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The 22q11.2 region is highly susceptible to genomic rearrangements leading to multiple genomic disorders, including 22q11.2 microdeletion syndrome (22q11.2 DS) (MIM# 188400), 22q11.2 microduplication syndrome (MIM# 608363), supernumerary der(22)t(11;22) syndrome (also known as Emanuel Syndrome; MIM# 609029), and Cat Eye Syndrome (MIM# 115470). In this study, we present data on causes of mortality, average age of death, and the existing associated risk factors in patients with 22q11.2 rearrangements. Our cohort included 223 patients (120 males and 103 females) with confirmed diagnoses of 22q11.2 rearrangements diagnosed through molecular techniques (FISH, MLPA, and CMA). Relatives from patients who have been molecularly confirmed with 22q11.2 rearrangements have also been added to the study, regardless of the presence or absence of symptoms. Of these 223 individuals, 21 (9.4%) died. Deceased patients' rearrangements include 19 microdeletions, 1 microduplication, and 1 patient with a marker chromosome. The median age of death was 3 months and 18 days (ranging from 3 days to 34 years). There were 17 patients who died at pediatric age (80.95%), 3 died at adult age (14.28%), and for 1 of whom, the age of death is unknown (4.76%). Eighteen patients were White Mediterranean (European non-Finnish) (85.71%) whereas three were Amerindian (South American) (14.28%). Mortality from cardiac causes accounted for 71.42%. The second most frequent cause of death was sepsis in two patients (9.52%). One patient died from respiratory failure (4.76%) and one from renal failure (4.76%). Information regarding the cause of death was not available in two patients (9.52%). Most patients who died were diagnosed within the first week of life, the majority on the first day. This study adds additional information on mortality in one of the largest cohorts of patients with 22q11.2 rearrangements in more than 30 years of follow-up. [ABSTRACT FROM AUTHOR]

Background: Retention in treatment is crucial for the success of interventions targeting alcohol use disorder (AUD), which affects over 100 million people globally. Most previous studies have used classical statistical techniques to predict treatment dropout, and their results remain inconclusive. This study aimed to use novel machine learning tools to identify models that predict dropout with greater precision, enabling the development of better retention strategies for those at higher risk. Methods: A retrospective observational study of 39,030 (17.3% female) participants enrolled in outpatient-based treatment for alcohol use disorder in a state-wide public treatment network has been used. Participants were recruited between 1 January 2015 and 31 December 2019. We applied different machine learning algorithms to create models that allow one to predict the premature cessation of treatment (dropout). With the objective of increasing the explainability of those models with the best precision, considered as black-box models, explainability technique analyses were also applied. Results: Considering as the best models those obtained with one of the so-called black-box models (support vector classifier (SVC)), the results from the best model, from the explainability perspective, showed that the variables that showed greater explanatory capacity for treatment dropout are previous drug use as well as psychiatric comorbidity. Among these variables, those of having undergone previous opioid substitution treatment and receiving coordinated psychiatric care in mental health services showed the greatest capacity for predicting dropout. Conclusions: By using novel machine learning techniques on a large representative sample of patients enrolled in alcohol use disorder treatment, we have identified several machine learning models that help in predicting a higher risk of treatment dropout. Previous treatment for other substance use disorders (SUDs) and concurrent psychiatric comorbidity were the best predictors of dropout, and patients showing these characteristics may need more intensive or complementary interventions to benefit from treatment. [ABSTRACT FROM AUTHOR]

In recent decades, city councils have become a powerful tool used to "motivate" entrepreneurship. Through a content analysis of the webpages of 50 Spanish city councils corresponding to the period 2015–2019, the evolution of the degree of disclosure of information on entrepreneurship has been analysed. A series of population, economic and political explanatory factors have researched the disclosure of this type of information in two ways. First, a cluster analysis was carried out based on a previously calculated disclosure index. Second, an analysis of variance was performed to verify the existence of an association between the proposed determining factors. The results show that the information disclosed on entrepreneurship by municipalities is related to the size of the population, municipal debt, institutional capacity, the unemployed population and political competition. [ABSTRACT FROM AUTHOR]

Functionality after upper limb replantation is a decisive factor when considering the success of the intervention. Therefore, its evaluation is fundamental. The aim of this article was to conduct a systematic review of upper limb functions after replantation or reimplantation, seeking to identify reported functional outcomes as well as the level and mechanism of injury. To achieve this objective, a literature search was conducted in PubMed, ScienceDirect, Cochrane and Web of Science. Studies from the last 10 years which included patients with upper limb replantation and reported their functional outcomes were included. Out of 523 articles, 12 studies (n = 607) were finally included. DASH and CISS were the most commonly used assessments to report functional outcomes. In conclusion, functional outcomes after replantation are assessed using widely varying scales; therefore, due to this methodological variability, it is difficult to compare functional success between studies and further studies on functionality are needed to provide new data. [ABSTRACT FROM AUTHOR]

Simple Summary: We have conducted a 10-year coprological study of animals housed in two zoological institutions with different housing conditions to assess parasite biodiversity and prevalence, their relationship with host class (mammal/bird), diet (carnivorous/omnivorous/herbivorous), and enclosure characteristics (soil type, isolation from wild fauna), and evaluated the risk of transmission to humans. A total of 4476 faecal samples from 132 mammal species and 951 samples from 86 avian species were examined, with 62.1% of mammal species and 12.8% of avian species testing positive. Statistically significant differences were found based on diet type; few carnivorous species were detected infected, primarily by nematodes, while many herbivorous and omnivorous species were primarily infected by protists. No statistically significant differences were observed based on soil type (artificial, natural, mixed) and isolation level (isolated/accessible). Several parasite species found in the study (Entamoeba spp., Giardia spp., Balantioides coli, Trichuris spp.) could potentially be transmitted between housed animals, wild fauna, and humans. Regular analyses of the animals and implementation and follow-up of health programs would minimise transmission risks between housed animals, wild fauna, and humans. We have conducted a 10-year-long coprological study of the animals housed in two zoological institutions (ZooAquarium and Faunia, Madrid, Spain) to assess the parasite biodiversity, prevalence, and their relation with host class, diet, and enclosure type (soil type and level of isolation from wild fauna). A total of 4476 faecal samples from 132 mammal species and 951 samples from 86 avian species were examined. The results indicated that only 12.8% of avian species had parasites at least once during the study period, whereas 62.1% of mammal species tested positive. Predominantly, protists (Entamoeba, flagellates, and ciliates) and nematodes (mainly Trichuris) were identified in the findings. Carnivorous species were primarily infected by nematodes, while herbivorous and omnivorous species were mainly infected by protists. The number of infected herbivorous and omnivorous species was significantly greater than carnivorous species. Differences were observed based on soil type (artificial, natural, mixed) and isolation level (isolated/accessible), but these differences were not statistically significant. Several parasites (Entamoeba spp., Giardia spp., Balantidoides coli, Trichuris spp.) could potentially be transmitted between humans and some mammals and birds. Regular animal analyses and a personnel health program in the institutions would minimise transmission risks between zoo animals, wildlife, and humans. [ABSTRACT FROM AUTHOR]

