative effects potentially beneficial for diseases with excessive cell turnover. However, RLZ possesses low water solubility and high light-sensibility. We present here optimized NLCs loaded with RLZ (RLZ-NLCs) as a potential topical treatment. RLZ-NLCs were prepared by the hot-pressure homogenization method using active essential oils as liquid lipids, and optimized using the design of experiments approach. RLZ-NLCs were developed obtaining optimal properties for dermal application (mean size below 200 nm, negative surface charge and high RLZ entrapment efficacy). In vitro release study demonstrates that RLZ-NLCs allow the successful delivery of RLZ in a sustained manner. Moreover, RLZ-NLCs are not angiogenic and are able to inhibit keratinocyte cell proliferation. Hence, a NLCs delivery system loading RLZ in combination with natural essential oils constitutes a promising strategy against keratinocyte hyperproliferative conditions.

Antibiotic consumption in infants of less than three years is higher than average the average consumption for general population. The aim of this study was to explore paediatricians’ opinions regarding factors influencing inappropriate use of antibiotics in early infancy in primary care. A qualitative study based on the grounded theory using convenience sampling was conducted in Murcia Region, Spain. Three focal discussion groups were developed with 25 participants from 9 health areas (HA) of Murcia Region. Paediatricians perceived that health care pressure was an influential factor in the prescribing behaviour, forcing them to prescribe antibiotics for a rapid cure in unjustified circumstances. Participants believed that antibiotic consuming was related to parents’ self-medication due to their perceptions about the curative potential of antibiotics together with facilities to obtain these agents from pharmacies without prescription. The misuse of antibiotics by paediatricians was associated to the lack of education on antibiotic prescription and the limited use of clinical guidelines. Not prescribing an antibiotic in the presence of a potentially severe disease generated more fear than an unnecessary prescription. The clinical interaction asymmetry was more evident, when paediatricians use trapping risk strategies as a mechanism to justify a restrictive prescribing behaviour. The rational model of clinical decision-making in antibiotic prescribing among paediatricians was determined by factors associated with health care management, social awareness and knowledge of the population and pressure of families’ demands. The present findings have contributed to the design and implementation of health interventions in the community for improving awareness of the appropriate use of antibiotics, as well as for a better quality of prescription by peadiatricians.

The Cantabrian capercaillie (Tetrao urogallus cantabricus) is one of the most severely threatened subspecies of capercaillie. Its current population range is restricted to a small area of the Cantabrian Mountains (northwestern Spain), with only around 200 individuals remaining. As part of the national strategy for the conservation of the subspecies, the Cantabrian capercaillie Captive Breeding Center of Sobrescobio opened in 2009. Here, we use the information provided by the necropsies performed in this facility on 29 individuals (11 males, 13 females and 5 undetermined; 16 chicks and 13 adults) in order to describe the main mortality causes of captive-bred Cantabrian capercaillies. After necropsy, tissue samples were taken for evaluation using standard methods in histology and microbiology. The majority of the captive animals (18/29, 62.07%) died due to infectious diseases, mainly due to Escherichia coli, Clostridium perfringens, or Aspergillus fumigatus infection. The remaining 11 animals died due to stress-related processes (i.e., rupture of the heart apex and cardiomyopathy or neurogenic shock) (8/29, 27.59%), duodenal obstruction and coelomitis (1/29, 3.45%), perforation of the proventriculus and heart with a briar branch (1/29, 3.45%) or euthanasia due to a valgus leg deformity that prevented proper animal welfare (1/29, 3.45%). Young animals (i.e., younger than 2 months) died mainly due to infectious diseases (14/16, 87.5%), while stress-related causes were responsible for most adult deaths (7/13, 53.85%). We additionally report that two free-ranging adult males died due to exertional myopathy. This study provides relevant information for reducing mortality in captive capercaillies and improving both living conditions in captivity and the adaptation of these animals to the wild.

