Search

The importance of attentional capacity for academic performance is highlighted by the increasing demands placed on students during primary school. Between the ages of 7 and 12, there is an evolutionary improvement in attentional capacity and the school environment is considered an appropriate setting in which to develop programmes to improve attention. Heart rate variability is an appropriate indicator of attentional capacity. For all these reasons, a heart rate variability biofeedback intervention focused on breathing was developed and implemented to improve attention. The intervention consisted of two phases. In the first phase, the school teachers were trained to develop the intervention; in the second, students received five individual sessions from their teachers. In each individual session, they learned to breathe to increase their heart rate variability. A total of 272 girls and 314 boys (N = 586) aged 7–12 years participated in the programme. To study the impact of the intervention on three primary school age groups, the attention of Control and Experimental groups was assessed before and after the implementation of the programme. According to the data obtained, despite developmental improvements, the students who participated in the programme showed an increase in heart rate variability and an improvement in attentional capacity, with a greater impact on the first cycle of primary school. The usefulness of heart rate variability biofeedback interventions in improving attention in primary school is discussed and arguments for their use in children are presented. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus leads to debilitating complications that affect the quality of life of many Filipinos. Genetic variability contributes to 30% to 70% of T2DM risk. Determining genomic variants related to type 2 diabetes mellitus susceptibility can lead to early detection to prevent complications. However, interethnic variability in risk and genetic susceptibility exists. This study aimed to identify variants associated with type 2 diabetes mellitus among Filipinos using a case-control design frequency matched for age and sex. A comparison was made between 66 unrelated Filipino adults with type 2 diabetes mellitus and 121 without. Genotyping was done using a candidate gene approach on genetic variants of type 2 diabetes mellitus and its complications involving allelic association and genotypic association studies with correction for multiple testing. Nine (9) significant variants, mostly involved in glucose and energy metabolism, associated with type 2 diabetes mellitus in Filipinos were found. Notably, a CDKAL1 variant (rs7766070) confers the highest level of risk while rs7119 (HMG20A) and rs708272 (CETP) have high risk allele frequencies in this population at 0.77 and 0.66, respectively, making them potentially good markers for type 2 diabetes mellitus screening. The data generated can be valuable in developing genetic risk prediction models for type 2 diabetes mellitus to diagnose and prevent the condition among Filipinos. [ABSTRACT FROM AUTHOR]

BACKGROUND: Atherosclerosis is the main medical problem in Hutchinson-Gilford progeria syndrome, a rare premature aging disorder caused by the mutant lamin-A protein progerin. Recently, we found that limiting progerin expression to vascular smooth muscle cells (VSMCs) is sufficient to hasten atherosclerosis and death in Apoe-deficient mice. However, the impact of progerin-driven VSMC defects on endothelial cells (ECs) remained unclear. METHODS: Apoe- or Ldlr-deficient C57BL/6J mice with ubiquitous, VSMC-, EC- or myeloid-specific progerin expression fed a normal or high-fat diet were used to study endothelial phenotype during Hutchinson-Gilford progeria syndrome-associated atherosclerosis. Endothelial permeability to low-density lipoproteins was assessed by intravenous injection of fluorescently labeled human low-density lipoprotein and confocal microscopy analysis of the aorta. Leukocyte recruitment to the aortic wall was evaluated by en face immunofluorescence. Endothelial-to-mesenchymal transition (EndMT) was assessed by quantitative polymerase chain reaction and RNA sequencing in the aortic intima and by immunofluorescence in aortic root sections. TGFß (transforming growth factor ß) signaling was analyzed by multiplex immunoassay in serum, by Western blot in the aorta, and by immunofluorescence in aortic root sections. The therapeutic benefit of TGFß1/SMAD3 pathway inhibition was evaluated in mice by intraperitoneal injection of SIS3 (specific inhibitor of SMAD3), and vascular phenotype was assessed by Oil Red O staining, histology, and immunofluorescence in the aorta and the aortic root. RESULTS: Both ubiquitous and VSMC-specific progerin expression in Apoe-null mice provoked alterations in aortic ECs, including increased permeability to low-density lipoprotein and leukocyte recruitment. Atherosclerotic lesions in these progeroid mouse models, but not in EC- and myeloid-specific progeria models, contained abundant cells combining endothelial and mesenchymal features, indicating extensive EndMT triggered by dysfunctional VSMCs. Accordingly, the intima of ubiquitous and VSMC-specific progeroid models at the onset of atherosclerosis presented increased expression of EndMT-linked genes, especially those specific to fibroblasts and extracellular matrix. Aorta in both models showed activation of the TGFß1/SMAD3 pathway, a major trigger of EndMT, and treatment of VSMC-specific progeroid mice with SIS3 alleviated the aortic phenotype. CONCLUSIONS: Progerin-induced VSMC alterations promote EC dysfunction and EndMT through TGFß1/SMAD3, identifying this process as a candidate target for Hutchinson-Gilford progeria syndrome treatment. These findings also provide insight into the complex role of EndMT during atherogenesis. [ABSTRACT FROM AUTHOR]

Oxford ragwort (Senecio squalidus) is one of only two homoploid hybrid species known to have originated very recently, so it is a unique model for determining genomic changes and stabilization following homoploid hybrid speciation. Here, we provide a chromosome-level genome assembly of S. squalidus with 95% of the assembly contained in the 10 longest scaffolds, corresponding to its haploid chromosome number. We annotated 30,249 protein-coding genes and estimated that ∼62% of the genome consists of repetitive elements. We then characterized genome-wide patterns of linkage disequilibrium, polymorphism, and divergence in S. squalidus and its two parental species, finding that (1) linkage disequilibrium is highly heterogeneous, with a region on chromosome 4 showing increased values across all three species but especially in S. squalidus ; (2) regions harboring genetic incompatibilities between the two parental species tend to be large, show reduced recombination, and have lower polymorphism in S. squalidus ; (3) the two parental species have an unequal contribution (70:30) to the genome of S. squalidus , with long blocks of parent-specific ancestry supporting a very rapid stabilization of the hybrid lineage after hybrid formation; and (4) genomic regions with major parent ancestry exhibit an overrepresentation of loci with evidence for divergent selection occurring between the two parental species on Mount Etna. Our results show that both genetic incompatibilities and natural selection play a role in determining genome-wide reorganization following hybrid speciation and that patterns associated with homoploid hybrid speciation—typically seen in much older systems—can evolve very quickly following hybridization. • The genome of S. squalidus , a recent homoploid hybrid species, is presented • Sorting of parental alleles is associated with presence of genetic incompatibilities • Fixed alleles from the major parent are associated with divergent natural selection • Typical patterns of hybrid speciation appear <300 generations after speciation Nevado et al. report genomic reorganization following hybrid speciation. They find that the typical genomic signatures of homoploid hybrid species are well established ∼300 generations after hybridization and that both pre-existing genetic incompatibilities and divergent natural selection play an important role following hybrid speciation. [ABSTRACT FROM AUTHOR]

