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Background/Objectives : Biallelic pathogenic variants in the CEP290 gene are typically associated with severe, early-onset inherited retinal dystrophies (IRDs) in both syndromic and non-syndromic forms. This study explores the phenotypic variability of non-syndromic IRDs associated with CEP290 variants, focusing on two siblings with biallelic variants, one of whom exhibits a remarkably mild phenotype, thereby expanding the clinical spectrum. Methods : Whole-exome sequencing (WES) and mRNA analysis were performed to identify and characterize CEP290 variants in the siblings. Comprehensive ophthalmologic evaluations assessed retinal function and disease progression. Results : Two CEP290 variants, a frameshift (c.955del, p.(Ser319LeufsTer16)) and a missense (c.5777G>C, p.(Arg1926Pro)), were identified in trans in both siblings. Despite sharing the same genetic variants, the sister exhibited significantly preserved retinal function, while the brother presented with a more severe, progressive retinal dystrophy. Conclusions : This study broadens the phenotypic spectrum of non-syndromic CEP290 -related IRDs, demonstrating variability in disease severity ranging from mild to severe. These findings highlight the importance of personalized monitoring and tailored management strategies based on individual clinical presentations of CEP290 -related IRDs.

Domestic cat blastocysts cultured without the zona pellucida exhibit reduced implantation capacity. However, the protein expression profile has not been evaluated in these embryos. The objective of this study was to evaluate the protein expression profile of domestic cat blastocysts cultured without the zona pellucida. Two experimental groups were generated: (1) domestic cat embryos generated by IVF and cultured in vitro (zona intact, (ZI)) and (2) domestic cat embryos cultured in vitro without the zona pellucida (zona-free (ZF group)). The cleavage, morula, and blastocyst rates were estimated at days 2, 5 and 7, respectively. Day 7 blastocysts and their culture media were subjected to liquid chromatography-tandem mass spectrometry (LC-MS/MS). The UniProt Felis catus database was used to identify the standard proteome. No significant differences were found in the cleavage, morula, or blastocyst rates between the ZI and ZF groups ( p > 0.05). Proteomic analysis revealed 22 upregulated and 20 downregulated proteins in the ZF blastocysts. Furthermore, 14 proteins involved in embryo development and implantation were present exclusively in the culture medium of the ZI blastocysts. In conclusion, embryo culture without the zona pellucida did not affect in vitro development, but altered the protein expression profile and release of domestic cat blastocysts.

Marine (blue) biotechnology is an emerging field enabling the valorization of new products and processes with massive potential for innovation and economic growth. In the Mediterranean region, this innovation potential is not exploited as well as in other European regions due to a lack of a clear identification of the different value chains and the high fragmentation of business innovation initiatives. As a result, several opportunities to create an innovative society are being missed. To address this problem, eight Northern Mediterranean countries (Croatia, France, Greece, Italy, Montenegro, Portugal, Slovenia and Spain) established five national blue biotechnology hubs to identify and address the bottlenecks that prevent the development of marine biotechnology in the region. Following a three-step approach (1. Analysis: setting the scene; 2. Transfer: identification of promising value chains; 3. Capitalization: community creation), we identified the three value chains that are most promising for the Northern Mediterranean region: algae production for added-value compounds, integrated multi-trophic aquaculture (IMTA) and valorization aquaculture/fisheries/processing by-products, unavoidable/unwanted catches and discards. The potential for the development and the technical and non-technical skills that are necessary to advance in this exciting field were identified through several stakeholder events which provided valuable insight and feedback that should be addressed for marine biotechnology in the Northern Mediterranean region to reach its full potential.