We conducted a retrospective study using a population of patients who were hospitalized at Dr. Juan Graham Casasus Hospital in Villahermosa (Tabasco, Mexico) and had a positive RT-PCR test for SARS-CoV-2 between June 2020 and January 2022. We analyzed all medical records, including demographic data, SARS-CoV-2 exposure history, underlying comorbidities, symptoms, signs at admission, laboratory findings during the hospital stay, outcome, and whole-genome sequencing data. Finally, the data were analyzed in different sub-groups according to distribution during waves of the COVID-19 pandemic regarding Mexican reports from June 2020 to January 2022. Of the 200 patients who tested positive via PCR for SARS-CoV-2, only 197 had samples that could be sequenced. Of the samples, 58.9% (n = 116) were males and 41.1% (n = 81) females, with a median age of 61.7 ± 17.0 years. Comparisons between the waves of the pandemic revealed there were significant differences in the fourth wave: the age of patients was higher (p = 0.002); comorbidities such as obesity were lower (p = 0.000), while CKD was higher (p = 0.011); and hospital stays were shorter (p = 0.003). The SARS-CoV-2 sequences revealed the presence of 11 clades in the study population. Overall, we found that adult patients admitted to a third-level Mexican hospital had a wide range of clinical presentations. The current study provides evidence for the simultaneous circulation of SARS-CoV-2 variants during the four pandemic waves.

Distributed power generation plays a critical role in the stability and reliability of modern power systems. Due to the rapid growth of renewable energy generation, the requirements of the transmission and distribution system operators are becoming more stringent. Among these requirements, one of the most important is the Low-Voltage Ride-Through (LVRT) capability, which demands that the inverters remain connected to the grid and provide support during voltage sags. For this purpose, flexible current control algorithms stand out because they can manage unbalanced voltages and simultaneously achieve other control objectives. With the aim of presenting a concrete document focused on describing fundamental principles and discussing common design guidelines, this paper presents an overview of flexible current control strategies applied to LVRT capability. The operation features and design aspects of experiences reported in the literature are reviewed. Moreover, the paper proposes a general methodology to design LVRT flexible current control algorithms. Finally, current and future trends are discussed.

Immunotherapies based on immune checkpoint blockade have shown remarkable clinical outcomes and durable responses in patients with many tumor types. Nevertheless, these therapies lack efficacy in most cancer patients, even causing severe adverse events in a small subset of patients, such as inflammatory disorders and hyper-progressive disease. To diminish the risk of developing serious toxicities, intratumor delivery of monoclonal antibodies could be a solution. Encouraging results have been shown in both preclinical and clinical studies. Thus, intratumor immunotherapy as a new strategy may retain efficacy while increasing safety. This approach is still an exploratory frontier in cancer research and opens up new possibilities for next-generation personalized medicine. Local intratumor delivery can be achieved through many means, but an attractive approach is the use of gene therapy vectors expressing mAbs inside the tumor mass. Here, we summarize basic, translational, and clinical results of intratumor mAb delivery, together with descriptions of non-viral and viral strategies for mAb delivery in preclinical and clinical development. Currently, this is an expanding research subject that will surely play a key role in the future of oncology.

Chimeric antigen receptor (CAR)-T adoptive cell therapy is one of the most promising advanced therapies for the treatment of cancer, with unprecedented outcomes in haematological malignancies. However, it still lacks efficacy in solid tumours, possibly because engineered T cells become inactive within the immunosuppressive tumour microenvironment (TME). In the TME, cells of the myeloid lineage (M) are among the immunosuppressive cell types with the highest tumour infiltration rate. These cells interact with other immune cells, mediating immunosuppression and promoting angiogenesis. Recently, the development of CAR-M cell therapies has been put forward as a new candidate immunotherapy with good efficacy potential. This alternative CAR strategy may increase the efficacy, survival, persistence, and safety of CAR treatments in solid tumours. This remains a critical frontier in cancer research and opens up a new possibility for next-generation personalised medicine to overcome TME resistance. However, the exact mechanisms of action of CAR-M and their effect on the TME remain poorly understood. Here, we summarise the basic, translational, and clinical results of CAR-innate immune cells and CAR-M cell immunotherapies, from their engineering and mechanistic studies to preclinical and clinical development.

Streptomyces species have been successfully used in diverse biotechnological processes; however, little is known about actinobacterial biofilm formation and its use as a biofilmed inoculant. The present study assessed and compared the ability of some plant growth-promoting actinobacterial strains to form biofilms on a carrier to improve microbial survival and colonize the rhizosphere and roots of Triticum aestivum, resulting in positive interactions and benefits to the plant. Forty-one actinobacterial isolates from Persea americana organic rhizosphere farms were tested on plant growth and biofilm-forming capacities, showing their potential use as bio-fertilizers in agriculture. Three Streptomyces strains were selected and tested for biofilm formation and plant growth-promoting (PGP) features. Biofilms were induced on the perlite carrier and used to inoculate seven treatments with T. aestivum in pot essays, resulting in a >200% increase in root weight and a >400% increase in total biomass. Endophytic colonization was achieved in all the treatments. Microbial survival ranged between 108 and 109 CFU/g after 12 weeks of treatment, indicating actinobacterial permanence on the carrier. Successful consortia formation was observed for mixed-strain treatments, suggesting long-term plant recolonization.

