AraBoard: A Multiplatform Alternative and Augmentative Communication Tool

AbstractWe present AraBoard: an Alternative and Augmentative Communication (AAC) tool developed to facilitate functional communication to people with complex communication needs. The tool is formed by two different applications: AraBoard Constructor, for the creation and edition of communication boards, and AraBoard Player, for the visualization of the boards previously generated. The main features that distinguish our tool are that it is multiplatform, it is low-cost, and it is highly configurable, adaptable to a wide range of users’ needs by modifying different parameters like the number and size of the cells, inclusion or not of audio, etc. The development has been assessed through 295 enquiries done via web. The answers have been analyzed and shown the high acceptance of the users

Experimental and Finite Element Study of Residual Thermal Stresses in Veneered Y-TZP Structures

The main complications of zirconia-based laminated systems are chipping and delamination of veneering porcelain, which has been found to be directly associated with the development of residual thermal stresses in the porcelain layer. This study investigates the effects of cooling rate and specimen geometry on the residual stress states in porcelain-veneered zirconia structures. Bilayers of three different shapes (bars, semi-cylindrical shells, and arch-cubic structures) with 1.5 mm and 0.7 mm thickness of dentin porcelain and zirconia framework, respectively, were subjected to two cooling protocols: slow cooling (SC) at 32 °C/min and extremely-slow cooling (XSC) at 2 °C/min. The residual thermal stresses were determined using the Vickers indentation method and validated by finite element analysis. The residual stress profiles were similar among geometries in the same cooling protocol. XSC groups presented significantly higher tensile stresses (p = 0.000), especially for curved interfaces. XSC is a time-consuming process that showed no beneficial effect regarding residual stresses compared to the manufacturer recommended slow cooling rate

Creación de herramientas software de apoyo a la comunicación alternativa y aumentativa

En el Colegio Público de Educación Especial Alborada se escolarizan alumnos que padecen graves trastornos en el habla, lo que les limita a la hora de comunicarse con el entorno que les rodea. En la gran mayoría de los alumnos se encuentran afectadas de forma importante las funciones de comunicación, así como los procesos de relación con el entorno físico y social, los de adquisición de habilidades de autonomía y, en general, los procesos básicos de aprendizaje. Para facilitarles la expresión sin utilizar la palabra hablada surgen los llamados Sistemas Aumentativos y Alternativos de Comunicación que complementan o sustituyen el lenguaje oral. Muchos de ellos recurren al uso de imágenes y símbolos pictográficos que representen, de forma clara, las palabras y conceptos más habituales en la comunicación cotidiana. Este Proyecto Fin de Carrera comprende el desarrollo de dos sistemas de apoyo a la Comunicación Alternativa y Aumentativa. La primera herramienta desarrollada se denomina AraBoard, y consiste en un software para la creación y reproducción de tableros de comunicación que permiten trasladar el concepto tradicional de tablero a diversas plataformas informáticas y sistemas operativos como dispositivos móviles y tablets, con sistema operativo Android; y pizarras digitales y equipos informáticos convencionales, con sistema operativo Windows. AraBoard se compone de dos aplicaciones diferenciadas pero complementarias entre sí: AraBoard Constructor: Esta herramienta se utiliza para la creación y edición de los tableros de comunicación, mediante la colección de pictogramas ARASAAC y cualquier otra imagen y audio almacenados en el dispositivo del usuario. AraBoard Player: Esta herramienta se utiliza para ejecutar los tableros de comunicación previamente creados con AraBoard Constructor. La segunda herramienta desarrollada se denomina Acoti, y permite la generación de actividades pedagógicas interactivas destinadas a funcionar el tabletop NIKVision, prototipo de superficie horizontal interactiva desarrollado por el Affective Lab y el cual se encuentra disponible en el colegio Alborada. Esta herramienta facilita la labor de los educadores del centro permitiéndoles, sin necesidad de tener conocimientos de programación, configurar las actividades de apoyo al aprendizaje utilizando sus propios recursos de imágenes o sonidos y ejecutarlos sobre el tabletop NIKVision. Ambas aplicaciones han sido probadas por los usuarios finales, tanto profesores como alumnos del CPEE Alborada a lo largo de todo el proceso de desarrollo, lo que ha permitido distribuir una versión robusta de las aplicaciones

CRISPR/Cas9-Mediated In Situ Correction of LAMB3 Gene in Keratinocytes Derived from a Junctional Epidermolysis Bullosa Patient

Deficiency of basement membrane heterotrimeric laminin 332 component, coded by LAMA3, LAMB3, and LAMC2 genes, causes junctional epidermolysis bullosa (JEB), a severe skin adhesion defect. Herein, we report the first application of CRISPR/Cas9-mediated homology direct repair (HDR) to in situ restore LAMB3 expression in JEB keratinocytes in vitro and in immunodeficient mice transplanted with genetically corrected skin equivalents. We packaged an adenovector carrying Cas9/guide RNA (gRNA) tailored to the intron 2 of LAMB3 gene and an integration defective lentiviral vector bearing a promoterless quasi-complete LAMB3 cDNA downstream a splice acceptor site and flanked by homology arms. Upon genuine HDR, we exploited the in vitro adhesion advantage of laminin 332 production to positively select LAMB3-expressing keratinocytes. HDR and restored laminin 332 expression were evaluated at single-cell level. Notably, monoallelic-targeted integration of LAMB3 cDNA was sufficient to in vitro recapitulate the adhesive property, the colony formation typical of normal keratinocytes, as well as their cell growth. Grafting of genetically corrected skin equivalents onto immunodeficient mice showed a completely restored dermal-epidermal junction. This study provides evidence for efficient CRISPR/Cas9-mediated in situ restoration of LAMB3 expression, paving the way for ex vivo clinical application of this strategy to laminin 332 deficiency

