Portugal’s EPAC silo network, initially planned in the 1930s but constructed and utilized primarily in the 1970s, consisted of 31 silos with a total capacity of 841,100 t. The network’s usage declined, however, due to market liberalization and Portugal’s accession to the European Economic Community in 1985. This study focuses on adapting a methodology to inventory and analyse the 31 silos in the EPAC network considering their general features, construction, technological facilities, and socioeconomic aspects. The silos are situated in 30 cities and towns, predominantly in the country’s key grain-growing regions, particularly the Alentejo region. While there are variations in design and construction, most EPAC silos contain two or three rows of circular reinforced-concrete cells and use the spaces between cells for storage. Their capacities range from 6,000 to 35,000 t. Some are inland grain reception and storage silos, while others are larger-capacity port silos designed to unload grain rapidly onto ships using mechanical or pneumatic unloaders. These structures are a significant part of Portugal’s agro-industrial heritage and have in some cases been repurposed as museums or event venues. Compared to other agro-industrial buildings, silos pose unique conversion challenges due to their height and design complexities. Examples of successful reuse in countries like Spain and Italy may provide insights for potential silo projects in Portugal. However, analysis suggests that such proposals and similar initiatives may be viable only in the more highly populated towns.

The intensive variables, geochemical, mineralogical and petrogenetic constraints of the Iberian rare metal granites, many of them unknown, are presented. It allows to distinguish two main granitic types with contrasting characteristics: Nb-Ta-rich granites and Nb-Ta-poor granites. The former have lower emplacement temperatures, higher water contents and probably lower emplacement pressures than Nb-Ta-poor granites. Nb-Ta-rich granites also have higher fluoride contents, strong fractionation into twin pairs such as Zr-Hf, Y-Ho and Nb-Ta, and an abundant, probably exsolved, fluid phase, which is not or not as evident in Nb-Ta-poor granites, probably in part because the Nb-Ta-rich granites reach their solidus later (about 550 ºC). The geochemical signature of the Iberian rare metal granites follows the trends of mainly two-mica granites and P-rich cordierite granites, but also of granodiorites and even type I granites, suggesting that the rare metal granites may have different parental magmas. Thermodynamic modeling shows that many of the geochemical characteristics of the RMGs can be explained by a process of extreme differentiation, while others cannot, e.g. Na evolution. In terms of ore deposition, white mica plays a very important role in explaining the variation of the Ta/Nb ratio, although the latter could also be controlled by late Nb-Ta oxides crystallization and even by acidic fluids that remove Nb relative to Ta from earlier Nb-Ta oxides.

HPV vaccine induces a herd immunity effect in genital warts when a large number of the population is vaccinated. That aspect should be taken into account when devising new vaccine strategies, like vaccination at older ages or male vaccination. Therefore it is important to develop mathematical models with good predictive capacities. We devised a sexual contact network that was calibrated to simulate the Spanish epidemiology of different HPV genotypes. Through this model we simulated the scenario that occurred in Australia in 2007, where 12-13 year-old girls where vaccinated with a three-dose schedule of a vaccine containing genotypes 6 and 11, that protect against genital warts, and also a catch-up program in women up to 26 years of age. Vaccine coverage were 73 % in girls with three doses and with coverage rates decreasing with age until 52 % for 20-26 year-olds. A fast 59 % reduction in the genital warts diagnoses occurred in the model in the first years after the start of the program, similar to what was described in the literature.

The search for a continuous continental record of interglacial periods in semi-arid regions is problematic due to the absence of stable and continuous sedimentary systems over time in this type of climate. In this work, a relatively stable basin is described and analyzed during the last interglacial in a semi-arid region of the western Mediterranean. For this purpose a geomorphological, stratigraphic and sedimentological study has been carried out, with dating through 230Th. A semi-endorrheic Pleistocene basin has been identified, with two units that correspond to a fluvial-lacustrine system (unit P1) and an alluvial system (unit P2). Unit P1 has been dated in the MIS 5e interglacial episode. A framework is described in which the Aljezares Quaternary basin can be considered as a possible source of paleoenvironmental and paleoclimatic information in semi-arid regions from the last interglacial period in future studies.

It is known that high N doses, N/K imbalances, and frequent irrigation favor verticillium wilt. The influence of fertilization and its interaction with the frequency of irrigation on the development of Verticillium wilt of olive (VWO) has been evaluated. A split-split-plot design in microplots with two naturally infested soils of different texture was established for studying three fertilization treatments (NO3Ca, N-P-K and without fertilization), plus two irrigation frequencies (daily and deficit). The treatments were applied by means of fertigation, evaluating the susceptible cultivar Picual. Final disease incidence in plants subjected to NO3Ca-daily treatment was 100% regardless soil texture. However, final mortality in these plants was 37% and 85.2% in clay and sandy loam soils, respectively. As well, the area under the disease progress curve values were significantly higher (49.1%) in plants subjected to NO3Ca fertilization compared to those not fertilized or fertilized with N-P-K when plants grown in clay soil. This value in the sandy loam soil was significantly higher in the NO3Ca-daily irrigation treatment (94.3%), followed by the N-P-K-daily treatment (61.1%) which also was significantly higher than the unfertilized-daily, N-deficit and NPK-deficit treatments (37.8, 42.6 and 44.9 %, respectively). The plants submitted to unfertilized-deficit treatment reached the lowest value 9.6%. In this work it can be concluded that the application of fertilizer or the application of fertilizer with daily frequency irrigations in naturally infested soils increases the development of VWO in 'Picual'.

This paper shows the development of a simultaneous tri-band (S: 2.2 - 2.7 GHz, X: 7.5 - 9 GHz and Ka: 28 - 33 GHz) low-noise cryogenic receiver for geodetic Very Long Baseline Interferometry (geo-VLBI) which has been developed by the technical staff of Yebes Observatory (IGN) laboratories in Spain. The receiver was installed in the first radio telescope of the Red Atlántica de Estaciones Geodinámicas y Espaciales (RAEGE) project, which is located in Yebes Observatory, in the frame of the VLBI Global Observing System (VGOS). After this, the receiver was borrowed by the Norwegian Mapping Autorithy (NMA) for the commissioning of two VGOS radiotelescopes in Svalbard (Norway). A second identical receiver was built for the Ishioka VGOS station of the Geospatial Information Authority (GSI) of Japan, and a third one for the second RAEGE VGOS station, located in Santa María (Açores Archipelago, Portugal). The average receiver noise temperatures are 21, 23 and 25 Kelvin and the measured antenna efficiencies are 70%, 75% and 60% in S-band, X-band and Ka-band, respectively.

‘Arrayana’ mandarin fruits have a short postharvest life and are sensitive to chilling injury (CI) during cold storage. Brassinosteroids (BR) have been used as a sustainable technology to alleviate CI in fruits and improve postharvest quality. This study evaluated the effect of applying the 24-epibrasinolide analogue (EBR), at doses of 5 mg L-1; DI-31 analogue, at 5 and 10 mg L-1; and control, on the main physical and biochemical characteristics of 'Arrayana' mandarin stored at 4°C for 40 days and, subsequently, 7 days at room temperature (shelf life). The application of EBR and DI-31 analogues reduced the appearance of CI in the exocarp of 'Arrayana' mandarin fruits by reducing electrolyte leakage, maintaining membrane integrity, and increasing antioxidant activity and phenol content at the end of cold storage and shelf life. This was especially pronounced with 5 mg L-1 of EBR. Similarly, the BR maintained the postharvest quality of mandarins by reducing weight loss, respiratory intensity and chlorophyll degradation; increasing β-carotene; and maintaining titratable acidity, and soluble solids. Our research reports for the first time CI tolerance in Arrayana mandarin using natural (EBR) and spirostanic (DI-31), analogues and illustrates the tolerance functionality of the DI-31 analog on CI in fruit postharvest.

A broad spectrum of lesions, including hyperplastic, metaplastic, inflammatory, infectious, and reactive, may mimic cancer all along the urinary tract. This narrative collects most of them from a clinical and pathologic perspective offering urologists and general pathologists their most salient definitory features. Together with classical, well-known, entities such as urothelial papillomas (conventional and inverted), nephrogenic adenoma, polypoid cystitis, fibroepithelial polyp, prostatic-type polyp, verumontanum cyst, xanthogranulomatous inflammation, reactive changes secondary to BCG instillations, schistosomiasis, keratinizing desquamative squamous metaplasia, post-radiation changes, vaginal-type metaplasia, endocervicosis/endometriosis (müllerianosis), malakoplakia, florid von Brunn nest proliferation, cystitis/ureteritis cystica and glandularis, among others, still other cellular proliferations with concerning histological features and poorly understood etiopathogenesis like IgG4-related disease, PEComa, and pseudosarcomatous myofibroblastic proliferations (post-operative spindle cell nodule, inflammatory myofibroblastic tumor), are reviewed. Some of these diagnoses are problematic for urologists, other for pathologists, and still others for both. Interestingly, the right identification of their definitory features will allow their correct diagnoses thus avoiding overtreatment. The literature selected for this review also focuses on the immunohistochemical and/or molecular data useful to delineate prognosis.

The silos built in the 1930s for Italy’s ammasso (obligatory grain stockpile) stood as powerful symbols of the country’s fascist era. Many of them were destroyed in World War II; only a few remain today, and recent demolitions underscore the urgency of their preservation. This study adapts a methodology developed for inventorying Spanish silos based on their general features, construction, technological facilities, and socioeconomic aspects and applies it to the 30 remaining ammasso silos. These silos are located in grain-producing areas near communication routes and are mostly owned by agricultural consortia. Over half of them are disused and in disrepair. All of them have machinery for receiving, storing, and dispatching grain, and most have equipment for cleaning, sorting, weighing, and packaging if needed. These structures are part of Italy’s agro-industrial heritage and should be protected. Some have been made over into commercial spaces, leisure areas, museums, and even homes. Vertical-cell silos are challenging to convert, unlike horizontally-oriented silos and other open-plan agro-industrial buildings. Examples of silo reuse in other countries, such as Spain and Portugal, can offer useful insights for the ammasso silos. However, socio-economic indicators suggest that such projects are most viable in large population centres.

This paper presents new above-ground biomass (AGB) and biomass components equations for seventeen forest species in the temperate forests of northwestern Mexico. A data set corresponding to 1336 destructively sampled oak and pine trees was used to fit the models. Generalized method of moments was used to simultaneously fit systems of equations for biomass components and AGB, to ensure additivity. Additionally, the carbon content of each tree component was calculated by the dry combustion method, in a TOC analyser. The fitted equations accounted for on average 91, 83, 84 and 78% of the observed variance in stem wood and stem bark, branch and foliage biomass, respectively, whereas the total AGB equations explained on average 93% of the total observed variance in AGB. The inclusion of h or d²h as additional predictor in the d-only based equations systems slightly improved estimates of stem wood, stem bark and total above-ground biomass, and greatly improved the estimates produced by the branch and foliage biomass equations. The fitted equations were used to estimate AGB stocks at stand level from a database on growing stock from 429 permanent sampling plots. Three machine-learning techniques were used to model the estimated stand level AGB and carbon contents; the selected models were applied to map the AGB and carbon distributions in the study area, which yielded mean values of 129.84 Mg ha^-1 and 63.80 Mg ha^-1, respectively.

Background: The relationship between adherence to the Mediterranean Diet (MD) and both physical fitness (PF) and physical activity (PA) level has been analysed in several studies. The aim of this research was to describe, compare and analyse the level of PF and PA in schoolchildren aged 6-13 in the Region of Murcia, according to adherence to the MD. Methods: A descriptive and cross-sectional study was performed. A total of 370 schoolchildren (44.9% girls) aged 6-13 (8.7±1.8) from six primary schools in the Region of Murcia (Spain). Results: Only 25.9% of the schoolchildren had optimal adherence to the MD. Regarding the scores of the different PF tests in MD groups, only statistically significant differences were found for CRF (p=0.048) in boys. PA level, showed statistically significant differences in both boys (p=0.040) and girls (p=0.016). A positive relationship was found between the KIDMED index and CRF (ρ=.127), standing broad jump (ρ=.133) and PA level (ρ=.235). A higher probability of having a greater CRF (OR=1.17; CI95%=1.02–1.34) and PA level (OR=7.84; CI95%=2.84–21.60) was found in High MD group. Conclusion: These results suggest that an optimal adherence to the MD is associated with higher CRF and PA level in the selected schoolchildren.

The purpose of this paper is to provide a structural review of the progress made on detection and localization of leaks in pipelines by using approaches based on the Kalman filter. This is, to the best of our knowledge, the first review on the t opic. In particular, it is the first to try to draw the attention of the leak detection community to the important contributions that use the Kalman filter as the core of a computational pipeline monitoring system. Without being exhaustive, we try to gather the results from different research groups and present them in a unified fashion. For this reason, we propose a classification of the current approaches based on the Kalman filter. For each of the existing approaches within this classification, the basic concepts, fundamental results, and relations with the other approaches are discussed in detail. The review starts from a short summary of basic concepts about state observers. Then, a brief history of the use of the Kalman filter for diagnosing leaks is described by mentioning the most outstanding approaches. At last, we briefly discuss some emerging research problems, such as the leak detection in pipelines transporting heavy oils, and we discuss the main challenges and some open problems.