Analysis of genetically defined immunodeficient patients allows study of the effect of the absence of specific proteins on human immune function in real‐world conditions. Here we have addressed the importance of type I interferon signalling for human NK cell development by studying the phenotype and function of circulating NK cells isolated from patients suffering primary immunodeficiency disease due to mutation of either the human interferon regulatory factor 9 (IRF9) or the signal transducer and activator of transcription 2 (STAT2) genes. IRF9, together with phosphorylated STAT1 and STAT2, form a heterotrimer called interferon stimulated gene factor 3 (ISGF3) which promotes the expression of hundreds of IFN‐stimulated genes that mediate antiviral function triggered by exposure to type I interferons. IRF9‐ and STAT2‐deficient patients are unable to respond efficiently to stimulation by type I interferons and so our experiments provide insights into the importance of type I interferon signalling and the consequences of its impairment on human NK cell biology. Surprisingly, the NK cells of these patients display essentially normal phenotype and function. [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]

Human inborn errors of immunity (IEI) comprise a group of diseases resulting from molecular variants that compromise innate and adaptive immunity. Clinical features of IEI patients are dominated by susceptibility to a spectrum of infectious diseases, as well as autoimmune, autoinflammatory, allergic, and malignant phenotypes that usually appear in childhood, which is when the diagnosis is typically made. However, some IEI patients are identified in adulthood due to symptomatic delay of the disease or other reasons that prevent the request for a molecular study. The application of next-generation sequencing (NGS) as a diagnostic technique has given rise to an ever-increasing identification of IEI-monogenic causes, thus improving the diagnostic yield and facilitating the possibility of personalized treatment. This work was a retrospective study of 173 adults with IEI suspicion that were sequenced between 2005 and 2023. Sanger, targeted gene-panel, and whole exome sequencing were used for molecular diagnosis. Disease-causing variants were identified in 44 of 173 (25.43%) patients. The clinical phenotype of these 44 patients was mostly related to infection susceptibility (63.64%). An enrichment of immune dysregulation diseases was found when cohorts with molecular diagnosis were compared to those without. Immune dysregulation disorders, group 4 from the International Union of Immunological Societies Expert Committee (IUIS), were the most prevalent among these adult patients. Immune dysregulation as a new item in the Jeffrey Model Foundation warning signs for adults significantly increases the sensitivity for the identification of patients with an IEI-producing molecular defect. [ABSTRACT FROM AUTHOR]

Although immunoglobulin (IgY) has therapeutic potential, extracts from conventional methods are generally parenterally incompatible. This present study aimed to design a method to generate an IgY composition in vivo administration. The proposed procedure incorporated the following modifications: delipidation using carrageenan, salt precipitation using sodium sulfate, desalting using gel filtration, and affinity chromatography using MgCl2 as a disrupting agent. Furthermore, specific IgY was generated against human histones (H3 or H4) or calf histones to demonstrate the maintenance of target specificity. Native polyacrylamide gel electrophoresis patterns showed increasing purity from crude to post-desalted samples. Affinity chromatography estimated specific antibodies in the crude extract at 3-8%. Using ELISA, specificity was demonstrated for plasma, serum, or bicarbonate buffer samples. No mortality was observed in Sprague-Dawley rats and BALB/c mice using OECD up-and-down limit protocol adjusted to wrote. LD50 was estimated at more than 500 mg/kg intraperitoneally and 300 mg/kg intravenously. Intravenously injected with limited doses, intraperitoneally in mice, and daily sublethal doses for up to 36 d. Curiously, nonspecific IgY - but not specific IgY - had a higher liver injury score than solvent alone for acute injections (P < 0.05). Thus, the proposed method of IgY isolation may offer a means for an IgY composition that can be compatible with both in vivo therapeutics. [ABSTRACT FROM AUTHOR]

We state the relation between the variety of binary forms of given rank and the dual of the multiple root loci. This is a new result for the suprageneric rank that appears as a continuation of the cited work by Buczyński, Han, Mella and Teitler. We describe the strata of these varieties and explore their singular loci. [ABSTRACT FROM AUTHOR]

The importance and prevalence of recent ice‐age and post‐glacial speciation and species diversification during the Pleistocene across many organismal groups and physiographic settings are well established. However, the extent to which Pleistocene diversification can be attributed to climatic oscillations and their effects on distribution ranges and population structure remains debatable. In this study, we use morphologic, geographic and genetic (RADseq) data to document Pleistocene speciation and intra‐specific diversification of the unifoliolate‐leaved clade of Florida Lupinus, a small group of species largely restricted to inland and coastal sand ridges across the Florida peninsula and panhandle. Phylogenetic and demographic analyses alongside morphological and geographic evidence suggest that recent speciation and intra‐specific divergence within this clade were driven by a combination of non‐adaptive allopatric divergence caused by edaphic niche conservatism and opportunities presented by the emergence of new post‐glacial sand ridge habitats. These results highlight the central importance of even modest geographic isolation and short periods of allopatric divergence following range expansion in the emergence of new taxa and add to the growing evidence that Pleistocene climatic oscillations may contribute to rapid diversification in a myriad of physiographic settings. Furthermore, our results shed new light on long‐standing taxonomic debate surrounding the number of species in the Florida unifoliate Lupinus clade providing support for recognition of five species and a set of intra‐specific variants. The important conservation implications for the narrowly restricted, highly endangered species Lupinus aridorum, which we show to be genetically distinct from its sister species Lupinus westianus, are discussed. [ABSTRACT FROM AUTHOR]

Human inborn errors of immunity (IEI) affecting the type I interferon (IFN-I) induction pathway have been associated with predisposition to severe viral infections. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening systemic hyperinflammatory syndrome that has been increasingly associated with inborn errors of IFN-I-mediated innate immunity. Here is reported a novel case of complete deficiency of STAT2 in a 3-year-old child that presented with typical features of HLH after mumps, measles, and rubella vaccination at the age of 12 months. Due to the life-threatening risk of viral infection, she received SARS-CoV-2 mRNA vaccination. Unfortunately, she developed multisystem inflammatory syndrome in children (MIS-C) after SARS-CoV-2 infection, 4 months after the last dose. Functional studies showed an impaired IFN-I-induced response and a defective IFNα expression at later stages of STAT2 pathway induction. These results suggest a possible more complex mechanism for hyperinflammatory reactions in this type of patients involving a possible defect in the IFN-I production. Understanding the cellular and molecular links between IFN-I-induced signaling and hyperinflammatory syndromes can be critical for the diagnosis and tailored management of these patients with predisposition to severe viral infection. [ABSTRACT FROM AUTHOR]

Somatic mutations in the ten-eleven translocation methylcytosine dioxygenase 2 gene (TET2) have been associated to hematologic malignancies. More recently, biallelic, and monoallelic germline mutations conferring susceptibility to lymphoid and myeloid cancer have been described. We report two unrelated autoimmune lymphoproliferative syndrome-like patients who presented with T-cell lymphoma associated with novel germline biallelic or monoallelic mutations in the TET2 gene. Both patients presented a history of chronic lymphoproliferation with lymphadenopathies and splenomegaly, cytopenias, and immune dysregulation. We identified the first compound heterozygous patient for TET2 mutations (P1) and the first ALPS-like patient with a monoallelic TET2 mutation (P2). P1 had the most severe form of autosomal recessive disease due to TET2 loss of function resulting in absent TET2 expression and profound increase in DNA methylation. Additionally, the immunophenotype showed some alterations in innate and adaptive immune system as inverted myeloid/plasmacytoid dendritic cells ratio, elevated terminally differentiated effector memory CD8 + T-cells re-expressing CD45RA, regulatory T-cells, and Th2 circulating follicular T-cells. Double-negative T-cells, vitamin B12, and IL-10 were elevated according to the ALPS-like suspicion. Interestingly, the healthy P1's brother carried a TET2 mutation and presented some markers of immune dysregulation. P2 showed elevated vitamin B12, hypergammaglobulinemia, and decreased HDL levels. Therefore, novel molecular defects in TET2 confirm and expand both clinical and immunological phenotype, contributing to a better knowledge of the bridge between cancer and immunity. [ABSTRACT FROM AUTHOR]

