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Green hydrogen production is a sustainable energy solution with great potential, offering advantages such as adaptability, storage capacity and ease of transport. However, there are challenges such as high energy consumption, production costs, demand and regulation, which hinder its large-scale adoption. This study explores the role of simulation models in optimizing the technical and economic aspects of green hydrogen production. The proposed system, which integrates photovoltaic and energy storage technologies, significantly reduces the grid dependency of the electrolyzer, achieving an energy self-consumption of 64 kWh per kilogram of hydrogen produced. By replacing the high-fidelity model of the electrolyzer with a reduced-order model, it is possible to minimize the computational effort and simulation times for different step configurations. These findings offer relevant information to improve the economic viability and energy efficiency in green hydrogen production. This facilitates decision-making at a local level by implementing strategies to achieve a sustainable energy transition.

Abstract Background Genome complexity is largely linked to diversification and crop innovation. Examples of regions with duplicated genes with relevant roles in agricultural traits are found in many crops. In both duplicated and non-duplicated genes, much of the variability in agronomic traits is caused by large as well as small and middle scale structural variants (SVs), which highlights the relevance of the identification and characterization of complex variability between genomes for plant breeding. Results Here we improve and demonstrate the use of CRISPR-Cas9 enrichment combined with long-read sequencing technology to resolve the MYB10 region in the linkage group 3 (LG3) of Japanese plum (Prunus salicina). This region, which has a length from 90 to 271 kb according to the P. salicina genomes available, is associated with fruit color variability in Prunus species. We demonstrate the high complexity of this region, with homology levels between Japanese plum varieties comparable to those between Prunus species. We cleaved MYB10 genes in five plum varieties using the Cas9 enzyme guided by a pool of crRNAs. The barcoded fragments were then pooled and sequenced in a single MinION Oxford Nanopore Technologies (ONT) run, yielding 194 Mb of sequence. The enrichment was confirmed by aligning the long reads to the plum reference genomes, with a mean read on-target value of 4.5% and a depth per sample of 11.9x. From the alignment, 3261 SNPs and 287 SVs were called and phased. A de novo assembly was constructed for each variety, which also allowed detection, at the haplotype level, of the variability in this region. Conclusions CRISPR-Cas9 enrichment is a versatile and powerful tool for long-read targeted sequencing even on highly duplicated and/or polymorphic genomic regions, being especially useful when a reference genome is not available. Potential uses of this methodology as well as its limitations are further discussed.

The Pyrenees are inhabited by scattered populations of earwigs of the genus Chelidura Latreille, 1825. There is some controversy about the specific assignment of these populations: while most authors assign them to C. pyrenaica (Gené, 1832), other consider that C. aptera (Mégerlé, 1825) is also present in the Pyrenees. The main objective of this work was to revise the identity and synonyms of Pyrenean Chelidura. Specimens from recent fieldwork and collections (MNCN-CSIC) were used for morphological and molecular studies (cytochrome oxidase 1). All Pyrenean specimens shared similar cox1 sequences, very divergent from those of Alpine C. aptera. As a consequence, the variability observed in male cerci morphology from the Pyrenees, ranging from long and slightly curved to short and very curved, corresponded to C. pyrenaica, and the presence of C. aptera in the Pyrenees can be rejected. As previously suggested by Maccagno (1933) and Fontana et al. (2021), the revision of the synonymic list uncovered the misplacement of the name F. simplex Germar, 1825 under the synonymy of C. aptera, while it rather represents a synonym of C. pyrenaica (syn. nov.). Forficula simplex has nomenclatural priority over C. pyrenaica, however both names meet the requirements of the article 23.9.1 of the International Code of Zoological Nomenclature to retain the prevailing usage of C. pyrenaica (nomen protectum) over F. simplex (nomen oblitum). Additionally, we discuss the taxonomic status of Chelidura arverna David & Van Herrewege, 1973 stat. nov. from the French Massif Central.

This work presents a study on the airborne bacteria recorded in three Andalusian show caves, subjected to different managements. The main differences within the caves were the absence of lighting and phototrophic biofilms in Cueva de Ardales, the periodic maintenance and low occurrence of phototrophic biofilms in Gruta de las Maravillas, and the abundance of phototrophic biofilms in speleothems and walls in Cueva del Tesoro. These factors conditioned the diversity of bacteria in the caves and therefore there are large differences among the CFU m-3, determined using a suction impact collector, equipment widely used in aerobiological studies. The study of the bacterial diversity, inside and outside the caves, indicates that the air is mostly populated by bacteria thriving in the subterranean environment. In addition, the diversity seems to be related with the presence of abundant phototrophic biofilms, but not with the number of visitors received by each cave.

Local field potential (LFP) deflections and oscillations define hippocampal sharp-wave ripples (SWRs), one of the most synchronous events of the brain. SWRs reflect firing and synaptic current sequences emerging from cognitively relevant neuronal ensembles. While spectral analysis have permitted advances, the surge of ultra-dense recordings now call for new automatic detection strategies. Here, we show how one-dimensional convolutional networks operating over high-density LFP hippocampal recordings allowed for automatic identification of SWR from the rodent hippocampus. When applied without retraining to new datasets and ultra-dense hippocampus-wide recordings, we discovered physiologically relevant processes associated to the emergence of SWR, prompting for novel classification criteria. To gain interpretability, we developed a method to interrogate the operation of the artificial network. We found it relied in feature-based specialization, which permit identification of spatially segregated oscillations and deflections, as well as synchronous population firing typical of replay. Thus, using deep learning-based approaches may change the current heuristic for a better mechanistic interpretation of these relevant neurophysiological events.

Madrigal and Jurado use brain clearing techniques and 3D imaging to generate high-resolution reconstructions of oxytocinergic and vasopressinergic circuits in the developing mouse brain, which are known to play a crucial role in social behaviours. They provide insight into the specification and consolidation of these circuits from embryonic to early postnatal stages of development.

Research on cave microorganisms has mainly focused on the microbial communities thriving on speleothems, rocks and sediments; however, drip water bacteria and calcite precipitation has received less attention. In this study, microbial communities of carbonate precipitates from drip waters in Nerja, a show cave close to the sea in southeastern Spain, were investigated. We observed a pronounced difference in the bacterial composition of the precipitates, depending on the galleries and halls. The most abundant phylum in the precipitates of the halls close to the cave entrance was Proteobacteria, due to the low depth of this sector, the direct influence of a garden on the top soil and the infiltration of waters into the cave, as well as the abundance of members of the order Hyphomicrobiales, dispersing from plant roots, and other Betaproteobacteria and Gammaproteobacteria, common soil inhabitants. The influence of marine aerosols explained the presence of Marinobacter, Idiomarina, Thalassobaculum, Altererythrobacter and other bacteria due to the short distance from the cave to the sea. Nineteen out of forty six genera identified in the cave have been reported to precipitate carbonate and likely have a role in mineral deposition.