This is an exercise to explore the concentration of Lithium, Lithium-7 isotope and the possible presence of black dirty ice in the lunar surface using spectral data obtained from the Clementine mission. The main interest in tracing the lithium and presence of dark ice in the lunar surface are closely related to future human settlement missions in the Moon. We investigate the distribution of Lithium and 7 Li isotope on the Lunar surface, employing spectral data from the Clementine images. We utilized Visible (VIS-NIR) imagery at wavelengths of 450, 750, 900, 950, and 1000 nm, along with Near-Infrared (NIR-SWIR) at 1100, 1250, 1500, 2000, 2600, and 2780 nm, encompassing 11 bands in total. This dataset offers a comprehensive coverage of about 80% of the lunar surface, with resolutions ranging from 100 to 500 meters, spanning latitudes from 80°S to 80°N. In order to extract quantitative abundance of Lithium, ground truth sites were used to calibrate the Clementine images. Samples (12045, 15058, 15475, 15555, 62255, 70035, 74220 and 75075) returned from Apollo missions 12, 15, 16 and 17 have been correlated to the Clementine VIS-NIR bands and five spectral ratios. The 5 spectral ratios calculated synthesize the main spectral features of sample spectra that were grouped by their Lithium and 7 Li content using Principal Component Analysis. The ratios spectrally characterize substrates of anorthosite, silica-rich basalts, olivine-rich basalts and High-T mare basalts and Orange soils. Our findings reveal a strong linear correlation between the spectral parameters and the lithium content in the 8 Apollo samples. With the values of the 11 Clementine bands and the 5 spectral ratios for each of the 8 lunar soils we performed linear regression models to estimate the concentration of Lithium and 7 Li. Also, we calculated Digital Terrain Models (DTMs; Altitude, Slope, Aspect, DirectInsolation and WindExposition) from LOLA-DTM to discover relations between relief and spatial distribution of the extended models of lithium and 7 Li. The analysis was conducted in a mask polygon extracted from Lunar Orbiter Laser Altimeter (LOLA) and located around the Apollo 15 landing site. This analysis seeks to uncover potential 7 Li enrichment through spallation processes, influenced by varying exposure to solar wind. To explore the possibility of find ice mixed with regolithe (black ice) we used a spectral library (350-2500nm) form ices dirty with different concentration of volcanic particles.

Experimental and epidemiological evidence has shown that modifications of the intrauterine environment can have deleterious consequences for individuals, expressed as an increased risk of suffering non-communicable pathologies in adult life, which is known as the hypothesis of the early origin of diseases or programming fetal. On the other hand, changes in gene expression patterns through epigenetic modifications can be the basis for long-term maintenance of the effects of fetal programming. In this sense, epigenetics comprises the study of intrauterine disturbances, which develop diseases in the adult, including Celiac Disease (CD). In addition, early feeding practices could influence the risk of CD development, such as breastfeeding timing and duration and age at gluten introduction in the diet. Gluten acts as a trigger for CD in genetically predisposed subjects, although approximately 30% of the world population has HLA DQ2 or DQ8, the prevalence of the disease is only 1-3%. It is not known what factors act to modify the risk of disease in genetically at risk subjects. Taking into account all these considerations, the aim of the current review is to elucidate the role of early programming and the effect of early nutrition on the development and progression of CD.

pump as turbine (PAT); computational fluid dynamics; variable rotational nominal speed; OpenFoam.

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by a persistent pattern of inattention and/or hyperactivity-impulsivity. Neurobiologically, ADHD impairments arise from abnormalities in different circuits involving the prefrontal cortex. In face of high rates of diagnosis, alternative/complementary pharmacological therapeutic approaches for ADHD are needed. Although the number of publications that study the potential effects of caf-feine consumption on ADHD treatment have been accumulating over the last years, and caffeine has recently been used in ADHD research in the context of animal models, an updated evi-dence-based systematic review on the effects of caffeine on ADHD-like symptoms in animal stud-ies is missing. To provide insight and value at the preclinical level, a systematic review based on PRISMA guidelines was performed for all publications available up to September 1, 2021. Caffeine treatment increases attention, improves learning, memory and olfactory discrimination, without altering blood pressure and body weight. These results are supported at the neuronal level. Nonetheless, the implication of caffeine in modulating ADHD-like symptoms of hyperactivity and impulsivity is contradictory, raising discrepancies that require further clarification. Our results strengthen the hypothesis that caffeine cognitive effects found in animal models could be trans-lated to human ADHD, particularly during adolescence.

An easier method for the calibration of differential drive robots is presented. Most of the calibration is done on-board and it is not necessary to expend too much time taking note of the robot's position. The calibration method does not need a big free space to perform the tests. The bigger space is just in a straight line, which is easy to find. Results with the proposed method are compared with those from UMB as a reference, and they show very little deviation while the proposed calibration is much simpler.

Trichomes are a common morphological defense against pests, in particular, type IV glandular trichomes have been associated with resistance against different invertebrates. Cultivated tomatoes usually lack or have a very low density of type IV trichomes. Thus, specific breeding programs to incorporate these natural defences, that are common within the Solanum genus, might improve a more sustainable management. We have identified a S. pimpinellifolium accession with very high density of this type of trichomes. Two F2 mapping populations using two different parents have been developed, characterized and genotyped using a new genotype methodology, K-seq. We have been able to build an ultra-dense genetic map with 147,326 markers with an average distance between markers of 0.2 cM that has allowed us to perform a detailed mapping. We have used two different families and two different approaches, QTL mapping and QTL-seq, to identify several QTLs implicated in the control of trichome type IV developed in this accession on the chromosomes 5, 6, 9 and 11. The QTL located on chromosome 9 is a major QTL that has not been previously reported in S. pimpinellifolium that increases by a factor of 9 the density of trichomes.

Sustainability enhancement is one of the main challenges of aquaculture. Since feeds represent one of the major costs from an environmental point of view, it is priority to find sustainable alterna-tive ingredients for aquaculture diet. Insect meals have some advantages as ingredients for aqua-culture, like its sustainability and nutritional value. However, the biggest drawback of full-fat in-sect meal is its fatty acid profile. The objective of this work was to assess the effects of partial plant or marine-derived ingredients replacements with full-fat Tenebrio molitor meal (TM) at two differ-ent levels on growth performance and fatty acids profiles of Solea senegalensis. For this purpose, a control diet and four experimental diets were tested, two of them contained 5 and 10% w/w TM that replaced mostly fish meal. Two other experimental diets included 10 and 15% w/w TM that replaced mostly plant meals. The inclusion of insect meal resulted in an improvement in growth rate and feed efficiency in both cases. Moreover, dietary inclusion of insect meal increased muscle total protein and decreased total lipid, without changes in phospholipids, and maintaining the relative level of n-3 PUFA. In conclusion, our study demonstrated that full-fat TM inclusion up to 15% in S. senegalensis diets had no negative effects or even positive effects on fish survival, growth performance, nutrient utilization and flesh quality.

Given the high number of vehicle-crash victims, it has been established as a priority to reduce this figure in the transportation sector. For this reason, many of the recent researches are focused on including control systems in existing vehicles, to improve their stability, comfort and handling. These systems need to know in every moment the behavior of the vehicle (state variables), among others, when the different maneuvers are performed, to actuate by means of the systems in the vehicle (brakes, steering, suspension) and, in this way, to achieve a good behavior. The main problem arises from the lack of ability to directly capture several required dynamic vehicle variables, such as roll angle, from low-cost sensors. Previous studies demonstrate that low-cost sensors can provide data in real-time with the required precision and reliability. Even more, other research works indicate that neural networks are efficient mechanisms to estimate roll angle. Nevertheless, it is necessary to assess that the fusion of data coming from low-cost devices and estimations provided by neural networks can fulfill the reliability and appropriateness requirements for using these technologies to improve overall safety in production vehicles. Because of the increasing of computing power, the reduction of consumption and electric devices size, along with the high variety of communication technologies and networking protocols using Internet have yield to Internet of Things (IoT) development. In order to address this issue, this study has two main goals: 1) Determine the appropriateness and performance of neural networks embedded in low-cost sensors kits to estimate roll angle required to evaluate rollover risk situations. 2) Compare the low-cost control unit devices (Intel Edison and Raspberry Pi 3 Model B), to provide the roll angle estimation with this artificial neural network-based approach. To fulfil these objectives an experimental environment has been set up composed of a van with two set of low-cost kits, one including a Raspberry Pi 3 Model B, low cost Inertial Measurement Unit (BNO055 - 37€) and GPS (Mtk3339 - 53€) and the other having an Intel Edison System on Chip linked to a SparkFun 9 Degrees of Freedom module. This experimental environment will be tested in different maneuvers for comparison purposes. Neural networks embedded in low-cost sensor kits provide roll angle estimations very approximated to real values. Even more, Intel Edison and Raspberry Pi 3 Model B have enough computing capabilities to successfully run roll angle estimation based on neural networks to determine rollover risks situation fulfilling real-time operation restrictions stated for this problem.

From June 18 to 19, 2013, the Ésera river in the Pyrenees, Northern Spain, caused widespread damage due to flooding as a result of torrential rains and sustained snowmelt. We estimate the contribution of snow melt to total discharge applying a snow energy balance to the catchment. Precipitation is derived from sparse local measurements and the WRF-ARW model over three nested domains, down to a grid cell size of 2 km. Temperature profiles, precipitation and precipitation gradient are well simulated, although with a possible displacement regarding the observations. Snowpack melting was correctly reproduced and verified in three instrumented sites, and according to satellite images. We found that the hydrological simulations agree well with measured discharge. Snowmelt represented 33% of total runoff during the main flood event and 23% at peak flow. The snow energy balance model indicates that most of the energy for snow melt during the day of maximum precipitation came from turbulent fluxes. This approach forecast correctly peak flow and discharge during normal conditions at least 24h in advance and could give an early warning of the extreme event 2.5 days before.

The mucopolysaccharidoses (MPS) are a group of 11 lysosomal storage diseases (LSDs) produced by mutations in the enzymes involved in the lysosomal catabolism of glycosaminoglycans. Most of the mutations affecting these enzymes may lead to changes in processing, folding, glycosylation, pH stability, protein aggregation, and defective transport to the lysosomes. The use of small molecules, called pharmacological chaperones (PCs), that can restore the folding, trafficking and biological activity of mutated enzymes has been extensively explored in LSDs as a therapeutic alternative. PCs have the advantage of wide tissue distribution, potential oral administration, lower production cost, and fewer issues of immunogenicity. In this paper, we will review the advances in the identification and characterization of PCs for the MPS. These molecules, mainly based in molecules mimicking the enzyme substrates, have been described for MPS II, IVA, and IVB, showing a mutation-dependent enhancement of the mutated enzymes. Although the results show the potential of this strategy, further studies should focus in the development of disease-specific cellular models that allow a proper screening and evaluation of the identified PCs. In addition, in vivo evaluation, both pre-clinical and clinical, should be performed, before they can become a real therapeutic strategy for the treatment of MPS patients.

We propose a novel adaptive importance sampling scheme for Bayesian inversion problems where the inference of the variables of interest and the power of the data noise is split. More specifically, we consider a Bayesian analysis for the variables of interest (i.e., the parameters of the model to invert), whereas we employ a maximum likelihood approach for the estimation of the noise power. The whole technique is implemented by means of an iterative procedure, alternating sampling and optimization steps. Moreover, the noise power is also used as a tempered parameter for the posterior distribution of the the variables of interest. Therefore, a sequence of tempered posterior densities is generated, where the tempered parameter is automatically selected according to the actual estimation of the noise power. A complete Bayesian study over the model parameters and the scale parameter can be also performed. Numerical experiments show the benefits of the proposed approach.

One of the IRDiRC goals for 2017-2027 is to achieve definitive diagnosis for rare undiagnosed diseases within one year, as diagnosis delay remains one of the pending issues in the rare diseases field. The Spanish Undiagnosed Rare Diseases Program (SpainUDP) was created in response to this challenging scenario to cover patients’ needs and after seeing the success of the UDP in USA. SpainUDP offers a multidisciplinary approach to those patients who have long sought a diagnosis without any success. During a first phase of the protocol, undiagnosed cases are sent to SpainUDP by individual patients, patient organizations or hospitals. After a carefully analysis of phenotype, data from sequencing experiments (WES) is processed with a standard pipeline and a detailed standardized phenotypic information (mapped to HPO) is connected to genetic data. In addition, the participation of SpainUDP in international initiatives such as the European projects RD-Connect and Solve RD, the Undiagnosed Diseases Network International (UDNI), and the MatchMaker Exchange platform, allows the establishment of a global data sharing strategy across multiple projects submitting data to these international initiatives. From the official beginning of the program (at the end of 2015) until early 2018, 147 cases were accepted in SpainUDP. During this time, 37 cases (25 %) dropped out the program due to several reasons. The remaining 110 cases are distributed as follows: phenotypic and genotypic (WES) characterization was finished in 30 cases, of which 20 (67 %) were diagnosed; 21 cases are pending on variants validation by Sanger; in 25 cases, WES is ongoing and 34 cases are in a deep phenotypic characterization. As a conclusion, SpainUDP aims to achieve a diagnosis following two recommendations of the IRDiRC: the patients’ diagnosis in a period of time as short as possible and the promotion of data sharing (especially genomic) at the international level.