Neuropsychological tests have commonly been used to determine the organization of cognitive functions by identifying latent variables. In contrast, an approach which has seldom been employed is network analysis. We characterize the network structure of a set of representative neuropsychological test scores in cognitively healthy older adults and MCI and dementia patients using network analysis. We employed the neuropsychological battery from the National Alzheimer's Coordinating Center which included healthy controls (n = 7623), mild cognitive impairment patients (n = 5981) and dementia patients (n = 2040), defined according to the Clinical Dementia Rating. The results showed that, according to several network analysis measures, the most central cognitive function is executive function followed by attention, language, and memory. At the test level, the most central test was the Trail Making Test B, which measures cognitive flexibility. Importantly, these results and most other network measures, such as the community organization and graph representation, were similar across the three diagnostic groups. Therefore, network analysis can help to establish a ranking of cognitive functions and tests based on network centrality and suggests that this organization is preserved in dementia. Central nodes might be particularly relevant both from a theoretical and clinical point of view, as they are more associated with other nodes, and their disruption is likely to have a larger effect on the overall network than peripheral nodes. The present analysis may provide a proof of principle for the application of network analysis to cognitive data. [ABSTRACT FROM AUTHOR]

Background: In recent years, cases of leishmaniosis have been described in animals housed in captivity in zoos in Spain [Bennett's wallaby (Macropus rufogriseus rufogriseus), orangutan (Pongo pygmaeus pygameus), and European otter (Lutra lutra)]. Some of these zoological parks are in endemic areas for both human and animal leishmaniosis, thus it should be very important to include this zoonosis in the differential diagnosis. Methods: The study was carried out in two zoological parks in Madrid, Madrid Zoo and Faunia, and analyzed seven meerkats. Serological tests [rK-39 and enzyme-linked immunosorbent assay (ELISA)] and molecular tests [nested polymerase chain reaction (PCR) and real-time PCR] were performed to detect Leishmania DNA. Additionally, an entomological study was carried out in both zoological parks, with molecular tests performed on female Phlebotomus perniciosus sand flies to determine their blood meal source and detect Leishmania DNA. Results: Two meerkats were positive for L. infantum. A 9-year-old male from the Madrid Zoo died suddenly, showing pale mucous membranes and bilateral noninflammatory alopecia and hyperpigmentation in the lateral area of the eyes. Positive results were obtained in serology, nested PCR, and real-time PCR (blood, conjunctival and oral swabs, hair, spleen, lymph node, liver, kidney, and skin), as well as numerous amastigotes in the liver and kidney tissue samples. The other meerkat, a 12-year-old male from Faunia that is still alive, presented an alopecic lesion at the base of the tail. Positive results were obtained by nested and real-time PCR from different tissues such as blood, hair, oral, and conjunctival swabs. It was treated with oral allopurinol (25 mg/kg) and miltefosine (2 mg/kg), but the molecular diagnosis remained positive after 8 months, regarding it as a mild stage of the disease. The rest of the tested meerkats were negative. The presence of P. perniciosus phlebotomine sand flies was also detected in both zoos. Although no L. infantum DNA was detected in any of sand flies analyzed, it was determined that their food sources were rabbits and humans. Conclusions: To our knowledge, this study describes, for the first time, the detection and infection by L. infantum in meerkats (Suricata suricatta). [ABSTRACT FROM AUTHOR]

Mutations in VAV1, a gene that encodes a multifunctional protein important for lymphocytes, are found at different frequencies in peripheral T‐cell lymphoma (PTCL), non‐small cell lung cancer, and other tumors. However, their pathobiological significance remains unsettled. After cataloguing 51 cancer‐associated VAV1 mutations, we show here that they can be classified in five subtypes according to functional impact on the three main VAV1 signaling branches, GEF‐dependent activation of RAC1, GEF‐independent adaptor‐like, and tumor suppressor functions. These mutations target new and previously established regulatory layers of the protein, leading to quantitative and qualitative changes in VAV1 signaling output. We also demonstrate that the most frequent VAV1 mutant subtype drives PTCL formation in mice. This process requires the concurrent engagement of two downstream signaling branches that promote the chronic activation and transformation of follicular helper T cells. Collectively, these data reveal the genetic constraints associated with the lymphomagenic potential of VAV1 mutant subsets, similarities with other PTCL driver genes, and potential therapeutic vulnerabilities. Synopsis: VAV1 encodes a multifunctional signaling protein involved in both RAC1 GTPase activation and adaptor‐like functions. Mutations in this gene have recently been found in PTCL and other tumor types. Here, we have catalogued 51 VAV1 tumor‐associated mutations according to their functional impact on the downstream signaling branches of the protein. Our work has revealed that: The VAV1 gain‐of‐function mutations belong to different subclasses according to impact on VAV1 downstream signaling.These mutations target both expected and hitherto unknown VAV1 regulatory layers.A VAV1 mutation representative of the most frequent functional subclass drives PTCL formation in mice.VAV1‐driven lymphomagenesis requires cooperating signals from the catalytic‐dependent and independent pathways of the mutant protein.The molecular features of VAV1‐driven lymphomas resemble those found in PTCL patients. [ABSTRACT FROM AUTHOR]

Constituting one of the most commonly used antihypertensive drug families are the angiotensin receptor blockers (ARBs). The aim of this study was to identify the variants associated with response to ARBs that may potentially be used as markers for designing a tailor-fit treatment strategy for hypertension. An unmatched case-control study was done among adult hypertensive Filipino patients maintained on ARBs. Genotypic analysis of blood DNA was conducted. Logistic regression analyses were performed to determine association of clinical and genetic variables with ARB response. A total of 69 poor responders and 126 normal responders were included in the study. After performing univariate logistic regression, five single nucleotide polymorphisms showed association with poor response to ARBs. The genetic variant rs6596140 remained significant (dominant model; OR 2.36, p = 0.009) after adjusting for female sex and age. Variant rs6596140 was found to be associated with poor response to ARBs among Filipinos. Prior to clinical application, verification is recommended prior to clinical application. As the function of this variant is presently unknown, an investigation to elucidate its role in ARB response in hypertension is also recommended. [ABSTRACT FROM AUTHOR]

Apoptosis plays an important role in controlling the adaptive immune response and general homeostasis of the immune cells, and impaired apoptosis in the immune system results in autoimmunity and immune dysregulation. In the last 25 years, inherited human diseases of the Fas-FasL pathway have been recognized. Autoimmune lymphoproliferative syndrome (ALPS) is an inborn error of immunity, characterized clinically by nonmalignant and noninfectious lymphoproliferation, autoimmunity, and increased risk of lymphoma due to a defect in lymphocyte apoptosis. The laboratory hallmarks of ALPS are an elevated percentage of T-cell receptor αβ double negative T cells (DNTs), elevated levels of vitamin B12, soluble FasL, IL-10, IL-18 and IgG, and defective in vitro Fas-mediated apoptosis. In order of frequency, the genetic defects associated with ALPS are germinal and somatic ALPS-FAS, ALPS-FASLG, ALPS-CASP10, ALPS-FADD, and ALPS-CASP8. Partial disease penetrance and severity suggest the combination of germline and somatic FAS mutations as well as other risk factor genes. In this report, we summarize human defects of apoptosis leading to ALPS and defects that are known as ALPS-like syndromes that can be clinically similar to, but are genetically distinct from, ALPS. An efficient genetic and immunological diagnostic approach to patients suspected of having ALPS or ALPS-like syndromes is essential because this enables the establishment of specific therapeutic strategies for improving the prognosis and quality of life of patients. [ABSTRACT FROM AUTHOR]