The embryo-maternal interaction occurs during the early stages of embryo development and is essential for the implantation and full-term development of the embryo. In bovines, the secretion of interferon Tau (IFNT) during elongation is the main signal for pregnancy recognition, but its expression starts around the blastocyst stage. Embryos release extracellular vesicles (EVs) as an alternative mechanism of embryo-maternal communication. The aim of the study was to determine whether EVs secreted by bovine embryos during blastulation (D5-D7) could induce transcriptomic modifications, activating IFNT signaling in endometrial cells. Additionally, it aims to assess whether the EVs secreted by embryos produced in vivo (EVs-IVV) or in vitro (EVs-IVP) have different effects on the transcriptomic profiles of the endometrial cells. In vitro- and in vivo-produced bovine morulae were selected and individually cultured for 48 h to collect embryonic EVs (E-EVs) secreted during blastulation. E-EVs stained with PKH67 were added to in vitro-cultured bovine endometrial cells to assess EV internalization. The effect of EVs on the transcriptomic profile of endometrial cells was determined by RNA sequencing. EVs from both types of embryos induced several classical and non-classical IFNT-stimulated genes (ISGs) and other pathways related to endometrial function in epithelial endometrial cells. Higher numbers of differentially expressed genes (3552) were induced by EVs released by IVP embryos compared to EVs from IVV (1838). Gene ontology analysis showed that EVs-IVP/IVV induced the upregulation of the extracellular exosome pathway, the cellular response to stimulus, and the protein modification processes. This work provides evidence regarding the effect of embryo origin (in vivo or in vitro) on the early embryo-maternal interaction mediated by extracellular vesicles.

Background: Hereditary hemorrhagic telangiectasia (HHT) is a rare vascular disease inherited in an autosomal dominant manner. Disease-causing variants in endoglin ( ENG ) and activin A receptor type II-like 1 ( ACVRL1 ) genes are detected in more than 90% of the patients undergoing molecular testing. The identification of variants of unknown significance is often seen as a challenge in clinical practice that makes family screening and genetic counseling difficult. Here, we show that the implementation of cDNA analysis to assess the effect of splice site variants on mRNA splicing is a powerful tool., Methods: Gene panel sequencing of genes associated with HHT and other arteriovenous malformation-related syndromes was performed. To evaluate the effect of the splice site variants, cDNA analysis of ENG and ACVRL1 genes was carried out., Results: three novel splice site variants were identified in ENG (c.68-2A > T and c.1311+4_1311+8del) and ACVLR1 (c.526-6C > G) genes correspondingly in three individuals with HHT that met ≥ 3 Curaçao criteria. All three variants led to an aberrant splicing inducing exon skipping ( ENG :c.68-2A > T and ACVRL1 :c.526-6C > G) or intron retention ( ENG :c.1311+4_1311+8del) allowing the confirmation of the predicted effect on splicing and the reclassification from unknown significance to pathogenic/likely pathogenic of two of them., Conclusions: RNA analysis should be performed to assess and/or confirm the impact of variants on splicing. The molecular diagnosis of HHT patients is crucial to allow family screening and accurate genetic counseling. A multidisciplinary approach including clinicians and geneticists is crucial when dealing with patients with rare diseases.

We report a novel proposal for reducing the digital divide in rural multigrade schools, incorporating knowledge of robotics with a STEM approach to simultaneously promote curricular learning in mathematics and science in several school grades. We used an exploratory qualitative methodology to implement the proposal with 12 multigrade rural students. We explored the contribution of the approaches to the promotion of curricular learning in mathematics and science and the perceptions of using robotics to learn mathematics and science. As data collection techniques, we conducted focus groups and semi-structured interviews with the participants and analyzed their responses thematically. We concluded that the proposal could contribute to meeting the challenges of multigrade teaching. Our findings suggest that the proposal would simultaneously promote the development of curricular learning in mathematics and science in several school grades, offering an alternative for addressing various topics with different degrees of depth.