PD-L1/PD-1 blockade immunotherapy has changed the therapeutic approaches for the treatment of many cancers. Nevertheless, the mechanisms underlying its efficacy or treatment failure are still unclear. Proficient systemic immunity seems to be a prerequisite for efficacy, as recently shown in patients and in mouse models. It is widely accepted that expansion of anti-tumor CD8 T cell populations is principally responsible for anti-tumor responses. In contrast, the role of CD4 T cells has been less studied. Here we review and discuss the evidence supporting the contribution of CD4 T cells to anti-tumor immunity, especially recent advances linking CD4 T cell subsets to efficacious PD-L1/PD-1 blockade immunotherapy. We also discuss the role of CD4 T cell memory subsets present in peripheral blood before the start of immunotherapies, and their utility as predictors of response.

Despite advances in diagnostic and therapeutic approaches for lung cancer, new therapies targeting metastasis by the specific regulation of cancer genes are needed. In this study, we screened a small library of epigenetic inhibitors in non-small-cell lung cancer (NSCLC) cell lines and evaluated 38 epigenetic targets for their potential role in metastatic NSCLC. The potential candidates were ranked by a streamlined approach using in silico and in vitro experiments based on publicly available databases and evaluated by real-time qPCR target gene expression, cell viability and invasion assays, and transcriptomic analysis. The survival rate of patients with lung adenocarcinoma is inversely correlated with the gene expression of eight epigenetic targets, and a systematic review of the literature confirmed that four of them have already been identified as targets for the treatment of NSCLC. Using nontoxic doses of the remaining inhibitors, KDM6B and PADI4 were identified as potential targets affecting the invasion and migration of metastatic lung cancer cell lines. Transcriptomic analysis of KDM6B and PADI4 treated cells showed altered expression of important genes related to the metastatic process. In conclusion, we showed that KDM6B and PADI4 are promising targets for inhibiting the metastasis of lung adenocarcinoma cancer cells.

The present work is focused on developing Ti-xTa porous alloys processed by the space holder method and solid-state sintering. The volume fraction of Ta ranged between 20 and 30 wt.%. The sintering kinetics was evaluated by dilatometry tests. Sintered materials were characterized by SEM, XRD and computed tomography. Porosity features and permeability were determined from 3D images, and their mechanical properties were evaluated from microhardness and compression tests. The sintering behavior and the final microstructure are driven by the Ta diffusion into the Ti, slowing down the densification and modifying the transition temperature of α-to-β. Due to β-stabilization, martensite α′ was obtained after sintering. Mechanical properties are reduced because of the β-stabilization and pore addition, being predominantly the pore effect. Permeability depended on the pore characteristics, finding values close to the human bones. It was concluded that powder metallurgy generates highly TixTa alloys with a combination of α, β and α′ Ti phases as well as remaining Ta particles that are beneficial to improve the biocompatibility and osseointegration of such materials. Being the Ti25Ta40salt alloy the most suitable for orthopedic implants because of its characteristics and properties.

In this paper, we experimented with a set of machine-learning classifiers for predicting the risk of a person being overweight or obese, taking into account his/her dietary habits and socioeconomic information. We investigate with ten different machine-learning algorithms combined with four feature-selection strategies (two evolutionary feature-selection methods, one feature selection from the literature, and no feature selection). We tackle the problem under a binary classification approach with evolutionary feature selection. In particular, we use a genetic algorithm to select the set of variables (features) that optimize the accuracy of the classifiers. As an additional contribution, we designed a variant of the Stud GA, a particular structure of the selection operator of individuals where a reduced set of elitist solutions dominate the process. The genetic algorithm uses a direct binary encoding, allowing a more efficient evaluation of the individuals. We use a dataset with information from more than 1170 people in the Spanish Region of Madrid. Both evolutionary and classical feature-selection methods were successfully applied to Gradient Boosting and Decision Tree algorithms, reaching values up to 79% and increasing the average accuracy by two points, respectively.

