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T-cell acute lymphoblastic leukemia (T-ALL) is a challenging childhood cancer to treat, with limited therapeutic options and high relapse rates. This study explores deamidated triosephosphate isomerase (dTPI) as a novel therapeutic target. We hypothesized that selectively inhibiting dTPI could reduce T-ALL cell viability without affecting normal T lymphocytes. Computational modeling and recombinant enzyme assays revealed that disulfiram (DS) and curcumin (CU) selectively bind and inhibit dTPI activity without affecting the non-deamidated enzyme. At the cellular level, treatment with DS and CU significantly reduced Jurkat T-ALL cell viability and endogenous TPI enzymatic activity, with no effect on normal T lymphocytes, whereas the combination of sodium dichloroacetate (DCA) with DS or CU showed synergistic effects. Furthermore, we demonstrated that dTPI was present and accumulated only in Jurkat cells, confirming our hypothesis. Finally, flow cytometry confirmed apoptosis in Jurkat cells after treatment with DS and CU or their combination with DCA. These findings strongly suggest that targeting dTPI represents a promising and selective target for T-ALL therapy.

This paper presents an analysis and optimization of a polygeneration power-production system that integrates a concentrating solar tower, a supercritical CO2 Brayton cycle, a double-flash geothermal Rankine cycle, and an internal combustion engine. The concentrating solar tower is analyzed under the weather conditions of the Mexicali Valley, Mexico, optimizing the incident radiation on the receiver and its size, the tower height, and the number of heliostats and their distribution. The integrated polygeneration system is studied by first and second law analyses, and its optimization is also developed. Results show that the optimal parameters for the solar field are a solar flux of 549.2 kW/m2, a height tower of 73.71 m, an external receiver of 1.86 m height with a 6.91 m diameter, and a total of 1116 heliostats of 6 m × 6 m. For the integrated polygeneration system, the optimal values of the variables considered are 1437 kPa and 351.2 kPa for the separation pressures of both flash chambers, 753 °C for the gasification temperature, 741.1 °C for the inlet temperature to the turbine, 2.5 and 1.503 for the turbine pressure ratios, 0.5964 for the air–biomass equivalence ratio, and 0.5881 for the CO2 mass flow splitting fraction. Finally, for the optimal system, the thermal efficiency is 38.8%, and the exergetic efficiency is 30.9%.

Chronic inflammatory diseases pose a substantial health challenge globally, significantly contributing to morbidity and mortality. Addressing this issue requires the use of effective anti-inflammatory strategies with fewer side effects than those provoked by currently used drugs. In this study, a range of phytochemicals (phenolic di-caffeoylquinic acid (Di-CQA), flavonoid cyanidin-3,5-diglucoside (Cy3,5DiG), aromatic isothiocyanate sinalbin (SNB) and aliphatic isothiocyanate sulforaphane (SFN)) sourced from vegetables and fruits underwent assessment for their potential anti-inflammatory activity. An in vitro model of human macrophage-like cells treated with a low dose of LPS to obtain a low degree of inflammation that emulates a chronic inflammation scenario revealed promising results. Cell viability and production of the key pro-inflammatory cytokines were assessed in the presence of various phytochemicals. The compounds Di-CQA and Cy-3,5-DiG, within low physiologically relevant doses, demonstrated notable anti-inflammatory effects by significantly reducing the production of key pro-inflammatory cytokines TNF-α and IL-6 without affecting cell viability. These findings underscore the potential of plant-derived bioactive compounds as valuable contributors to the prevention or treatment of chronic inflammatory diseases. These results suggest that these compounds, whether used individually or as part of natural mixtures, hold promise for their inclusion in nutritional interventions designed to mitigate inflammation in associated pathologies.

This study investigates the effect of daily consumption of a concentrated garlic and onion extract on COVID-19 symptoms among elderly nursing home residents. Volunteers consumed a daily capsule of the concentrated powder rich in organosulfur compounds over 36 weeks during lunch. The incidence and severity of COVID-19 symptoms between the treatment and control groups were compared, along with monitoring the safety of consumption, incidence of other diseases, and medicine usage. The treatment group showed a significant reduction in both the number and severity of COVID-19 symptoms compared to the control group, with no significant adverse effects observed. No significant reduction in symptom duration was detected. This study provides preliminary evidence that concentrated garlic and onion extract may aid in the treatment of COVID-19 among older adults. These findings suggest potential public health benefits, emphasizing the need for further research to explore the immunomodulatory properties of these natural compounds.

Fluoropyrimidines (FPs) are commonly prescribed in many cancer streams. The EMA and FDA-approved drug labels for FPs recommend genotyping the DPYD*2A (rs3918290), *13 (rs55886062), *HapB3 (rs56038477), alleles, and DPYD rs67376798 before treatment starts. We implemented the DPYD genotyping in our daily clinical routine, but we still found patients showing severe adverse drug events (ADEs) to FPs. We studied among these patients the DPYD rs1801265, rs17376848, rs1801159, rs1801160, rs1801158, and rs2297595 as explanatory candidates of the interindividual differences for FP-related toxicities, examining the association with the response to FPs . We also studied the impact of DPYD testing for FP dose tailoring in our clinical practice and characterized the DPYD gene in our population. We found a total acceptance among physicians of therapeutic recommendations translated from the DPYD test, and this dose tailoring does not affect the treatment efficacy. We also found that the DPYD*4 (defined by rs1801158) allele is associated with a higher risk of ADEs (severity grade ≥ 3) in both the univariate (O.R. = 5.66; 95% C.I. = 1.35–23.67; p = 0.014) and multivariate analyses (O.R. = 5.73; 95% C.I. = 1.41–28.77; p = 0.019) among FP-treated patients based on the DPYD genotype. This makes it a candidate variant for implementation in clinical practice.