Although the overall survival of advanced soft-tissue sarcoma (STS) patients has increased in recent years, the median progression-free survival is lower than 5 months, meaning that there is an unmet need in this population. Among second-line treatments for advanced STS, eribulin is an anti-microtubule agent that has been approved for liposarcoma. Here, we tested the combination of eribulin with gemcitabine in preclinical models of L-sarcoma. The effect in cell viability was measured by MTS and clonogenic assay. Cell cycle profiling was studied by flow cytometry, while apoptosis was measured by flow cytometry and Western blotting. The activity of eribulin plus gemcitabine was evaluated in in vivo patient-derived xenograft (PDX) models. In L-sarcoma cell lines, eribulin plus gemcitabine showed to be synergistic, increasing the number of hypodiploid events (increased subG1 population) and the accumulation of DNA damage. In in vivo PDX models of L-sarcomas, eribulin combined with gemcitabine was a viable scheme, delaying tumour growth after one cycle of treatment, being more effective in leiomyosarcoma. The combination of eribulin and gemcitabine was synergistic in L-sarcoma cultures and it showed to be active in in vivo studies. This combination deserves further exploration in the clinical context.

The objectives of this study were: (a) to determine asymmetries, both lower limb (LL) and upper limb (UL), in Chilean older adults, and (b) to relate asymmetries to FA in both LL and UL. Forty-one older adults voluntarily participated in this study (mean ± standard deviation [SD]: age 72.0 ± 8.0 years, LL asymmetries 13.78 ± 14.87%, UL asymmetries 10.70 ± 8.85%, FA 40.35 ± 16.26 points). The variables were: (1) asymmetries of LL and UL, assessed through a force platform and handgrip, respectively; (2) FA, assessed through the Latin American Group for Maturity (GDLAM) and the GDLAM index of autonomy (GI) protocol. The relationship between the variables was performed through Spearman's correlation. The analysis showed that 39% of the participants presented asymmetries above 15% in the LL. Likewise, this 39% of older adults presented a lower FA than their peers with asymmetries below 15% in the LL (≤15%: 35.64 ± 12.26 points vs. >15%: 47.69 ± 19.23 points, p = 0.003). The analysis showed a small correlation between LL and GI asymmetries ( r = 0.27, p = 0.07) and a small but negative correlation between UL and GI ( r = -0.21). The mean values of asymmetries of both LL and UL are within 'normal' parameters. However, several older adults were identified as being at risk. In parallel, older adults who presented a higher level of asymmetries in LL showed a lower level of FA.

(1) Background: The gut microbiota might play a part in affecting athletic performance and is of considerable importance to athletes. The aim of this study was to search the recent knowledge of the protagonist played by high-intensity and high-duration aerobic exercise on gut microbiota composition in athletes and how these effects could provide disadvantages in sports performance. (2) Methods: This systematic review follows the PRISMA guidelines. An exhaustive bibliographic search in Web of Science, PubMed, and Scopus was conducted considering the articles published in the last 5 years. The selected articles were categorized according to the type of study. The risk of bias was assessed using the Joanna Briggs Institute's Critical Appraisal Tool for Systematic Reviews. (3) Results: Thirteen studies had negative effects of aerobic exercise on intestinal microbiota such as an upsurge in I-FABP, intestinal distress, and changes in the gut microbiota, such as an increase in Prevotella , intestinal permeability and zonulin. In contrast, seven studies observed positive effects of endurance exercise, including an increase in the level of bacteria such as increased microbial diversity and increased intestinal metabolites. (4) Conclusions: A large part of the studies found reported adverse effects on the intestinal microbiota when performing endurance exercises. In studies carried out on athletes, more negative effects on the microbiota were found than in those carried out on non-athletic subjects.

Chromatin organization is essential to maintain a correct regulation of gene expression and establish cell identity. However, during cell division, the replication of the genetic material produces a global disorganization of chromatin structure. In this paper, we describe the new scientific breakthroughs that have revealed the nature of the post-replicative chromatin and the mechanisms that facilitate its restoration. Moreover, we highlight the implications of these chromatin alterations in gene expression control and their impact on key biological processes, such as cell differentiation, cell reprogramming or human diseases linked to cell proliferation, such as cancer.