Background: Galectin-1 (Gal-1) plays major roles in cancer by modulating different processes leading to tumor development and progression. In the last years, it has been suggested as a promising target for anticancer therapy. Recently, aflibercept has shown high affinity for Gal-1. Here, we investigated how aflibercept could exert its antitumor activity via Gal-1-driven pathways in neuroendocrine carcinomas (NECs). Methods and Results: NEC tumor xenografts were used to assess the effect of aflibercept on Gal-1 functions. Aflibercept induced a significant reduction of Gal-1 at epithelial, stromal, and extracellular localizations in lung NEC, whereas this was not observed in colon NECs, which displayed low expression of Gal-1. Additionally, aflibercept significantly reduced p-VEGFR2 protein, extracellular matrix remodeling, epithelial-mesenchymal transition, and activation of cancer-associated fibroblast hampering cell invasion in lung NEC but not in colon NEC. Gal-1 screening in human NECs confirmed that pulmonary and pancreatic tumors displayed higher levels of Gal-1 than colon NECs, becoming good candidates to benefit from aflibercept treatment. Conclusions: The lack of validated predictive markers of aflibercept is a weakness for guaranteeing the best treatment management with this drug. This work provides new mechanistic insight of aflibercept depending on Gal-1. Thus, in tumors overexpressing Gal-1, aflibercept has not only an antiangiogenic effect but also prevents Gal-1-mediated tumor-stroma cross talk. The stronger aflibercept effect in tumors with high levels of Gal-1 points out this protein as a molecular marker to predict the efficacy of this agent not only for NECs but also for other tumors with high levels of this protein. [ABSTRACT FROM AUTHOR]

Hybridisation can lead to homoploid hybrid speciation, i.e., the origin of new species without change in chromosome number between parents and offspring. Central to homoploid hybrid speciation is the role of hybridisation in the establishment of reproductive isolation between the hybrid and the parental species in the early stages of speciation, when typically all species occur at least partly in sympatry. In this work we analyse genome‐wide polymorphism data obtained by transcriptome sequencing of the British hybrid species Oxford ragwort (Senecio squalidus, Asteraceae), its two Italian parental species (S. aethnensis and S. chrysanthemifolius) and their naturally occurring hybrids on Mt Etna (Italy). We show that Oxford ragwort most likely originated from de novo hybridisation between its two Italian parental species whilst they were in cultivation in British gardens at the turn of the 18th century. Reproductive isolation between the new hybrid species and its parental species probably resulted from inheritance of genetic incompatibilities between the two parental species and subsequent ecological segregation – both of which have been shown in previous studies. Our results imply that S. squalidus meets the most stringent criteria set forth to identify homoploid hybrid speciation, and call attention to the creative role of hybridisation in responding to novel environmental conditions. [ABSTRACT FROM AUTHOR]

The Europe 2020 development strategy prioritizes the so-called Smart Regions, reflecting the European Commission's commitment to geographical 'specialization.' Accordingly, the European regions have developed innovation strategies for smart specialization. A key element in these development strategies is the technological factor, which is clearly influenced by the level of human development in the region. This article analyses the convergence between citizens' capacities and technological development in a region. Specifically, we analyse 129 NUTS 2 regions in Europe, using official data provided by Eurostat. To measure human development, this article proposes a Smart Human Index based on a synthetic indicator incorporating three dimensions; in addition, we use two dimensions to construct an indicator of regional technological development. The results show that a region's technological capacity clearly depends on its inhabitants' degree of formal education, while their use of technologies depends on the citizens' degree of social openness and cultural level. [ABSTRACT FROM AUTHOR]

The proximal 19p13.3 microdeletion/microduplication (prox19p13.3del/dup) syndrome is a recently described disorder with common clinical features including developmental delay, intellectual disability, speech delay, facial dysmorphic features with ear defects, anomalies of the hands and feet, umbilical hernia and hypotonia. While deletions are associated with macrocephaly, patients with duplications have microcephaly. The smallest region of overlap in multiple patients (113.5 kb) included three genes and one pseudogene, with a suggested major role of PIAS4 in determination of the phenotype and head size in these patients. Here, we refine the prox19p13.3del/dup with four additional patients: two with microdeletions, one with microduplication and one family with single‐nucleotide nonsense variant in PIAS4. The patient with the PIAS4 loss of function variant displayed a phenotype quite similar to deletion patients ‐including the macrocephaly and many other core features of the syndrome. Patient's SNV was inherited from her mother who is similarly affected. Thus, our data indicate that PIAS4 is a major contributor to the proximal 19p13.3del/dup syndrome phenotype. In summary, we report the first patient with a pathogenic variant in PIAS4‐ and three additional rearrangements at the proximal 19p13.3 locus. These observations add further evidence about the molecular basis of this microdeletion/microduplication syndrome. [ABSTRACT FROM AUTHOR]

Aging is the main risk factor for vascular disease and ensuing cardiovascular and cerebrovascular events, the leading causes of death worldwide. In a progressively aging population, it is essential to develop early-life biomarkers that efficiently identify individuals who are at high risk of developing accelerated vascular damage, with the ultimate goal of improving primary prevention and reducing the health care and socioeconomic impact of age-related cardiovascular disease. Studies in experimental models and humans have identified 9 highly interconnected hallmark processes driving mammalian aging. However, strategies to extend health span and life span require understanding of interindividual differences in age-dependent functional decline, known as biological aging. This review summarizes the current knowledge on biological age biomarkers, factors influencing biological aging, and antiaging interventions, with a focus on vascular aspects of the aging process and its cardiovascular disease related manifestations. [ABSTRACT FROM AUTHOR]

Cough is a common side effect of angiotensin converting enzyme inhibitor (ACEi) therapy. The incidence of ACEi-induced cough has been shown to correlate with genetic variation among different populations. This study aimed to determine the association of candidate genetic polymorphisms with ACEi-induced cough among Filipinos. Two hundred twenty (220) participants on ACEi therapy pressure-lowering in an unmatched case-control study (82 cases with ACEiinduced cough and 138 controls). Genomic DNA samples were extracted and genotyped for selected genetic variants. The association of genetic variants and clinical factors with ACEi-induced cough was determined using regression analyses. Univariate logistic regression showed that the BAG6 variant rs805303 is nominally associated with ACEi-induced cough among Filipinos, at a percomparison error rate (PCER) of 0.05 (OR 2.10, p = 0.016). The association of the variant with ACEi cough was statistically significant after multiple regression analysis (adjusted OR 2.09, p = 0.022) while adjusting for confounding clinical factors (sex, alcohol intake, and diastolic blood pressure). Further studies are needed to validate these findings. [ABSTRACT FROM AUTHOR]