Mines, like other subterranean environments, have ecological conditions which allow the thriving of microorganisms. Prokaryotes and fungi are common inhabitants of mines, developing a metabolism suitable for growing in such inhospitable environments. The mine of Lousal, Portugal, is an interesting site for the study of microorganisms present in their galleries. Aerobiological studies resulted in the isolation of a Pseudomonas sp., strain L5B5, closely related to the opportunistic fish pathogen P. piscis MC042T, and to the soil bacteria P. protegens CHA0T, P. protegens Cab57, and P. protegens Pf-5. Strain L5B5 was able to inhibit the growth of the pathogenic bacteria Bacillus cereus, Staphylococcus aureus, and Acinetobacter baumanii, as well as the cave fungi Aspergillus versicolor, Penicillium chrysogenum, Cladosporium cladosporioides, Fusarium solani, and Ochroconis lascauxensis. In silico analyses based on de novo genome hybrid assembly and RNA-Seq, performing seven conditions based on culture and phases of growth resulted in the prediction and detection of genetic mechanisms involved in secondary metabolites, with the presence of a possible new gene cluster transcribed under the tested conditions, as well as feasible virulence factors and antimicrobial resistance mechanisms.

Introduction: Psychotic disorders are a mental illness that affect 3% of the world’s population. The external (cannabis) and internal vulnerability factors (polymorphisms of the AKT1 gene, the COMT gene and the DAT1 gene) acquire special relevance in the appearance of psychosis; this is known as the vulnerability–stress model. Objective: To analyze the scientific evidence that reflects the relationship between the polymorphism of the AKT1 gene and the consumption of cannabis in the appearance of psychosis. Material and Methods: The bibliographic search was made using databases such as Scopus, WoS, Cochrane Library, TRIP Database, PubPsych and PubMed. The criteria of the “MeSH” terminology and the inclusion and exclusion criteria were followed, obtaining a total of 22 articles that comprises this narrative review. Results: The presence of genetic variation in the locus rs2494732 of the AKT1 gene in a cannabis user raises the risk of the appearance of psychosis, especially if homozygous with the C allele. Likewise, consumption entails a slowdown in the functionality of the AKT1 gene, releasing a greater amount of dopamine in the striatum through the involvement of indirect mechanisms. Similarly, the COMT gene and the interaction of the AKT1 gene with the DAT1 gene raise the risk of developing psychotic disorder. Conclusion: The genetic polymorphism rs2494732 of AKT1 is the main factor responsible for the appearance of psychosis, although polymorphisms of the COMT and DAT1 gene are also implicated. Regarding the AKT1 gene, subjects with two copies of the C allele have a higher risk of developing psychosis compared to subjects with two copies of the T allele. It should also be noted that the muscarinic receptors rs115455482 and rx74722579 are related to a greater vulnerability to psychosis and the development of psychotic disorders.

Introduction: Diabetic foot is the infection, ulceration or destruction of the deep tissues of the foot in patients with diabetes mellitus. This pathology occurs when there are high levels of glucose in the blood, as well as other factors such as high blood pressure and hypercholesterolemia. These factors cause damage to the vessels and nerves, producing medium and long-term complications. This is a health problem that affects diabetic patients throughout their lives. Objective: To know the different techniques and strategies that allow to carry out an appropriate management of the diabetic foot. Methodology: A narrative review was carried out between November 2021 and July 2022 in the different databases of Pubmed (Medline), Scielo, Scopus and Web of Science (WOS), with a search string that combined the keywords derived from thesauri, namely Descriptors of Health Sciences (DeCS) and Medical Subject Headings (MeSH), combined with the Boolean operators “AND”, “NOT” and “NOT”. Results: After applying the article selection criteria and evaluating the quality of the methodology, a total of 22 articles were obtained. The results affirm the existence of promising therapies for the treatment of diabetic foot ulcers such as negative-pressure therapy and hyperbaric oxygen therapy. It is highlighted that the use of therapeutic footwear and health education are deficient aspects that must be reinforced. Conclusions: After comparing the different articles, it was possible to determine that negative-pressure therapy and hyperbaric oxygen therapy should be promoted as they are suitable for the treatment of diabetic foot ulcers. In addition, therapeutic footwear is a baseline in the diabetic foot approach. On the other hand, it is necessary to reinforce interdisciplinary work in this area and health education for patients suffering from this disease.

Introduction: Ventilator-associated pneumonia (VAP) constitutes a real iatrogenic health problem, which can lead to a higher rate of hospital admission days associated with the morbidity and mortality that it could cause. Objective: To study and learn about the different preventive measures used to reduce the incidence of VAP, as well as to study the microorganisms that most frequently cause VAP. To determine the nursing staff’s knowledge of this phenomenon and the social and health care costs derived from the disease. Methodology: The bibliographic search of the existing literature was carried out between November 2021 and June 2022. In order to gather all the necessary information, different databases were searched. For this purpose, a search strategy was developed using keywords included in “DeCS” and “MeSH” and using boolean operators such as “AND and OR”, and all articles meeting the chosen inclusion criteria were included. Results: After applying the article selection criteria and assessing the quality of the methodology, a total of 33 articles were finally included for systematic review. The results show the usefulness of various preventive measures against the micro-organisms that most frequently cause this type of pneumonia, as well as the true cost associated with this pathology and the still insufficient knowledge of healthcare personnel about it. Conclusion: Although many advances have reduced the incidence and mortality of this pathology, further research, training of healthcare personnel and implementation of new protocols are still required.

Sarcoglycanopathies are a group of recessive limb-girdle muscular dystrophies, characterized by progressive muscle weakness. Sarcoglycan deficiency produces instability of the sarcolemma during muscle contraction, leading to continuous muscle fiber injury eventually producing fiber loss and replacement by fibro-adipose tissue. Therapeutic strategies aiming to reduce fibro-adipose expansion could be effective in muscular dystrophies. We report the positive effect of nintedanib in a murine model of alpha-sarcoglycanopathy. We treated 14 Sgca-/- mice, six weeks old, with nintedanib 50 mg/kg every 12 h for 10 weeks and compared muscle function and histology with 14 Sgca-/- mice treated with vehicle and six wild-type littermate mice. Muscle function was assessed using a treadmill and grip strength. A cardiac evaluation was performed by echocardiography and histological study. Structural analysis of the muscles, including a detailed study of the fibrotic and inflammatory processes, was performed using conventional staining and immunofluorescence. In addition, proteomics and transcriptomics studies were carried out. Nintedanib was well tolerated by the animals treated, although we observed weight loss. Sgca-/- mice treated with nintedanib covered a longer distance on the treadmill, compared with non-treated Sgca-/- mice, and showed higher strength in the grip test. Moreover, nintedanib improved the muscle architecture of treated mice, reducing the degenerative area and the fibrotic reaction that was associated with a reversion of the cytokine expression profile. Nintedanib improved muscle function and muscle architecture by reducing muscle fibrosis and degeneration and reverting the chronic inflammatory environment suggesting that it could be a useful therapy for patients with alpha-sarcoglycanopathy.