Dietary supplements are commonly used among athletes. The Australian Institute of Sport (AIS) groups supplements into 4 categories, being group D considered by the World Anti-Doping Agency (WADA) as prohibited supplements. The online availability of four doping substances: oxandrolone, dehydroepiandrosterone (DHEA), androstenedione and Tribulus terrestris, purchased from Spain, Puerto Rico, Canada, USA, Ukraine and Russia was evaluated. The characteristics of the websites, the countries the webs sold to, the pharmaceutical forms offered and the recommendations for its use were analyzed by using a computer tool designed ad hoc. There were significant differences between countries in the number of webpages that sold the products (Chi-square test, p<0.05). Oxandrolone was available for purchase mainly in Spain (27.12%) and Ukraine (26.58%), coming from websites dedicated to sports (77.26%). For DHEA, most of the pages were located in Canada (23.34%) and Russia (21.44%). Tribulus terrestris was the compound with the highest number of web pages. In the case of androstenedione, none of the pages for its sale requested prescription. Products such as androstenedione or DHEA are claimed to enhance sports performance or for sports use without providing details. The results showed that a limited number of Internet sites request prescriptions. Most of the doping substances are purchased from the country where they are requested. Athletes should be encouraged to consult health professionals about which supplements are suitable for their type of training and sports objectives.

The ongoing expansion in volume, velocity and variety of geospatial data has stimulated the development of artificial intelligence applications and associated online cartographic visualizations. In this context, the cartographic communication through peer-reviewed media evolved to incorporate Findability, Accessibility, Interoperability and Re-usability (FAIR) principles. In this paper, we review the functionalities proposed by current international peer-reviewed media for accessing, exploring and re-using geospatial data, and situate them on a diagram conceived for peer-reviewed cartography in the artificial intelligence era. We then present an overview of the cartographic infrastructure and workflow currently available in the Terra Digitalis journal for the online publication of massive spatiotemporal data. This free and opensource based solution allows a smooth integration, from data submission to final peer reviewed publication, of dynamic, interactive 2D and 3D maps. As a proof of concept, we present two maps derived from massive spatiotemporal data, related, respectively, to a climate numerical model (raster data) and a bike sharing system’s origin-destination dataset (vector data). We argue that the combination of technologies used in the journal provides an efficient and low-cost solution, unmatched by other publication media, to boost the accessibility and FAIR principles for geospatial big data.

In this work, an evaluation and quantification of the impact of using mixtures based on Supercritical Carbon Dioxide "s-CO2" (s-CO2/COS, s-CO2/H2S, s-CO2/NH3, s-CO2/SO2) are made as a working fluid in simple and complex recompression Brayton s-CO2 power cycles configurations that have pressure drops in their components. These cycles are coupled to a solar thermal plant with parabolic-trough collector (PTC) technology. The methodology used in the calculation performance is to establish values of the heat recuperator total conductance (UAtotal) between 5 and 25 MW/K. The main conclusion of this work is that the cycle's efficiency has improved due to s-CO2 mixtures as working fluid; this is significant compared to that obtained using the standard fluid (pure s-CO2). Furthermore, a techno-economic analysis is carried out that compares each configuration's costs using pure s-CO2 and a mixture of s-CO2/COS with a molar fraction (70/30) respectively as working fluid where relevant results are obtained. These results show that the best configuration in terms of thermal efficiency and cost is the RCC-RH for pure sCO2 with values ​​of 41.25% and 2811 $/kWe, while for the mixture sCO2/COS, the RCC-2RH configuration with values ​​of 45, 05% and 2621 $/kWe is optimal. Using the mixture costs 6.75% less than if it is used the standard fluid (s-CO2).

heterocycles are particularly common moieties within marine natural products. Specifically, tetrahydrofuranyl rings are present in a variety of compounds which present complex structures and interesting biological activities. Focusing on terpenoids, a high number of tetrahydrofuran-containing metabolites have been isolated during the last decades. They show promising biological activities, making them potential leads for novel antibiotics, antikinetoplastid drugs, amoebicidal substances or anticancer drugs. Thus, they have attracted the attention of the synthetic community, and numerous approaches to their total syntheses have appeared. Here, we offer the reader an overview of marine-derived terpenoids and related compounds, with a special focus on their isolation, structure determination, biological profiles and total syntheses.

Physical exercise is the greatest stress on the cardiovascular system, not only in humans but also in all vertebrates. Consequently, the cardiovascular response cannot be thought of as having only one "anthropocentric" interpretation. The modulation of cardiac output (Q) in response to exercise in the five major groups of vertebrates exhibits considerable variability. Moreover, the response of the heart rate (HR) and the stroke volume (SV), the fundamental factors that cause the rise in Q, is also highly variable. The difference in the range of HR is difficult to determine in many vertebrates, both at rest and at maximal effort. Additionally, the increase in SV varies among vertebrates. For example, while rainbow trout and leopards increase their SV by increasing end diastolic volume (EDV), humans do so at the expense of both increasing EDV and reducing end systolic volume (ESV). The variation in arterial pressure that arises during exercise varies notably among vertebrates, such as amphibians, whose blood pressure values do not increase as significantly as in mammals. Such differences in cardiovascular response among vertebrates may be linked to their habitat or living environment. This review aims to analyze the cardiovascular response of vertebrates to physical exercise as the most common stressor.

Cornea severe inflammation produces opacity or even perforation, scarring, and angiogenesis, resulting in blindness. The cornea can be used to study the effect of new anti-angiogenic chemopreventive agents. We researched the anti-angiogenic effect of two extracts, Methanol (Met) and Hexane (Hex), from the seed of Cucurbita argyrosperma, in the inflamed corneas. The corneas of Wistar rats were alkali-injured and treated intragastrically for seven successive days. Clinical manifestation as opacity score, corneal neovascularization (CNV) area, re-epithelialization percentage, and histological evaluation were performed. Inflammatory (COX-2, NF-κB, and IL-1β), and angiogenic (VEGF-A, VEGFR1, VEGFR2) markers were assessed by immunohistochemistry. Cox-2, Il-1β, and Vegf-a mRNA levels were also determined. After treatments, we observed slim corneal thickness with lower opacity scores and low cell infiltration compared to untreated rats. Treatment also accelerated wound healing and decreased CNV area. The staining of inflammatory and angiogenic factors was significantly decreased. These effects are related to a down-expression of Cox-2, Il-1β, and Vegf. These results suggest that intake of C. argyrosperma seed can be used to attenuate the angiogenesis secondary to inflammation in corneal chemical damage.

Mexico shows a high prevalence of obesity in children and adolescents. Geographical location and cultural environment could play a role in the promotion of healthy lifestyles in terms of physical activity (PA), sedentary behavior (SB) and nutrition. The purpose of this study was to assess rural and urban differences in body composition (BC), physical fitness (PF), PA and nutritional status of adolescents from the state of Jalisco (Mexico). The study involved 469 students aged 13-17 years (55.0% girls) from 8 high schools. BC was analyzed by bioimpedance, and PF by standardized field tests. Objective measurements of PA and SB were taken in a subsample (n=240). Energy intake (EI) was calculated from two 24h recalls. Rural residents presented a higher prevalence of overweight, waist circumference, trunk fat mass, regional fat free mass and muscle handgrip strength (all p&lt;0.05, ηp2&lt;0.06). Cardiorespiratory fitness was similar among participants, whereas urban adolescents showed higher muscle power, speed-agility and flexibility scores (all p&lt;0.05, ηp2&lt;0.07). Overall lifestyle behavior in urban adolescents was more sedentary (p&lt;0.05, ηp2= 0.11). EI was similar in both locations. In conclusion, urban Mexican adolescents presented a generally higher sedentary behavior and better fitness and fatness profile than their rural peers.

The current study aims to first, isolate H. pylori in cultures from gastric biopsy samples and test their susceptibility. Secondly, we aim to assess the efficacy of the standard triple therapy from patients coming of the western central region of Colombia. Patients with H. pylori positive re-ceived standard triple therapy with PPI [40 mg b.i.d.], clarithromycin [500 mg b.i.d.], amoxicillin [1g b.i.d.] for 14 days. Thereafter, antibiotic susceptibility of the isolates was assessed by E-Test. From 94 patients enrolled, 67 were positive for H. pylori by histology or culture. Resistance to metronidazole, levofloxacin, rifampicin, clarithromycin and amoxicillin was 81, 26.2, 23.9, 19 and 9.5%, respectively. No resistance was found for tetracycline. 54 patients received standard triple therapy, 48 attended follow-ups testing and of them, 30 had resistance test reports. Overall eradication rate was 81.2%, 4 patients underwent second-line management and only one patient remained H. pylori positive by urea breath test during the follow-up [six weeks]. Eradication was significantly higher in patients with clarithromycin susceptible than in resistant strains [95.6% vs. 42.8% p= 0.001]. The updated percentages of resistance to clarithromycin in this geographical area have increased, so this value must be considered when choosing the treatment regimen.

Background. Increasing evidence demonstrate that concentration of protein in infant formula >1.9g/100Kcal with high levels of insulinogenic aminoacids is associated with accelerated weight gain, increased fat mass accumulation and risk of adiposity. Purpose of this study was to conduct a systematic review to determine the metabolic effects in infants feed with infant formula optimized in protein. Methods. Systematic review was conducted according PRISMA Statement. RCTs with one intervention group (infant formula with 1.6-1.9gr of protein/100Kcal) and at least one comparative control group (infant formula with >1.9gr of protein/100Kcal) were included. Standardized mean differences (SMD), through random model were calculated. Results. 15 RCT were included. Optimized protein in infant formula was associated with less gain of BMI at 24 months of follow-up (SMD -0.25, IC95% -0.36 to -0.13, p 0.01) and less fat mass accumulation (SMD -0.68, IC95% -0.98 to -0.37, p 0.01). Optimized protein was also associated to less gain of weight, weight/age Z-score, weight/length Z-score, BUN (mmol/dL) and IGF1 (ng/ml). No effect on length/age Z-score was observed. Conclusions. Robust evidence showed optimized protein (1.6gr/100Kcal to 1.9gr/100Kcal) in infant formula is associated with metabolic benefits in infants with less weight gain, BMI and fat mass accumulation.

As companies increasingly undergo digital transformation, the role of talent management pro-cesses becomes pivotal in enhancing overall organizational performance. The research addresses the significance of talent management in corporate digital transformation, examining whether variations in the digitalization of these processes can be attributed to company size. A qualitative approach was employed, utilizing a questionnaire, collecting responses from 202 organizations across diverse sectors. Findings reveal disparities in digitalization throughout the talent man-agement process, with pronounced presence in the attracting, selecting, and rewarding phases, but diminishing in deployment and development, further declining in planning. A positive cor-relation between company size and adoption of specific digital platforms was observed. Larger enterprises exhibit greater utilization of digital platforms in talent deployment and development. Moreover, corporate communication tools are consistently utilized in the rewarding phase, irre-spective of company size. These findings offer practical insights for organizations to optimize their digitalization strategies based on their scale, thereby contributing to more effective and tailored digitalization endeavors. The uniqueness of this research lies in its exploration of the in-fluence of company size on the digitalization of talent management processes and its potential to explain variations across different stages of these processes.

Frosty pod rot, caused by Moniliophthora roreri, is the most damaging disease of cacao in Latin America. However, to better comprehend its epidemiology, we must understand its dissemination and proliferation. Still, we ignore how loads of M. roreri spores fluctuate across growing seasons since we lack a reliable technique to quantify M. roreri spores in the fields. Therefore, we developed a method that uses a spore trap to capture M. roreri spores and qPCR to quantify them. This study demonstrated that this technique could quantify 3.9 x104 M. roreri spores with a 95 % confidence level. However, it could not differentiate between M. roreri and its close relative, M. perniciosa. Despite this limitation, we could detect and quantify Moniliophthora spores from environmental samples taken from a cacao field. This technique can help the phytopathologist address studies more accurately in disseminating cacao pathogens.

A new layout optimization method for offshore wind farms is proposed to minimize power deficits due to wake effect. The main engine of the algorithm is a gradient-descent method, in which an analogy is established between power deficit and repulsive electrostatic potential energy. To achieve a maximum dispersion in the initial solution, throughout the optimization process, new turbines are included in the centre of the concession area, and quickly expand outward looking for areas with less potential, in turn pushing the previous ones. When the optimization process ends, to avoid local maximums, it enters into a process of suppression of the set of locations that cause the greatest potential (power deficit). Then, a potential map of the entire area is created and a greedy algorithm includes new turbines to complete the layout with the final number of turbines. To speed up the search process and the creation of the potential map, two simplifications have been validated and added: the spatial distribution of velocities has been converted into its equivalent with point symmetry; and, for turbines affected by multiple wakes, the power deficit has been calculated by using a linear aggregation of powers, instead of the usual linear (or quadratic) aggregation of speeds. Owing to this type of aggregation, the process is accelerated in a factor of 90.

Up to 25% of early human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) patients will relapse despite the improvement achieved by the introduction of HER2-targeted therapy. Beyond trastuzumab, other agents approved for early HER2+ BC include the monoclonal antibody pertuzumab, the antibody-drug conjugate (ADC) trastuzumab-emtansine (T-DM1) and the reversible HER2 inhibitor lapatinib. New agents, such as trastuzumab-deruxtecan or tucatinib in combination with capecitabine and trastuzumab, have also shown an improvement in the metastatic setting. Other therapeutic strategies to overcome treatment resistance have been explored in HER2+ BC, mainly in HER2+ that also overexpress estrogen receptors (ER+). One strategy has been to target the cyclin-dependent kinases 4/6 (CDK4/6) as they are downstream of HER2 and many of the cellular pathways associated with resistance to HER2-targeted therapies play a key role in cell cycle and proliferation. Different trials have explored these strategies with encouraging results, but definitive results are needed. In addition, HER2+ BC is known to be more immunogenic than other BC subgroups, with high variability between tumors. Different immunotherapeutic agents have been investigated in this setting, with promising but controversial results obtained to date.