Overgrowth syndromes (OGS) comprise a heterogeneous group of disorders whose main characteristic is that the weight, height or the head circumference are above the 97th centile or 2–3 standard deviations above the mean for age, gender, and ethnic group. Several copy‐number variants (CNVs) have been associated with the development of OGS, such as the 5q35 microdeletion or the duplication of the 15q26.1‐qter, among many others. In this study, we have applied 850K SNP‐arrays to 112 patients and relatives with OGS from the Spanish OverGrowth Registry Initiative. We have identified CNVs associated with the disorder in nine individuals (8%). Subsequently, whole genome sequencing (WGS) analysis was performed in these nine samples in order to better understand these genomic imbalances. All the CNVs were detected by both techniques, settling that WGS is a useful tool for CNV detection. We have found six patients with genomic abnormalities associated with previously well‐established disorders and three patients with CNVs of unknown significance, which may be related to OGS, based on scientific literature. In this report, we describe these findings and comment on genes associated with OGS that are located within the CNV regions. [ABSTRACT FROM AUTHOR]

Hutchinson‐Gilford progeria syndrome (HGPS) is a rare genetic disorder caused by a mutation in the LMNA gene that provokes the synthesis of progerin, a mutant version of the nuclear protein lamin A that accelerates aging and precipitates death. The most clinically relevant feature of HGPS is the development of cardiac anomalies and severe vascular alterations, including massive loss of vascular smooth muscle cells, increased fibrosis, and generalized atherosclerosis. However, it is unclear if progerin expression in endothelial cells (ECs) causes the cardiovascular manifestations of HGPS. To tackle this question, we generated atherosclerosis‐free mice (LmnaLCS/LCSCdh5‐CreERT2) and atheroprone mice (Apoe−/−LmnaLCS/LCSCdh5‐CreERT2) with EC‐specific progerin expression. Like progerin‐free controls, LmnaLCS/LCSCdh5‐CreERT2 mice did not develop heart fibrosis or cardiac electrical and functional alterations, and had normal vascular structure, body weight, and lifespan. Similarly, atheroprone Apoe−/−LmnaLCS/LCSCdh5‐CreERT2 mice showed no alteration in body weight or lifespan versus Apoe−/−LmnaLCS/LCS controls and did not develop vascular alterations or aggravated atherosclerosis. Our results indicate that progerin expression in ECs is not sufficient to cause the cardiovascular phenotype and premature death associated with progeria. [ABSTRACT FROM AUTHOR]

• Experiments demonstrate correlations between long-term stress and renewal. • Long term stress had no relation to conditioning or extinction. • Perceived control of stressful events was related to greater renewal. • Effects of long-term stress and acute stress prior to test are similar. • The PSS-10 as a measure of stress may predict susceptibility to relapse. Two online experiments evaluated the relationship between long-term stress, as measured with the Perceived Stress Scale-10, and the Renewal Effect. In the first experiment renewal was assessed with a behavioral suppression task in a science-fiction based video game. Participants learned to suppress mouse clicking during a signal for an upcoming attack to avoid losing points. The signal was first paired with an attack in Context A and extinguished in Context B and tested back in Context A. The contexts were different space galaxies where the gameplay took place. Experiment 2 used a food/illness predictive-learning paradigm. Two food items were paired with stomachache in one restaurant (A) and extinguished in Context B prior to testing in both contexts without feedback. Positive correlations were obtained between renewal and stress in each experiment. Unlike acute stress (Drexler et al., 2017), long term stress was associated with greater renewal. The effects of stress, both chronic and punctual, on renewal are discussed. [ABSTRACT FROM AUTHOR]

Waveguides fabrication in Z- and X-cut LiNbO[sub 3] crystals by vapor zinc diffusion has been studied by secondary ion mass spectrometry and optical measurements. Compositional analysis of diffused substrates shows the formation of a Zn rich superficial layer, followed by a deeper region with decreasing Zn concentration. A subsequent thermal annealing process has been performed to let zinc ions further diffuse into the substrates. The composition profiles have been correlated with the refractive index profiles, reconstructed by optical reflectivity measurements. The results and the nature of the detected layers are discussed and correlated with previous x-ray studies obtained in the same samples. © 2000 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Recently diverged species present particularly informative systems for studying speciation and maintenance of genetic divergence in the face of gene flow. We investigated speciation in two closely related Senecio species, S. aethnensis and S. chrysanthemifolius, which grow at high and low elevations, respectively, on Mount Etna, Sicily and form a hybrid zone at intermediate elevations. We used a newly generated genome‐wide single nucleotide polymorphism (SNP) dataset from 192 individuals collected over 18 localities along an elevational gradient to reconstruct the likely history of speciation, identify highly differentiated SNPs, and estimate the strength of divergent selection. We found that speciation in this system involved heterogeneous and bidirectional gene flow along the genome, and species experienced marked population size changes in the past. Furthermore, we identified highly‐differentiated SNPs between the species, some of which are located in genes potentially involved in ecological differences between species (such as photosynthesis and UV response). We analysed the shape of these SNPs' allele frequency clines along the elevational gradient. These clines show significantly variable coincidence and concordance, indicative of the presence of multifarious selective forces. Selection against hybrids is estimated to be very strong (0.16–0.78) and one of the highest reported in literature. The combination of strong cumulative selection across the genome and previously identified intrinsic incompatibilities probably work together to maintain the genetic and phenotypic differentiation between these species – pointing to the importance of considering both intrinsic and extrinsic factors when studying divergence and speciation. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effects of fatigue induced by repeated sprint in the kicking accuracy and velocity in female soccer players. Eighteen Under-23 female soccer players from a Spanish professional club were subjected to a fatigue protocol based on a repeated-sprint ability (RSA) test. Measurements of the kicking velocity (maximal ball velocity) and accuracy (Loughborough Soccer Shooting Test) were taken before and after fatigue induction. Correlations between the change in the maximal ball velocity/accuracy and the heart rate (HR), the fatigue index (FI), the sprint decrement (Sdec) and the rating of perceived exertion (RPE) were made. There was a significant difference between maximal ball velocity under fatigue conditions with respect to non-fatigue conditions (p = 0.001; ES = 0.89). However, despite a lower kicking accuracy punctuation with fatigue, this was not statistically significant (p = 0.433; ES = 0.22). Significant correlations were found between the maximal kicking velocity and the FI (r = 0.632, p < 0.01) and the Sdec (r = -0.554, p < 0.05) and between the kicking accuracy and the RPE (r = -0.506, p < 0.05). In conclusion, there was a significant reduction in the maximal kicking velocity, but not in the kicking accuracy, under fatigued conditions. The RSA-related FI and Sdec were the best predictors of the maximal kicking velocity and the RPE for the kicking accuracy. [ABSTRACT FROM AUTHOR]

Increasing evidence indicates that in wild ecosystems plant viruses are important ecological agents, and with potential to jump into crops, but only recently have the diversity and population dynamics of wild plant viruses begun to be explored. Theory proposes that biotic factors (e.g., ecosystem biodiversity, host abundance, and host density) and climatic conditions would determine the epidemiology and evolution of wild plant viruses. However, these predictions seldom have been empirically tested. For 3 years, we analyzed the prevalence and genetic diversity of Potyvirus species in preserved riparian forests of Spain. Results indicated that potyviruses were always present in riparian forests, with a novel generalist potyvirus species provisionally named Iberian hop mosaic virus (IbHMV), explaining the largest fraction of infected plants. Focusing on this potyvirus, we analyzed the biotic and climatic factors affecting virus infection risk and population genetic diversity in its native ecosystem. The main predictors of IbHMV infection risk were host relative abundance and species richness. Virus prevalence and host relative abundance were the major factors determining the genetic diversity and selection pressures in the virus population. These observations support theoretical predictions assigning these ecological factors a key role in parasite epidemiology and evolution. Finally, our phylogenetic analysis indicated that the viral population was genetically structured according to host and location of origin, as expected if speciation is largely sympatric. Thus, this work contributes to characterizing viral diversity and provides novel information on the determinants of plant virus epidemiology and evolution in wild ecosystems. [ABSTRACT FROM AUTHOR]