Background Direct Acting Antivirals (DAAs) represent a large improvement in the treatment of chronic hepatitis C, resulting in

Antimicrobial resistance has become a global problem in recent decades. A gradual reduction in drug discoveries has led to the current antimicrobial resistance crisis. Caves and other subsurface environments are underexplored thus far, and they represent indispensable ecological niches that could offer new molecules of interest to medicine and biotechnology. We explored Spanish show caves to test the bioactivity of the bacteria dwelling in the walls and ceilings, as well as airborne bacteria. We reported the isolation of two strains of the genus Crossiella, likely representing a new species, isolated from Altamira Cave, Spain. In vitro and in silico analyses showed the inhibition of pathogenic Gram-positive and Gram-negative bacteria, and fungi, as well as the taxonomical distance of both strains from their closest relative, Crossiella cryophila. The presence of an exclusive combination of gene clusters involved in the synthesis of lanthipeptides, lasso peptides, nonribosomal peptides and polyketides indicates that species of this genus could represent a source of new compounds. Overall, there is promising evidence for antimicrobial discovery in subterranean environments, which increases the possibility of identifying new bioactive molecules.

Los Lactobacillus inhiben múltiples agentes patógenos causales de toxiinfecciones alimentarias, relacionándose su mecanismo de acción con la modulación del sistema inmune. Por su parte, E. coli O157:H7 es considerado un microorganismo causal de alteraciones, principalmente, a nivel intestinal y renal y es encontrado, por lo general, en matrices alimentarias contaminadas o en mal estado. La incidencia de este tipo de problemática se ha relacionado a la resistencia a los antibióticos, que limita su control y mitigación de manera eficaz. Por lo tanto, el objetivo del trabajo fue evaluar el efecto inhibitorio de Lactobacillus plantarum microencapsulado in vitro sobre Escherichia coli O157:H7, con el fin de encontrar estrategias inocuas para el control de agentes patógenos. Se determinó la cinética de fermentación, evaluando variables, como consumo de azúcar, producción de proteínas, acidez, pH y fase logarítmica (UFC/mL). La microencapsulación, se realizó mediante la técnica de spray drying, utilizando inulina y maltodextrina, como materiales encapsulantes. Se determinó la viabilidad de L. plantarum bajo condiciones gastrointestinales simuladas. Además, se evaluaron las características físicas del microorganismo microencapsulado y el efecto inhibitorio de L. plantarum y su sobrenadante sobre E. coli O157:H7. Posteriormente, se valoró la susceptibilidad de ambas cepas a diferentes antibióticos. Como resultado, se encontró resistencia de ambas cepas a algunos antibióticos evaluados, como penicilina. La cepa láctica y el sobrenadante inhibieron el crecimiento de E. coli O157:H7. L. plantarum presentó una viabilidad óptima a condiciones gastrointestinales simuladas después de 45 días de almacenamiento (1,4x107-3,0x1010UFC/150µL). La microencapsulación incrementa su vialidad y su establecimiento en el huésped.

Lava caves differ from karstic caves in their genesis and mineral composition. Subsurface microbiology of lava tube caves in Canary Islands, a volcanic archipelago in the Atlantic Ocean, is largely unknown. We have focused the investigation in a representative lava tube cave, Fuente de la Canaria Cave, in La Palma Island, Spain, which presents different types of speleothems and colored microbial mats. Four samples collected in this cave were studied using DNA next-generation sequencing and field emission scanning electron microscopy for bacterial identification, functional profiling, and morphological characterization. The data showed an almost exclusive dominance of Bacteria over Archaea. The distribution in phyla revealed a majority abundance of Proteobacteria (37–89%), followed by Actinobacteria, Acidobacteria and Candidatus Rokubacteria. These four phyla comprised a total relative abundance of 72–96%. The main ecological functions in the microbial communities were chemoheterotrophy, methanotrophy, sulfur and nitrogen metabolisms, and CO2 fixation; although other ecological functions were outlined. Genome annotations of the especially representative taxon Ga0077536 (about 71% of abundance in moonmilk) predicted the presence of genes involved in CO2 fixation, formaldehyde consumption, sulfur and nitrogen metabolisms, and microbially-induced carbonate precipitation. The detection of several putative lineages associated with C, N, S, Fe and Mn indicates that Fuente de la Canaria Cave basalts are colonized by metabolically diverse prokaryotic communities involved in the biogeochemical cycling of major elements.

Understanding brain operation demands linking basic behavioral traits to cell-type specific dynamics of different brain-wide subcircuits. This requires a system to classify the basic operational modes of neurons and circuits. Single-cell phenotyping of firing behavior during ongoing oscillations in vivo has provided a large body of evidence on entorhinal-hippocampal function, but data are dispersed and diverse. Here, we mined literature to search for information regarding the phase-timing dynamics of over 100 hippocampal/entorhinal neuron types defined in Hippocampome.org. We identified missing and unresolved pieces of knowledge (e.g., the preferred theta phase for a specific neuron type) and complemented the dataset with our own new data. By confronting the effect of brain state and recording methods, we highlight the equivalences and differences across conditions and offer a number of novel observations. We show how a heuristic approach based on oscillatory features of morphologically identified neurons can aid in classifying extracellular recordings of single cells and discuss future opportunities and challenges towards integrating single-cell phenotypes with circuit function.

Summary: There is an urgent need for antivirals to treat the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To identify new candidates, we screen a repurposing library of ∼3,000 drugs. Screening in Vero cells finds few antivirals, while screening in human Huh7.5 cells validates 23 diverse antiviral drugs. Extending our studies to lung epithelial cells, we find that there are major differences in drug sensitivity and entry pathways used by SARS-CoV-2 in these cells. Entry in lung epithelial Calu-3 cells is pH independent and requires TMPRSS2, while entry in Vero and Huh7.5 cells requires low pH and triggering by acid-dependent endosomal proteases. Moreover, we find nine drugs are antiviral in respiratory cells, seven of which have been used in humans, and three are US Food and Drug Administration (FDA) approved, including cyclosporine. We find that the antiviral activity of cyclosporine is targeting Cyclophilin rather than calcineurin, revealing essential host targets that have the potential for rapid clinical implementation.