A multicenter cross-sectional study was conducted among 245 experienced Spanish paediatricians, who completed an online survey based on clinically relevant topics in nutrition during the first two years of life and their recommendations to parents in daily clinical practice. Most participants advise about the choking risk associated with baby-led weaning (BLW) and more than 60% consider that infants can receive an insufficient variety and quantity of nutrients with this practice. The general opinion is that there is a lack of evidence for delaying the introduction of gluten and other allergenic foods in the complementary feeding of healthy infants. Most participants agree/strongly agree that two servings of dairy products are the adequate daily amount in a diversified diet and 93.4% disagree/strongly disagree with the use of vegetal beverages under 1 year of life. There is a general agreement to avoid added salt and sugar before 12 months of life, the consideration that organic foods do not have a better nutritional profile than non-organic ones, and the limitations of vegetarian diets especially for adequate provision of micronutrients. Overall, there is an adequate knowledge of the new trends by paediatricians and younger ones seemed more in favor of them and interested in receiving more information on most topics.

(1) Background: This study aimed to determine the diagnostic accuracy that optical coherence tomography (OCT) can add to fundus photography (FP) in assessing the condition of the retinal posterior pole. (2) Methods: We conducted two blocks of analysis: First, the posterior pole of each eye was examined using an FP non-mydriatic imaging device. Second, OCT was used in addition to FP. After consolidating the specific diagnostic criteria, the assessments were evaluated using two blinded independent investigation groups (by optometrists, and by ophthalmologists who were considered the gold standard). (3) Results: We calculated the diagnostic accuracy of FP compared to OCT and found that they had similar sensitivity. FP had a slightly higher specificity (p-value: 0.01), and OCT had a higher kappa coefficient with 0.50 (95% CI: 0.46–0.55) vs. 0.39 (95% CI: 0.34–0.45) for FP. (4) Conclusions: On the basis that the role of the optometrist in Spain is not to diagnose but to detect lesions and refer patients to an ophthalmologist, the results of this study support the use of OCT, which provided gradable images in almost all examined eyes (97.5%), compared to FP (73.5%). However, optometrists need a detailed and standardized guide in order to conduct evaluations according to the ophthalmologist’s criteria.

The cancer stem cell (SC) theory proposes that a population of SCs serves as the driving force behind fundamental tumor processes, including metastasis, recurrence, and resistance to therapy. The standard of care for patients with stage III and high-risk stage II colorectal cancer (CRC) includes surgery and adjuvant chemotherapy. Fluoropyrimidines and their combination with oxaliplatin increased the cure rates, being able to eradicate the occult metastatic SC in a fraction of patients. The treatment for unresectable metastatic CRC is based on chemotherapy, antibodies to VEGF and EGFR, and tyrosine-kinase inhibitors. Immunotherapy is used in MSI-H tumors. Currently used drugs target dividing cells and, while often effective at debulking tumor mass, these agents have largely failed to cure metastatic disease. SCs are generated either due to genetic and epigenetic alterations in stem/progenitor cells or to the dedifferentiation of somatic cells where diverse signaling pathways such as Wnt/β-catenin, Hedgehog, Notch, TGF-β/SMAD, PI3K/Akt/mTOR, NF-κB, JAK/STAT, DNA damage response, and Hippo-YAP play a key role. Anti-neoplastic treatments could be improved by elimination of SCs, becoming an attractive target for the design of novel agents. Here, we present a review of clinical trials assessing the efficacy of targeted treatment focusing on these pathways in CRC.

This paper addresses the issue of LED short-circuit fault detection in signaling and lighting systems in the automotive industry. The conventional diagnostic method commonly implemented in newer vehicles relies on measuring the voltage drop across different LED branches and comparing it with threshold values indicating faults caused by open circuits or LED short circuits. With this algorithm, detecting cases of a few LEDs short-circuited within a branch, particularly a single malfunctioning LED, is particularly challenging. In this work, two easily implementable algorithms are proposed to address this issue within the vehicle’s control unit. One is based on a mathematical prediction model, while the other utilizes a neural network. The results obtained offer a 100% LED short-circuit fault detection rate in the majority of analyzed cases, representing a significant improvement over the conventional method, even in scenarios involving a single malfunctioning LED within a branch. Additionally, the neural network-based model can accurately predict the number of failed LEDs.

Laser cladding (LC) is a versatile additive manufacturing process where strands of metallic material are deposited and melted by a laser. However, there are some limitations associated with this process that may affect the performance of the final manufactured parts. In the present work, the influence of laser shock peening (LSP) on the fatigue life of 304 stainless steel flat specimens with a cobalt-based alloy (Stellite 6) coating applied by LC was investigated. The analysis was carried out both experimentally and numerically. In the LSP simulation, the ABAQUS/Explicit code was used to determine the residual stress distribution of specimens with double central notches with a radius of curvature of 5, 10, 15, and 20 mm. From the numerical results, an improvement was found regarding fatigue life up to 48% in samples with LSP. Experimentally, 14% in fatigue life enhancement was observed. The residual stress, determined by the contour method, showed good agreement with the LSP simulation. The SEM images revealed that the fatigue failure started at the Stellite 6 coating and propagated towards the center of the specimen. LSP has been shown to be a suitable postprocessing alternative for laser-cladded parts that will be subjected to fatigue loading since it led to fatigue improvement through the introduction of compressive residual stresses on clad coatings.

Cancer involves a series of diseases where cellular growth is not controlled. Cancer is a leading cause of death worldwide, and the burden of cancer incidence and mortality is rapidly growing, mainly in developing countries. Many drugs are currently used, from chemotherapeutic agents to immunotherapy, among others, along with organ transplantation. Treatments can cause severe side effects, including remission and progression of the disease with serious consequences. Increased glycolytic activity is characteristic of cancer cells. Triosephosphate isomerase is essential for net ATP production in the glycolytic pathway. Notably, some post-translational events have been described that occur in human triosephosphate isomerase in which functional and structural alterations are provoked. This is considered a window of opportunity, given the differences that may exist between cancer cells and their counterpart in normal cells concerning the glycolytic enzymes. Here, we provide elements that bring out the potential of triosephosphate isomerase, under post-translational modifications, to be considered an efficacious target for treating cancer.