Background: Neuroendocrine carcinoma (NEC) is a rare and very aggressive tumor. It has been greatly understudied, and very little is known about optimal treatment strategy for patients with this disease. The purpose of this study was to evaluate in vivo whether anti-vascular endothelial growth factor (VEGF) drugs could be a therapeutic alternative for these tumors with a poor prognosis. Methods: We have developed 2 xenograft models using either human cell line derived from lung (H460) or from colon (COLO320) NEC to assess the effect of 2 antiangiogenic drugs, aflibercept and bevacizumab, on tumor growth and their pathological characteristics. Additionally, tumors were subjected to immunohistochemistry staining and proteins were measured with Western blot and ELISA. Results: Both aflibercept and bevacizumab showed significant antitumor activity (p < 0.001). In the H460 model, aflibercept resulted in 94% tumor growth inhibition (TGI) and bevacizumab treatment resulted in 72.2% TGI. Similarly, in the COLO320 model, aflibercept and bevacizumab resulted in 89.3 and 84% TGI, respectively. Moreover, antitumor activity occurs early after treatment initiation. Using Tumor Control Index score, which address the kinetics of tumor growth in a way comparable to the methods used in human clinical studies, we confirmed that both drugs inhibit significantly tumor growth. When tumor stabilization was evaluated, aflibercept shows higher ability to stabilize NEC tumors than bevacizumab. Conclusion: Results derived from this study strongly support anti-VEGF therapies, especially aflibercept, as a novel therapeutic option in NECs. Further studies are necessary, but our observations encourage the evaluation of antiangiogenics in clinical trials combined with standard chemotherapy. [ABSTRACT FROM AUTHOR]

As part of 'parental authority', the legal system recognizes the parents' power to moderately correct their children and their right-obligation to interact with them in cases where parents are separated. The purpose of this paper is to analyze the configuration of the parental rights to correct, as well as their rights to visitation in different Latin American ordinances, making a comparison with Spain, while studying how police, as the called upon authority, can collaborate with parents, as well as outlining the actions that police should take when confronted with breaches of visitation rights with minors. For this, the comparative method between laws will be used. It is concluded that the regulation of parental rights to correct varies between countries, as does the breach of visitation rights, which some countries consider to be a crime, while others consider it civil order. [ABSTRACT FROM AUTHOR]

Background: Intimate partner violence (IPV) against women is associated with a wide range of adverse outcomes. Although mental disorders have been linked to an increased risk of perpetrating IPV against women, the direction and magnitude of the association remain uncertain. In a longitudinal design, we examined the association between mental disorders and IPV perpetrated by men towards women in a population-based sample and used sibling comparisons to control for factors shared by siblings, such as genetic and early family environmental factors.Methods and Findings: Using Swedish nationwide registries, we identified men from 9 diagnostic groups over 1998-2013, with sample sizes ranging from 9,529 with autism to 88,182 with depressive disorder. We matched individuals by age and sex to general population controls (ranging from 186,017 to 1,719,318 controls), and calculated the hazard ratios of IPV against women. We also estimated the hazard ratios of IPV against women in unaffected full siblings (ranging from 4,818 to 37,885 individuals) compared with the population controls. Afterwards, we compared the hazard ratios for individuals with psychiatric diagnoses with those for siblings using the ratio of hazard ratios (RHR). In sensitivity analyses, we examined the contribution of previous IPV against women and common psychiatric comorbidities, substance use disorders and personality disorders. The average follow-up time across diagnoses ranged from 3.4 to 4.8 years. In comparison to general population controls, all psychiatric diagnoses studied except autism were associated with an increased risk of IPV against women in men, with hazard ratios ranging from 1.5 (95% CI 1.3-1.7) to 7.7 (7.2-8.3) (p-values < 0.001). In sibling analyses, we found that men with depressive disorder, anxiety disorder, alcohol use disorder, drug use disorder, attention deficit hyperactivity disorder, and personality disorders had a higher risk of IPV against women than their unaffected siblings, with RHR values ranging from 1.7 (1.3-2.1) to 4.4 (3.7-5.2) (p-values < 0.001). Sensitivity analyses showed higher risk of IPV against women in men when comorbid substance use disorders and personality disorders were present, compared to risk when these comorbidities were absent. In addition, increased IPV risk was also found in those without previous IPV against women. The absolute rates of IPV against women ranged from 0.1% to 2.1% across diagnoses over 3.4 to 4.8 years. Individuals with alcohol use disorders (1.7%, 1,406/82,731) and drug use disorders (2.1%, 1,216/57,901) had the highest rates. Our analyses were restricted to IPV leading to arrest, suggesting that the applicability of our results may be limited to more severe forms of IPV perpetration.Conclusions: Our results indicate that most of the studied mental disorders are associated with an increased risk of perpetrating IPV towards women, and that substance use disorders, as principal or comorbid diagnoses, have the highest absolute and relative risks. The findings support the development of IPV risk identification and prevention services among men with substance use disorders as an approach to reduce the prevalence of IPV. [ABSTRACT FROM AUTHOR]

Abstract Conventional chemical analyses of meat products are time-consuming, expensive and destructive. The advantages of NIR spectroscopy are its speed, portability, suitability for both at-line and on-line analysis, low cost and the possibility of simultaneously measuring many different parameters in a large number of samples. The purpose of this study was to develop and validate calibrations for the prediction of moisture, protein and fat in Iberian pig pork loins using an FT-NIR instrument coupled to a 5-m fibre optic sensor head. The best equations obtained for intact loin in both modes of analysis (full and optimal spectral range) displayed Standard Error of Cross-Validation (RMSECV) of 1.06% and 1.09% and Determination Coefficient of Cross-Validation (R CV 2) of 0.69 and 0.77 for fat: RMSECV of 0.87% and 0.77% and R CV 2 of 0.67 and 0.73 for moisture; while for protein, the RMSECV values were 0.51% and 0.49% and the R CV 2 values were 0.66 and 0.70. [ABSTRACT FROM AUTHOR]