Tension and mechanical properties of muscle tissue are tightly related to proper skeletal muscle function, which makes experimental access to the biomechanics of muscle tissue formation a key requirement to advance our understanding of muscle function and development. Recently developed elastic in vitro culture chambers allow for raising 3D muscle tissue under controlled conditions and to measure global tissue force generation. However, these chambers are inherently incompatible with high-resolution microscopy limiting their usability to global force measurements, and preventing the exploitation of modern fluorescence based investigation methods for live and dynamic measurements. Here, we present a new chamber design pairing global force measurements, quantified from post-deflection, with local tension measurements obtained from elastic hydrogel beads embedded in muscle tissue. High-resolution 3D video microscopy of engineered muscle formation, enabled by the new chamber, shows an early mechanical tissue homeostasis that remains stable in spite of continued myotube maturation.

The Cross of the Inquisition, sculpted in 1903 and raised on a column with a fluted shaft and ornamented with vegetable garlands, is located in a corner of the Plateresque façade of the Seville City Hall. The Cross was vandalized in September 2019 and the restoration concluded in September 2021. A geological and microbiological study was carried out in a few small fragments. The data are consistent with the exposure of the Cross of the Inquisition to an urban environment for more than 100 years. During that time, a lichen community colonized the Cross and the nearby City Hall façades. The lichens, bryophytes and fungi colonizing the limestone surface composed an urban community, regenerated from the remains of the original communities, after superficial cleaning of the limestone between 2008 and 2010. This biological activity was detrimental to the integrity of the limestone, as showed by the pitting and channels, which evidence the lytic activity of organisms on the stone surface. Stone consolidation was achieved with Estel 1000. Preventol RI80, a biocide able to penetrate the porous limestone and active against bacteria, fungi, lichens, and bryophytes, was applied in the restoration.

Nannochloropsis gaditana is a microalga with interesting nutritional and functional value due to its high content of protein, polyunsaturated fatty acids, and bioactive compounds. However, the hardness of its cell wall prevents accessibility to these components. This work aimed to study the effect of a treatment to increase the fragility of the cell wall on the bioavailability of its nutrients and functional compounds. The antioxidant and antiproliferative capacity of functional extracts from treated and untreated N. gaditana was assessed, and the profile of bioactive compounds was characterized. Furthermore, to study the effect of treatment on its nutrient availability and functional capacity, an in vivo experiment was carried out using a rat experimental model and a 20% dietary inclusion level of microalgae. Functional extracts from treated N. gaditana exhibited higher antioxidant activity than the untreated control. Furthermore, the treated microalga induced hypoglycemic action, higher nitrogen digestibility, and increased hepatic antioxidant activity. In conclusion, N. gaditana has interesting hepatoprotective, antioxidant, and anti-inflammatory potential, thus proving itself an ideal functional food candidate, especially if the microalga is treated to increase the fragility of its cell wall before consumption.

The Columbretes archipelago consists of a group of small volcanic islets located in the western Mediterranean near the east of the Iberian Peninsula. Four of its islands are inhabited by the wall lizard Podarcis liolepis, whose populations have been considered vulnerable. The purpose of this study was to assess the level of genetic diversity across the archipelago and the possible evolutionary origin of the Columbretes lizard populations. Additionally, we investigated the evolutionary ecology of these populations using a DNA-based metabarcoding approach to characterise both their microbiota and trophic interactions. The genetic results reported very low genetic diversity and corroborated the conspecificity between insular populations and P. liolepis from the mainland (Peñagolosa region). The results of the metabarcoding analyses based on faecal samples were in accordance with an omnivorous ecology, suggesting that specific microbiota communities in the insular populations might be correlated with differences in host ecology and phylogeny. These results are a valuable contribution to the current understanding of the evolution of Columbretes’ lizards and provide important information for conservation management.

Microsclerotia (MS) produced by some species of Metarhizium can be used as active ingredients in mycoinsecticides for the control of soil-dwelling stages of geophilic pests. In this study, the MS production potential of two Metarhizium brunneum strains and one M. robertsii strain was evaluated. The three strains were able to produce MS in liquid fermentation, yielding between 4.0 × 106 (M. robertsii EAMa 01/158-Su strain) and 1.0 × 107 (M. brunneum EAMa 01/58-Su strain) infective propagules (CFU) per gram of MS. The EAMa 01/58-Su strain was selected for further investigation into the effects of key abiotic factors on their survival and conidial yield. The MS were demonstrated to be stable at different storage temperatures (−80, −18, and 4 °C), with a shelf-life up to one year. The best temperature for MS storage was −80 °C, ensuring good viability of MS for up to one year (4.9 × 1010 CFU/g MS). Moreover, soil texture significantly affected CFU production by MS; sandy soils were the best driver of infective propagule production. Finally, the best combination of soil temperature and humidity for MS germination was 22.7 °C and 7.3% (wt./wt.), with no significant effect of UV-B exposure time on MS viability. These results provide key insights into the handling and storage of MS, and for decision making on MS dosage and timing of application.

Skin fibroblasts were obtained from four patients with Williams-Beuren syndrome (WBS) carrying the typical 1.5 Mb or 1.8 Mb deletion at the 7q11.23 genomic region. Induced pluripotent stem cells (iPSCs) were generated by retroviral infection of fibroblasts with polycystronic vectors. The generated iPSC clones ESi059A, ESi060B and ESi068A had the 1.5 Mb deletion of 7q11.23 and ESi069A the 1.8 Mb, with no novel additional genomic alterations, stable karyotype, expressed pluripotency markers and could differentiate towards the three germ layers in vitro via embryoid body formation and in vivo by teratoma formation. WBS patient’s lines are a valuable resource for in vitro modelling of WBS.

Skin fibroblasts were obtained from four patients with 7q11.23 microduplication syndrome carrying the reciprocal rearrangement of Williams-Beuren syndrome at the 7q11.23 genomic region. Induced pluripotent stem cells (iPSCs) were generated by retroviral infection of fibroblasts with polycystronic vectors. The generated iPSC clones ESi058B, ESi057B, ESi070A and ESi071A had the 7q11.23 duplication with no additional genomic alterations, a stable karyotype, expressed pluripotency markers and could differentiate towards the three germ layers in vitro via embryoid body formation and in vivo by teratoma formation. Patient’s derived iPSCs are a valuable resource for in vitro modeling of 7q11.23 microduplication syndrome.Resource Table:

El sector avícola ha disminuido los antibióticos por problemas de resistencia, lo que ha generado interés investigativo en alternativas para el manejo sanitario. Por ello, se evaluó el efecto del suministro de Lactobacillus casei microencapsulado en los parámetros productivos y salud intestinal del pollo de engorde. La investigación incluyó 240 pollos, en 4 tratamientos: alimento sin antibióticos ni anticoccidiales (T0), alimento con probiótico comercial (T1) y T2 y T3 con inclusión de L. casei microencapsulado y sin microencapsular, respectivamente. Se evaluó la eficiencia y la viabilidad de la conservación de la bacteria por parte del microencapsulado, además de sus características físicas. Se valoró in vivo el suministro de la bacteria láctica, mediante los parámetros productivos, bioquímicos en sangre, la morfología intestinal y la respuesta inmunológica. Se observó viabilidad y eficiencia de 75,9 y 89,4%, para el microencapsulado. El grupo de tratamiento con probiótico microencapsulado tuvo incremento significativo en la ganancia de peso y de consumo de alimento (p

Rhizobial NodD proteins and appropriate flavonoids induce rhizobial nodulation gene expression. In this study, we show that the nodD1 gene of Sinorhizobium fredii HH103, but not the nodD2 gene, can restore the nodulation capacity of a double nodD1/nodD2 mutant of Rhizobium tropici CIAT 899 in bean plants (Phaseolus vulgaris). S. fredii HH103 only induces pseudonodules in beans. We have also studied whether the mutation of different symbiotic regulatory genes may affect the symbiotic interaction of HH103 with beans: ttsI (the positive regulator of the symbiotic type 3 protein secretion system), and nodD2, nolR and syrM (all of them controlling the level of Nod factor production). Inactivation of either nodD2, nolR or syrM, but not that of ttsI, affected positively the symbiotic behavior of HH103 with beans, leading to the formation of colonized nodules. Acetylene reduction assays showed certain levels of nitrogenase activity that were higher in the case of the nodD2 and nolR mutants. Similar results have been previously obtained by our group with the model legume Lotus japonicus. Hence, the results obtained in the present work confirm that repression of Nod factor production, provided by either NodD2, NolR or SyrM, prevents HH103 to effectively nodulate several putative host plants.

The discovery of new antibiotics and other bioactive microbial metabolites is a priority given the frequency of the emerging multi-drug resistant pathogenic microorganisms. Thus, scientists are searching for new antibiotics in microorganisms isolated from extreme habitats such as caves. In the present study, we aimed to perform the first analysis on culturable microorganisms in the Chaabe Cave (Algeria), and to test the antimicrobial activities of the isolates (Streptomyces spp. and Penicillium spp.). The potential for antimicrobial activity of 47 strains of actinomycetes and 23 strains of fungi were tested on Candida albicans, Staphylococcus aureus, Micrococcus luteus, Listeria monocytogenes, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa. The identification of the most active actinomycetes strains by 16S rRNA gene sequence analysis revealed that these isolates were exclusively affiliated to the genus Streptomyces. On the other hand, the fungi were determined by phylogenetic analysis based on the ITS region or on the β tubulin gene and were affiliated to the genera Readeriella, Cladosporium, Aspergillus, Penicillium, Beauveria, Alternaria, Rhizopus, and Rhizomucor. The strains showed strong inhibitory activity against pathogenic microorganisms and the diameters of the inhibition zones vary between 7.5 and 34 mm for Streptomyces strains, and between 6.5 and 19.50 mm for Penicillium strains. The data indicated that the majority (72.86%) of the 70 isolates were active against at least one of the tested microorganisms. The production of nonpolyenic antifungal substances by active Streptomyces isolates was investigated using several criteria (antibacterial activity, ergosterol inhibition, and UV-visible spectra) of active extracts. The results were promising and showed that the metabolites produced by the actinomycete strains do not have a UV-visible spectrum characteristic of a polyenic structure. The Chaabe Cave possesses a diversity of microorganisms that could lead to new antibiotics necessary in the fight against drug-resistant pathogens and warrant further study.

This editorial focuses on the studies published within the present Special Issue presenting advances in the field of biodeterioration of cultural heritage caused by microbial communities with a particular focus on new methods for their elimination and control.

This paper presents an analysis and optimization of an isolated hybrid renewable power system to operate in the Alrashda village in the Dakhla Oasis, which is situated in the New Valley Governorate in Egypt. The proposed hybrid system is designed to integrate a biomass system with a photovoltaic (PV), wind turbine (WT) and battery storage system (Bat). Four different cases are proposed and compared for analyzing and optimizing. The first case is a configuration of PV and WT with a biomass system and battery bank. The second case is the integration of PV with a biomass system and battery bank. The third case is WT integrated with biomass and a battery bank, and the fourth case is a conventional PV, WT, and battery bank as the main storage unit. The optimization is designed to reduce component oversizing and ensure the dependable control of power supplies with the objective function of reducing the levelized cost of energy and loss of power supply probability. Four optimization algorithms, namely Heap-based optimizer (HBO), Franklin’s and Coulomb’s algorithm (CFA), the Sooty Tern Optimization Algorithm (STOA), and Grey Wolf Optimizer (GWO) are utilized and compared with each other to ensure that all load demand is met at the lowest energy cost (COE) for the proposed hybrid system. The obtained results revealed that the HBO has achieved the best optimal solution for the suggested hybrid system for case one and two, with the minimum COE 0.121171 and 0.1311804 $/kWh, respectively, and with net present cost (NPC) of $3,559,143 and $3,853,160, respectively. Conversely, STOA has achieved the best optimal solution for case three and four, with a COE of 0.105673 and 0.332497 $/kWh, and an NPC of $3,103,938 and $9,766,441, respectively.

Olive anthracnose caused by Colletotrichum species causes dramatic losses of fruit yield and oil quality worldwide. A total of 185 Colletotrichum isolates obtained from olives and other hosts showing anthracnose symptoms in Spain and other olive-growing countries over the world were characterized. Colony and conidial morphology, benomyl-sensitive, and casein-hydrolysis activity were recorded. Multilocus alignments of ITS, TUB2, ACT, CHS-1, HIS3, and/or GAPDH were conducted for their molecular identification. The pathogenicity of the most representative Colletotrichum species was tested to olive fruits and to other hosts, such as almonds, apples, oleander, sweet oranges, and strawberries. In general, the phenotypic characters recorded were not useful to identify all species, although they allowed the separation of some species or species complexes. ITS and TUB2 were enough to infer Colletotrichum species within C. acutatum and C. boninense complexes, whereas ITS, TUB2, ACT, CHS-1, HIS-3, and GADPH regions were necessary to discriminate within the C. gloesporioides complex. Twelve Colletotrichum species belonging to C. acutatum, C. boninense, and C. gloeosporioides complexes were identified, with C. godetiae being dominant in Spain, Italy, Greece, and Tunisia, C. nymphaeae in Portugal, and C. fioriniae in California. The highest diversity with eight Colletotrichum spp. was found in Australia. Significant differences in virulence to olives were observed between isolates depending on the Colletotrichum species and host origin. When other hosts were inoculated, most of the Colletotrichum isolates tested were pathogenic in all the hosts evaluated, except for C. siamense to apple and sweet orange fruits, and C. godetiae to oleander leaves.