Objective: Our objective is the description of the technique of vagus nerve stimulation in carotid triangle in order to monitor the recurrent laryngeal nerve (RLN) during thyroid and parathyroid surgery. Methods: We stimulated the vagus nerve in the carotid triangle during 150 thyroid or parathyroid surgeries using a monopolar electromyography electrode inserted under the mastoid process towards the jugular foramen as a cathode, and using another subdermal electrode in the mastoid as an anode. Another complementary method of vagus stimulation was achieved with a pair of subdermal electrodes, placing the cathode at the mandibular angle and the anode at the mastoid. Results: In all patients, compound muscle action potential (CMAP) was recorded in the vocal cords with both stimulation techniques, allowing semi-continuous monitoring to be carried out. Intraoperative lesions were detected in 16 of the cases; 9 of them were transient with CMAP recovery achieved when modifying surgical maneuvers. Conclusions: Vagus nerve stimulation in the carotid triangle is a reliable technique for monitoring the RLN in thyroid surgery. Vagus nerve stimulation in the carotid triangle is effective and safe for RLN monitoring, and it is a clear alternative to direct continuous stimulation of the nerve that by contrast requires its dissection in the carotid sheath. [ABSTRACT FROM AUTHOR]

Simple Summary: Successful establishment of patient-derived xenografts (PDXs) requires a profound understanding of the involved factors influencing engraftment success. Little work has focused on analyzing baseline patient's characteristics that associate with a better outcome in the PDX development process. In a PDX development program of an Oncology Center, data from 585 tumor models are fully analyzed and characterized with this purpose. Background: patient-derived xenografts (PDXs) have defined the field of translational cancer research in recent years, becoming one of the most-used tools in early drug development. The process of establishing cancer models in mice has turned out to be challenging, since little research focuses on evaluating which factors impact engraftment success. We sought to determine the clinical, pathological, or molecular factors which may predict better engraftment rates in PDXs. Methods: between March 2017 and January 2021, tumor samples obtained from patients with primary or metastatic cancer were implanted into athymic nude mice. A full comprehensive evaluation of baseline factors associated with the patients and patients' tumors was performed, with the goal of potentially identifying predictive markers of engraftment. We focused on clinical (patient factors) pathological (patients' tumor samples) and molecular (patients' tumor samples) characteristics, analyzed either by immunohistochemistry (IHC) or next-generation sequencing (NGS), which were associated with the likelihood of final engraftment, as well as with tumor growth rates in xenografts. Results: a total of 585 tumor samples were collected and implanted. Twenty-one failed to engraft, due to lack of malignant cells. Of 564 tumor-positive samples, 187 (33.2%) grew at time of analysis. The study was able to find correlation and predictive value for engraftment for the following: the use of systemic antibiotics by the patient within 2 weeks of sampling (38.1% (72/189) antibiotics- group vs. 30.7% (115/375) no-antibiotics) (p = 0.048), and the administration of systemic steroids to the patients within 2 weeks of sampling (41.5% (34/48) steroids vs. 31.7% (153/329), no-steroids) (p = 0.049). Regarding patient's baseline tests, we found certain markers could help predict final engraftment success: for lactate dehydrogenase (LDH) levels, 34.1% (140/411) of tumors derived from patients with baseline blood LDH levels above the upper limit of normality (ULN) achieved growth, against 30.7% (47/153) with normal LDH (p = 0.047). Histological tumor characteristics, such as grade of differentiation, were also correlated. Grade 1: 25.4% (47/187), grade 2: 34.8% (65/187) and grade 3: 40.1% (75/187) tumors achieved successful growth (p = 0.043), suggesting the higher the grade, the higher the likelihood of success. Similarly, higher ki67 levels were also correlated with better engraftment rates: low (Ki67 < 15%): 8.9% (9/45) achieved growth vs. high (Ki67 ≥ 15%): 31% (35/113) (p: 0.002). Other markers of aggressiveness such as the presence of lymphovascular invasion in tumor sample of origin was also predictive: 42.2% (97/230) with lymphovascular vs. 26.9% (90/334) of samples with no invasion (p = 0.0001). From the molecular standpoint, mismatch-repair-deficient (MMRd) tumors showed better engraftment rates: 62.1% (18/29) achieved growth vs. 40.8% (75/184) of proficient tumors (p = 0.026). A total of 84 PDX were breast models, among which 57.9% (11/19) ER-negative models grew, vs. 15.4% (10/65) of ER-positive models (p = 0.0001), also consonant with ER-negative tumors being more aggressive. BRAFmut cancers are more likely to achieve engraftment during the development of PDX models. Lastly, tumor growth rates during first passages can help establish a cutoff point for the decision-making process during PDX development, since the higher the tumor grades, the higher the likelihood of success. Conclusions: tumors with higher grade and Ki67 protein expression, lymphovascular and/or perineural invasion, with dMMR and are negative for ER expression have a higher probability of achieving growth in the process of PDX development. The use of steroids and/or antibiotics in the patient prior to sampling can also impact the likelihood of success in PDX development. Lastly, establishing a cutoff point for tumor growth rates could guide the decision-making process during PDX development. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders characterized by deficiencies in communication, social interaction, and repetitive and restrictive behaviors. The discovery of genetic involvement in the etiology of ASD has made this condition a strong candidate for genome-based diagnostic tests. Next-generation sequencing (NGS) is useful for the detection of variants in the sequence of different genes in ASD patients. Herein, we present the implementation of a personalized NGS panel for autism (AutismSeq) for patients with essential ASD over a prospective period of four years in the clinical routine of a tertiary hospital. The cohort is composed of 48 individuals, older than 3 years, who met the DSM-5 (The Diagnostic and Statistical Manual of Mental Disorders) diagnostic criteria for ASD. The NGS customized panel (AutismSeq) turned out to be a tool with good diagnostic efficacy in routine clinical care, where we detected 12 "pathogenic" (including pathogenic, likely pathogenic, and VUS (variant of uncertain significance) possibly pathogenic variations) in 11 individuals, and 11 VUS in 10 individuals, which had previously been negative for chromosomal microarray analysis and other previous genetic studies, such as karyotype, fragile-X, or MLPA/FISH (Multiplex Ligation dependent Probe Amplification/Fluorescence in situ hybridization) analysis. Our results demonstrate the high genetic and clinical heterogeneity of individuals with ASD and the current difficulty of molecular diagnosis. Our study also shows that an NGS-customized panel might be useful for diagnosing patients with essential/primary autism and that it is cost-effective for most genetic laboratories. [ABSTRACT FROM AUTHOR]