The use of technologies that allow for the utilization of renewable energies wasted around buildings is one of the ways to ensure the decarbonization of the sector. Wastewater from buildings is a renewable source of thermal energy. Groundwater and rainwater are important components of wastewater that flow into sewerage systems. The main objective of this research is to estimate the thermal potential of wastewater for the heating and cooling of buildings. In this paper, an office building with a low-energy system (TABS) was studied for one year to assess the energy contribution of wastewater in a hybrid system that includes geothermal exchangers and a wastewater exchanger. This study shows that wastewater from sewerage systems that flows faster than 5 L/s can make enough heat to power an office building with a power demand of 45 kW (60 W/m2). The energy contribution of wastewater from the sewerage system is more favorable in heating scenarios than in cooling ones, improving the system efficiency by over 22% compared to geothermal systems. Rainwater enhances cooling efficiency by over 14% compared to geothermal systems. This finding could help to establish a predictive method or guidelines for the design and sizing of heat exchangers in sewerage systems.

There is little information on the evaluation of family functioning in adult patients with chronic non-psychiatric illness. The objective of this systematic review was to identify family functioning assessment instruments of known validity and reliability that have been used in health research on patients with a chronic non-psychiatric illness. We conducted a search in three biomedical databases (PubMed, Science Direct, and Web of Science), for original articles available in English or Spanish published between 2000 and 2019. The review was conducted in accordance with PRISMA guidelines. Fourteen articles were included in the review. The instruments Family Assessment Device, Family Adaptability and Cohesion Evaluation Scales, Family Functioning Health and Social Support, Family APGAR, Assessment of Strategies in Families-Effectiveness, Iceland Expressive Family Functioning, Brief Family Assessment Measure-III, and Family Relationship Index were identified. All of them are reliable instruments to evaluate family functioning in chronic patients and could be very valuable to help nurses identify families in need of a psychosocial intervention. The availability and clinical application of these instruments will allow nurses to generate knowledge on family health and care for non-psychiatric chronic conditions, and will eventually contribute to the health and wellbeing of adults with a non-psychiatric chronic disease and their families.

Researchers primarily dedicate their time to teaching in Latin American universities. For this reason, it is essential to determine how teaching time affects (or contributes to) the scientific productivity of researchers working under these conditions. We analyzed the incidence of gender, groups taught at undergraduate and graduate levels, the researcher proficiency level, and the number of thesis students advised, among others, for the impact on the scientific productivity (annual publications) of a group of professors. We analyzed the data using both statistical and regression methods. Contrary to our initial hypothesis, the number of groups taught does not significantly influence research productivity; it is affected by other factors such as belonging to the Mexican Researcher System (SNI) or having a researcher or administrative position at the institution. Our results can help guide the formulation of academic and research policies that contribute to the scientific productivity of Latin American universities.

Three novel biomaterials obtained via inclusion complexes of β–cyclodextrin, 6-deoxi-6-amino-β–cyclodextrin and epithelial growth factor grafted to 6-deoxi-6-amino-β–cyclodextrin with polycaprolactone. Furthermore, some physicochemical, toxicological and absorption properties were predicted using bioinformatics tools. The electronic, geometrical and spectroscopical calculated properties agree with the properties obtained via experimental methods, explaining the behaviors observed in each case. The interaction energy was obtained, and its values were −60.6, −20.9 and −17.1 kcal/mol for β–cyclodextrin/polycaprolactone followed by the 6-amino-β–cyclodextrin-polycaprolactone complex and finally the complex of epithelial growth factor anchored to 6-deoxy-6-amino–β–cyclodextrin/polycaprolactone. Additionally, the dipolar moments were calculated, achieving values of 3.2688, 5.9249 and 5.0998 Debye, respectively, and in addition the experimental wettability behavior of the studied materials has also been explained. It is important to note that the toxicological predictions suggested no mutagenic, tumorigenic or reproductive effects; moreover, an anti-inflammatory effect has been shown. Finally, the improvement in the cicatricial effect of the novel materials has been conveniently explained by comparing the poly-caprolactone data obtained in the experimental assessments.

Objectives: Dental treatment in special needs patients, including children with autism, can be accomplished by reducing the behaviors that can reduce fear, as it has been demonstrated in other studies. The present study aims to examine the influence of the latency time elapsing between desensitization and the real dental situation on facilitating the access of children with autism to dental treatment. Study design: Nineteen patients with autism, who were aged 3–14 years and attended the Special Education Center in Madrid but were living with their parents at home, were selected for the study. All children in the sample were subjected to a desensitization process before attending the real dental office. Two study groups were established: the latency period between the last desensitization and the real situation was one day for the first group and seven days for the second group. An experimental study was conducted to assess the child’s cooperation in the dental chair; the dental examination was divided into several steps and the highest step reached by each child was recorded. Results: There is a statistical difference in the number of steps reached between the children who received the information just before the examination date and the children who experienced a longer latency period between receiving the information and experiencing the examination. Conclusions: We would like to emphasize the importance of providing information in advance when dealing with autistic children; this information should be as close as possible to the real situation. Additionally, we would like to stress the importance of inter-cooperation between parents, educators, and pediatric dentists in order to guarantee adequate oro-dental care for autistic children. Further studies with larger sample sizes and a control group are recommended.