The Salón de Reinos, a remnant of the 17th century Palacio del Buen Retiro, was built as a recreational residence under the reign of Felipe IV between 1632 and 1640 and was the main room for the monarch’s receptions. This Salón owes its name to the fact that the coats of arms (shields) of the 24 kingdoms that formed Spain in Felipe IV’s time were painted on the vault, above the windows. In addition, the ceiling shows an original decorative composition. The painted ceiling and window vaults showed deterioration evidenced by fissures, water filtration, detachments of the paint layer, and black stains denoting fungal colonization related to humidity. Ten strains of bacteria and 14 strains of fungi were isolated from the deteriorated paintings. Their biodeteriorative profiles were detected through plate assays. The most frequent metabolic functions were proteolytic and lipolytic activities. Other activities, such as the solubilization of gypsum and calcite and the production of acids, were infrequent among the isolates.

Municipal solid waste and sewage sludge are produced in large quantities that are often managed through industrial composting treatment. Because of their origin, composition, and complexity, ensuring adequate stabilization of the organic matter, and sanitation of fecal contaminants during composting is of the utmost significance, and difficult to achieve on an industrial scale. In this study, the operations of six industrial composting facilities that process municipal solid waste and sewage sludge were evaluated from the point of view of the sanitation achieved and the quality of the compost produced. In addition, the results were compared using the model of industrial compost from green waste. Differences between the plants were ascribable to operations other than composting systems. High phytotoxicity and fecal contamination above legislation thresholds were found in compost produced from municipal solid waste. In contrast, compost from sewage sludge were more stable and mature than those produced from green waste, and also had an adequate level of sanitation. The raw material and operational factors are of great relevance to obtain a stable, mature, and pathogen-free compost.

This paper presents a novel Power-Flow solution paradigm based on the structure of the members of the Runge–Kutta family. Solution approaches based on the introduced solution paradigm are intrinsically robust and can achieve high-order convergences rates. It is demonstrated that some well-known Power-Flow solution methods are in fact special cases of the developed framework. Explicit and embedded formulations are discussed, and two novel solution methodologies based on the Explicit Heun and Embedded Heun–Euler’s methods are developed. The introduced solution techniques are validated in the EU PEGASE systems, considering different starting points and loading levels. Results show that the developed methods are quite reliable and efficient, outperforming other robust and standard methodologies. On the basis of the results obtained, we can affirm that the introduced solution paradigm constitutes a promising framework for developing novel Power-Flow solution techniques.

Nerja Cave, Southern Spain, was revealed as an important biodiversity reservoir from which several novel species of Aspergillus were described. We carried out an aerobiological study in Nerja Cave to assess the origin of airborne fungi. This study quantified the fungi present in the air of ten representative halls covering the three sectors comprising the cave: Touristic Galleries, High Galleries, and New Galleries. Microclimatological monitoring allowed us to understand the dynamic of airborne fungi in two seasons of the year (winter and summer), corresponding to the strongest and the lowest cave ventilation, and to validate the influence that the transport of airborne fungi from outside may have on the cave itself. The data show that cold air enters in winter, as confirmed by the abundant presence of Aspergillus and Penicillium spores inside and outside the cave. In summer, the abundance of some fungi in the air of Nerja Cave, which are not detected outside, indicates a stagnation or low ventilation, and therefore, the concentration of fungal spores is maxima. The high occurrence of Cladosporium outside the cave and the scarce abundance inside support the cave stagnation in this season.

The paper proposes a real-time model for electric vehicles (EVs) controlled load charging. The proposed demand-side management (DSM) of EVs is implemented based on queuing analysis with a nonhomogeneous arrival rate and charging service periods dataset. An electric vehicle model is used which is based on a statistical survey to represent the uncontrolled demand of the EVs. A probability distribution for the time at which EVs are plugged and the corresponding value of the state of charges (SOCs) are considered. The preferences of individual EVs have been fully exploited through a set of instructions to fulfill the needs of the vehicles’ owners. The designated preferences include the owner setting for both, charging price preferences (OPR), and the maximum estimated parking time duration (EPTD). The quasi-static time-series (QSTS) simulation is used to simulate real-time scenarios of the 24-h simulation period. The IEEE 123 nodes radial test feeder is analyzed with different daily load curves, EV charging scenarios, and wind power penetrations. The results show the effectiveness of the proposed DSM in avoiding excessive levels of charging with/without penetration of non-dispatchable wind power generation. The proposed DSM enables the EVs to charge with low tariff rates either at excessive renewable power generation or late evening hours with available committed bulk power plants and light loading conditions.

Cellular antiviral programs encode molecules capable of targeting multiple steps in the virus lifecycle. Zinc-finger antiviral protein (ZAP) is a central and general regulator of antiviral activity that targets pathogen mRNA stability and translation. ZAP is diffusely cytoplasmic, but upon infection ZAP is targeted to particular cytoplasmic structures, termed stress granules (SGs). However, it remains unclear if ZAP's antiviral activity correlates with SG localization, and what molecular cues are required to induce this localization event. Here, we use Sindbis virus (SINV) as a model infection and find that ZAP's localization to SGs can be transient. Sometimes no apparent viral infection follows ZAP SG localization but ZAP SG localization always precedes accumulation of SINV non-structural protein, suggesting virus replication processes trigger SG formation and ZAP recruitment. Data from single-molecule RNA FISH corroborates this finding as the majority of cells with ZAP localization in SGs contain low levels of viral RNA. Furthermore, ZAP recruitment to SGs occurred in ZAP-expressing cells when co-cultured with cells replicating full-length SINV, but not when co-cultured with cells replicating a SINV replicon. ZAP recruitment to SGs is functionally important as a panel of alanine ZAP mutants indicate that the anti-SINV activity is correlated with ZAP's ability to localize to SGs. As ZAP is a central component of the cellular antiviral programs, these data provide further evidence that SGs are an important cytoplasmic antiviral hub. These findings provide insight into how antiviral components are regulated upon virus infection to inhibit virus spread.