Background: Testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is neither always accessible nor easy to perform in children. We aimed to propose a machine learning model to assess the need for a SARS-CoV-2 test in children (<16 years old), depending on their clinical symptoms., Methods: Epidemiological and clinical data were obtained from the REDCap ® registry. Overall, 4434 SARS-CoV-2 tests were performed in symptomatic children between 1 November 2020 and 31 March 2021, 784 were positive (17.68%). We pre-processed the data to be suitable for a machine learning (ML) algorithm, balancing the positive-negative rate and preparing subsets of data by age. We trained several models and chose those with the best performance for each subset., Results: The use of ML demonstrated an AUROC of 0.65 to predict a COVID-19 diagnosis in children. The absence of high-grade fever was the major predictor of COVID-19 in younger children, whereas loss of taste or smell was the most determinant symptom in older children., Conclusions: Although the accuracy of the models was lower than expected, they can be used to provide a diagnosis when epidemiological data on the risk of exposure to COVID-19 is unknown.

Background: Dry needling (DN) is often used for the treatment of muscle pain among physiotherapists. However, little is known about the mechanisms of action by which its effects are generated. The aim of this randomized controlled trial was to determine if the use of DN in healthy subjects activates the sympathetic nervous system, thus resulting in a decrease in pain caused by stress., Methods: Sixty-five healthy volunteer subjects were recruited from the University of Alcala, Madrid, Spain, with an age of 27.78 (SD = 8.41) years. The participants were randomly assigned to participate in a group with deep DN in the adductor pollicis muscle or a placebo needling group. The autonomic nervous system was evaluated, in addition to local and remote mechanical hyperalgesia., Results: In a comparison of the moment at which the needling intervention was carried out with the baseline, the heart rate of the dry needling group significantly increased by 20.60% (SE = 2.88), whereas that of the placebo group increased by 5.33% (SE = 2.32) ( p = 0.001, d = 1.02). The pressure pain threshold showed significant differences between both groups, being significantly higher in the needling group (adductor muscle p = 0.001; d = 0.85; anterior tibialis muscle p = 0.022, d = 0.58)., Conclusions: This work appears to indicate that dry needling produces an immediate activation in the sympathetic nervous system, improving local and distant mechanical hyperalgesia.

The aim of this study was to determine whether the lactones dehydroleucodine, xanthatin and 3-benzyloxymethyl-5H-furan-2-one, would be effective in an animal model of gastric ulcer induced by mast cell activation. Rats were divided into ten groups. Treatments were repeated for four days. The degree of gastric erosion was assessed with a scoring system and histological preparations. Gastric mast cell morphology was analyzed by histological procedures. Serum serotonin levels were determined as markers of mast cell activation. Statistical analyses were done using ANOVA and Tukey-Kramer test. We demonstrated that the repeated administration of compound 48/80 results in extensive mucosal lesions in the gastric mucosa and that such lesions occurred in association with mast cell degranulation and a significant increase of serum serotonin. We showed that these lesions were prevented by dehydroleucodine, xanthatin, and 3-benzyloxymethyl-5H-furan-2-one and that this effect was similar to that obtained with sodium cromoglycate. In conclusion, the results of the present study indicate that the optimal gastric cytoprotective dose of dehydroleucodine, xanthatin, and 3-benzyloxymethyl-5 H -furan-2-one is efficacious in an animal model of gastric ulcer induced by mast cell activation. Our findings suggest that these lactones could be valuable tools for designing novel therapeutic agents for digestive disorders associated with inappropriate mast cell activation.