The number of people that are 65 years old or older has been increasing due to the improvement in medicine and public health. However, this trend is not accompanied by an increase in quality of life, and this population is vulnerable to most illnesses, especially to infectious diseases. Vaccination is the best strategy to prevent this fact, but older people present a less efficient response, as their immune system is weaker due mainly to a phenomenon known as immunosenescence. The adaptive immune system is constituted by two types of lymphocytes, T and B cells, and the function and fitness of these cell populations are affected during ageing. Here, we review the impact of ageing on T and B cells and discuss the approaches that have been described or proposed to modulate and reverse the decline of the ageing adaptive immune system.

Vaccination, being able to prevent millions of cases of infectious diseases around the world every year, is the most effective medical intervention ever introduced. However, immunosenescence makes vaccines less effective in providing protection to older people. Although most studies explain that this is mainly due to the immunosenescence of T and B cells, the immunosenescence of innate immunity can also be a significant contributing factor. Alterations in function, number, subset, and distribution of blood neutrophils, monocytes, and natural killer and dendritic cells are detected in aging, thus potentially reducing the efficacy of vaccines in older individuals. In this paper, we focus on the immunosenescence of the innate blood immune cells. We discuss possible strategies to counteract the immunosenescence of innate immunity in order to improve the response to vaccination. In particular, we focus on advances in understanding the role and the development of new adjuvants, such as TLR agonists, considered a promising strategy to increase vaccination efficiency in older individuals.

Immune checkpoint inhibitors (ICIs) have revolutionized medical practice in oncology since the FDA approval of the first ICI 11 years ago. In light of this, Lymphocyte-Activation Gene 3 (LAG-3) is one of the most important next-generation immune checkpoint molecules, playing a similar role as Programmed cell Death protein 1 (PD-1) and Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4). 19 LAG-3 targeting molecules are being evaluated at 108 clinical trials which are demonstrating positive results, including promising bispecific molecules targeting LAG-3 simultaneously with other ICIs. Recently, a new dual anti-PD-1 (Nivolumab) and anti-LAG-3 (Relatimab) treatment developed by Bristol Myers Squibb (Opdualag), was approved by the Food and Drug Administration (FDA) as the first LAG-3 blocking antibody combination for unresectable or metastatic melanoma. This novel immunotherapy combination more than doubled median progression-free survival (PFS) when compared to nivolumab monotherapy (10.1 months versus 4.6 months). Here, we analyze the large clinical trial responsible for this historical approval (RELATIVITY-047), and discuss the preclinical and clinical developments that led to its jump into clinical practice. We will also summarize results achieved by other LAG-3 targeting molecules with promising anti-tumor activities currently under clinical development in phases I, I/II, II, and III. Opdualag will boost the entry of more LAG-3 targeting molecules into clinical practice, supporting the accumulating evidence highlighting the pivotal role of LAG-3 in cancer.

Anaerobic digestion (AD) is an efficient wastewater bioprocess, suitable for treating agroindustrial residues with high organic loads and characterized by both a low environmental impact and energy generation. This process is conformed by several chemical and biological reactions in an oxygen free atmosphere, that degrades high molecular weight organic compounds into carbon dioxide and methane mainly but also into traces of hydrogen and ammonia. This process is potentially unstable to volatile fatty acids (VFA), and the alkalinity. variations and is satisfactorily described by the non-linear AM2 model. In this contribution, the AM2 model is modified to include a more general expression for the pH, a cheap and continuous measurement, and also to add more detail in the interactions of the VFA, bicarbonates, and the alkalinity, key factors in the process stability. The stability of the AM2 modified model is explored through a rigorous bifurcation analysis that identifies unstable operation zones and viability of operation trajectories as a function of the dilution rate. Finally, an experimental validation is carried out to show the feasibility and accuracy of the proposed modifications.

The focus of this article is inland waterway transport. Different problems in this domain have been studied due to the increase in waterway traffic globally. Industry 4.0 technologies have become an alternative for the possible solution of these problems. For this reason, this paper aims to answer the following research questions: (1) What are the main problems in transporting cargo by inland waterway? (2) What technological strategies are being studied to solve these problems? (3) What technologies from Industry 4.0 are used within the technological strategies to solve the exposed problems? This study adopts a Systematic Literature Review (SLR) approach. For this work, were recovered 645 articles, 88 of which were eligible, from which we could identify five domains corresponding to (1) traffic monitoring, (2) smart navigation, (3) emission reduction, (4) analytics with big data, and (5) cybersecurity. The strategies currently being considered combine navigation technologies, such as AIS (Automatic Identification System), which offers a large amount of data, with Industry 4.0 tools and mainly machine learning techniques, to take advantage of data collected over a long time. This study is, to our knowledge, one of the first to show how Industry 4.0 technologies are currently being used to tackle inland waterway transport problems and current application trends in the scientific community, which is a first step for the development of future studies and more advanced solutions.