The aim of this research work is to get a method for Galfenol electrodeposition thought which we can control the desired percentage of Ga versus Fe that has the maximum magnetostriction constant. Galfenol is electrodeposited on an optical fiber with an imbedded Fiber Bragg Grating (FBG) in its core. The final objective, that goes further of the scope of this research, is to get an optical magnetostrictive sensor. The device will sense magnetic field or current based on the combination of this magnetostrictive Galfenol, that will stress the optical fiber with the application of magnetic field or current and will change the reflected wavelength of the FBG as a consequence of the variation of the Bragg wavelength. We have developed a method of electrodeposition that allows controlling the density of current in the electrodeposition process in order to get the desired percentage of Ga and Fe in the alloy Ga X Fe 1-x. We have manufactured a set of samples with different parameters (as density of current and pH) and we have characterized these samples morphological, structural and magnetically. With this research we want to give to the scientific community the groundwork to design magnetostrictive optical sensors based on and FBG coated by giant magnetostrictive material. In this paper we have developed a method of covering the optical fiber controlling the composition of (Ga X Fe 1-X) in order to be able to get the maximum magnetostriction constant.

CagY is the largest and most complex protein from Helicobacter pylori's type IV secretion system (T4SS) and may participate in the modulation of gastric tissue inflammation. A three-dimensional structure has been reported for only two segments of the protein. To build a more complete model, particularly the region that spans between the outer membrane (OM) and the inner membrane (IM), we employed different approaches, including homology modeling, ab initio, and deep learning techniques. For the long-middle repeat region (MRR), modeling was performed using deep learning techniques and Molecular Dynamics. The modeled segments were assembled into a chain of 1595 aa, and a 14-chain CagY multimer structure was composed by structural alignment. The final multimer structure correlated with previously published struc-tures and allows to show how the multimer may form the T4SS channel through which CagA and other molecules are translocated to gastric epithelial cells. The model further confirmed that MRR, the most polymorphic and complex region of CagY, presents numerous cysteine residues forming disulfide bonds that stabilize the protein and suggest this domain probably functions as a contractile region that may play an essential role in the modulatory activity of CagY on tissue inflammation.

Objectives: 1) to demonstrate the anti-inflammatory and anabolic effect of Ozone by determining in serum samples the biochemical levels of IL-6 and IGF-1 in knee osteoarthritis (OA) patients in a real world in Rehabilitation Setting; 2) to evaluate clinical effectiveness by Visual Analog Scale (VAS) and WOMAC scale, and biochemical effect by C-reactive protein (CRP), uric acid and erythrocyte sedimentation rate (ESR). Material and methods: 65 patients with knee OA Kellgren Lawrence (KL) grade 2 or more were analyzed in a retrospective observational study. The study run from January 2018 to September 2021. Inclusion criteria: a) patients 18 years or older; b) with knee OA KL 2º or more; c) biochemical analysis before-and-after treatment; d) pain more than 3 on VAS. Exclusion Criteria: a) previous knee surgery; b) favism; c) pregnancy; d) any other disease that originates lack of collaboration for infiltration. Primary Outcome variables: a) IL-6; b) IGF-1 in diabetes mellitus (DM)/obese and non-DM/non-obese patients; both before-and-after Ozone treatment. Secondary Outcome variables: a) CRP, b) ESR, c) uric acid, d) VAS pain, e) WOMAC pain, function and stiffness. Ozone protocol consisted of 4 sessions (once a week) of an intra-articular infiltration of 20 mL (20µg/mL concentration) of a gas mixture of Oxygen-Ozone 95-5% (produced by Ozone generator Ozonosan-α Plus ®). For biochemical evaluation, SNIBE MAGLUMI ™ IL-6 (CLIA) and SNIBE MAGLUMI ™ IGF-1 (CLIA) kits were used. CRP and uric acid were analyzed by Abbott Alinity c kit; and ESR was evaluated by DIESSE VES MATIC CUBE 30. Results: There is a linear correlation between age and OA severity. IL-6 decreased both in DM and non-DM patients and in all OA KL grades (from 2.7 to 1.59 pg/mL). IGF-1 decreased in total group (OA + DM + obesity) from 112.09 to 107.19 ng/mL. When only knee OA patients were analyzed, Ozone improved IGF-1 levels (from 100.17 to 102.03 ng/mL). Ozone decreased CRP, ESR, uric acid, and improved VAS pain, WOMAC pain, function and stiffness (p<0.05). Conclusions: Ozone is a valid option for the management of knee osteoarthritis in real world Rehabilitation Setting, because of its anti-inflammatory, metabolic and anabolic properties. Ozone downregulates pro-inflammatory IL-6 cytokine. Ozone has a metabolic/hypoglycemic effect on obese/diabetic knee osteoarthritis patients by reducing IGF-1. Ozone has an anabolic effect on non-diabetic/non-obese patients by improving IGF-1. Ozone reduces other biomarkers of inflammation (CRP, ESR and uric acid) and improves, pain, function and quality of life.

This study describes the implementation of IoT sensors in drinking water systems and fog collector systems in low-income communities in Ecuador. The influence and handling of these sensors are analyzed, as well as the materials and methods used in their implementation. The importance of validating the accuracy and reliability of IoT sensors compared to professional devices, especially in mountain areas, is highlighted. In addition, it is mentioned that the cost-benefit of using IoT sensors in fog catchers and drinking water networks depends on several factors, such as the scale of the project, specific objectives, and available resources. Finally, it is highlighted that the use of IoT sensors in smart construction and water collection systems has proven to be beneficial in preventing effects on the operation.

The main commercial variety of coffee is the Coffea arabica specie, however, it is very susceptible to damage caused by nematodes, for this reason scions of the C. arabica specie are used on ro-busta (Coffea canephora) rootstocks to improve tolerance to these microorganisms, because they modify the organoleptic, nutraceutical and nutritional characteristics. The objective of this work was to assess the effect of five roasting degrees on commercial beans (light, medium light, medi-um, medium, medium dark and dark) in two varieties of Coffea arabica species (Colombia and Costa Rica) and their respective scions on C. canephora of the Romex variety. The scion of the Co-lombia variety with the medium dark roast had the highest concentration of caffeine, while the coffee beans of the Costa Rica variety with the light roast grade had the highest concentration of chlorogenic acid (5-CQA), while the highest acrylamide content was found in the scion of the Co-lombia variety with the medium light roast beans and nutritional content differs considerably between varieties, however, there is similarity between roasting degrees. The degree of roasting, variety and scion of coffee influences the organoleptic, nutraceutical and nutritional content of the coffee infusion.

In recent years, several Ultrawideband (UWB) localization systems have already been proposed and evaluated for accurate position estimation of pedestrians. However, most of them are evaluated for a particular wearable sensor position; hence the accuracy obtained is subject to a given wearable sensor position. In this paper, we study the effects of body wearable sensor positions i.e., chest, arm, ankle, wrist, thigh, fore-head, hand, on the localization accuracy. The conclusion drawn is that the fore-head is the best, and the chest is the worst body sensor location for tracking a pedestrian. While the fore-head position is able to set an error lower than 0.35 m (90th percentile), the chest is able to set 4 m. The reason for such a contrast in the performance lies in the fact that in NLOS situations, the chest as an obstacle is larger in size and thickness than any other part of the human body, which the UWB signal needs to overcome to reach the target wearable sensor. And so, the large errors arise due to the signal arriving at the target wearable sensor from reflections of a nearby object or a wall in the environment.

Background/Objectives: Instability is one of the main symptoms in patients with vestibular and neurological disorders and therapeutic exercise interventions are increasing its popularity as a way of treatment for those. Additionally, the limits of stability measurement are known to be a good tool for balance evaluation and monitoring of this interventions. The aim of this work is to understand better how a specific protocol provokes changes on this variable and study the characteristics of those who respond and non-respond to it. Methods: A retrospective study was developed with the data of 40 patients treated in the Otorhinolaryngology department in Clínica Universidad de Navarra (Madrid, Spain). Those had an initial reduction in limits of stability, completed the protocol proposed with home-based and hospital-based exercises with frequent limits of stability remeasurement, and assist to the follow-up retest after 1-2 months. Results: A progressive improvement in limits of stability measure was developed through the intervention and partially retained at follow-up visit. Differences were found between responders and non-responders patients. More specifically an initial measure of the limits of stability was able to differentiate those groups with a cut-off data of 56cm2. Conclusions: The protocol proposed was able to induce motor learning in patients included in this study with good retention after 1-2 months. Besides, there is some variability in how patients respond to the treatment. Age and diagnostic should be considered, and an interesting cut-off data for clinal decision making was found.

The latest EU regulation on geographical indications (EU Regulation No. 1151/2012) has intro-duced a set of new tools for the protection and enhancement of food products in rural areas, under the group name of optional quality term (OQT). The Commission Delegated EU Regulation, No. 665/2014, regulated the conditions for the use of the optional quality term «mountain product» (MP), to support the implementation of a mountain value chain. This new tool is aimed at pro-moting local development, maintaining the economic activities in mountain areas and redistrib-uting wealth, whilst, at the same time, promoting the territory. Pecorino and goat cheeses are typ-ical Italian cheeses made usually with whole raw ewe's or raw goat's milk, without starter cul-ture addition. In an attempt to characterize these productions, the aim of this study was to inves-tigate the evolution of enterococci during the production and ripening of Pecorino cheese made in three different farms, located in Umbria, Italy in areas facing natural or other specific constraints as stipulated by Regulation 1305/2013 on support for rural development by the European Agri-cultural Fund for Rural Development (EAFRD). Enterococci are enteric organisms which are commonly isolated from ewe and goat's milk production in Umbria, Italy. Counts of enterococci in raw milk ranged from 1.75 for ovine milk to 3.62 for ewe milk and a marked reduction was observed after thermization especially in ovine milk. Out of 100 isolates, 69 were E. faecium, 23 E. durans, 8 E. faecalis and 2 E. casseliflavus and the distribution of species between farms and be-tween samples showed a prevalence of E. faecium in ovine farms and E. durans in ewes farms, with an equal distribution between samples. High percentages of susceptible isolates were found for amoxicillin/clavulanic acid, ampicillin, chloramphenicol, sulphamethoxazole, sulphameth-oxazole/trimethoprim, ticarcillin, vancomycin. A high prevalence of resistant strains (> 30%) was observed for amikacin, ciprofloxacin, ceftriaxone, kanamycin, tetracycline. A comparison of this results with those of previous works on similar dairy products revealed high levels of resistance to antimicrobials which needs to be addressed.

Groundwater flow and transport models are essential tools for assessing and quantifying the mi-gration of organic contaminants at polluted sites. Uncertainties in the hydrodynamic and transport parameters of the aquifer have a significant effect on model predictions. Uncertainties can be quantified with advanced sensitivity methods such as Sobol’s High Dimensional Model Reduction (HDMR) and Variogram Analysis of Response Surfaces (VARS). Here we present the application of VARS and HDMR to assess the global sensitivities of the outputs of a transient groundwater flow model of the Gállego alluvial aquifer which is located downstream the Sardas landfill in Huesca (Spain). The aquifer is subject to the tidal effects caused by the daily oscillations of the water level in the Sabiñánigo reservoir. Global sensitivities are analysed for hydraulic heads, aquifer/reservoir fluxes, groundwater Darcy velocity and hydraulic head calibration metrics. Input parameters in-clude aquifer hydraulic conductivities and specific storage, aquitard vertical hydraulic conductiv-ities, and boundary inflows and conductances. VARS, HDMR and graphical methods agree to identify the most influential parameters which for most of the outputs are the hydraulic conduc-tivities of the zones closest to the landfill, the vertical hydraulic conductivity of the most permeable zones of the aquitard, and the boundary inflow coming from the landfill. The sensitivity of heads and aquifer/reservoir fluxes with respect to specific storage change with time. The aquifer/reservoir flux when the reservoir level is high shows interactions between specific storage and aquitard conductivity. VARS and HDMR parameter rankings are similar for the most influential parameters. However, there are discrepancies for the less relevant parameters. The efficiency of VARS was demonstrated by achieving stable results with a relatively small number of simulations.

In this research, the adsorption of gallium onto natural zeolite (clinoptilolite) and two mesoporous activated carbons was compared and evaluated. The clinoptilolite was treated with HCl (HCPL) while mesoporous activated carbons (MCSG60A and MCO1) were synthesized by replica method, using sucrose as carbon precursor and silica gel as template. These carbonacenous materials showed large pore sizes and mesoporous surface, as well as a suitable surface chemistry for cation adsorption, which promotes a high negative charge density. On the other hand, zeolites have narrower pore sizes, which hinders the material diffusion inside the particle; however, its strength is their ion exchange capacity. Regarding the gallium kinetic studies, it is described by Pseudo-second order model for both sorts of adsorbents. MCO1 is the best carbonaceous adsorbent studied, with a capacity of 4.58 mg/g. As for zeolites, between the two zeolites studied, HCPL showed the best results, with a gallium adsorption capacity of 3.1 mg/g. The gallium adsorption mechanism onto MCO1 material is based on physisorption while HCPL is mainly retained due to an ion-exchange process. Regarding Giles classification, MCO1 isotherm described an H-4 pattern of high affinity, characteristic of multilayer adsorption. Double-Langmuir model fits properly these experimental results. In the case of zeolites, HCPL adsorption isotherm followed an L-2 pattern, typical of monolayer adsorption, being the Sips model the one which better describes the adsorption of gallium onto the zeolite.