The European Union recognizes the importance of public procurement as one of the instruments that must be used to achieve smart, sustainable and inclusive growth. In Spain, Law 9/2017, of November 8, on Public Sector Contracts, transposes the European Parliament and Council Directives 2014/23 / EU and 2014/24 / EU into the Spanish legal system. This law aims to incorporate transversally socially responsible criteria when preparing and executing public contracts. In addition, it obliges bidding companies to meet specific requirements on gender equality, fair labor conditions, fair trade consumption or energy efficiency. Specifically, the basic objectives pursued by the Law are; the impartiality and objectivity of procedures, greater transparency in public procurement and improving the quality- price ratio. All this means guaranteeing the correctness of the procedures, avoiding any hint of corruption and using public procurement in a strategic manner to implement, with the resources that are managed through the contracts, public policies at communitarian and national levels in the social, environmental, and development fields and the innovation and promotion of the participation of small and medium enterprises in public procurement. Faced with this situation, public administrations have begun to develop guidelines and approve instructions for the implementation of socially responsible clauses in their hiring. However, despite its importance, there is no specific measurement instrument that evaluates this type of behavior. In this context, we propose this research with the aim of facilitating a tool, composed of a series of ethical and sustainable indicators, in line with the new Law, which allow comparative measurement and comparison of the responsible behavior of administrations in relation to their public contracts. In this way, the contracting bodies must present in their specifications concrete measures to guarantee, on the one hand, integrity in their contracting procedures and, on the other hand, the strategic use of their contracts. All this it will allow to implement, with the resources that are managed through contracts, national and international policies in social, environmental, promotion of innovation and of the participation of small and medium enterprises in public procurement. The research has revealed the existence of numerous guides and publications for the implementation of social, ethical and environmental clauses in public procurement, as well as instructions or agreements on sustainable public procurement. Specifically, in Spain, there are many administrations that, in recent years, have published good practice guides for the inclusion of Social Responsibility clauses in their contracts. In addition, it has been observed the continued existing commitment of the Spanish public administrations with the Social Responsibility, through the approval of Agreements or Instructions. Indeed, since 2005, in which the Good Governance Code of the General State Administration was approved in Spain, and in 2009, when the Spanish Federation of Municipalities and Provinces approved its own Code of Good Governance, very significant steps have been taken in terms of Social Responsibility and sustainability. In the second stage of the study, a series of social and environmental indicators were created to evaluate and compare responsible practices in public procurement throughout the different phases of the contract (preparation, awarding, execution). This first investigation has some limitations derived from the lack of quantitative data, however, like any exploratory study, it constitutes a hypothesis-generating element and serves as the basis for future investigations that allow evaluating the hiring of the entities that make up the public sector in relationship to social, environmental and ethical issues. At the same time, this proposal may favor focusing the practices and responsible policies to address the observed shortcomings, contributing to obtain economic and social environmental benefits, for the Administration and for the private sector and society in general. According to the objectives formulated in this exploratory study, it has been proven that, increasingly and with a general nature, public administrations are aware and are concerned about the aspects that have to do with Transparency, Social Responsibility and sustainability. From the analysis of the current situation of sustainable public procurement, the important efforts of the initiatives, both national and international, aimed at strengthening a regulatory framework in this area are confirmed. Specifically, in Spain, it is observed that there are many administrations that adopt the commitment to be socially responsible in their hiring. However, the great task that remains to be done to adapt to the regulatory framework in these matters has been verified. The importance of this work, because it is a pioneer, is that it has defined a series of indicators that serve to evaluate sustainability in public procurement. In addition, the proposed indicators allow to guide the implementation of good practices and can be used in future research as a basic methodological instrument to advance in the understanding and improvement of sustainable public procurement processes. All this will allow knowing the current situation of sustainable public procurement and being able to compare them over time, evaluate the impact of the approval of procurement laws in local administrations, determine good practices in public procurement, measure the effects of instructions or agreements on public procurement, identify if there are patterns of behavior among public administrations in relation to their responsible contracting and what could be the conditioning factors of sustainable practices in public procurement. [ABSTRACT FROM AUTHOR]

This article is based on fieldwork carried out at the Adult Education Center of a women's prison. The objective is to show how both institutions intertwine and collide, underlining the contradictions between a legislation that foments schooling and a functional logic that hinders it. The narratives of the women who attend school become the axes that articulate conclusions that present the classroom as a place in which to reconnect with their lives outside the prison walls and resignify their time in prison. [ABSTRACT FROM AUTHOR]

Aims/Purpose: The aim of this study was to evaluate changes in peripheral refraction by the use of a contact lens to control the progression of myopia. In addition, the response of electrophysiological activity in different areas of the retina with and without contact lens was also determined. Methods: We recruited 7 myopic individuals (23.71 ± 5.41 years) with refraction up to −4.50D (spherical equivalent), without eye pathologies and surgeries. Visual acuity was recorded, high and low contrast, with the updated refraction and with the Misight 1 Day contact lens. Peripheral refraction measurements were obtained using an open‐field autorefractometer. Multifocal electrophysiology measurements were performed binocularly with and without contact lens, with dilated pupil. Topography and aberrometry values were also recorded. Results: lens, peripheral refractions become significantly more myopic. The change in peripheral refraction induced at 30° Nasal is −0.66D. High Contrast Visual Acuity was always superior to Low Contrast VA in both conditions. The Misight 1 Day contact lens manifests a different behaviour along the anterior surface of the cornea. LC induces a significant increase in high‐order aberrations, especially in comatic aberrations, which increase three times their initial value. Conclusions: Regarding the electrophysiological response of the retina, with the use of the LC Misight 1 Day, it presented a greater implicit time and amplitude of the P1 component, in the superior temporal retina, these differences being statistically significant. The implicit time of the P2 component increased in the temporal retina and in the retinal area delimited by Rings 3, 4 and 5. [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]

The article presents the research papers on blood-based review of preclinical alzheimer’s disease (AD) therapeutic trials. The research involves cognitively unimpaired individuals from the AIBL and KARVIAH cohorts defined as negative or positive by positron emission tomography. Nontargeted proteomic analysis is conducted with incorporated peptide fractionation and high-resolution mass spectrometry

Abstract Foods and beverages are nutrient-rich ecosystems in which most microorganisms are able to grow. Moreover, several factors, such as physicochemical characteristics, storage temperature, culinary practices, and application of technologies for storage, also define the microbial population of foods and beverages. The yeast population has been well-characterised in fresh and processed fruit and vegetables, dairy products, dry-cured meat products, and beverages, among others. Some species are agents of alteration in different foods and beverages. Since the most comprehensive studies of spoilage yeasts have been performed in the winemaking process, hence, these studies form the thread of the discussion in this review. The natural yeast populations in raw ingredients and environmental contamination in the manufacturing facilities are the main modes by which food contamination occurs. After contamination, yeasts play a significant role in food and beverage spoilage, particularly in the alteration of fermented foods. Several mechanisms contribute to spoilage by yeasts, such as the production of lytic enzymes (lipases, proteases, and cellulases) and gas, utilisation of organic acids, discolouration, and off-flavours. This review addresses the role of yeasts in foods and beverages degradation by considering the modes of contamination and colonisation by yeasts, the yeast population diversity, mechanisms involved, and the analytical techniques for their identification, primarily molecular methods. Highlights • Raw material, plant facilities, air and water are main source of spoilage yeasts. • Origin of contamination by Brettanomyces / Dekkera during winemaking • Independent- and dependent-culture molecular methods of yeast identification • Recent reports of yeast spoilage in foodstuffs [ABSTRACT FROM AUTHOR]

The acrylamide content in oxidised black olives and the influence of baking treatments on the concentrations of acrylamide and phenolic compounds were determined. Twenty different randomly selected commercial brands of olives were purchased from industries located in Spain and Portugal, for analysis of the acrylamide contents. A wide variation in acrylamide concentration was obtained for the commercial canned black ripe olives and brine. Various baking temperatures and times were applied to the table olives with the lowest acrylamide content. The baking treatments significantly increased the acrylamide amount in olives and drastically reduced the phenolic compounds. The phenolic compounds had a strong negative linear correlation with the acrylamide content. [ABSTRACT FROM AUTHOR]