Adenosine triphosphate (ATP) determination has been used for many decades to assess microbial contamination for hygiene monitoring in different locations and workplace environments. Highly sophisticated methods have been reported, yet commercially available kits rely on a luciferase–luciferin system and require storage and shipping at controlled temperatures (+4 or −20 °C). The applicability of these systems is limited by the need for a secure cold chain, which is not always applicable, especially in remote areas or low-resource settings. In this scenario, easy-to-handle and portable sensors would be highly valuable. Prompted by this need, we developed a bioluminescence paper biosensor for ATP monitoring in which a new luciferase mutant was combined with a metal–organic framework (MOF); i.e., zeolitic imidazolate framework-8 (ZIF-8). A paper biosensor was developed, ZIF-8@Luc paper sensor, and interfaced with different portable light detectors, including a silicon photomultiplier (SiPM) and smartphones. The use of ZIF-8 not only provided a five-fold increase in the bioluminescence signal, but also significantly improved the stability of the sensor, both at +4 and +28 °C. The ATP content in complex biological matrices was analyzed with the ZIF-8@Luc paper sensor, enabling detection down to 7 × 10−12 moles of ATP and 8 × 10−13 moles in bacterial lysates and urine samples, respectively. The ZIF-8@Luc sensor could, therefore, be applied in many fields in which ATP monitoring is required such as the control of microbial contamination.

The objective of this study is to identify the usage of ICT tools among social educators within their professional activity. Technology among social educators is currently a very up-to-date topic. This is a professional group with its own characteristics that are different from those of teachers or other professionals in formal education. A mixed sequential two-phase method was proposed for the study: both quantitative and qualitative. In the first phase, the EdSocEval_V2 questionnaire was applied to a sample of 504 social educators from 17 autonomous communities. In the second phase, four focus groups were formed. The results presented reduced and basic usage of ICT: in management and administrative tasks and for communication with conventional tools. The COVID-19 pandemic has likewise increased the need for the use of ICT in socio-educational interventions, although their use for intervention among these groups is still very scarce. Training in and raising awareness of ICT among professionals for social interventions are priorities, as is the construction of a referential framework for professional training.

In this work, titanium dioxide scaffolds were synthesized. Titanium isopropoxide (IV) was used as a precursor in its formation, using a polymeric network of galactopyranose as a template. The powder sample obtained was evaluated by scanning tunneling microscopy (STM), transmission electron microscopy (TEM), X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) analysis, and thermal gravimetric analysis (TGA-DTA). According to the results, it was found that these scaffolds can be successfully synthesized in solution using the sol-gel method. The synthesized scaffolds have diameters from 50 nm with porosity of approximately 0.3–10 nm. Important parameters, such as pH and the concentration of the metallic precursors, were optimized in this solution. The values of maximum average roughness R(max) and roughness value (Ra) were 0.50 and 1.45, respectively. XRD diffraction analysis shows the formation of crystalline phases in the TiO2 scaffold at 700 °C. The use of biological polymers represents an alternative for the synthesis of new materials at low cost, manipulating the conditions in the production processes and making the proposed system more efficient.

It is not known whether sequential outpatient parenteral antimicrobial (OPAT) is as safe and effective as conventional hospitalization in patients with S. aureus bacteremia (SAB). A post-hoc analysis of the comparative effectiveness of conventional hospitalization versus sequential OPAT was performed in two prospective Spanish cohorts of patients with S. aureus bacteremia. The PROBAC cohort is a national, multicenter, prospective observational cohort of patients diagnosed in 22 Spanish hospitals between October 2016 and March 2017. The DOMUS OPAT cohort is a prospective observational cohort including patients from two university hospitals in Seville, Spain from 2012 to 2021. Multivariate regression was performed, including a propensity score (PS) for receiving OPAT, stratified analysis according to PS quartiles, and matched pair analyses based on PS. Four hundred and thirteen patients were included in the analysis: 150 in sequential OPAT and 263 in the full hospitalization therapy group. In multivariate analysis, including PS and center effect as covariates, 60-day treatment failure was lower in the OPAT group than in the full hospitalization group (p < 0.001; OR 0.275, 95%CI 0.129–0.584). In the PS-based matched analyses, sequential treatment under OPAT was not associated with higher 60-day treatment failure (p = 0.253; adjusted OR 0.660; % CI 0.324–1.345). OPAT is a safe and effective alternative to conventional in-patient therapy for completion of treatment in well-selected patients with SAB, mainly those associated with a low-risk source and without end-stage kidney disease.

The scarcity of energy and water resources and rising temperatures due to climate change has set the focus on improving the energy efficiency of power plant thermodynamic cycles to adapt to higher heat sink temperatures and use fewer resources for energy production. In this work, a review of power production thermodynamic cycles is presented: from Brayton to Rankine and combined cycles, alongside particular cycles such as Organic Rankine Cycles, Kalina, Goswami or the more recently developed Hygroscopic Cycle. The efficiency of these cycles and their possible improvements are considered, as well as their environmental impact. Costs associated with existing power plants found in the literature have also been included in the study. The main existing facilities for each cycle type are assessed, and the most sustainable options in terms of resource consumption (fuel, water, etc.) and future perspectives to ensure both their energy efficiency and sustainability are identified.

The reconciliation of societies in negotiated transitions from civil war to peace represents a practical challenge. While the political dimension concerns the construction of socio-political relations, the interpersonal dimension focuses on intergroup relationships. Empirical evidence shows that reconciliation should not assign primacy to one dimension over another; rather, it should address the interaction between them. However, research on this topic is scarce. There is a need to develop an instrument to assess the political and interpersonal dimensions of reconciliation in peacebuilding contexts. This study developed the Political and Interpersonal Reconciliation Scale (PIRS) and assessed its psychometric properties based on a sample of Colombian population after the peace agreement between the Colombian government and the FARC guerrilla group. The results show the validity of a factorial structure for two components as well as an acceptable Cronbach’s alpha. Concerning external validity, in line with the existing literature, the scale under study was positively related to confidence in the peace agreement, trust in the ex-combatants, willingness to share with the adversary and community identification. This study provides evidence that the Political and Interpersonal Reconciliation Scale is a valid and reliable instrument for evaluating reconciliation in peacebuilding contexts.