In this paper we use the Mellin convolution theorem, which is related to Perron's formula. Also we introduce new explicit formulae for arithmetic function which generalize the explicit formulae of Weil for other arithmetic functions different from the Von-Mangoldt function.

Necrotizing fasciitis is a life-threatening soft-tissue infection affecting the deep fascia and subcutaneous tissue. It is characterized by a fulminant course and high mortality rates. NF of the head and neck is very rare, most cases being odontogenic in origin. Streptococcus spp. and Staphylococcus spp. are the most common isolated organisms. If the infection progresses to descending mediastinitis the prognosis becomes very poor. Since the initial clinical features can be similar to those of a non-necrotizing deep cervical infection, a high degree of suspicion is critical for an early diagnosis. Computed tomography scan can be useful in the diagnosis and to define the extent of the infection. Early and aggressive surgical debridement of all compromised tissue and antibiotic therapy and fluid resuscitation are essential and should not wait for bacterial culture results. Despite prompt and adequate treatment, mortality of CNF can be as high as 35%.

In the last decade several projects have been developed for the digitization and semantization of cultural heritage data. They were developed to preserve and maintain this heritage, but bringing it closer to all types of users and allowing access to this information to other sectors such as tourism, education, etc. In these developments, web technologies are combined, along with the use of knowledge graphs and interactive visualisation tools. Although remarkably interesting projects have been developed, in those projects, the data visualization tools are usually focused on the project context. This makes it difficult to reuse these jobs. Additionally, there are peculiarities of cultural heritage data considered with little depth, such as uncertainty, spatial and temporal granularity, as well as other aspects, such as relationships between data. In this article, these problems are described and based on other works such as VUMO or VISO, the design of an ontology that formalizes how to visualise this information is proposed, considering these problems. In addition, the development of a platform that allows the visualisation of this information through a web application and its evaluation of its use in projects such as SILKNOW, or Arxiu Valencià del Disseny is exposed

The emergence of prosumers, who actively participate in designing and producing goods, has generated interest in domestically manufactured products. Factors such as innovation, design methods, component reuse, prototyping, and digital fabrication empower prosumer designers to realize their ideas and enhance products to meet their specific design requirements. This article presents a case that combines bioinspired design methods with prosumer characteristics from the perspective of a designer who uses biological research results acting as a prosumer. By analyzing prosumer needs, bioinspired design, and domestic fabrication requirements, designers define the methods that best suit their possibilities. As a result of using biological information, the geometry of Samara seeds, propeller sizing, wind tunnel tests, and subsequent improvements, the custom design of a bioinspired microgenerator has been refined to the final design of a bicycle flashlight. The aim is to popularize a working approach that facilitates the interaction of design methods and reinforces domestic manufacturing processes. Implementing bioinspired design methods within the prosumer context offers a methodological alternative to transform the current economic model, promoting systemic sustainability and the development of proprietary technologies.

During the COVID-19 pandemic, the high prevalence of comorbidities in Mexico, as well as the disparities between public and private health subsystems, substantially contributed to the severe impact it had in the country. The objective of this study was to evaluate and compare risk factors present at admission for mortality of hospitalized patients with COVID-19. A 2-year retrospective cohort study of hospitalized adult patients with COVID-19 was conducted at a private tertiary care center. The study population consisted of 1,258 patients with a median age of 56 ± 16.5 years, of whom 1,093 recovered (86.8%) and 165 died (13.1%). In the univariate analysis, older age (p &lt;0.001), comorbidities such as hypertension (p &lt;0.001) and diabetes (p &lt;0.001), signs and symptoms of respiratory distress, and markers of acute inflammatory response were significantly more frequent in non-survivors. The multivariate analysis showed that older age (p &lt;0.001), the presence of cyanosis (p 0.005) and previous myocardial infarction (p 0.032) were independent predictors for mortality. In the studied cohort, risk factors present at admission associated with an increased risk of death were older age, cyanosis and a previous myocardial infarction, which can be used as valuable predictors for patients’ outcomes. To our knowledge, this is the first study analyzing predictors of mortality in COVID-19 patients attended on a private tertiary hospital in Mexico.

Introduction: Pre-Exposure Prophylaxis (PrEP) for HIV prevention has been implemented in several countries. Previous literature has shown that its cost-effectiveness (and, under some specifications, cost-saving character) is dependent on the reduction in price due to generics, the time-horizon and its effectiveness. The intervention has never been studied in Catalonia, a territory with extensive implementation. Methods: Economic evaluation of the implementation of HIV pre-exposition prophylaxis using administrative data from Men who have Sex with Men (MSM) who receive the treatment (at the generic price). A deterministic compartmental model and a social perspective with a micro-costing approach over the time horizon 2022-2062 are used. A baseline 86% effectiveness of PrEP is assumed. Results: Daily oral PrEP is found to be cost-saving: discounted savings in costs are attained after 16 years, and after 40 years they reach 81 million euros. In terms of health indicators, 10,322 additional discounted QALYs are generated by the intervention. Results are sensitive to sexual behavioral patterns among MSM, the price of PrEP (reduced if offered on-demand), its effectiveness and the discount rate. Conclusions: The use and promotion of PrEP in Catalonia is predicted to result in substantial health and monetary benefits because of reductions in HIV infections. Short-term investments in the promotion of PrEP will result in important cost-savings in the long term.

High-resolution GPS/GSM dataloggers provide spatial information of the highest quality, which outperform previous tracking methods, such as Argos telemetry or conventional VHF ground-tracking. As a result, this has improved our knowledge of home-range behavior and spatial ecology of many species, including large raptors. In this paper, we use high-resolution GPS/GSM dataloggers to assess the home-range size and the role of sex, season (breeding or non-breeding season), and breeding status (reproductive or non-reproductive individuals) on the space use of Bonelli’s eagle (Aquila fasciata). To this end, 51 territorial individuals (25 females and 26 males) were equipped with GPS/GSM transmitters and were tracked over 7 years (2015–2021) in eastern Spain. Overall, we recorded 4,791,080 fixes that were analyzed through kernel density methods (50%, 75%, and 95% fixed kernels). The average individual home-range size according to the 95%, 75%, and 50% kernels was 54.84 ± 20.78 km², 24.30 ± 10.18 km², and 11.17 ± 4.90 km², respectively. Overall, the home-range size of individuals occupying the same territory was similar, mainly due to the cooperative hunting behavior exhibited by the species. We did not find interannual differences in the home-range size (95% fixed kernel) of the majority of individuals, showing a strong territorial fidelity of the breeding pairs. In general, females’ home-range size was slightly smaller than males’ size due to the decrease in activity in the breeding season as a result of laying, incubation, and chick attendance at nests. No seasonal variation in the 95% kernel was found, but it was found in the 75% and 50% kernels. In regard to the breeding status, higher home-range size was recorded in the non-reproductive individuals. Moreover, we found a low neighbor overlap among the territories (4.18% ± 3.06%), which evidences a high level of intraspecific competition in the Bonelli’s eagle. Finally, this study highlights the advantages of the use of accurate telemetry information to improve our understanding of the spatial ecology of the endangered Bonelli’s eagle, which ultimately will serve to better inform management actions for its conservation.

In this work we discuss the insights from activity landscape, docking and molecular dynamics towards the understanding of the structure-activity relationships of dual inhibitors of major epigenetic targets: lysine metiltransferase (G9a) and DNA metiltranferase 1 (DNMT1). The study was based on a novel data set of 50 published compounds with reported experimental activity for both targets. The activity landscape analysis revealed the presence of activity cliffs, e.g., pairs of compounds with high structure similarity but large activity difference. Activity cliffs were further rationalized at the molecular level by means of molecular docking and dynamics simulations that led to the identification of interactions with key residues involved in the dual activity or selectivity with the epigenetic targets.

Self-consciousness can be considered as the internal disposition to direct attention to oneself. This dispositional tendency can be focused on private aspects of the self, but also on public characteristics of the individual. We examine self-consciousness in online consumer behavior. This concept has been poorly investigated in consumer research. The main objective of this paper is to analyze the influence of the dimensions of self-consciousness in consumer adoption of online shopping. This study is based on a sample of 725 Spanish undergraduates. Results indicated that public self-consciousness is a significant predictor of the adoption of online shopping.

Aging is a major risk factor for the higher incidence and prevalence of chronic conditions, such as cancer, cardiovascular and metabolic diseases, and neurodegenerative diseases. Closely linked with the onset of all these age-related diseases is immunosenescence, a condition defined as progressive reconfiguration of the immune functions leading to an increased susceptibility to infectious diseases, poorer response to vaccination, increased prevalence of cancer, rheumatoid arthritis, and other chronic diseases characterized by a pro-inflammatory state named inflammaging. Given that immunosenescence frames age-related diseases, it is natural to ask how these illnesses are related under the context of innate and adaptative components of the immune system. Knowledge processing by Formal Concept Analysis (FCA) of age-related diseases framed in an immunosenescence multivalued context shows that a hierarchy among these diseases emerges with a subconcept-superconcept nested structure, with two clusters, first made of metabolic diseases, cancer, and cardiovascular diseases. Second metabolic and neurodegenerative diseases and rheumatoid arthritis. Metabolic diseases seem to be a pivot illness and they must be a primary target given their global incidence and prevalence and their cost-effective treatments like regular physical activity, weight loss, healthy diet, stopping smoking, and reducing or managing stress. Another implication of the ontological analysis of age-related diseases is about the nature of immunosenescence, suggesting that initial symptoms of age-related diseases are mainly related to innate immune mechanisms, and developing of severe symptoms of age-related diseases like cancer, cardiovascular or neurodegenerative diseases depends on the activation of acquired immunity processes.

The article presents the results and conclusions of a series of tests of wedge-shaped blocks armoring carried out on a new experimental facility (‘Hydraulic Experimentation Facility - Luis Ruano’) in quasi-prototype conditions. The article describes the singular testing facility that was built at the inlet channel of the Acequia de Sora channel, immediately upstream of the Laverné reservoir (Zaragoza, Spain). The inflow of the testing facility has a maximum discharge of 9 m³s^-1. The aim is to perform experimental research on technologies to protect embankment dams and dikes against overflowing erosion under quasi-prototype conditions. The results of the tests showed the ability of the WSBs to withstand high unit discharges under extremely negative conditions. Furthermore, conclusions were drawn about potential threats to the sound behavior of the armor.

This research concerns the virtual reconstruction and technical constructive analysis of the emblematic and disappeared Matriz church of Ambato city, whose structure was demolished after the collapse of its vaults in the 1949 earthquake, about which it was said to have had deficiencies in its construction. Through an exhaustive historical review of documents and images, its constructive hypothesis was achieved, and using photogrammetry technique, its virtual reconstruction was obtained, where, through the interpretation and understanding of the generated plans, the verification of its technical and constructive characteristics associated with its hypothetical mechanical behavior inherent to its stone construction was carried out. For the structural study, the principle of the Limit Analysis of Structures was used, where through a graphic static approach, the technical stability conditions of a masonry structure are established, in this case, to give an interpretation to the possible poor execution of the church's work, and eventual cause that could have contributed to the collapse of its vaults.

Background: Cutaneous squamous skin cell carcinoma (SCC) is the second most frequent type of non- melanoma skin cancer and the second cause of death by skin cancer in caucasian population. However, at present it is difficult to predict patients with worst SCC prognosis. Objective: To identify proteins whose expression level could predict SCC infiltration in SCC arising from actinic keratosis (AC). Methods: A total of 20 biopsies of 20 different patients were studied, 10 were from SCC-AK samples and 10 from normal skin. Early infiltrated SCC-AK were selected on histological examination and to determine the expression of proteins fresh skin samples were processed by 2DE-electrophoresis Results: The expression levels of three proteins namely alpha-hemoglobin, heat shock protein (Hsp)-27 and 70 were significantly increased in SCC-AK samples with respect to normal control skin. However, only the expression level of Hsp70 protein positively correlated with the level of SCC-AK dermis infiltration. Immnunohistological examination suggested that the increased expression of Hsp70 proteins seems to mainly occur in the keratinocytes cytoplasm. The increased cytoplasmic Hsp70 expression in SCC-AK was confirmed by Western-blot experiments. Conclusion: Cytoplasmic expression of Hsp70 could be potential biomarker of early infiltration of SCC arising from an AK. Keywords: actinic keratosis, cutaneous squamous cell carcinoma; cytoplasm, skin cancer; heat shock protein.