Aniseed, Pimpinella anisum, as a source of new agrochemicals: phytochemistry and insights on insecticide and acaricide development

Pimpinella anisum L. (Apiaceae), known around the world as aniseed, is a widely cultivated crop, native of the sub-Mediterranean area. Its essential oil (EO) is exploitable in different fields such as food and beverages, pharmaceutics, cosmetics, and nutraceuticals. Regardless of the geographic origin, the EO exhibited consistent transanethole predominancy. Among the numerous biological properties exerted by aniseed EO, its antimicrobial, antifungal, insecticidal, and acaricidal effects have been extensively investigated for the formulation of biopesticides against larvae and adults of various pests and vectors. Hereafter, the published data on the insecticidal and acaricidal activity of aniseed EO and its major compounds on agricultural pests, stored-product pests, and arthropods of medical and veterinary interest is reviewed. For each study, the arthropod and the developmental stage on which the aniseed EO or the aniseed EO-based formulation were tested, the mode of action, the main constituents, and the exerted mortality, as well as the toxicity to non-target organisms and the possible sub-lethal effects are reported. The advantages of the possible use of aniseed EO as a biopesticide are analysed, as well as the current weaknesses and the critical points to be overcome to open the doors to the industrial utilization of Apiaceae EOs by the agrochemical industry

Nanomechanical Characterization of Canine Femur Bone for Strain Rate Sensitivity in the Quasistatic Range under Dry versus Wet Conditions

As a strain rate-dependent material, bone has a different mechanical response to various loads. Our aim was to evaluate the effect of water and different loading/unloading rates on the nanomechanical properties of canine femur cortical bone. Six cross-sections were cut from the diaphysis of six dog femurs and were nanoindented in their cortical area. Both dry and wet conditions were taken into account for three quasistatic trapezoid profiles with a maximum force of 2000 μN (holding time = 30 s) at loading/unloading rates of 10, 100, and 1000 μN/s, respectively. For each specimen, 254±9 (mean ± SD) indentations were performed under different loading conditions. Significant differences were found for the elastic modulus and hardness between wet and dry conditions (P<0.001). No influence of the loading/unloading rates was observed between groups except for the elastic modulus measured at 1000 μN/s rate under dry conditions (P<0.001) and for the hardness measured at a rate of 10 μN/s under wet conditions (P<0.001). Therefore, for a quasistatic test with peak load of 2000 μN held for 30 s, it is recommended to nanoindent under wet conditions at a loading/unloading rate of 100–1000 μN/s, so the reduced creep effect allows for a more accurate computation of mechanical properties

An explainable model of host genetic interactions linked to COVID-19 severity

We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with the training of multiple supervised classifiers, to predict severity based on screened features. Feature importance analysis from tree-based models allowed us to identify 16 variants with the highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with high accuracy (ACC = 81.88%; AUCROC = 96%; MCC = 61.55%). Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome-Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response. It also identified additional processes cross-talking with immune pathways, such as GPCR signaling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as "Respiratory or thoracic disease", supporting their link with COVID-19 severity outcome.A multifaceted computational strategy identifies 16 genetic variants contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing dataset of a cohort of Italian patients

Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19

Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF-platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage

Gain- and Loss-of-Function CFTR Alleles Are Associated with COVID-19 Clinical Outcomes

Carriers of single pathogenic variants of the CFTR (cystic fibrosis transmembrane conductance regulator) gene have a higher risk of severe COVID-19 and 14-day death. The machine learning post-Mendelian model pinpointed CFTR as a bidirectional modulator of COVID-19 outcomes. Here, we demonstrate that the rare complex allele [G576V;R668C] is associated with a milder disease via a gain-of-function mechanism. Conversely, CFTR ultra-rare alleles with reduced function are associated with disease severity either alone (dominant disorder) or with another hypomorphic allele in the second chromosome (recessive disorder) with a global residual CFTR activity between 50 to 91%. Furthermore, we characterized novel CFTR complex alleles, including [A238V;F508del], [R74W;D1270N;V201M], [I1027T;F508del], [I506V;D1168G], and simple alleles, including R347C, F1052V, Y625N, I328V, K68E, A309D, A252T, G542*, V562I, R1066H, I506V, I807M, which lead to a reduced CFTR function and thus, to more severe COVID-19. In conclusion, CFTR genetic analysis is an important tool in identifying patients at risk of severe COVID-19

The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired macroautophagy/autophagy and reduced TNF/TNFα production was demonstrated in HEK293 cells transfected with TLR3L412F-encoding plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (p = 0.038). An increased frequency of autoimmune disorders such as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways. Abbreviations: AP: autophagosome; AUC: area under the curve; BafA1: bafilomycin A1; COVID-19: coronavirus disease-2019; HCQ: hydroxychloroquine; RAP: rapamycin; ROC: receiver operating characteristic; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TLR: toll like receptor; TNF/TNF-α: tumor necrosis factor