The availability of new bioluminescent proteins with tuned properties, both in terms of emission wavelength, kinetics and protein stability, is highly valuable in the bioanalytical field, with the potential to improve the sensitivity and analytical performance of the currently used methods for ATP detection, whole-cell biosensors, and viability assays among others. We present a new luciferase mutant, called BgLuc, suitable for developing whole-cell biosensors and in vitro biosensors characterized by a bioluminescence maximum of 548 nm, narrow emission bandwidth, favorable kinetic properties, and excellent pH- and thermo-stabilities at 37 and 45 °C and pH from 5.0 to 8.0. We assessed the suitability of this new luciferase for whole-cell biosensing with a cell-based bioreporter assay for Nuclear Factor-kappa B (NF-kB) signal transduction pathway using 2D and 3D human embryonic kidney (HEK293T) cells, and for ATP detection with the purified enzyme. In both cases the luciferase showed suitable for sensitive detection of the target analytes, with better or similar performance than the commercial counterparts.

We have previously reported the presence of m6A in the AMV (Alfamovirus, Bromoviridae) genome. Interestingly, two of these putative m6A-sites are in hairpin (hp) structures in the 3’UTR of the viral RNA3. One site (2012AAACU2016) is in the loop of hpB, within the coat protein binding site 1 (CPB1), while the other (1900UGACC1904) is in the lower stem of hpE, a loop previously associated with AMV negative-strand RNA synthesis. In this work, we have performed in vivo experiments to assess the role of these two regions, containing the putative m6A-sites in the AMV cycle, by introducing compensatory point mutations to interfere with or abolish the m6A-tag of these sites. Our results suggest that the loop of hpB could be involved in viral replication/accumulation. Meanwhile, in the 1900UGACC1904 motif of the hpE, the maintenance of the adenosine residue and the lower stem hpE structure are necessary for in vivo plus-strand accumulation. These results extend our understanding of the requirements for hpE in the AMV infection cycle, indicating that both the residue identity and the base-pairing capacity in this structure are essential for viral accumulation.

We consider the effective evolution of a phenomenological model from FLRW supersymmetric quantum cosmology with a scalar field. The scalar field acts as a clock and inflaton. We examine a family of simple superpotentials that produce an inflation whose virtual effect on inhomogeneous fluctuations shows very good agreement with PLANCK observational evidence for the tensor-to-scalar ratio and the scalar spectral index.

Epigenetic modifications could drive some of the molecular events implicated in proliferation, drug resistance and metastasis of pancreatic ductal adenocarcinoma (PDAC). Thus, epigenetic enzyme inhibitors could be the key to revert those events and transform PDAC into a drug-sensitive tumor. We performed a systematic study with five different epigenetic enzyme inhibitors (1, UVI5008, MS275, psammaplin A, and BIX01294) targeting either Histone Deacetylase (HDAC) 1 or 1/4, DNA methyltransferase 3a (DNMT3a), Euchromatic histone lysine methyltransferase 2 (EHMT2), or Sirtuin 1 (SIRT1), as well as one drug that restores the p53 function (P53R3), in three different human PDAC cell lines (SKPC-1, MIA PaCa-2, and BxPC-3) using 2D and 3D cell cultures. The synergistic effect of these antitumoral drugs with gemcitabine was tested and the most efficient combinations were characterized by RNA-seq. The inhibition of HDAC1/4 (MS275), HDAC1/4/SIRT1/DNMT3a (UVI5008) or EHMT2 (BIX01294) induced a significant reduction on the cell viability, even in gemcitabine-resistance cells. The combination of UVI5008 or MS275 with gemcitabine induced a synergistic effect at low concentration and the RNA-Seq analysis revealed some synergy candidate genes as potential biomarkers. Reverting aberrant epigenetic modifications in combination with gemcitabine offers an alternative treatment for PDAC patients, with an important reduction of the therapeutic dose.

Community-onset bloodstream infections (CO-BSI) caused by gram-negative bacilli are common and associated with significant mortality; those caused by Pseudomonas aeruginosa are associated with worse prognosis and higher rates of inadequateempirical antibiotic treatment. The aims of this study were to describe the characteristics of patients with CO-BSI caused by P. aeruginosa, to identify predictors, and to develop a predictive score for P. aeruginosa CO-BSI. Materials/methods: PROBAC is a prospective cohort including patients >14 years with BSI from 26 Spanish hospitals between October 2016 and May 2017. Patients with monomicrobial P. aeruginosa CO-BSI and monomicrobial Enterobacterales CO-BSI were included. Variables of interest were collected. Independent predictors of Pseudomonas aeruginosa CO-BSI were identified by logistic regression and a prediction score was developed. Results: A total of 78patients with P. aeruginosa CO-BSI and 2572 with Enterobacterales CO-BSI were included. Patients with P. aeruginosa had a median age of 70 years (IQR 60–79), 68.8% were male, median Charlson score was 5 (IQR 3–7), and 30-daymortality was 18.5%. Multivariate analysis identified the following predictors of CO-BSI-PA [adjusted OR (95% CI)]: male gender [1.89 (1.14–3.12)], haematological malignancy [2.45 (1.20–4.99)], obstructive uropathy [2.86 (1.13–3.02)], source of infection other than urinary tract, biliary tract or intra-abdominal [6.69 (4.10–10.92)] and healthcare-associated BSI [1.85 (1.13–3.02)]. Anindex predictive of CO-BSI-PA was developed; scores ≥ 3.5 showed a negative predictive value of 89% and an area under the receiver operator curve (ROC) of 0.66. Conclusions: We did not find a good predictive score of P. aeruginosa CO-BSI due to its relatively low incidence in the overall population. Our model includes variables that are easy to collect in real clinical practice and could be useful to detect patients with very low risk of P. aeruginosa CO-BSI.