(1) Background: Gordon syndrome (GS) or familial hyperkalemic hypertension is caused by pathogenic variants in the genes WNK1, WNK4, KLHL3, and CUL3. Patients presented with hypertension, hyperkalemia despite average glomerular filtration rate, hyperchloremic metabolic acidosis, and suppressed plasma renin (PR) activity with normal plasma aldosterone (PA) and sometimes failure to thrive. GS is a heterogeneous genetic syndrome, ranging from severe cases in childhood to mild and sometimes asymptomatic cases in mid-adulthood. (2) Methods: We report here a sizeable Spanish family of six patients (four adults and two children) with GS. (3) Results: They carry a novel heterozygous missense variant in exon 7 of WNK1 (p.Glu630Gly). The clinical presentation in the four adults consisted of hypertension (superimposed pre-eclampsia in two cases), hyperkalemia, short stature with low body weight, and isolated hyperkalemia in both children. All patients also presented mild hyperchloremic metabolic acidosis and low PR activity with normal PA levels. Abnormal laboratory findings and hypertension were normalized by dietary salt restriction and low doses of thiazide or indapamide retard. (4) Conclusions: This is the first Spanish family with GS with a novel heterozygous missense variant in WNK1 (p.Glu630Gly) in the region containing the highly conserved acidic motif, which is showing a relatively mild phenotype, and adults diagnosed in mild adulthood. These data support the importance of missense variants in the WNK1 acidic domain in electrolyte balance/metabolism. In addition, findings in this family also suggest that indapamide retard or thiazide may be an adequate long-standing treatment for GS. [ABSTRACT FROM AUTHOR]

To improve the energy efficiency and performance of buildings, it is essential to understand the factors that influence indoor thermal comfort. Through an extensive analysis of various variables, actions can be developed to enhance the thermal sensation of the occupants, promoting sustainability and economic benefits in conditioning systems. This study identifies eight key variables: indoor air temperature, mean radiant temperature, indoor globe temperature, CO2, age, outdoor temperature, indoor humidity, and the running mean temperature, which are relevant for predicting thermal comfort in Mediterranean office buildings. The proposed methodology effectively analyses the relevance of these variables, using five techniques and two different databases, Mediterranean climate buildings published by ASHRAE and a study conducted in Seville, Spain. The results indicate that the extended database to 21 variables improves the quality of the metrics by 5%, underscoring the importance of a comprehensive approach in the analysis. Among the evaluated techniques, random forest emerges as the most successful, offering superior performance in terms of accuracy and other metrics, and this method is highlighted as a technique that can be used to assist in the design and operation or control of a building's conditioning system or in tools that recommend adaptive measures to improve thermal comfort. [ABSTRACT FROM AUTHOR]

(1) Background: 5p minus Syndrome (S5p-) is a neurodevelopmental disorder caused by a deletion in the short arm of chromosome 5. Among the phenotypic characteristics of S5p-, the most characteristic and representative element is a monochromatic cry with a high-pitched tone reminiscent of a cat's meow. Individuals may also show great phenotypic heterogeneity and great genetic variability. Regarding cognitive–behavioral aspects of the syndrome, the studies are scarce and do not establish a general profile of the main cognitive–behavioral particularities that this syndrome presents. The main objective of this work was to describe the development profile of a cohort of 45 children with 5p minus Syndrome, concerning the biomedical, genetic, cognitive, and behavioral aspects. Establishing putative genotype–phenotype (cognitive–behavioral profiles) relationships in our cohort, from an interdisciplinary approach. (2) Methods: A selection of instruments of measures was selected for neuropsychological assessment (3) Results: In general, children with S5p- have a higher cognitive level than a communicative and motor level. Language difficulties, especially expressive ones, influence the frequency and severity of the most frequent behavioral problems in S5p. The most significant problem behavior of children with S5p-, especially girls, is self-harm. Compulsive behavior, limited preferences, and interest in monotony are significantly more frequent in subjects with better cognitive levels. We also find a significant correlation between the size of the loss of genetic material on 5p and the cognitive level of the subjects. (4) Conclusions: We described for the first time, the cognitive–behavioral profile of a cohort of minors with S5p-. Remarkably, it was found that language, especially of an expressive nature, modulates the most frequent behavioral aspects in subjects with lower cognitive levels, so it is essential to develop verbal or alternative communication strategies adjusted to these individuals. [ABSTRACT FROM AUTHOR]