High porosity and mass transport properties of microfiltration polymeric membranes benefits nutrients supply to cells when used as scaffolds in interstitial perfusion bioreactors for tissue engineering. High nutrients transport is assumed when pore size and porosity of the membrane are in the micrometric range. The present work demonstrates that the study of membrane fouling by proteins present in the culture medium, though not done usually, should be included in the routine testing of new polymer membranes for this intended application. Two poly(ε-caprolactone) microfiltration membranes presenting similar average pore size (~0.7µm) and porosity (>80%) but different external surface porosity and pore size have been selected as case study. The present work demonstrates that a membrane with lower surface pore abundance and smaller external pore size (~0.67 µm), combined with adequate hydrodynamics and tangential flow filtration mode is usually more convenient to guarantee high flux of nutrients. On the contrary, having large external pore size (~1.70µm) and surface porosity would incur in important internal protein fouling that could not been prevented with the operation mode and hydrodynamics of the perfusion system. Additionally, the use of glycerol in the drying protocols of the membranes might cause plasticization and a consequent reduction of mass transport properties due to membrane compaction by the pressure exerted to force perfusion. Therefore, preferentially, drying protocols that omit the use of plasticizing agents are recommended.

While digitization can make the health industry faster and more efficient, there are many financial, social and organizational obstacles and barriers to its implementation. This article offers a systematic review of the main troubles detected from the literature review. Also there is a proposal of new kind of restrictions to pay attention. Finally, its offer an heterodox reading about the problem analyzed.

As consequence of COVID-19, millions of households suffered mobility restrictions and changes in their lifestyle during several months. The aim of this study was to evaluate the effects of COVID-19 home confinement in food habits, lifestyle and emotional balance of the Spanish population. This cross-sectional study used data collected via an anonymous online questionnaire during the last month before lockdown finished in Spain in a total of 675 participants. 38.8% of the respondents experienced weight gain while 31.1% lost weight during confinement. The increase in body weight was positively correlated with the age (Rs = 0.14, p &lt;0.05) and BMI (Rs = 0.20, p &lt;0.05). We also identified that 39.7% reported poorer quality sleep, it was positively correlated with BMI (Rs = -0.18, p &lt;0.05) and with age (Rs = -0.21, p &lt;0.05). 44.7% of the participants had not performed physical exercise during confinement with differences by sex (p &lt;0.05), by age (p &lt;0.05), by BMI (p &lt;0.05) and sleep quality (p &lt;0.05). According to emotional-eater questionnaire, 21.8% and 11% were classified as emotional eater and very emotional eater, respectively. We emphasize the importance of adopting a healthy lifestyle, as the COVID-19 pandemic nowadays is ongoing.

Ticks drive a wide diversity of pathogens to a great variety of hosts, including humans. We conducted a tick surveillance study in northwestern Spain between 2014 and 2019. Ticks were removed from people and were identified. Tick numbers, species, development stages, evolution over time, seasonal and geographical distribution, and epidemiological characteristics of people bitten by ticks were studied. We collected ticks from 8143 people. Nymphs of Ixodes ricinus were the most frequently collected. Rhipicephalus bursa, Rhipicephalus sanguineus sensu lato (s.l), Hyalomma marginatum, Hyalomma lusitanicum, Dermacentor marginatus, Dermacentor reticulatus and Haemaphysalis punctata were also found, with adults as the main stage. Hyalomma spp. and R. bursa have been progressively increasing over time. Although bites occurred throughout the year, the highest number of incidents were reported from April to July. The distribution patterns of the tick species were different between the north and the south of the region, which was related to cases detected in humans of the pathogens they carried. Adult men were more likely to be bitten by ticks than women. Ticks were most frequently removed from adults from the lower limbs, while for children they were mainly attached to the head. Epidemiological surveillance is essential given the increase in tick populations in recent years, mainly of species potentially carrying pathogens causing emerging diseases in Spain, such as the Crimean Congo Hemorraghic Fever (CCFH).

We consider a discrete-time random walk (xt) which at random times is reset to the starting position and performs a deterministic motion between them. We show that the quantity Prxt+1=n+1|xt=n,n→∞ determines if the system is averse, neutral or inclined towards resetting. It also classifies the stationary distribution. Double barrier probabilities, first passage times and the distribution of the escape time from intervals are determined.

BACKGROUND Detecting total cholesterol in dried blood spots could aid in identifying individuals with a high likelihood of familial hypercholesterolemia and could be used as a screening measure. This study aims to assess the diagnostic accuracy of dried blood spots on Whatman 903 paper cards using a manual enzymatic technique. METHODS A total of 394 samples collected as serum and dried blood spots were compared. Cholesterol was determined in serum using the automated reference method, while cholesterol on paper was measured using a manual enzymatic method. Within- and between-day diagnostic variability were analyzed. The correlation between both methods was assessed using Passing-Bablok regression and Bland-Altman plot. Internal validation of our correlation formula was performed on 149 samples, along with external validation of the formula proposed by Corso et al. RESULTS The within- and between-day coefficient of variation was found to be lower than 10.14% and 14.09%, respectively. Method comparison yielded an area under the curve of 0.976, with a standard error of 0.009. Passing-Bablok regression indicated a precision of 0.803 and an accuracy of 0.96. Internal validation precision was measured at 0.716. Regarding internal validation, calculated cholesterol with our regression line did not differ from serum cholesterol analysis, while significant differences were observed in calculated cholesterol levels using the external formula. CONCLUSIONS Total cholesterol analysis in dot blood spots demonstrates high precision and reproducibility. This method reliably enables the incorporation of this biological marker into neonatal screening for familial hypercholesterolemia detection.

Pinus patula is one of the most planted wood conifer species worldwide; however, no foliar nutrient standards exist for this species up to date. The objective of the present study was to generate and verify two sets of foliar nutrient standards for nearly ten-year-old P. patula trees: critical nutrient concentrations and DRIS norms. Nutrients studied were N, P, K, Ca, Mg, Fe, Cu, Zn, Mn, and B. The reference standards were verified experimentally by installing two fertilization trials; one of them located in Huayacocotla, state of Veracruz and the other one in Aquixtla, state of Puebla, Mexico. Nutrient status of each fertilization trial was correctly predicted by critical nutrient values and DRIS as well. Both standards were able to detect the secondary growth-limiting nutrient deficiency in the Huayacocotla trial, where the primary limitation for growth was scarcity of solar radiation within tree crowns. The limiting nutrient in both experimental trials was K.

Industry 4.0 is an industrial paradigm that is causing changes in form and substance in factories, companies and businesses around the world, and is impacting work and education in general. In fact, the disruptive technologies that frame the fourth industrial revolution have the potential to improve and optimize manufacturing processes and the entire value chain, which can lead to an exponential evolution in the production and distribution of goods and services. All these changes imply that the fields of engineering knowledge must be oriented towards the concept of Industry 4.0, for example Mechanical Engineering. The development of various physical assets that are used by cyber-physical systems and digital twins is based on Mechanics. However, the specialized literature on Industry 4.0 says little about the importance of Mechanics in the new industrial era and more importance is given to the evolution of Information and Communication Technologies and Artificial Intelligence. This article presents a frame of reference about the importance of Mechanical Engineering in Industry 4.0 and proposes an extension to the concept of Mechanics 4.0, recently defined as the relationship between Mechanics and Artificial Intelligence. For the analysis of Mechanical Engineering in Industry 4.0, the criteria of the four driving forces that defined Mechanics in the third industrial revolution was used. An analysis of Mechanical Engineering Education in Industry 4.0 is presented, and the concept of Mechanical Engineering 4.0 Education is improved. Finally, the importance of making changes in the educational models of engineering education is described.

This study proposes a methodology for identifying time intervals in which time-of-use (ToU) energy tariffs can be set. This is achieved by analyzing the variability in electric power demand and esti-mating the potential for demand flexibility. The proposed methodology is as follows: first, data preprocessing is performed, focusing on the organization and cleaning of individual consumption records. Subsequently, the data are processed and classified by using consumption variability analysis and clustering techniques. Then, representative clusters are selected and time intervals are analyzed to identify periods of high electric power consumption variability. This methodology was tested with real data from smart meters in the Colombian electrical system, in which time intervals with potential for settinh ToU tariffs were ultimately identified. This work promotes the implementation of demand response strategies that enhance sustainability and facilitate the transition to a more resilient energy landscape both nationally and internationally. The findings are expected to contribute to the formulation of tariff schemes that encourage con-scious changes in electric energy consumption patterns.

There is an urgent need to develop new therapies for cancer treatment due to high rates of resistance and tumor relapse. Moreover, chemotherapy and radiation weaken the immune system and leave patients susceptible to sudden death from infections and organ failure since antineoplastic drugs lack specificity. Hence, scientists worldwide continue the search for natural alternatives with anticancer activities and fewer side effects. In this regard, traditional medicine offers strategies for preventing and treating numerous diseases and nowadays scientific studies worldwide highlight some of the mechanisms underlying their potential as an effective alternative for the management of cancer. In Mexico, Mayan healers have been prescribed mainly medicinal plants for more than 2,000 years. Furthermore, their ethnomedical knowledge has led to drug discovery or the development of herbal remedies. Medicinal plants from the genus of Cissus remain an important element of all indigenous medical systems in Mexico including the Mayan tribes in Yucatan, particularly for the management of gastrointestinal illnesses, sores, cutaneous diseases, and tumors. In this review, we present the reported bioactivities against cancer cells of the extract and compounds from the species of Cissus with a particular focus on recent studies on the phytochemistry of C. trifoliata which is widely distributed in Mexican territory and used for tumor management in traditional medicine.

Current pharmacological treatments of Fibromyalgia (FM) are merely symptom palliative, as clinical trials have so far failed to provide overall benefits without associated harms. Polypharmacy often leads to patient´s health deterioration and chronic drug use to an eventual lack of patient´s response. Emerging evidence support that physiotherapy treatments based on mechanical triggers improve FM symptoms and therefore could be used for therapeutic purposes by themselves, or in combination with current pharmacological treatments, as part of integrative medicine programs. However, a paucity of studies rigorously and systematically evaluating this possibility exists. This study uses scores from validated standardized questionnaires, algometer pressure point threshold (PPT) readings and responses from a custom self-developed questionnaire to determine the impact of a pressure-controlled manual protocol on FM hyperalgesia/allodynia, fatigue and patient´s quality of life. The results show that patient´s baseline sensitivity to pain inversely correlates with treatment response in FM. Moreover, patients presenting comorbid ME/CFS do not seem to respond to the applied therapy as those presenting FM only. Thus, pre-treatment PPTs and ME/CFS comorbidity may serve as indicators to predict patient´s response to physiotherapy programs based on mechanical triggers, as the one evaluated here. These unexpected findings grant further explorations including the study of gene expression profiles associating to patient´s treatment response in the blood collection of samples generated by this study.

The changes in consumer preferences and the increasingly competitive global market have demanded that food entrepreneurs engage in innovative value-added activities. The date is a delicatessen fruit known by its content of active compounds (e.g., dietary fiber and antioxidants) and its biological activity which has a vast potential in the design of new products such as bioactive ingredients, sugar substitutes, dietary supplements, functional foods, among others. In the current paper, innovative approaches to the value addition to date fruits and their processing by-products have been reviewed from recent high-quality scientific works. New processes such as ultrafiltration and hydrothermal treatments are shown as a useful alternative to obtain differentiated date-based ingredients (e.g., fiber concentrates, sap syrups, and date powders). Moreover, the use of date fruits and their byproducts as natural sources of value-added active compounds in the preparation of dairy, meat, and bakery and cereal products is also presented.

The tourism sector in general and the hotelier in particular face the challenge of managing appropriate measures to deal with the covid-19 pandemic. In this sense it is useful to know what the measures are most demanded by the clientele. This research, by analyzing the variance (ANOVA) of a factor concluded that women are more demanding than men in terms of the level of demand in relation to the measures to be taken in hotels. This, as a practical application, allows to know more accurately the expectations, demands and demands of the client segmented by sex, in order to satisfy and improve the tourist experiences.

The tourism sector in general and the hotelier in particular face the challenge of managing appropriate measures to deal with the covid-19 pandemic. In this sense it is useful to know what the measures are most demanded by the clientele. This research, by analyzing the variance (ANOVA) of a factor concluded that women are more demanding than men in terms of the level of demand in relation to the measures to be taken in hotels. This, as a practical application, allows to know more accurately the expectations, demands and demands of the client segmented by sex, in order to satisfy and improve the tourist experiences.

The tourism sector in general and the hotelier in particular face the challenge of managing appropriate measures to deal with the covid-19 pandemic. In this sense it is useful to know what the measures are most demanded by the clientele. This research, by analyzing the variance (ANOVA) of a factor concluded that women are more demanding than men in terms of the level of demand in relation to the measures to be taken in hotels. This, as a practical application, allows to know more accurately the expectations, demands and demands of the client segmented by sex, in order to satisfy and improve the tourist experiences.

Gene expression data is key for the functional annotation of single nucleotide polymorphisms (SNPs) identified in genome-wide association studies (GWAS). Expression and splicing quantitative trait loci (e/sQTLs) in normal colon tissue, such as those from the University of Barcelona and University of Virginia RNA sequencing project (BarcUVa-Seq) and the Genotype-Tissue Expression project (GTEx), are required to gain biological insight of colon-related diseases risk loci. Moreover, transcriptome-wide association studies (TWAS) rely on reference gene expression imputation panels in the tissue of interest to nominate susceptibility genes. Also, it is of high interest to study the relationships between genes in a network framework. For facilitating these analyses, we have updated and expanded the scope of the Colon Transcriptome Explorer (CoTrEx) to the version 2.0. This web-based resource provides exhaustive visualization and analysis of transcriptome-wide gene expression profiles of normal colon tissue from BarcUVa-Seq and GTEx. In addition to the integration of new datasets, CoTrEx 2.0 provides additional e/sQTLs sets, as well as gene expression prediction models and regulatory and co-expression networks. It is freely available at https://barcuvaseq.org/cotrex/. Overall, it is of high interest for researchers aiming to investigate the genetic susceptibility to colon-related complex traits and diseases.