The novel coronavirus SARS-CoV-2, which has similarities to the 2002–2003 severe acute respiratory syndrome coronavirus known as SARS-CoV-1, causes the infectious disease designated COVID-19 by the World Health Organization (Coronavirus Disease 2019). Although the first reports indicated that activity of the virus is centered in the lungs, it was soon acknowledged that SARS-CoV-2 causes a multisystem disease. Indeed, this new pathogen causes a variety of syndromes, including asymptomatic disease; mild disease; moderate disease; a severe form that requires hospitalization, intensive care, and mechanical ventilation; multisystem inflammatory disease; and a condition called long COVID or postacute sequelae of SARS-CoV-2 infection. Some of these syndromes resemble previously described disorders, including those with no confirmed etiology, such as Kawasaki disease. After recognition of a distinct multisystem inflammatory syndrome in children, followed by a similar syndrome in adults, various multisystem syndromes occurring during the pandemic associated or related to SARS-CoV-2 began to be identified. A typical pattern of cytokine and chemokine dysregulation occurs in these complex syndromes; however, the disorders have distinct immunological determinants that may help to differentiate them. This review discusses the origins of the different trajectories of the inflammatory syndromes related to SARS-CoV-2 infection.

Adoptive cell therapy with genetically modified T lymphocytes that express chimeric antigen receptors (CAR-T) is one of the most promising advanced therapies for the treatment of cancer, with unprecedented outcomes in hematological malignancies. However, the efficacy of CAR-T cells in solid tumors is still very unsatisfactory, because of the strong immunosuppressive tumor microenvironment that hinders immune responses. The development of next-generation personalized CAR-T cells against solid tumors is a clinical necessity. The identification of therapeutic targets for new CAR-T therapies to increase the efficacy, survival, persistence, and safety in solid tumors remains a critical frontier in cancer immunotherapy. Here, we summarize basic, translational, and clinical results of CAR-T cell immunotherapies in lung cancer, from their molecular engineering and mechanistic studies to preclinical and clinical development.

Advanced monitoring methods are required to identify stop criteria in proof-load tests. In this study, the combined methodology of two-dimensional digital image correlation and acoustic emission is investigated for its applicability for future implementation in field tests. The two monitoring systems are deemed to provide valuable insight with external measurements from digital image correlation and internal measurements from acoustic emission. Two overturned T-section reinforced concrete slabs (0.37 × 1.7 × 8.4 m) tested under laboratory conditions are used for the assessment. The first slab test served as a preliminary test to enable sensor placement and creation of a relevant loading protocol. The main scientific results lead to a proposal for a test procedure using the combined methodology based on results, observations, and experiences from an individual stop criteria assessment for the two methods. The results include full-field plots, an investigation of the time of crack detection and monitoring of crack widths with digital image correlation, and a qualitative assessment of activity vs. load followed by a quantitative evaluation of calm ratios using acoustic emission. The individual results show that both digital image correlation and acoustic emission can identify damage occurrence earlier than other secondary methods. At crack detection (415 kN), crack widths were measured at widths between 0.078 mm to 0.125 mm and can be monitored until reaching the stop criterion at 463 kN (Eurocode SLS threshold of wmax = 0.2 mm). The acoustic emission results were limited by the pre-defined loading protocol and thus, only indicated that damage occurred sometime between 300 kN and 500 kN (pre-defined load levels). Therefore, the proposal for test procedure involves a methodology, where the loading protocol may be updated during testing based on monitoring results and thus provide even more valuable data.