The development of abnormal scars has a great impact on people's well-being, and improving scarring outcomes after surgery is a field that currently lacks consensus. This review aims to identify newly researched approaches to improving the quality of surgical scars. A systematic search of PubMed, Scopus, Web of Science, and ScienceDirect was conducted between 13 May 2023 and 17 May 2023, in accordance with the recommendations of the PRISMA Statement. Study selection and analysis of methodological quality were performed in parts, independently and blindly, based on eligibility criteria. The 21 prospective, comparative, and randomized studies reviewed included 1057 subjects and studied approaches such as topical applications of creams with herbal extracts and silicone gels, growth factors, negative pressure dressings, oligonucleotides, intralesional injection of compounds such as botulinum toxin, skin closure techniques such as suturing and tissue adhesive, and laser treatments. There are recent research techniques that generate good results and are really promising to improve the results of surgical scars; however, the available evidence is extremely limited in some cases, and it is necessary to deepen its analysis to obtain reliable action protocols in each type of surgery. [ABSTRACT FROM AUTHOR]

Background: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have benefits for survival in some cancers with peritoneal metastasis. Hematologic toxicity described rate is 2 to 38%. Methods: Patients admitted to an intensive care unit (ICU) after CRS and HIPEC over 78 months. The data recorded were demographic characteristics, the severity of illness, complete blood samples, the type of cancer and extension, HIPEC drug and temperature, ICU and hospital stay and mortality, bleeding, and the need for transfusion of blood products. Results: Of the 96 patients included, 77.1% presented hematological complications: 8.3% leukopenia (<4000/mm3 leucocytes), 66.7% anemia (hemoglobin < 10 mg/dL), and 22.9% coagulopathy (INR < 1.5, or/and aPTT < 45 s, or/and platelet count < 100,000/mm3, or/and <100 mg/dL of serum fibrinogen). Leukopenia was higher in ovarian cancer or those treated with doxorubicin. Females with anemia, ovarian cancer, and those treated with cisplatin or doxorubicin had longer ICU stays. Bleeding complications were low-corrected in a conservative manner. The median ICU stay was 5 (4.0–5.0) days. The ICU mortality rate was 1.0%. Conclusions: In our study, 77.1% of patients treated with CRS and HIPEC developed hematological complications during the postoperative period; the majority of them were not severe and resolved spontaneously, without an effect on mortality or hospital stay. [ABSTRACT FROM AUTHOR]

Autism spectrum disorders (ASD) comprise a group of neurodevelopmental disorders (NDD) characterized by deficits in communication and social interaction, as well as repetitive and restrictive behaviors, etc. The genetic implications of ASD have been widely documented, and numerous genes have been associated with it. The use of chromosomal microarray analysis (CMA) has proven to be a rapid and effective method for detecting both small and large deletions and duplications associated with ASD. In this article, we present the implementation of CMA as a first-tier test in our clinical laboratory for patients with primary ASD over a prospective period of four years. The cohort was composed of 212 individuals over 3 years of age, who met DSM-5 diagnostic criteria for ASD. The use of a customized array-CGH (comparative genomic hybridization) design (KaryoArray®) found 99 individuals (45.20%) with copy number variants (CNVs); 34 of them carried deletions (34.34%) and 65 duplications (65.65%). A total of 28 of 212 patients had pathogenic or likely pathogenic CNVs, representing approximately 13% of the cohort. In turn, 28 out of 212 (approximately 12%) had variants of uncertain clinical significance (VUS). Our findings involve clinically significant CNVs, known to cause ASD (syndromic and non-syndromic), and other CNVs previously related to other comorbidities such as epilepsy or intellectual disability (ID). Lastly, we observed new rearrangements that will enhance the information available and the collection of genes associated with this disorder. Our data also highlight that CMA could be very useful in diagnosing patients with essential/primary autism, and demonstrate the existence of substantial genetic and clinical heterogeneity in non-syndromic ASD individuals, underscoring the continued challenge for genetic laboratories in terms of its molecular diagnosis. [ABSTRACT FROM AUTHOR]

The School of Agricultural Engineering has been involved in English-medium instruction (EMI) within the framework of the internationalization strategy of the University of Extremadura (Spain). Several years after these actions were initiated, it has become necessary to analyze them, with the main objective of researching the attitude of the students towards it, keeping the focus on finding common trends. With this aim, a segmentation of the students was carried out based on a questionnaire that included aspects related to their attitudes towards English-medium instruction, their socio-demographic characteristics and the program they were enrolled in. A total of 251 students were surveyed, and the data were analyzed by performing a multiple correspondence analysis and a cluster analysis. They revealed three typologies of students with clearly different underlying features, especially related to the program and year in which they were enrolled, their age and English level, and their perceived skills. The main conclusion is that the multivariate techniques applied are useful tools to identify groups of students with different features in the EMI frame, which may facilitate the launch of specific actions focused on the needs and expectations of each group to ensure that EMI programs and students achieve their goals. [ABSTRACT FROM AUTHOR]

This work presents the attempt to develop a production technology for grape–plum low-alcohol beverages and enhance their chemical composition and flavor complexity through the non-Saccharomyces species. Saccharomyces cerevisiae (SC) pure cultures were used as reference beverages. Pure cultures of Lachancea thermotolerans (LT) and co-inoculated Lachancea thermotolerans with Saccharomyces cerevisiae (MIX) were included for grape–plum must fermentation at a pilot scale. The process involves two steps: a primary alcoholic fermentation in stainless steel tanks (F1) and a secondary fermentation in a bottle after dextrose syrup addition (F2). The chemical compositions of all beverages obtained in F1 and F2 were studied. Compared to SC, must inoculated with L. thermotolerans (LT and MIX) required four more days to complete the fermentation of sugars during F1. SC fermentation tended to have slightly higher pH and titratable acidity values and lower concentrations of total phenols. Final levels of aromatic precursor nitrogen and sulfur amino nitrogen were obtained more in SC than in LT and MIX. SC treatment had higher final levels of histidine, phenylalanine, isoleucine, lysine, methionine, threonine, valine, and cysteine. Related to individual amino acids, SC treatment had higher final levels of histidine, phenylalanine, isoleucine, lysine, methionine, threonine, valine, and cysteine. Analysis of the volatile composition showed that, compared with SC, MIX had the highest percentage of higher alcohols (3-methyl-1-butanol and 2-methyl-1-butanol) and acetates (isoamyl acetate and isobutyl acetate) which are associated with fruity and banana aromas. A decreasing trend in volatile fatty acids was observed in LT and MIX compared to SC. LT application, both in pure and mixed culture, significantly modified the values of the percentage of 5 of the 10 ethyl ester compounds analyzed. Finally, the sensory analysis showed that there were no significant differences, even though the non-Saccharomyces had a higher percentage of volatile metabolites. The results have shown that through this process an innovative and high-quality product was obtained: a low-alcohol beverage made from grapes and plums, which could be developed at an industrial level due to the increasing interest of consumers in this type of product. [ABSTRACT FROM AUTHOR]