Large datasets play a crucial role in the progression of surgical robotics, facilitating advancements in the fields of surgical task recognition and automation. Moreover, public datasets enable the comparative analysis of various algorithms and methodologies, thereby assessing their effectiveness and performance. The ROSMA (Robotics Surgical Maneuvers) dataset provides 206 trials of common surgical training tasks performed with the da Vinci Research Kit (dVRK). In this work, we extend ROSMA dataset with two annotated subsets: ROSMAT24, which contains bounding box annotations for instrument detection, and ROSMAG40, which contains high and low level gesture annotations. We propose an annotation method that provides independent labels for the right-handed tool and the left-handed tool. For instrument identification, we validate our proposal with a YOLOv4 model in two experimental scenarios. We demonstrate the generalization capabilities of the network to detect instruments in unseen scenarios. For gesture segmentation, we propose two label categories: high-level annotations that describe gestures at a maneuvers level, and low-level annotations that describe gestures at a fine-grain level. To validate this proposal, we have designed a recurrent neural network based on a bidirectional long-short term memory layer. We present results for four cross-validation experimental setups, reaching up to a 77.35% mAP.

In this paper, we present a method for estimating GPS signals from visual information captured by a monocular camera mounted on a fixed-wing Unmanned Aerial Vehicle. The main challenge in visual odometry from aerial images is the computation of scale due to irregularities in the elevation of the terrain. That is, it is not possible to accurately convert from pixels in the image to meters in space, and the error accumulates. The contribution of this work is to reduce the accumulated error by comparing the images from the camera with satellite images. The algorithm has been tested in real-time experiments, and the results show that it is possible to eliminate the accumulated error using satellite images.

Transport of hydrophobic drugs in the human body exhibits complications due to the low solubility of these compounds. With the purpose of enhancing the bioavailability and biodistribution of such drugs, recent studies have reported the use of amphiphilic molecules, such as phospholipids, for synthesis of nanoparticles or nanocapsules. Given that phospholipids can self–assemble in liposomes or micellar structures, they are ideal candidates to function as vehicles of hydrophobic molecules. In this work, we report mesoscopic simulations of nanoliposomes, constituted by lecithin and coated with a shell of chitosan. The stability of such structure and the efficiency of encapsulation of capsaicin, as well as the internal and superficial distribution of capsaicin and chitosan inside the nanoliposome were analyzed. The characterization of the system was carried out through density maps and the potentials of mean force for the lecithin–capsaicin, lecithin–chitosan and capsaicin–chitosan interactions. The results of these simulations show that chitosan is deposited on the surface of the nanoliposome, as has been reported in some experimental works. It was also observed that a nanoliposome of approximately 18 nm in diameter is stable during the simulation. The deposition behavior was found to be influenced by pattern of N-acetylation of chitosan.

The purpose of this study is to analyse the feasibility of using waste from granite gang saws (GCW-GS) to manufacture ultra-high performance, steel-fibre reinforced concrete (UHPFRC). These machines cut granite blocks by abrasion using a steel blade and slurry containing fine steel grit. The waste generated by gang saws (GCW-GS) contains up to 15% Fe2O3 and up to 5% CaO. This is the main difference from the waste produced by diamond saws (GCW-D). Consequently, the second objective of this study is to compare the results of the waste obtained with gang saws with that from diamond saws, in order to determine the influence of iron and calcium oxides. The waste from cutting granite with gang saws was used in different percentages to replace micronized quartz powder of natural origin in the manufacture of UHPRFC. All the test specimens were analysed to determine their compressive strength, elasticity modulus, flexural strength and indirect tensile strength. The final conclusion is that wastes from both gang saws and diamond saws can be used to manufacture UHPFRC with an improvement in the mechanical properties up to a 35% replacement. The results for GCW-GS are better, mainly due to the pozzolanic effect of the iron dioxide. For higher percentage replacements the mechanical properties are close to the control concrete with small decreases.

Biopolymers based on plant and animal proteins are interesting alternatives in the development of films with future prospects as food packaging. Considering that in recent years there has been an increasing interest in the valorization of agro-industrial residues and by-products and that the blending of polymers can lead to materials with improved properties, in this work, keratin-rich feather fibers and gliadins were blended at different ratios in order to develop sustainable and biodegradable films. Control gliadin G100, feather F100 films and their blends at 3:1 (G75F25) , 2:2 (G50F50) and 1:3 (G25F75) ratios were successfully developed through thermoprocessing. The physical properties were differentiated as a function of the concentration of both polymeric matrices. Although gliadins showed higher hydrophilicity confirmed by its highest swelling degree, films with high gliadin ratios exhibited lower water permeability values at low and medium relative humidities. On the other hand, the feathers displayed the highest Young´s modulus values and provided oxygen barrier to the blends, principally at the highest relative humidity. In conclusion, the blend of these protein-based polymers at different ratio resulted on interesting composites whose physical properties could be adjusted.

Background: The treatment plan of prosthetic restorations supported by dental implants require comprehensive scientific knowledge to deliver prostheses with good prognosis, even before the implant insertion. This review aims to analyze the main prosthetic determinants of the prognosis of implant-supported prostheses. Methods: A systematic review of the literature was conducted with a PICO question: "For partially or complete edentulous subjects treated with implant-supported prostheses, which prosthetic factors could affect clinical outcomes?". A literature search was performed electronically in PubMed (MEDLINE), Scopus and Cochrane Library with the following equation [PROGNOS* OR RISK] FACTOR IMPLANT DENTAL, and by hand search in relevant journals and throughout the selected papers. Results: This revision was carried out based on 50 papers focused on several prosthodontics-related risk factors that were grouped as follows: implant-connection, loading protocol, transmucosal abutments, prosthetic fit, provisionalization, type of retention, impression technique, fabrication technique, and occlusion. More than a half of the studies were systematic reviews (30%), meta-analysis (16%) or prospective evaluations of prosthesis with various kinds of events (18%). But also narrative reviews of literature (14%) and in vitro/animal studies (16%) were found. Conclusions: The current literature provides insufficient evidence for most of the investigated topics. However, based on the accumulated data, it seems reasonable to defend that the best treatment approach is the use of morse taper implants with transmucosal abutments, recorded by means of rigidly splinted copings through the pick-up technique, and screwed by milled prosthesis occlusally adjusted to minimize functional overloading.

We present an ontology log-OLOG- representation of the classical Miller-Urey experiment, usually considered as a paradigm for spontaneous generation of biomolecules on the prebiotic Earth and also, as a key in understanding the chemical evolution phenomena linked to the origins of life. Ologging The Miler-Urey experiment enables us, through the categorical notion of fibre product or pullback, to define the concept of Biogenic Space, as a space containing low complexity biogenic units subjected to appropriate physical and chemical conditions, facilitating the synthesis of highly complex organic molecules. Also, we characterize the Biogenic Space as a concrete universal object that could be associated with the preconditions for life inside various structures in the universe such as exoplanets and exomoons located in habitable zones, but also in interstellar and intergalactic organic clouds.

COVID-19 sepsis immune response remains unclear. Here we propose a new perspective in host response against pathogenic proteins that may lead to a vaccine design by polymerization of antigens of <70 kDa. In COVID-19, initial Th1 response kills infected cells releasing viral proteins. SARS-CoV-2 viral structural proteins are Spike (140 kDa), Nucleocapsid (50 kDa), Membrane (25 kDa) and Envelope (10 kDa). B cell receptor cannot capture antigens >70 kDa. The Spike protein (140 kDa) cannot be captured by B cells and triggers inflammatory Th1 response via the macrophages. Only proteins with a size <70 kDa can activate B cell receptor and trigger Th2 adaptative humoral response. Moreover, M-25 kDa and E-12 kDa glycoproteins can activate IgM-BCR like oligovalent or monovalent antigens. The sustained infected cells lysis overfeeds high levels of viral proteins <70 kDa, increases B cells activation and, in the shift from Th1 to Th2 immune response, triggers the cytokine storm. The continuous BCR activation increases IL-10 releasing and may lead to immune paralysis.

The diagnosis and treatment of autoimmune diseases are major challenges. Their signs, symptoms, and their clinical severity change throughout the course of the disease. The available treatments for these conditions do not result in complete remission, and their long-term use generates several side effects. The main challenges in this field are the development of more sensitive diagnostic tools, and effective treatments. Studies in patients and animal models reported alterations in monocyte phenotype, activation, and function. These cells play an essential role in the pathogenesis of chronic inflammatory states and have become a target for extracorporeal monitoring and specific intervention. Nanoparticles (NPs) are ultrafine particles that can be used as contrast agents in diagnostic imaging techniques to detect specific cells in inflammatory infiltrates in tissues that are not easily accessible by biopsy. In addition, NPs can be designed to deliver drugs to a cell population or tissue. This review describes several experimental pieces of evidence demonstrating that monocytes and macrophages can specifically uptake various types of NPs, thus becoming detectable in vivo by magnetic resonance imaging and susceptible to be modulated by therapeutic agents. Hence, nanoparticles targeting mononuclear phagocytes represent promising tools for diagnosing and treatment.

The use of probiotics in reproductive-related dysbiosis is an area of continuous progress due to the growing interest from clinicians and patients suffering recurrent reproductive microbiota disorders. An imbalance in the natural colonization sites related to reproductive health: vaginal, cervicovaginal, endometrial and also pregnancy-related altered microbiota could play decisive role in reproductive outcomes. Oral and vaginal administrations are in continuous discussion regarding the clinical effect pursued, but probiotics as oral supplement therapy is the route administration better studied. To complement and summarise with qualitative and quantitative information of vaginal probiotics clinical studies, the main objective of this work was to retrieve the standardised protocols commonly used and their microbiota modulation capacities. The studies selected were related to treat bacterial vaginosis (BV) as the most commonly disorder, few studies on vulvovaginal candidiasis (VVC) and also administration to stabilise microbiota before in vitro fertilisation (IVF). Probiotic doses administered were similar to oral probiotics protocols, ranging from ≥ 107 CFU/day to 2.5 x 1010 CFU/day, and variable regarding posology duration from 1 day to 12 weeks, being 1 week commonly applied. Moderate modulation was achieved regarding the relative abundance decrease of abnormal microbiota, coinciding with parallel increase in Lactobacillus species.

Groundwater degradation is a global problem linked to irrigation agriculture and aggravated by climate change. In drylands, where aquifer recharge is low, irrigation has emerged as an engine of economic growth. This problem falls under the paradigm of desertification, as it fits the definition of this complex problem in that the degradation of drylands is due to climatic variations and inappropriate human activities. Land Degradation Neutrality (LDN), the response of the United Nations Convention to Combat Desertification to the lack of progress in tackling desertification, is integrated into Sustainable Development Goal 15.3 and provides the adequate framework for implementing effective solutions. LDN prioritizes prevention strategies, and early warning systems coupled to integrated simulation models is a sound approach. We analyze the dynamics of a coastal aquifer in southern Spain, a “desertification landscape” according to the Spanish National Action Plan to Combat Desertification. For this purpose, we have (i) adapted a generic desertification model that considers socio-ecological systems as a particular case of predator-prey systems; and (ii) coupled to this model a risk analysis to calculate the probabilities of groundwater salinization under the current scenario of water resources use, driven by the expansion of greenhouse agriculture supported by external water transfer. The risk of desertification is close to 100%: groundwater salinity is 40 dS m-1 (well above tomato tolerance, 3.5 dS m-1), and 2.4 Mm3 yr–1 water transfer is needed to support the 631 ha of greenhouses. This worrying result suggests that complimentary solutions should be promoted to deactivate the ongoing process of desertification. Among them, we propose reclaimed water, diversifying the economy, or promoting crops adapted to aridity. This simulation framework shows how to explore the future of a socio-ecosystem under current scenarios and others that consider climate change, the energy crisis, or the impact of alternative solutions.

Artificial Intelligence (AI) has emerged as a disruptive technology in various areas, and medicine is no exception. In the last decade, there has been rapid progress in the application of AI in healthcare, from diagnosing and prognosticating diseases to improving operational efficiency in hospitals. This literature review explores the advances of artificial intelligence in the field of medicine, discusses its benefits, and discusses the ethical and regulatory challenges that need to be addressed to maximize its potential.

Appropriate use of perioperative antimicrobials can significantly reduce the risk of postoperative infections. However, inappropriate antimicrobial use can result in the creation of multidrug resistant bacteria, increased costs, host flora disruption, side effects, and increased risk of hospital-acquired infections This survey evaluated the current perioperative use of antimicrobials in small animals by Spanish veterinarians using a web-based questionnaire. Responses were represented using descriptive statistics and a statistical analysis of the association between demographic data and perioperative antimicrobial use was performed. Preoperative antimicrobials were administered in clean surgery by up to 68.3% of participants, 81.0% in clean-contaminated surgery and 71.3% in dirty surgery, while in the postoperative period, antimicrobials were administered by up to 86.3% of participants in clean surgery, 93.2% in clean-contaminated surgery and 87.5% in dirty surgery. Factors considered “very important” for antimicrobial selection were the degree of wound contamination, patient immunosuppression, and use of prosthesis. The most frequently used antimicrobial was beta-lactamase-resistant penicillin. Postoperative antimicrobial use was associated with participants without postgraduate training. This study highlights an overuse of antimicrobials in perioperative procedures in small animal surgery in Spain. Therefore, evidence-based guidelines and further education regarding the correct use of antimicrobial prophylaxis are recommended.