Omicron is the most mutated SARS-CoV-2 variant—a factor that can affect transmissibility, disease severity, and immune evasiveness. Its genomic surveillance is important in cities with millions of inhabitants and an economic center, such as Mexico City. Results. From 16 November to 31 December 2021, we observed an increase of 88% in Omicron prevalence in Mexico City. We explored the R346K substitution, prevalent in 42% of Omicron variants, known to be associated with immune escape by monoclonal antibodies. In a phylogenetic analysis, we found several independent exchanges between Mexico and the world, and there was an event followed by local transmission that gave rise to most of the Omicron diversity in Mexico City. A haplotype analysis revealed that there was no association between haplotype and vaccination status. Among the 66% of patients who have been vaccinated, no reported comorbidities were associated with Omicron; the presence of odynophagia and the absence of dysgeusia were significant predictor symptoms for Omicron, and the RT-qPCR Ct values were lower for Omicron. Conclusions. Genomic surveillance is key to detecting the emergence and spread of SARS-CoV-2 variants in a timely manner, even weeks before the onset of an infection wave, and can inform public health decisions and detect the spread of any mutation that may affect therapeutic efficacy.

The use of surface relief structures is increasing in the field of optics. A study of photoinduced relief using dichromated gelatin films with different thickness is described in this paper. Two light sources were used: a laser (λ = 468 nm) and an ultraviolet mercury-metal halide lamp. Gratings with low spatial frequencies were contact-copied on the DCG (dichromated gelatin) films. Two development processes were used, one included washing the plates with just water and the other with a mixture of water and papain. This enzyme is used to improve the gratings’ relief which was studied with a profilometer. For the development process with just water, it was found that when gratings were recorded using visible or UV light, the height profile inversely correlated to spatial frequencies. For short exposure times, the reliefs showed a sinusoidal profile. When visible light was used, the DCG areas where the Ronchi grating had transparent slits showed a flat relief and the areas where the Ronchi grating had opaque slits showed a round peak, with the peak being taller than the flat surface. In contrast, when UV light was used, the flat surfaces were taller than the peaks. The relief height increased up to seven times when papain was used.

A non-isothermal transformation model was proposed to determine the austenite formation kinetics in a steel alloyed with 2.6% wt. Si by dilatometric analysis, considering that the nucleation mechanism does not change with the heating rate. From the dilatometric analysis, it was observed that the austenite formation occurs in two stages; critical temperatures, degree and austenite formation rate were determined. The activation energies associated with each of the stages were obtained employing the Kissinger method (226.67 and 198.37 kJ·mol−1 for the first and second stage) which was used in concert with the austenite formation rate in the non-isothermal model as a first approximation, with acceptable results in the second stage, but not in the first due to the activation energies magnitude. Then, the activation energies were adjusted by minimizing the minimal squares error between estimated and experimental austenite formation degree, obtaining values of 158.50 kJ·mol−1 for the first and 165.50 kJ·mol−1 for the second stage. These values are consistent with those reported for the diffusion of carbon in austenite-FCC in silicon steels. With these activation energies it was possible to predict the austenite formation degree with a better level of convergence when implementing the non-isothermal model.

The preferential CO oxidation (so-called CO-PROX) is the selective CO oxidation amid H2-rich atmospheres, a process where ceria-based materials are consolidated catalysts. This article aims to disentangle the potential CO–H2 synergism under CO-PROX conditions on the low-index ceria surfaces (111), (110) and (100). Polycrystalline ceria, nanorods and ceria nanocubes were prepared to assess the physicochemical features of the targeted surfaces. Diffuse reflectance infrared Fourier-transformed spectroscopy (DRIFTS) shows that ceria surfaces are strongly carbonated even at room temperature by the effect of CO, with their depletion related to the CO oxidation onset. Conversely, formate species formed upon OH + CO interaction appear at temperatures around 60 °C and remain adsorbed regardless the reaction degree, indicating that these species do not take part in the CO oxidation. Density functional theory calculations (DFT) reveal that ceria facets exhibit high OH coverages all along the CO-PROX reaction, whilst CO is only chemisorbed on the (110) termination. A CO oxidation mechanism that explains the early formation of carbonates on ceria and the effect of the OH coverage in the overall catalytic cycle is proposed. In short, hydroxyl groups induce surface defects on ceria that increase the COx–catalyst interaction, revealed by the CO adsorption energies and the stabilization of intermediates and readsorbed products. In addition, high OH coverages are shown to facilitate the hydrogen transfer to form less stable HCOx products, which, in the case of the (110) and (100), is key to prevent surface poisoning. Altogether, this work sheds light on the yet unclear CO–H2 interactions on ceria surfaces during CO-PROX reaction, providing valuable insights to guide the design of more efficient reactors and catalysts for this process.