Key message: This study revealed that the western Mediterranean provided the founder population for domesticated narrow-leafed lupin and that genetic diversity decreased significantly during narrow-leafed lupin domestication.Abstract: The evolutionary history of plants during domestication profoundly shaped the genome structure and genetic diversity of today’s crops. Advances in next-generation sequencing technologies allow unprecedented opportunities to understand genome evolution in minor crops, which constitute the majority of plant domestications. A diverse set of 231 wild and domesticated narrow-leafed lupin (Lupinus angustifolius L.) accessions were subjected to genotyping-by-sequencing using diversity arrays technology. Phylogenetic, genome-wide divergence and linkage disequilibrium analyses were applied to identify the founder population of domesticated narrow-leafed lupin and the genome-wide effect of domestication on its genome. We found wild western Mediterranean population as the founder of domesticated narrow-leafed lupin. Domestication was associated with an almost threefold reduction in genome diversity in domesticated accessions compared to their wild relatives. Selective sweep analysis identified no significant footprints of selection around domestication loci. A genome-wide association study identified single nucleotide polymorphism markers associated with pod dehiscence. This new understanding of the genomic consequences of narrow-leafed lupin domestication along with molecular marker tools developed here will assist plant breeders more effectively access wild genetic diversity for crop improvement. [ABSTRACT FROM AUTHOR]

• Mountain ranges are amongst the most species-rich habitats, with many large and rapid evolutionary radiations. The tempo and mode of diversification in these systems are key unanswered questions in evolutionary biology. Here we study the Andean Lupinus radiation to understand the processes driving very rapid diversification in montane systems. • We use genomic and transcriptomic data of multiple species and populations, and apply phylogenomic and demographic analyses to test whether diversification proceeded without interspecific gene flow – as expected if Andean orogeny and geographic isolation were the main drivers of diversification – or if diversification was accompanied by gene flow, in which case other processes were probably involved. • We uncover several episodes of gene flow between species, including very recent events likely to have been prompted by changes in habitat connectivity during Pleistocene glacial cycles. Furthermore, we find that gene flow between species was heterogeneously distributed across the genome. • We argue that exceptionally fast diversification of Andean Lupinus was partly a result of Late Pleistocene glacial cycles, with associated cycles of expansion and contraction driving geographic isolation or secondary contact of species. Furthermore, heterogeneous gene flow across the genome suggests a role for selection and ecological speciation in rapid diversification in this system. [ABSTRACT FROM AUTHOR]

The influence of maturation of different olive fruit varieties and the effect of these olives fermented at room temperature in a spontaneous fermentation were studied. Also, table olives from Carrasqueña variety harvested in two consecutive weeks in green stage of maturation, were fermented at different thermal temperature by heat transfer to the brine. Initially, an olive growth characterization was carried out. The largest variety was “Manzanilla Cacereña” and presented less texture and the lowest total phenolic and antioxidant activity. However, “Carrasqueña” variety, which had the highest firmness, showed a slower size. The color index of “Manzanilla Sevillana” was rather higher than the color index of the other varieties. After fermentation process, the highest color index and free acidity in “Manzanilla Sevillana” table olive could be caused by the highest temperature of the brine achieved. In general, the varieties studied had a good texture during fermentation. On the other hand, the effect of thermal applications in table olive color was higher when the olives were harvested later and by thermal application. Finally, the effect of thermal application depended on initial maturation stage achieving an increase of phenols with determined temperatures and conditions. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: As electronic mental health records become more widely available, several approaches have been suggested to automatically extract information from free‐text narrative aiming to support epidemiological research and clinical decision‐making. In this paper, we explore extraction of explicit mentions of symptom severity from initial psychiatric evaluation records. We use the data provided by the 2016 CEGS N‐GRID NLP shared task Track 2, which contains 541 records manually annotated for symptom severity according to the Research Domain Criteria. Methods: We designed and implemented 3 automatic methods: a knowledge‐driven approach relying on local lexicalized rules based on common syntactic patterns in text suggesting positive valence symptoms; a machine learning method using a neural network; and a hybrid approach combining the first 2 methods with a neural network. Results: The results on an unseen evaluation set of 216 psychiatric evaluation records showed a performance of 80.1% for the rule‐based method, 73.3% for the machine‐learning approach, and 72.0% for the hybrid one. Conclusions: Although more work is needed to improve the accuracy, the results are encouraging and indicate that automated text mining methods can be used to classify mental health symptom severity from free text psychiatric notes to support epidemiological and clinical research. [ABSTRACT FROM AUTHOR]

Abstract: Accumulating evidence indicates that biodiversity has an important impact on parasite evolution and emergence. The vast majority of studies in this area have only considered the diversity of species within an environment as an overall measure of biodiversity, overlooking the role of genetic diversity within a particular host species. Although theoretical models propose that host genetic diversity in part shapes that of the infecting parasite population, and hence modulates the risk of parasite emergence, this effect has seldom been tested empirically. Using Rabies virus (RABV) as a model parasite, we provide evidence that greater host genetic diversity increases both parasite genetic diversity and the likelihood of a host being a donor in RABV cross‐species transmission events. We conclude that host genetic diversity may be an important determinant of parasite evolution and emergence. [ABSTRACT FROM AUTHOR]

Background and Objective. The thumb represents 40-50%of hand function making its stability and functional reconstruction essential. Despite the development in microsurgery, the correct use of local flaps for thumb coverage can provide us appropriate solutions to difficult reconstructive problems. The aim of this paper is to present our systematic reconstruction treatment of small and moderate thumb defects using local flaps. We use the concept of functional aesthetic units of the thumb describing the flaps to be consider as first reconstructive line in each type of defect. Methods. We present a descriptive, retrospective review of 56 cases of loss of thumb substance that presented exposure of the bone, tendon or both, which could benefit from coverage by local flaps. We include age, injured hand, type of accident and injury mechanism, digital subunit affected and geometry of the lesion. We describe reconstructive technique indicated in each case. Results. 95% of the cases (53 cases) corresponded to defects in the thumb distal subunit (distal to the interphalangeal joint (IJ)) compromising the pulp and the nail plate; including 2 of them associated with proximal palmar subunit injury and 8 associated with a proximal dorsal subunit injury. The other 5% (3 cases) corresponded to the proximal dorsal subunit exclusively. We performed 17 dorsal ulnar artery modified Brunelli flaps (30%); 3 Brunelli classic (5%); 12 first dorsal metacarpal artery flap (Foucher's flap) (22%); 9 Elliot's flap (16%); 4 Elliot's flaps associated with eponychial flap (7%); 6 Littler's heterodigital flaps (12%); 3 dorsoradial collateral artery flap (Moschella's flap) (5%); and 2 Buchler's heterodigital flaps (3%). Conclusions. In application of the functional aesthetic units of the thumb reconstructive concepts for volar defects, our first reconstructive line are the palmar flaps or the heterodigital flaps due to theirmechanical characteristics and the possibility of neurotization. In some cases, we would consider the Backach eponychial flap, which provides a considerable aesthetic improvement. On the other hand, in defects of dorsal preponderance, our preference are the dorsal ulnar and radial flaps and the firstmetacarpal artery flap formajor defects cases. These types of flaps only contributeminimally for the sensitivity, but present similar characteristics with the dorsal skin in terms of thickness and elasticity. [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]