By analyzing the urban landscape, this investigation focuses on commercial typologies in historical urban areas and its relationship with the urban landscape and its heritage values. Trade plays an essential role in historical urban areas, both in the past and in the present, since it is part of the urban landscape—creating it and modifying it, but also preserving it. Historical protected urban areas contain diverse elements reflecting the impacts of commercial activities that have existed in cities throughout history. At present, the urban landscape of commercial activity is made up of a multiplicity of typologies and formats which interact with the historical landscape and its values, using them to strengthen its strategies of attraction, differentiation, and sales. Shop owners contribute to the preservation of historic urban areas by maintaining the commercial functions within them. Therefore, we affirm that the role of commercial activity in the preservation of urban protected areas is essential. However, further research is needed because this aspect has not been addressed in depth by the scientific community specializing in the management of cultural heritage.

The extra precession of Mercury - 42.9 seconds of arc per century - explained by General Relativity (GR), is the result of a secular addition of 5.02 × 10⁻⁷ rad. at the end of every orbit around the Sun. We will analyze, the instantaneous precession and its addition along one orbit, determine the magnitude and oscillations around the mean value, comparing key theoretical proposals. This angular precession, should be the result reaction of Mercury to the gravitoelectric action produced by the geometric curve space-time at each single point of the elliptic orbit. The better we should know about this instantaneous precession, the better we will determine the external action and its quantum core nature, if that is the case. The Doppler tracking of the MESSENGER spacecraft, produces only 1 m error, enough precision to deduce the complete geodesic orbit of Mercury as an open free-fall path, isolated from other planets gravitational interference. The aim of this article is also to encourage JPL, IMCCE. and other scientific teams to do so because, as far as I know, it has not been entirely measured yet, by accurately tracking that motion.

Renewable methanol, obtained from CO₂ and hydrogen provided from renewable energy, has been proposed as a way to close the CO₂ loop. In industry, methanol synthesis using the catalyst CuO/ZnO/Al₂O₃ occurs at a high pressure. We intend to make certain modification on the traditional catalyst in order to work at lower pressure, maintaining high selectivity. Therefore, three heterogeneous catalysts have been synthesized by co-precipitation in order to improve the activity and the selectivity to methanol under mild conditions of temperature and pressure. Certain modifications on the traditional catalyst Cu/Zn/Al₂O₃ were employed such as the modification of the synthesis time and the addition of Pd as a dopant agent. The most efficient catalyst among those tested was a palladium-doped catalyst, 5% Pd/Cu/Zn/Al₂O₃. This had a selectivity of 64% at 210C and 5 bar.

Hybrid Renewable Energy Systems (HRES) integrate renewable sources, storage, and optionally conventional energies, offering an eco-friendly solution to fossil fuels. Microgrids (MGs) bolster HRES integration, enhancing energy management, resilience, and reliability at various levels. This study, emphasizing the need for refined optimization methods, investigates three themes: renewable energy, microgrid, and multiobjective optimization (MOO), through a bibliometric analysis of 470 Scopus documents from 2010-2023, analyzed with SciMAT software. It segments the research into two periods, 2010-2019 and 2020-2023, revealing a surge in MOO focus, especially in the latter period, with a 35% increase in MOO-related research. This indicates a shift towards com-prehensive energy ecosystem management that balances environmental, technical, and economic elements. The initial focus on MOO, genetic algorithms, and energy management systems has expanded to include smart grids and electric power systems, with MOO remaining a primary theme in the second period. The increased application of Artificial Intelligence (AI) in optimizing HMGS within the MOO framework signals a move towards more sustainable, intelligent energy solutions. Despite progress, challenges remain, including high battery costs, the need for reliable MOO data, the intermittency of renewable energy sources, and HMGS network scalability issues, highlighting directions for future research.

This paper presents a novel improvement of MuSIASEM (Multiscale Integrated Analysis of the Societal and Ecological Metabolism) by incorporating a new regional analysis of the electricity metabolism across levels. An analysis of Mexico illustrates this toolkit and shows that the industry sector had Economic Energy Intensity (EEI) with 40.3 MWh/MMXN reached a higher value than the commerce and services sector with 0.84 MWh/MMXN. Regarding the Economic Labor Productivity (ELP) indicator (AV/h), the industrial sector with 208.5 TMXN/Kh reached a higher value than the Commercial and services sector with 114.3 TMXN/Kh. With reference to the Exosomatic Metabolic Rate (EMR), the Household sector obtained 59.3 KWh/Kh whereas the paid sector reached 2,486.4 KWh/Kh. Disaggregation of the EMR indicator into economic sectors shows that the Industrial sector obtained 8.4 KWh/Kh and the commercial and services sector reached 0.10 KWh/Kh. The lack of complete data for the agricultural sector does not allow us to calculate EEI, ELP, and EMR indicators accurately. Considering the analysis of indicators by regions, regarding the EEI rate, the Central region had the lowest value with 12.7 MWh/MMXN, followed by the Northeast with 21.4 MWh/MMXN and Western with 29.4 MWh/ MMXN, which means that they require less electricity to produce more added value. In terms of the ELP indicator, it was found regions with higher values were Northeast with 182.3 MMXN/Mh, Central with 177.5 MMXN/Mh, and North with 127 MMXN/Mh, which means that these regions produce more added value per hour of work. About the EMR, it is observed that regions in the northern part of the country had higher values: Northwest with 337 KWh/Kh, Baja California Sur with 334 KWh/Kh, Baja California with 328 KWh/Kh, North with 313 KWh/Kh and Northeast with 274 KWh/Kh, which means that these regions consume more electricity per hour. This innovative approach is useful for governance because it helps to understand and reduce asymmetries across regions, resulting in more social equality and a better economic equilibrium across sectors and regions.

The binding affinity of trastuzumab and pertuzumab to HER2 has been studied using both experimental and in-silico methods. The experiments were conducted using the antibodies in their complete IgG form, as used in clinical therapy, and the extracellular domain of the HER2 protein in solution. This approach provides a precise, reproducible, and reliable view of the interaction between them in physiological conditions. Dynamic light scattering and size exclusion chromatography coupled with tetra detection were utilized to characterize the protein complexes, measure their concentrations, and calculate the equilibrium free binding energy, ΔGbind. In addition, PRODIGY, a QSAR-like model with excellent predictive ability, was employed to obtain in-silico ΔGbind estimations. The results obtained indicate that pertuzumab exhibits a slightly higher binding affinity to HER2 than trastuzumab. The difference in binding affinity was explained based on the contribution of the different interfacial contact (IC) descriptors to the ΔGbind value estimated by the PRODIGY model. Furthermore, experiments revealed that the pertuzumab IgG antibody binds preferentially to two HER2 proteins, one per Fab fragment, while trastuzumab mainly forms a monovalent complex. This finding was interpreted based on a geometrical model that identified steric crowding in the trastuzumab-HER2 complex as compared to the pertuzumab-HER2 complex.

Breast cancer (BC) is the most common cancer diagnosed in women worldwide. Approximately 70% of BC patients have the luminal subtype, which expresses hormone receptors (HR+). Adjuvant endocrine treatments are the standard of care for HR+/HER2- BC patients. Over time, approximately 30% of those patients develop endocrine resistance and metastatic disease. Cyclin-dependent kinase inhibitors (CDKi) in combination with an aromatase inhibitor or fulvestrant have demonstrated superior efficacies in increasing progression-free survival, with a safe toxicity profile, in HR+/HER2- metastatic BC patients. CDKi blocks kinases 4/6, preventing G1/S cell cycle transition. However, not all patients respond to CDKi, and those who do respond ultimately develop resistance to the combined therapy. Studies in tumour tissues and cell lines have tried to elucidate the mechanisms underlying this progression, but there are still no conclusive data. Over the last few years, liquid biopsy has contributed relevant information. Circulating tumour materials are potential prognostic markers for determining patient prognosis in metastatic luminal BC, for monitoring disease and for treatment selection. This review outlines the different studies performed using liquid biopsy in patients with HR+ metastatic BC treated with CDKi plus endocrine therapy. We focus mainly on those studies that describe possible resistance mechanisms in circulating tumour-derived material.

Breast cancer is the most commonly diagnosed cancer in women worldwide. Approximately, 70 % of breast cancer patients express hormone receptors (HR) (Luminal subtype). Adjuvant endocrine treatments are the standard of care in HR+/HER2- breast cancer. Over time, about 50% of those patients develop endocrine resistance and metastatic breast cancer. Cyclin-dependent kinase inhibitors (CDKi) in combination with an aromatase inhibitor or fulvestrant have demonstrated superior efficacy increasing progression-free survival, with a safe toxicity profile, in HR+/HER2- metastatic breast cancer patients. CDKi blocks kinases 4/6 ATP-binding domain preventing G1/S cell cycle transition. Despite this, not all patients respond to CDKi and those who respond, finally develop resistance to combination therapy. Different studies, in tumour tissue or cell lines, have tried to elucidate the mechanisms underlying this progression, but there are still no conclusive data. In the last few years, liquid biopsy has contributed relevant information to this knowledge. Liquid biopsy can be performed in real-time, non-invasively and be repeated whenever needed. Circulating tumour material are potential prognostic markers in metastatic luminal breast cancer to determine patient prognosis, monitor disease and treatment selection. The objective of this review is to outline the different studies carried out in HR+ metastatic breast cancer patients treated with CDKi plus endocrine therapy using liquid biopsy approaches looking for possible resistance mechanisms.

The goal of this study is both to determine the opinion that professors and students at the University of (details removed for peer review) have of active methodologies and to describe the perception and opinion of the modes of organization, methodological focuses, and evaluation systems that define the teaching-learning process. On surveying the professors and the students in their classes, we found significant differences in 32 of the 92 variables in common. The content of these results shows that professors and students are believe they are making progress toward a learning-centered model, that implementation of active methodologies implies new functions in their teaching practice.

Background and aims: Only one cohort study exists on the incidence of the risk of malnutrition (RM) in older adults, though numerous cross-sectional –and that cohort research– have reported several risk factors associated with the prevalence and incidence of this condition. However, alterations of body composition and impaired physical performance as exposition variables of RM have not been explored. This study assessed the incidence of RM and determined its association with excess fat mass, low total lean tissue, gait speed, and handgrip strength as exposition variables for RM in community-dwelling older adults. Methods: This is a secondary analysis in older adults (≥60 years old) derived from the study “Frailty, dynapenia, and sarcopenia in Mexican adults (FraDySMex)” a prospective cohort project conducted from 2014 to 2019 in Mexico City. At baseline, volunteers underwent body composition analysis and physical performance tests. Several covariates were identified through comprehensive geriatric assessment. At baseline and follow-up, RM was assessed using the long form of the mini nutritional assessment (MNA-LF) scale. Associations between the exposition variables and RM were assessed by multiple logistic regression. Results: The cohort included 241 subjects. Average age was 75.6±7.8 years; 83.4% were women. The mean follow-up period was 4.1 years, during which 28.6% of subjects developed RM. This condition was less likely to occur in subjects with excess fat mass index, even after adjusting for several covariates. RM was also more likely to occur in subjects with low total lean tissue index, according to both an unadjusted model and after adjusting for the corresponding variables. Regarding the association between RM and gait speed, RM was also more likely to occur in subjects with low gait speed according to both the unadjusted and adjusted models. Similar results were found for RM in relation to low handgrip strength; however, after adjusting for the associated covariates, models 1 and 2 no longer reached the level of significance. Conclusion: The risk of malnutrition diagnosed by MNA-LF was significantly less likely to occur among subjects with excess fat mass, but possibility was significantly higher in those with low total lean tissue and low gait speed after 4.1 years of follow-up in community-dwelling older adults. These results highlight that excess fat mass, low total lean tissue, and low gait speed are first than risk of malnutrition and not vice versa.

The analysis of curated genomic, metagenomic, and proteomic data are of paramount importance in the fields of biology, medicine, education, and bioinformatics. Although this type of data is usually hosted in raw form in free international repositories, its access requires plenty of computing, storage, and processing capacities for the domestic user. The purpose of the study is to offer a comprehensive set of genomic and proteomic reference data, in an accessible and easy-to-use form to the scientific community. A representative type material set of genomes, proteomes and metagenomes were directly downloaded from the site: https://www.ncbi.nlm.nih.gov/assembly/ and from Genome Taxonomy Database, associated with the major groups of Bacteria, Archaea, Virus, and Fungi. Sketched databases were subsequently created and stored on handy raw reduced representations, by using Mash software. Our dataset contains near to 100 GB of space disk reduced to 585.78 MB and represents 87,476 genomics/proteomic records from eight informative contexts, which have been prefiltered to make them accessible, usable, and user-friendly with computational resources. Potential uses of this dataset include but are not limited to, microbial species delimitation, estimation of genomic distances, genomic novelties, paired comparisons between proteomes, genomes, and metagenomes.