Biodegradable polymers of natural origin are ideal for the development of processes in tissue engineering due to their immunogenic potential and ability to interact with living tissues. However, some synthetic polymers have been developed in recent years for use in tissue engineering, such as Poly-ε-caprolactone. The nanotechnology and the electrospinning process are perceived to produce biomaterials in the form of nanofibers with diverse unique properties. Biocompatibility tests of poly-ε-caprolactone nanofibers embedded with hydroxyapatite and alumina nanoparticles manufactured by means of the electrospinning technique were carried out in Wistar rats to be used as oral dressings. Hydroxyapatite as a material is used because of its great compatibility, bioactivity, and osteoconductive properties. The PCL, PCL-HA, PCL-α-Al2O3, and PCL-HA-α-Al2O3 nanofibers obtained in the process were characterized by infrared spectroscopy and scanning electron microscopy. The nanofibers had an average diameter of (840 ± 230) nm. The nanofiber implants were placed and tested at 2, 4, and 6 weeks in the subcutaneous tissue of the rats to give a chronic inflammatory infiltrate, characteristic foreign body reaction, which decreased slightly at 6 weeks with the addition of hydroxyapatite and alumina ceramic particles. The biocompatibility test showed a foreign body reaction that produces a layer of collagen and fibroblasts. Tissue loss and necrosis were not observed due to the coating of the material, but a slight decrease in the inflammatory infiltrate occurred in the last evaluation period, which is indicative of the beginning of the acceptance of the tested materials by the organism.

The bacterial SAR324 cluster is ubiquitous and abundant in the ocean, especially around hydrothermal vents and in the deep sea, where it can account for up to 30% of the whole bacterial community. According to a new taxonomy generated using multiple universal protein-coding genes (instead of the previously used 16S rRNA single gene marker), the former Deltaproteobacteria cluster SAR324 has been classified since 2018 as its own phylum. Yet, very little is known about its phylogeny and metabolic potential. We downloaded all publicly available SAR324 genomes (65) from all natural environments and reconstructed 18 new genomes using publicly available oceanic metagenomic data and unpublished data from the waters underneath the Ross Ice Shelf. We calculated a global SAR324 phylogenetic tree and identified six clusters (namely 1A, 1B, 2A, 2B, 2C and 2D) within this clade. Genome annotation and metatranscriptome read mapping showed that SAR324 clades possess a flexible array of genes suited for survival in various environments. Clades 2A and 2C are mostly present in the surface mesopelagic layers of global oceans, while clade 2D dominates in deeper regions. Our results show that SAR324 has a very versatile and broad metabolic potential, including many heterotrophic, but also autotrophic pathways. While one surface water associated clade (2A) seems to use proteorhodopsin to gain energy from solar radiation, some deep-sea genomes from clade 2D contain the complete Calvin–Benson–Bassham cycle gene repertoire to fix carbon. This, in addition to a variety of other genes and pathways for both oxic (e.g., dimethylsulfoniopropionate degradation) and anoxic (e.g., dissimilatory sulfate reduction, anaerobic benzoate degradation) conditions, can help explain the ubiquitous presence of SAR324 in aquatic habitats.

Evidence suggests that pregnant women are at a higher risk of complications compared to the general population when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the reasons that lead them to need intensive care are not clear. This is a prospective multicenter study of SARS-CoV-2 positive pregnant women, registered by the Spanish Obstetric Emergency Group, with the objective to define the characteristics of the mothers who were admitted to the Intensive Care Unit (ICU) and to investigate the causes and risk factors for ICU admission. A total of 1347 infected pregnant women were registered and analyzed, of whom, 35 (2.6%) were admitted to the ICU. No differences in maternal characteristics or comorbidities were observed between ICU and non-ICU patients, except for in vitro fertilization and multiple pregnancies. The main causes of admission to the ICU were non-obstetric causes (worsening of the maternal condition and respiratory failure due to SARS-CoV-2 pneumonia, 40%) and a combination of coronavirus disease 2019 (COVID-19) symptoms and obstetrical complications (31.4%). The multivariable logistic analysis confirmed a higher risk of ICU admission when pre-eclampsia or hemorrhagic events coexist with pneumonia. The incidence of thromboembolic events and disseminated intravascular coagulation were also significantly higher among patients admitted to the ICU. Therefore, surveillance and rapid intervention should be intensified in SARS-CoV-2 infected pregnant women with the mentioned risk factors and complications. Emphasis should always be placed on anticoagulant therapy in these patients due to the increased thromboembolic risk, C-section surgery and immobilization in the ICU.

Procyanidins are bioactive molecules with industrial and pharmaceutical relevance, they are present in recalcitrant agro-industrial wastes that are difficult to degrade. In this study, we evaluated the potential consumption of procyanidins from Aspergillus niger and Trichoderma harzianum strains in submerged fermentations. For this purpose, a culture medium containing salts, glucose, and procyanidins was formulated, where procyanidins were added to the medium after the near-total consumption of glucose. The submerged cultures were carried out in amber flasks at 30 °C and 120 rpm. The addition of procyanidins to the culture medium increased the formation of micellar biomass for all the strains used. The use of glucose affected the growth of A. niger GH1 and A. niger HS1, however, in these assays, a total consumption of procyanidins was obtained. These results show that the consumption of procyanidins by fungal strains in submerged fermentations was influenced by the pH, the use of glucose as the first source of carbon, and the delayed addition of procyanidins to the medium. The study showed that A. niger and T. harzianum strains can be used as a natural strategy for the consumption or removal of procyanidins present in recalcitrant residues of risk to the environment and human health.