The aim of this work was analyzing the use of olive leaf extracts (OLE) obtained from two local Tunisian olive tree cultivars 'Chemlali' and 'Sayali' to reduce the acrylamide in Californian-style black olives. The phenol profile, antioxidant, and antibacterial activity of the two OLE extracts were evaluated. The principal phenols found were hydroxytyrosol (1809.6 ± 25.3 mg 100 g−1), oleuropein (2662.2 ± 38 mg 100 g−1) and luteolin-7-O-glucoside (438.4 ± 38 mg 100 g−1) presented higher levels in 'Sayali' variety. Small differences were observed between the two kinds of extracts used; the greatest activity of OLE was observed against S. choleraesuis, with values up to 50% inhibition. The extract of 'Chemlali' cultivar was added to the Californian-style table olive, improving its phenol content and its antioxidant characteristics without negatively affecting its sensorial characteristics; these olives showed the highest firmness and proper quality characteristics. The gastrointestinal activity on the acrylamide concentration showed a partial degradation of this compound through the digestion, although the addition of the extract does not seem influence in its gastrointestinal digestion. These findings prove the usefulness of by-products to generate a high-quality added-value product, and this would also be relevant as a step towards a more sustainable, circular economy model. [ABSTRACT FROM AUTHOR]

Oxidized black table olives are frequently consumed in the Mediterranean diet. To improve food quality, the use of by-products is an emergent strategy that should be more studied. With a better understanding of the use of by-products, healthier food with the highest possible quality could be obtained, increasing its added value. Different by-products at different concentrations (1:10 and 1:100) and phenol-rich aromatized hydrocolloids were added to Californian-style black olive in order to evaluate its effect in acrylamide. In general, the addition of by-products before the sterilization process resulted in a significant reduction of the acrylamide content (10–60%). The highest inhibition was obtained with the phenolic extract at a 1:10 dilution. Furthermore, flavored olives stuffed with higher concentrations caused a greater reduction in acrylamide content. The 'Garlic' and 'Thyme' flavors showed the greatest reduction of this toxic substance. The tasting panel considered that olives with a 1:10 dilution and olives filled with flavored hydrocolloids at low concentrations had a pleasant odor and positive sensory attributes. Orange peel was the recommended by-product to mitigate the effects of acrylamide since it obtained the highest score both in acrylamide inhibition and in the taste panel. As for the hydrocolloids, 'Thyme' showed the greatest inhibition effect but did not perform well in the taste panel, with similar effects to 'Oregano' and 'Garlic.' The current research attempts to underline the use of local by-products to obtain additives rich in antioxidant activity that could enhance oxidized black table olives, becoming a healthier, safer and better-quality products. Moreover, this connects with the idea of moving from a linear economy to a circular economy, obtaining a product of high economic value from a by-product. [ABSTRACT FROM AUTHOR]

Simple Summary: Beckwith–Wiedemann syndrome (BWS) is an overgrowth disorder caused by imprinting or genetic alterations at the 11p15.5 locus. BWS is considered a spectrum disorder (BWSp) with an increased neoplasm incidence. CDKN1C variants have been reported in 5–10% of patients, with a higher incidence in familial cases. In this study, we examined the clinical and molecular features of all cases of BWSp identified by the Spanish Overgrowth Registry Initiative with CDKN1C variants, ascertained by Sanger sequencing or next-generation sequencing. We present 21 cases, 19 of which were classified as classical BWS and 1 that developed a mediastinal ganglioneuroma. Our study supports the high heterogeneity of the clinical features of BWSp and adds evidence on tumour development in this BWSp molecular subgroup. Genotype–phenotype correlation studies of patients with suspected BWS are essential for improving the diagnosis and assessing whether its cause can be directly related to the BWS clinical spectrum in the few cases that develop tumours. Beckwith–Wiedemann syndrome spectrum (BWSp) is an overgrowth disorder caused by imprinting or genetic alterations at the 11p15.5 locus. Clinical features include overgrowth, macroglossia, neonatal hypoglycaemia, omphalocele, hemihyperplasia, cleft palate, and increased neoplasm incidence. The most common molecular defect observed is hypomethylation at the imprinting centre 2 (KCNQ1OT1:TSS DMR) in the maternal allele, which accounts for approximately 60% of cases, although CDKN1C pathogenic variants have been reported in 5–10% of patients, with a higher incidence in familial cases. In this study, we examined the clinical and molecular features of all cases of BWSp identified by the Spanish Overgrowth Registry Initiative with pathogenic or likely pathogenic CDKN1C variants, ascertained by Sanger sequencing or next-generation sequencing, with special focus on the neoplasm incidence, given that there is scarce knowledge of this feature in CDKN1C-associated BWSp. In total, we evaluated 21 cases of BWSp with CDKN1C variants; 19 were classified as classical BWS according to the BWSp scoring classification by Brioude et al. One of our patients developed a mediastinal ganglioneuroma. Our study adds evidence that tumour development in patients with BWSp and CDKN1C variants is infrequent, but it is extremely relevant to the patient's follow-up and supports the high heterogeneity of BWSp clinical features associated with CDKN1C variants. [ABSTRACT FROM AUTHOR]

The digital transformation of the defence sector is not exempt from innovative requirements and challenges, with the lack of availability of reliable, unbiased and consistent data for training automatisms (machine learning algorithms, decision-making, what-if recreation of operational conditions, support the human understanding of the hybrid operational picture, personnel training/education, etc.) being one of the most relevant gaps. In the context of cyber defence, the state-of-the-art provides a plethora of data network collections that tend to lack presenting the information of all communication layers (physical to application). They are synthetically generated in scenarios far from the singularities of cyber defence operations. None of these data network collections took into consideration usage profiles and specific environments directly related to acquiring a cyber situational awareness, typically missing the relationship between incidents registered at the hardware/software level and their impact on the military mission assets and objectives, which consequently bypasses the entire chain of dependencies between strategic, operational, tactical and technical domains. In order to contribute to the mitigation of these gaps, this paper introduces CYSAS-S3, a novel dataset designed and created as a result of a joint research action that explores the principal needs for datasets by cyber defence centres, resulting in the generation of a collection of samples that correlate the impact of selected Advanced Persistent Threats (APT) with each phase of their cyber kill chain, regarding mission-level operations and goals. [ABSTRACT FROM AUTHOR]