In rodents, the hippocampal dentate gyrus gives rise to newly generated dentate granule cells (DGCs) throughout life. This process, named adult hippocampal neurogenesis (AHN), converges in the functional integration of mature DGCs into the trisynaptic hippocampal circuit. Environmental enrichment (EE) is one of the most potent positive regulators of AHN. This paradigm includes the combination of three major stimulatory components, namely increased physical activity, constant cognitive stimulation, and higher social interaction. In this regard, the pro-neurogenic effects of physical activity and cognitive stimulation have been widely addressed in adult rodents. However, the pro-neurogenic potential of the social aspect of EE has been less explored to date. Here we tackled this question by specifically focusing on the effects of a prolonged period of social enrichment (SE) in adult female C57BL6 mice. To this end, 7-week-old mice were housed in groups of 12 per cage for 8 weeks. These mice were compared with others housed under control housing (2–3 mice per cage) or EE (12 mice per cage plus running wheels and toys) conditions during the same period. We analyzed the number and morphology of Doublecortin-expressing (DCX+) cells. Moreover, using RGB retroviruses that allowed the labeling of three populations of newborn DGCs of different ages in the same mouse, we performed morphometric, immunohistochemical, and behavioral determinations. Both SE and EE increased the number and maturation of DCX+ cells, and caused an increase in dendritic maturation in certain populations of newborn DGCs. Moreover, both manipulations increased exploratory behavior in the Social Interaction test. Unexpectedly, our data revealed the potent neurogenesis-stimulating potential of SE in the absence of any further cognitive stimulation or increase in physical activity. Given that an increase in physical activity is strongly discouraged under certain circumstances, our findings may be relevant in the context of enhancing AHN via physical activity-independent mechanisms.

Although there are e-health systems for the care of elderly people, the reactive characteristics to enhance scalability and extensibility, and the use of this type of system in smart cities, have been little explored. To date, some studies have presented healthcare systems for specific purposes without an explicit approach for the development of health services. Moreover, software engineering is hindered by agile management challenges regarding development and deployment processes of new applications. This paper presents an approach to develop health Internet of Things (IoT) reactive applications that can be widely used in smart cities for the care of elderly individuals. The proposed approach is based on the Rozanski and Woods’s iterative architectural design process, the use of architectural patterns, and the Reactive Manifesto Principles. Furthermore, domain-driven design and the characteristics of the emerging fast data architecture are used to adapt the functionalities of services around the IoT, big data, and cloud computing paradigms. In addition, development and deployment processes are proposed as a set of tasks through DevOps techniques. The approach validation was carried out through the implementation of several e-health services, and various workload experiments were performed to measure scalability and performance in certain parts of the architecture. The system obtained is flexible, scalable, and capable of handling the data flow in near real time. Such features are useful for users who work collaboratively in the care of elderly people. With the accomplishment of these results, one can envision using this approach for building other e-health services.

The aerobiology of caves in Southern Spain possesses special characteristics, different from caves located in Northern Spain. Previous studies demonstrated the influence of outdoor air on caves in the north and the existence of two different patterns, depending on the season. In summer there is an abundance of Ascomycota, whereas in winter Basidiomycota predominates, which are related to the periods of stagnation and ventilation, respectively. In caves in Southern Spain the presence of airborne Basidiomycota is scarce and Ascomycota represents the main group of fungi widely distributed across the caves in all seasons. The most characteristic features were the abundant presence of entomopathogenic fungi (Beauveria bassiana, Parengyodontium album, Pochonia chlamydosporia, Leptobacillium symbioticum, Leptobacillium leptobactrum) and Cladosporium cladosporioides in Cueva del Tesoro, Cueva de Ardales and Gruta de las Maravillas. However, the presence of yeasts of the genera Cutaneotrichosporon, Trichosporon, Cryptococcus, Naganishia, Cystobasidium, Microstroma and Phragmotaenium was exclusive to Gruta de las Maravillas. Fungal hazard in the three show caves were determined using an ecological indicator based on the concentration of spores in cave air.

This work presents an analysis of the crystallization process and the influence of laser surface modification on the crystalline phases and optical responses of Al2O3/glass–ceramic coatings deposited on a brass substrate. We used a CO2 laser at different irradiation powers to change the structure of the superficial layer. The photoluminescence response enhanced the resolution of its line shape as the irradiation power increased. X-ray diffraction patterns exhibit the presence of different crystalline phases for the samples irradiated.

Implementing a wireless sensor and actuator network (WSAN) in Internet of Things (IoT) applications is a complex task. The need to establish the number of nodes, sensors, and actuators, and their location and characteristics, requires a tool that allows the preliminary determination of this information. Additionally, in IoT scenarios where a large number of sensors and actuators are present, such as in a smart city, it is necessary to analyze the scalability of these systems. Modeling and simulation can help to conduct an early study and reduce development and deployment times in environments such as a smart city. The design-time verification of the system through a network simulation tool is useful for the most complex and expensive part of the system formed by a WSAN. However, the use of real components for other parts of the IoT system is feasible by using cloud computing infrastructure. Although there are cloud computing simulators, the cloud layer is poorly developed for the requirements of IoT applications. Technologies around cloud computing can be used for the rapid deployment of some parts of the IoT application and software services using containers. With this framework, it is possible to accelerate the development of the real system, facilitate the rapid deployment of a prototype, and provide more realistic simulations. This article proposes an approach for the modeling and simulation of IoT systems and services in a smart city leveraged in a WSAN simulator and technologies of cloud computing. Our approach was verified through experiments with two use cases. (1) A model of sensor and actuator networks as an integral part of an IoT application to monitor and control parks in a city. Through this use case, we analyze the scalability of a system whose sensors constantly emit data. (2) A model for cloud-based IoT reactive parking lot systems for a city. Through our approach, we have created an IoT parking system simulation model. The model contains an M/M/c/N queuing system to simulate service requests from users. In this use case, the model replication through hierarchical modeling and scalability of a distributed parking reservation service were evaluated. This last use case showed how the simulation model could provide information to size the system through probability distribution variables related to the queuing system. The experimental results show that the use of simulation techniques for this type of application makes it possible to analyze scalability in a more realistic way.

The aim of this study was to explore the anthropometric profile and evaluate physical fitness variables of the members of the Chile women’s national football team based on their playing positions. Fifty football players participated in this study, which was carried out during the period of training for the France 2019 Women’s World Cup and the Japan 2020 Olympic Games. Body composition and physical condition (muscular strength, sprint, agility, and aerobic fitness) were assessed. The goalkeepers showed greater weight (p < 0.001), height (p = 0.002), and %Fat (p = 0.010) compared to the rest of the playing positions. There were also differences between positions in relative strength (RS) (p = 0.001), running speed at 10 and 30 m (T10 and T30, respectively), agility (AGI) (p < 0.001), and yo-yo test (MYYR1) (p < 0.001). RS, T10, T30, and countermovement jump (CMJ) were significantly correlated (p ≤ 0.05) with anthropometric variables (p ≤ 0.05). MYYR1 was also significantly correlated with anthropometric variables (p ≤ 0.05). In conclusion, goalkeepers show greater weight and height, as well as worse results in MYYR1, AGI, T10, T30, and RS compared to the rest of the players. Forwards present better performance in running speed and agility. Better performance in physical condition is associated with better body composition values (greater muscle mass and lower fat mass). Greater relative strength indicates greater performance in explosive actions. Therefore, to meet the demands of high competition, it is important to establish ideal profiles in anthropometry and physical condition variables based on the playing position.