Objectives: Vaginal and endocervical infections are considered a global health problem, especially after recent evidence of their association with preterm delivery and other adverse obstetric outcomes. Still, there is no consensus on the efficacy of a screening strategy for these infections in the first trimester of pregnancy. This study evaluated their prevalence and whether screening and treatment resulted as effective in reducing pregnancy and perinatal complications. Methods: A single-center prospective observational study was designed; a sample size of 400 first-trimester pregnant women was established and they were recruited between March 2016–October 2019 at the Puerta de Hierro University Hospital (Spain). They were screened for vaginal and endocervical infections and treated in case of abnormal flora. Pregnancy and delivery outcomes were compared between abnormal and normal flora groups by univariate analysis. Results: 109 patients had an abnormal flora result (27.2%). The most frequently detected infection was Ureaplasma urealyticum (12.3%), followed by Candida spp. (11.8%), bacterial vaginosis (5%), Mycoplasma hominis (1.2%) and Trichomonas vaginalis (0.8%). Patients with abnormal flora had a 5-fold increased risk of preterm premature rupture of membranes (5.3% vs. 1.1% of patients with normal flora, Odds Ratio 5.11, 95% Confidence Interval 1.20–21.71, p = 0.028). No significant differences were observed regarding preterm delivery or neonatal morbidity. Conclusions: Considering the morbimortality related to prematurity and that the results of our study suggest that the early treatment of abnormal flora could improve perinatal outcomes, the implementation of a screening program during the first trimester should be considered.

Pregnant women are particularly vulnerable to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. In addition to unfavorable perinatal outcomes, there has been an increase in obstetric interventions. With this study, we aimed to clarify the reasons, using Robson’s classification model, and risk factors for cesarean section (C-section) in SARS-CoV-2-infected mothers and their perinatal results. This was a prospective observational study that was carried out in 79 hospitals (Spanish Obstetric Emergency Group) with a cohort of 1704 SARS-CoV-2 PCR-positive pregnant women that were registered consecutively between 26 February and 5 November 2020. The data from 1248 pregnant women who delivered vaginally (vaginal + operative vaginal) was compared with those from 456 (26.8%) who underwent a C-section. C-section patients were older with higher rates of comorbidities, in vitro fertilization and multiple pregnancies (p < 0.05) compared with women who delivered vaginally. Moreover, C-section risk was associated with the presence of pneumonia (p < 0.001) and 41.1% of C-sections in patients with pneumonia were preterm (Robson’s 10th category). However, delivery care was similar between asymptomatic and mild–moderate symptomatic patients (p = 0.228) and their predisposing factors to C-section were the presence of uterine scarring (due to a previous C-section) and the induction of labor or programmed C-section for unspecified obstetric reasons. On the other hand, higher rates of hemorrhagic events, hypertensive disorders and thrombotic events were observed in the C-section group (p < 0.001 for all three outcomes), as well as for ICU admission. These findings suggest that this type of delivery was associated with the mother’s clinical conditions that required a rapid and early termination of pregnancy.

We study two homogeneous supersymmetric extensions for the f(R) modified gravity model of Starobinsky with the FLRW metric. The actions are defined in terms of a superfield R that contains the FLRW scalar curvature. One model has N = 1 local supersymmetry, and its bosonic sector is the Starobinsky action; the other action has N = 2, its bosonic sector contains, in additional to Starobinsky, a massive scalar field without self-interaction. As expected, the bosonic sectors of these models are consistent with cosmic inflation, as we show by solving numerically the classical dynamics. Inflation is driven by the R2 term during the large curvature regime. In the N = 2 case, the additional scalar field remains in a low energy state during inflation. Further, by means of an additional superfield, we write equivalent tensor-scalar-like actions from which we can give the Hamiltonian formulation.

Complex engineering challenges are revealed in the wind industry; one of them is erosion at the leading edge of wind turbine blades. Water jet erosive wear tests on carbon-fiber reinforced polymer (CFRP) and glass-fiber reinforced polymer (GFRP) were performed in order to determine their resistance at the conditions tested. Vacuum Infusion Process (VIP) was used to obtain the composite materials. Eight layers of bidirectional carbon fabric (0/90°) and nine glass layers of bidirectional glass cloth were used to manufacture the plates. A water injection platform was utilized. The liquid was projected with a pressure of 150 bar on the surface of the specimens through a nozzle. The samples were located at 65 mm from the nozzle at an impact angle of 75°, with an exposure time of 10, 20 and 30 min. SEM and optical microscopy were used to observe the damage on surfaces. A 3D optical profilometer helped to determine the roughness and see the scar profiles. The results showed that the volume loss for glass fiber and carbon fiber were 10 and 19 mm3, respectively. This means that the resistance to water jet erosion in uncoated glass fiber was approximately two times lower than uncoated carbon fiber.

Pregnant women who are infected with SARS-CoV-2 are at an increased risk of adverse perinatal outcomes. With this study, we aimed to better understand the relationship between maternal infection and perinatal outcomes, especially preterm births, and the underlying medical and interventionist factors. This was a prospective observational study carried out in 78 centers (Spanish Obstetric Emergency Group) with a cohort of 1347 SARS-CoV-2 PCR-positive pregnant women registered consecutively between 26 February and 5 November 2020, and a concurrent sample of PCR-negative mothers. The patients’ information was collected from their medical records, and the association of SARS-CoV-2 and perinatal outcomes was evaluated by univariable and multivariate analyses. The data from 1347 SARS-CoV-2-positive pregnancies were compared with those from 1607 SARS-CoV-2-negative pregnancies. Differences were observed between both groups in premature rupture of membranes (15.5% vs. 11.1%, p < 0.001); venous thrombotic events (1.5% vs. 0.2%, p < 0.001); and severe pre-eclampsia incidence (40.6 vs. 15.6%, p = 0.001), which could have been overestimated in the infected cohort due to the shared analytical signs between this hypertensive disorder and COVID-19. In addition, more preterm deliveries were observed in infected patients (11.1% vs. 5.8%, p < 0.001) mainly due to an increase in iatrogenic preterm births. The prematurity in SARS-CoV-2-affected pregnancies results from a predisposition to end the pregnancy because of maternal disease (pneumonia and pre-eclampsia, with or without COVID-19 symptoms).