NK degranulation plays an important role in the cytotoxic activity of innate immunity in the clearance of intracellular infections and is an important factor in the outcome of the disease. This work has studied NK degranulation and innate immunological profiles and functionalities in COVID-19 patients and its association with the severity of the disease. A prospective observational study with 99 COVID-19 patients was conducted. Patients were grouped according to hospital requirements and severity. Innate immune cell subpopulations and functionalities were analyzed. The profile and functionality of innate immune cells differ between healthy controls and severe patients; CD56dim NK cells increased and MAIT cells and NK degranulation rates decreased in the COVID-19 subjects. Higher degranulation rates were observed in the non-severe patients and in the healthy controls compared to the severe patients. Benign forms of the disease had a higher granzymeA/granzymeB ratio than complex forms. In a multivariate analysis, the degranulation capacity resulted in a protective factor against severe forms of the disease (OR: 0.86), whereas the permanent expression of NKG2D in NKT cells was an independent risk factor (OR: 3.81; AUC: 0.84). In conclusion, a prompt and efficient degranulation functionality in the early stages of infection could be used as a tool to identify patients who will have a better evolution. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) is a severe clinical condition characterized by an increase in mean pulmonary artery pressure, which leads to a right ventricular hypertrophy and potentially heart failure and death. In the last several years, many genes have been associated with PAH, particularly in idiopathic and heritable forms but also in associated forms. Here we described the identification of two unrelated families in which the AQP1 variant was found from a cohort of 300 patients. The variants were identified by whole exome sequencing (WES). In the first family, the variant was detected in three affected members from a hereditary PAH, and in the second family the proband had PAH associated with scleroderma. In addition, we have reviewed all cases published in the literature thus far of patients with PAH and AQP1 variants. Functional studies have led to some contradictory conclusions, and the evidence of the relationship of AQP1 and PAH is still limited. However, we describe two further families with PAH and variants in AQP1, expanding both the number of cases and the clinically associated phenotype. We provide further evidence of the association of AQP1 and the development of hereditary and associated forms of PAH. [ABSTRACT FROM AUTHOR]

Olives treated according to the Spanish-style are firstly treated with caustic soda and then fermented in brine to reduce phenols. Next, olives are packed and subjected to pasteurization. The effect of different high hydrostatic pressure treatments (400 MPa, 4 and 6 min) was evaluated in Spanish-style table olives fermented with olive leaf extract (OLE) and S. cerevisiae compared with thermal pasteurization (P) at 80 °C for 15 min. HHP and P led to a significant reduction in yeast and aerobic mesophiles after the conservation treatment and during storage (300 days). The physical–chemical properties changed slightly during storage, except for olive hardness; olives treated with HHP presented a higher hardness than pasteurized ones. The CIELAB parameter L* decreased until day 300 in most of the treatments, as well as phenols. The HHP treatment led to significantly higher contents of phenolics (even during storage) than olives submitted to P. Some sensory attributes (colour, aspect, hardness, and overall evaluation) decreased during storage. P treatment caused a decrease in appearance, aroma, hardness, and overall evaluation compared to olives treated with HHP. Thus, the application of HHP in table olives to increase the shelf-life can be considered a valid alternative to P. [ABSTRACT FROM AUTHOR]

Phelan–McDermid syndrome (PMS) is a rare, heterogeneous, and complex neurodevelopmental disorder. It is generally caused by a heterozygous microdeletion of contiguous genes located in the distal portion of the long arm of chromosome 22, including the SHANK3 gene. Sequence variants of SHANK3, including frameshift, nonsense mutations, small indels and splice site mutations also result in PMS. Furthermore, haploinsufficiency in SHANK3 has been suggested as the main cause of PMS. SHANK3 is also associated with intellectual disability, autism spectrum disorder and schizophrenia. The phenotype of PMS is variable, and lacks a distinctive phenotypic characteristic, so the clinical diagnosis should be confirmed by genetic analysis. PMS is a multi-system disorder, and clinical care must encompass various specialties and therapists. The role of risperidone, intranasal insulin, insulin growth factor 1, and oxytocin as potential therapeutic options in PMS will be discussed in this review. The diagnosis of PMS is important to provide an appropriate clinical evaluation, treatment, and genetic counseling. [ABSTRACT FROM AUTHOR]

Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenetic hereditary renal disease, promoting end-stage renal disease (ESRD). Klinefelter syndrome (KS) is a consequence of an extra copy of the X chromosome in males. Main symptoms in KS include hypogonadism, tall stature, azoospermia, and a risk of cardiovascular diseases, among others. Gitelman syndrome (GS) is an autosomal recessive disorder caused by SLC12A3 variants, and is associated with hypokalemia, hypomagnesemia, hypocalciuria, normal or low blood pressure, and salt loss. The three disorders have distinct and well-delineated clinical, biochemical, and genetic findings. We here report a male patient with ADPKD who developed early chronic renal failure leading to ESRD, presenting with an intracranial aneurysm and infertility. NGS identified two de novo PKD1 variants, one known (likely pathogenic), and a previously unreported variant of uncertain significance, together with two SLC12A3 pathogenic variants. In addition, cytogenetic analysis showed a 47, XXY karyotype. We investigated the putative impact of this rare association by analyzing possible clinical, biochemical, and/or genetic interactions and by comparing the evolution of renal size and function in the proband with three age-matched ADPKD (by variants in PKD1) cohorts. We hypothesize that the coexistence of these three genetic disorders may act as modifiers with possible synergistic actions that could lead, in our patient, to a rapid ADPKD progression. [ABSTRACT FROM AUTHOR]