This research work presents a techno-economic analysis of a biomass gasification plant fueled with residues from the olive oil and almond industries for combined heat and power generation in the agrifood sector. The experimental plant consists of a downdraft fixed bed gasifier, a producer gas cleaning and cooling system and a spark-ignition engine–generator set as a power generation unit, which generates about 10–12 kW of rated electric power. With an average consumption between 13–14 kg/h of exhausted olive pomace pellets as feedstock, the producer gas volumetric flow rate was 31 Nm3/h (vol. %: 19.2 H2, 12.9 CO, 1.9 CH4, 19.2 CO2, 46.7 N2). The average cold gas efficiency was nearly 63%. This work also addresses the characterization and potential application of the carbonaceous solid residue (biochar), discharged from the gasifier at 1.7 kg/h. Finally, an economic feasibility analysis was developed, wherein the payback period ranges between 5–9 years.

Risk taking (RT) measurement constitutes a challenge for researchers and practitioners and has been addressed from different perspectives. Personality traits and temperamental aspects such as sensation seeking and impulsivity influence the individual’s approach to RT, prompting risk-seeking or risk-aversion behaviors. Virtual reality has emerged as a suitable tool for RT measurement, since it enables the exposure of a person to realistic risks, allowing embodied interactions, the application of stealth assessment techniques and physiological real-time measurement. In this article, we present the assessment on decision making in risk environments (AEMIN) tool, as an enhanced version of the spheres and shield maze task, a previous tool developed by the authors. The main aim of this article is to study whether it is possible is to discriminate participants with high versus low scores in the measures of personality, sensation seeking and impulsivity, through their behaviors and physiological responses during playing AEMIN. Applying machine learning methods to the dataset we explored: (a) if through these data it is possible to discriminate between the two populations in each variable; and (b) which parameters better discriminate between the two populations in each variable. The results support the use of AEMIN as an ecological assessment tool to measure RT, since it brings to light behaviors that allow to classify the subjects into high/low risk-related psychological constructs. Regarding physiological measures, galvanic skin response seems to be less salient in prediction models.

Table tennis has recently evolved towards a more spectacular sport increasing match-play demands and the intensity and speed of actions by regulations and equipment modification. Since these changes can alter the body composition and performance, this study aimed to analyze the differences in anthropometric attributes of 495 table tennis players (288 men, 207 women) according to sex, age, and ranking. Players were classified according to sex, age categories (Senior, Under-18, Under-15, Under 13, and Under 11), and ranking position. Anthropometry measurements included eight skinfolds’ thicknesses (biceps brachii, triceps, subscapular, iliac crest, supraspinal, abdominal, thigh, and medial calf), four girths (biceps brachii relaxed and contracted, thigh, and calf), and three breadths (biepicondylar femur, biepicondylar humerus, and bistiloyd wrist) to determine fat mass, lean mass, bone, cross sectional area (CSA) for arm, leg, and thigh, and somatotype. Results revealed that table tennis players presented differences in body mass composition, anthropometry, and somatotype according to sex and age category and ranking. It seems confirmed that regular table tennis practice during the childhood is associated with a healthy body composition status, that appears to be maintained across older ages if keeping the practice. Senior table tennis players showed a fat mass

Obstructive sleep apnea (OSA) in children is a prevalent, albeit largely undiagnosed disease associated with a large spectrum of morbidities. Overnight in-lab polysomnography remains the gold standard diagnostic approach, but is time-consuming, inconvenient, and expensive, and not readily available in many places. Simplified Home Respiratory Polygraphy (HRP) approaches have been proposed to reduce costs and facilitate the diagnostic process. However, evidence supporting the validity of HRP is still scarce, hampering its implementation in routine clinical use. The objectives were: Primary; to establish the diagnostic and therapeutic decision validity of a simplified HRP approach compared to PSG among children at risk of OSA. Secondary: (a) Analyze the cost-effectiveness of the HRP versus in-lab PSG in evaluation and treatment of pediatric OSA; (b) Evaluate the impact of therapeutic interventions based on HRP versus PSG findings six months after treatment using sleep and health parameters and quality of life instruments; (c) Discovery and validity of the urine biomarkers to establish the diagnosis of OSA and changes after treatment.

Candidiasis caused by species of the Candida haemulonii complex (Candida haemulonii and Candida duobushaemulonii) and closely related species, Candida auris and Candida pseudohaemulonii are increasing. These species often show reduced susceptibility to antifungal drugs, such as azoles and amphotericin B or, less frequently, echinocandins. However, conventional phenotypic identification methods are unable to accurately differentiate these species and, therefore, their prevalence may have been underestimated. In this study, 150 isolates that were probably misidentified were reanalyzed using two novel PCR approaches. We found that one isolate previously identified in 1996 as Candida intermedia was C. duobushaemulonii, being one of the oldest isolates of this species described to date. We also found that this isolate had reduced susceptibility to fluconazole, itraconazole, and amphotericin B.

Here, we assessed whether 36 single nucleotide polymorphisms (SNPs) within the TNFSF4 and MAPKAPK2 loci influence the risk of developing invasive aspergillosis (IA). We conducted a two-stage case control study including 911 high-risk patients diagnosed with hematological malignancies that were ascertained through the aspBIOmics consortium. The meta-analysis of the discovery and replication populations revealed that carriers of the TNFSF4rs7526628T/T genotype had a significantly increased risk of developing IA (p = 0.00022). We also found that carriers of the TNFSF4rs7526628T allele showed decreased serum levels of TNFSF14 protein (p = 0.0027), and that their macrophages had a decreased fungicidal activity (p = 0.048). In addition, we observed that each copy of the MAPKAPK2rs12137965G allele increased the risk of IA by 60% (p = 0.0017), whereas each copy of the MAPKAPK2rs17013271T allele was estimated to decrease the risk of developing the disease (p = 0.0029). Mechanistically, we found that carriers of the risk MAPKAPK2rs12137965G allele showed increased numbers of CD38+IgM-IgD- plasmablasts in blood (p = 0.00086), whereas those harboring two copies of the allele had decreased serum concentrations of thymic stromal lymphopoietin (p = 0.00097). Finally, we also found that carriers of the protective MAPKAPK2rs17013271T allele had decreased numbers of CD27-IgM-IgD- B cells (p = 0.00087) and significantly lower numbers of CD14+ and CD14+CD16- cells (p = 0.00018 and 0.00023). Altogether, these results suggest a role of the TNFSF4 and MAPKAPK2 genes in determining IA risk.