Continuous authentication systems have been proposed as a promising solution to authenticate users in smartphones in a non-intrusive way. However, current systems have important weaknesses related to the amount of data or time needed to build precise user profiles, together with high rates of false alerts. Voice is a powerful dimension for identifying subjects but its suitability and importance have not been deeply analyzed regarding its inclusion in continuous authentication systems. This work presents the S3 platform, an artificial intelligence-enabled continuous authentication system that combines data from sensors, applications statistics and voice to authenticate users in smartphones. Experiments have tested the relevance of each kind of data, explored different strategies to combine them, and determined how many days of training are needed to obtain good enough profiles. Results showed that voice is much more relevant than sensors and applications statistics when building a precise authenticating system, and the combination of individual models was the best strategy. Finally, the S3 platform reached a good performance with only five days of use available for training the users’ profiles. As an additional contribution, a dataset with 21 volunteers interacting freely with their smartphones for more than sixty days has been created and made available to the community.

Polycaprolactone (PCL) is a well-known FDA approved biomaterial for tissue engineering. However, its hydrophobic properties limit its use for skin wound healing which makes its functionalization necessary. In this work, we present the fabrication and evaluation of PCL nanofibers by the electrospinning technique, as well as PCL functionalized with 6-deoxy-6-amino-β-cyclodextrin (aminated nanofibers). Afterwards, epithelial growth factor (EGF) was anchored onto hydrophilic PCL/deoxy-6-amino-β-cyclodextrin. The characterization of the three electrospun fibers was made by means of field emission scanning electron microscopy (FESEM), Fourier transform infrared spectroscopy-attenuated total reflectance (FTIR-ATR); Confocal-Raman Spectroscopy were used for elucidated the chemical structure, the hydrophilicity was determined by Contact Angle (CA). In vitro cell proliferation test was made by seeding embryonic fibroblast cell line (3T3) onto the electrospun mats and in vivo studies in a murine model were conducted to prove its effectivity as skin wound healing material. The in vitro studies showed that aminated nanofibers without and with EGF had 100 and 150% more cell proliferation of 3T3 cells against the PCL alone, respectively. In vivo results showed that skin wound healing in a murine model was accelerated by the incorporation of the EGF. In addition, the EGF had favorable effects in epidermal cell proliferation. The study demonstrates that a protein of high biological interest like EGF can be attached covalently to the surface of a synthetic material enriched with amino groups. This kind of biomaterial has a great potential for applications in skin regeneration and wound healing.

Web platforms are gaining relevance in eHealth, where they ease the interaction between patients and clinician. However, some clinical fields, such as the cardiovascular one, still need more effort because cardiovascular diseases are the principal cause of death and medical resources expenditure worldwide. The lack of daily control is the main reason hypertension is a current health problem, and medical web services could improve this situation. To face this challenge, this work proposes a novel intelligent web-based ecosystem, called SENIOR, capable of predicting adverse blood pressure events. The innovation of the SENIOR ecosystem relies on a wearable device measuring patient’s biomarkers such as blood pressure, a mobile application acquiring patient’s information, and a web platform consulting environmental services, processing data, and predicting blood pressure. The second contribution of this work is to consider novel environmental features based on the users’ location, such as climate and pollution data, to increase the knowledge about known variables affecting hypertension. Finally, our last contribution is a proof of concept with several machine learning algorithms predicting blood pressure values both in real-time and future temporal windows within one day has demonstrated the suitability of SENIOR.

This study evaluates the capacity of four hydrolytic enzymes to limit the interactions between grape cell-walls and tannins and/or to favor tannin desorption. Adsorption and desorption tests were conducted by mixing a commercial seed tannin with purified skin cell-walls from Syrah grapes, in the presence or absence of hydrolytic enzymes, in a model-wine solution. The effects of the enzymes were evaluated by measuring the tannins in solution by High Performance Liquid Chromatography (HPLC) and the changes in the cell wall polysaccharide network by Comprehensive Microarray Polymer Profiling (COMPP) while the polysaccharides liberated from cell walls were analyzed by Size Exclusion Chromatography (SEC). The results showed that the enzymes limited the interaction between tannins and cell walls, especially cellulase, pectinase and xylanase, an effect associated with the cell wall structural modifications caused by the enzymes, which reduced their capacity to bind tannins. With regards to the tannin desorption process, enzymes did not play a significant role in liberating bound tannins. Those enzymes that showed the highest effect in limiting the adsorption of tannins and in disorganizing the cell wall structure, cellulase and pectinase, did not lead to a desorption of bound tannins, although they still showed a capacity of affecting cell wall structure. The results indicate that enzymes are not able to access those polysaccharides where tannins are bound, thus, they are not a useful tool for desorbing tannins from cell walls. The practical importance implications of these findings are discussed in the manuscript.

We discuss quantum time states formed with a finite number of energy eigenstates with the purpose of obtaining a time coordinate. These time states are eigenstates of the recently introduced discrete time operator. The coordinate and momentum representations of these time eigenstates resemble classical time curves and become classical at high energies. To illustrate this behavior, we consider the simple example of the particle-in-a-box model. We can follow the quantum-classical transition of the system. Among the many existing solutions for the particle in a box, we use a set which leads to time eigenstates for use as a coordinate system.