Control of highly nonlinear processes such as solar collector fields is usually a challenging task. A common approach to this problem involves deploying a set of operation point range-specific controllers, whose actions are to be combined in a switching strategy. Discontinuities in control actions upon switching may lead to instabilities and, therefore, achieving bumpless transitions is always a concern. In addition, linear adaptive predictive controllers need to cope with nonlinearities by using high adaptation speeds, often leading to model vulnerability in the presence of aggressive perturbations. Finally, most of the proposed solutions rely on complex plant model developments. In this work, a multivariable nonlinear model-based adaptive predictive controller has been developed and tested against a parabolic trough solar power plant simulation. Since the model employed by this controller accounts for process nonlinearities, adaptation speed can be dramatically reduced, therefore increasing model robustness. The controller is easily initialized and is able to identify and track the process dynamics, including its nonlinearities as it evolves with time, thus requiring neither process up-front modeling nor switching. The presented controller outperforms its linear counterpart both in terms of accuracy and robustness and, due to the generality of its design, it is expected to be applicable to a wide class of linear and nonlinear processes. [ABSTRACT FROM AUTHOR]

Storm water overflows have an important impact on the environment in many European countries. Nowadays, a better knowledge of combined sewer overflows (CSOs) pollution is required for implementing measures to reduce these emissions. In this work, pollution flows mobilized during rainy events have been monitored and modeled in two urban catchments located in the city of Murcia (southeast Spain). For each analyzed event, rainfall volume, in-sewer turbidity and water flow depth have been continuously measured. Therefore, sets of pollutographs and hydrographs have been obtained for each event analyzed. Characteristic variables have been defined and obtained for each event such as the maximum concentration of turbidity, the total event rainfall, the previous dry weather period, the time to the peak of the hydrograph and to the peak of the pollutograph, among others. Relations between variables have been adjusted through a statistical model. The adjusted parameters are used to generate pollutographs that are compared with those measured in field. The present work provides tools to assist in the knowledge of pollution transported through sewer network during stormy events, suggesting the creation of design pollutographs which may facilitate the evaluation of measures to reduce urban runoff pollution. [ABSTRACT FROM AUTHOR]

Urban sustainability is a key factor that must be considered at the local level, however, there are few studies that consider sustainability using the triple bottom line approach and apply it to a large number of cities. In this paper, we develop a sustainability city index based on the triple bottom line using an intellectual capital approach that attempts to solve the negative aspects identified in the main indices proposed in the existing literature, such as the use of: subjective weightings, an arithmetic average or index that is not comparable. Here, we have used information available in the Urban Audit database for 2009. The results for 158 cities in 24 European countries show that the cities with the best positions are in the northern European countries. German cities occupied the best positions in the three dimensions of sustainability, albeit with a slightly worse performance in the social dimension. Moreover, the proposal index is consistent, without redundancy among the variables considered in the three dimensions. [ABSTRACT FROM AUTHOR]

The urban canyon model has been recurrently used as a basis for many solar access studies. However, its conception as endless structures disregards the effect of street intersections, despite being characteristic elements of urban fabrics. This paper aims to evaluate the impact of street discontinuities on solar access over building façades. The potential of crossings to increase the available radiation has been assessed through computer simulations in dense urban environments in a Mediterranean location. For the cases studied, results show that local effects of an intersection almost disappear beyond a specific distance for each aspect ratio, which can be helpful to determine the suitable level of detail for solar analyses at an urban fabric scale. [ABSTRACT FROM AUTHOR]

Parabolic trough solar power plants use a thermal fluid to transfer thermal energy from solar radiation to a water-steam Rankine cycle in order to drive a turbine that, coupled to an electrical generator, produces electricity. These plants have a heat transfer fluid (HTF) system with the necessary elements to transform solar radiation into heat and to transfer that thermal energy to the water-steam exchangers. In order to get the best possible performance in the Rankine cycle and, hence, in the thermal plant, it is necessary that the thermal fluid reach its maximum temperature when leaving the solar field (SF). Also, it is mandatory that the thermal fluid does not exceed the maximum operating temperature of the HTF, above which it degrades. It must be noted that the optimal temperature of the thermal fluid is difficult to obtain, since solar radiation can change abruptly from one moment to another. The aim of this document is to provide a model of an HTF system that can be used to optimize the control of the temperature of the fluid without interfering with the normal operation of the plant. The results obtained with this model will be contrasted with those obtained in a real plant. [ABSTRACT FROM AUTHOR]

The concept of sustainable development, which has emerged over the last few decades, has moved away from the global to the local level. The sustainability measurements at the global level use the triple bottom line, considering environmental, economic and social dimensions; however, the limited data available at the local level has driven what little research there is to use these optics when considering cities sustainability. In this paper, we use a sustainability city index based on the intellectual capital approach, which considers the three dimensions for European cities. Concretely, we use the environmental and social dimensions of this city index to analyze the effect of different levels of development in terms of sustainability over the main economic variables with available information. The results highlight the importance of the social and environmental dimensions of sustainability in cities economic recovery and show that cities with best positions in sustainability have better performance in economic terms. [ABSTRACT FROM AUTHOR]

Happiness is a very important aspect in the life and well-being of all citizens; as such, it has become a key factor in personal preferences. For these reasons, it is relevant to study what factors principally affect the happiness of the population. However, the difficulties involved in measuring this concept mean that there are no clear criteria as to which aspects should be promoted in order for citizens to achieve greater happiness. This paper uses variance-based structural equation modelling (SEM)—partial least squares path modelling (PLS)—to analyse the direct and indirect effects of European citizens' assessment of different aspects of their city related to safety, environmental quality and urban planning on their happiness. The source of information used in this study is the Flash Eurobarometer 419 prepared by Eurostat in 2015, with a total of 9799 observations. The results show how quality of life, safety, the environment and city planning have a positive and significant influence on European citizens' happiness, especially safety. In addition, quality of life acts as a mediating variable, primarily increasing the influence of urban planning on happiness. The findings of the study point to the relevant policies that governments should undertake to ensure the happiness of their citizens. [ABSTRACT FROM AUTHOR]

Background: physiological differences between males and females could contribute to the development of Alzheimer's Disease (AD). Here, we examined metabolic pathways that may lead to precision medicine initiatives. Methods: We explored whether sex modifies the association of 540 plasma metabolites with AD endophenotypes including diagnosis, cerebrospinal fluid (CSF) biomarkers, brain imaging, and cognition using regression analyses for 695 participants (377 females), followed by sex-specific pathway overrepresentation analyses, APOE ε4 stratification and assessment of metabolites' discriminatory performance in AD. Results: In females with AD, vanillylmandelate (tyrosine pathway) was increased and tryptophan betaine (tryptophan pathway) was decreased. The inclusion of these two metabolites (area under curve (AUC) = 0.83, standard error (SE) = 0.029) to a baseline model (covariates + CSF biomarkers, AUC = 0.92, SE = 0.019) resulted in a significantly higher AUC of 0.96 (SE = 0.012). Kynurenate was decreased in males with AD (AUC = 0.679, SE = 0.046). Conclusions: metabolic sex-specific differences were reported, covering neurotransmission and inflammation pathways with AD endophenotypes. Two metabolites, in pathways related to dopamine and serotonin, were associated to females, paving the way to personalised treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Ras-GTPases play a key role in the control of fundamental cellular processes such as proliferation, survival, adhesion, and differentiation. These functions make them particularly relevant in the development and progression of numerous types of cancer. Activating mutations in some of these proteins are particularly relevant in colorectal cancer and largely determine its response to available therapies. In this review, we will discuss the role of Ras-GTPases in colorectal cancer, the strategies available to inhibit them and their implication in overcoming resistance to the therapies currently used in clinical practice. Colorectal cancer remains among the cancers with the highest incidence, prevalence, and mortality worldwide. Although the development of targeted therapies against the EGFR and VEGFR membrane receptors has considerably improved survival in these patients, the appearance of resistance means that their success is still limited. Overactivation of several members of the Ras-GTPase family is one of the main actors in both tumour progression and the lack of response to cytotoxic and targeted therapies. This fact has led many resources to be devoted over the last decades to the development of targeted therapies against these proteins. However, they have not been as successful as expected in their move to the clinic so far. In this review, we will analyse the role of these Ras-GTPases in the emergence and development of colorectal cancer and their relationship with resistance to targeted therapies, as well as the status and new advances in the design of targeted therapies against these proteins and their possible clinical implications. [ABSTRACT FROM AUTHOR]

A library of seventeen novel ether phospholipid analogues, containing 5-membered heterocyclic rings (1,2,3-triazolyl, isoxazolyl, 1,3,4-oxadiazolyl and 1,2,4-oxadiazolyl) in the lipid portion were designed and synthesized aiming to identify optimised miltefosine analogues. The compounds were evaluated for their in vitro antiparasitic activity against Leishmania infantum and Leishmania donovani intracellular amastigotes, against Trypanosoma brucei brucei and against different developmental stages of Trypanosoma cruzi. The nature of the substituents of the heterocyclic ring (tail) and the oligomethylene spacer between the head group and the heterocyclic ring was found to affect the activity and toxicity of these compounds leading to a significantly improved understanding of their structure–activity relationships. The early ADMET profile of the new derivatives did not reveal major liabilities for the potent compounds. The 1,2,3-triazole derivative 27 substituted by a decyl tail, an undecyl spacer and a choline head group exhibited broad spectrum antiparasitic activity. It possessed low micromolar activity against the intracellular amastigotes of two L. infantum strains and T. cruzi Y strain epimastigotes, intracellular amastigotes and trypomastigotes, while its cytotoxicity concentration (CC50) against THP-1 macrophages ranged between 50 and 100 μM. Altogether, our work paves the way for the development of improved ether phospholipid derivatives to control neglected tropical diseases. [ABSTRACT FROM AUTHOR]

Simple Summary: The assessment of animals' personalities can help manage decisions concerning zoo animals more appropriately; for example, a proper personality evaluation helps create stable social groups or increase the chances of breeding success if compatible breeding pairs are chosen. In zoos, the animals' personality is often evaluated by the caretakers due to their familiarity with the animals and their behaviours. In this study, we aimed to evaluate how reliable caretakers' ratings are when assessing dolphins' personalities. With this aim in mind, we asked 24 caretakers to score a variety of personality traits of bottlenose dolphins under their care through a questionnaire in two periods. Our findings showed fair to good degrees of agreement within scores of the same rater and across raters within the same centre. We were also able to identify which raters and centres showed significant score mean differences systematically. We believe the study of raters' outcomes reliability is crucial to make appropriate management decisions based on the animals' personalities. The evaluation of zoo animals' personalities can likely lead to a range of benefits, including improving breeding success, creating stable social groups, and designing and developing environmental enrichment programmes. The goal of this study was to use caretakers scores to evaluate personality in bottlenose dolphins and to assess the reliability of scores within each rater and among raters from each centre. To this end, 24 caretakers from 3 countries (Spain, France, and Argentina), including a total of 5 dolphinariums and 6 groups of dolphins, used a questionnaire based on the Five-Factor Model of Personality to score bottlenose dolphins on a number of personality traits in three different contexts. Each caretaker evaluated the animals under their care twice, ensuring that raters did not share thoughts nor impressions with other raters. Our findings showed a good degree of agreement between each rater's scores and a fair degree of agreement among scores of raters from the same centre. We also identified which raters and centres had significant mean score differences and detected that 4 out of 24 raters from two different centres showed such differences systematically. The evaluation of raters' reliability and the identification of particular inconsistent raters and centres is critical to make more appropriate and realistic management decisions that, in turn, directly impact animals' welfare. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate, from a technological and nutritional point of view, the chemical composition and functional properties of the industrial winemaking by-products, namely skins, stems and lees. The chemical and physical characteristics, as well as the functional properties (fat and water retention and swelling capacity, antioxidant capacity, and their prebiotic effect), of the dietary fibre of these by-products were studied. The results showed that the skins, stems, and lees are rich in fibre, with the stem fibre containing the highest amounts of non-extractable polyphenols attached to polysaccharides with high antioxidant activity and prebiotic effect. Lee fibre had the highest water retention capacity and oil retention capacity. The results reveal that winemaking by-products could be used as a source of dietary fibre with functional characteristics for food applications. [ABSTRACT FROM AUTHOR]