Recent research has shown that good sleep quality has a positive effect on physical performance. However, sleep quality in Chilean professional soccer players is unknown. The purpose of this study was to determine sleep quality in Chilean professional soccer players. It was a cross-sectional, explanatory study with observable variables. The sample consisted of 94 Chilean male soccer players belonging to four professional clubs. The main variable was the Sleep Quality Index, evaluated through the Pittsburgh questionnaire (Spanish version). After estimating sleep quality individually, the four professional soccer clubs' comparison was performed through a one-factor ANOVA. The Pearson test was used to relate the questionnaire variables; the significance level was p < 0.05. In the global analysis of the Pittsburgh Sleep Quality Index, a value of 4.75 ± 2.29 on a scale of 0-21 was observed, with no significant differences between the clubs evaluated ( p > 0.05). Based on the results obtained, Chilean male professional soccer players present good sleep quality. However, the high values of "sleep latency" and "sleep disturbances" are indicators that should be worked on by the multidisciplinary team of each professional club. They should develop strategies to improve sleep hygiene, encourage good sleep, and fall asleep efficiently.

This study aimed to compare the effects of dry needling (DN) versus placebo DN applied to the peroneus longus (PL) and tibialis anterior (TA) on neuromuscular control and static postural control in basketball players with chronic ankle instability (CAI). A single-blinded randomized controlled trial was conducted. Thirty-two male and female basketball players with CAI were randomly assigned to receive either DN ( n = 16) or placebo DN ( n = 16). Pre-activation amplitudes of PL and TA were assessed with surface electromyography (EMG) during a dynamic landing test. Center of pressure (CoP) displacement and sway variability in anterior-posterior (AP) and medio-lateral (ML) directions were measured with a force platform during a single leg balance test (SLBT). Measures were obtained prior to a single DN intervention, immediately after, at 48 h, and 1 month after. The DN group displayed a significant increase in PL and TA pre-activation values, which were maintained 1 month later. Significant reductions in the ML and AP displacements and sway variability of CoP were found for the DN group. These results showed improvements in feedback/feed-forward strategies following DN, including enhanced neuromuscular control and static postural control, with the potential to become a convenient and accessible preventive treatment in CAI subjects.

Background : Sentinel lymph node (SLN) status is recognized as the most important prognostic factor for patients with cutaneous melanoma. However, sometimes it is not possible to identify SLN. The phenomenon of non-identification of SLN and its prognostic role have not been thoroughly evaluated in melanoma literature. The objective of this study was to identify which patient or tumor variables may be associated to non-identification of SLN and to evaluate the prognostic role of non-identification of SLN. Methods : Observational retrospective study of 834 cutaneous melanoma patients who underwent SLN biopsy at Instituto Valenciano de Oncología. Results : Forty-two patients (5%) presented non-identification of SLN. Patients with age at diagnosis of ≥ 64 years, obesity (BMI ≥ 30), and head and neck localization were at higher risk of non-identification of SLN. Non-identified SLN patients had worse nodal disease-free survival with respect to negative SLN patients, but not worse melanoma-specific survival. Conclusions : Our findings suggest a need to follow-up patients with non-identified SLN in the same way as patients with positive SLN.

Background: the present study aimed to investigate the effects of a single nutritional preventive session previous to a critical period linked to fat gain in university students with overweightness and obesity, emulating a nutritional session of a public health system., Methods: In this single-blind randomized controlled trial, 23 students met all the criteria to be included (20.91 ± 2.52-year-old; 52.2% women) who were divided into two groups: intervention group (IG) and control group (CG). Fat mass (FM) by dual-energy X-ray absorptiometry (DXA), physical activity by accelerometry, feeding evaluation through three questionnaires, and a set of healthy lifestyle recommendations were evaluated before and after the national holidays (NH)., Results: Our findings showed that FM increased significantly in the CG, but not in the IG (CG = 428.1 g; IG = 321.9 g; Δ = 106.2 g; p = 0.654 [95% CI = -379.57, 591.92]). However, no differences were found during the NH between them (Hedges' g effect size = 0.19; p = 0.654). In addition, no statistical differences were observed between groups in feeding evaluations, the set of recommendations performed, and physical activity., Conclusion: a single preventive session before a critical period, using a similar counselling approach as used in the public health system, might not be enough to promote changes in eating and physical activity patterns and preventing fat gain in overweight/obese university students. Long-term interventions are a must.

Current CNN-based stereo depth estimation models can barely run under real-time constraints on embedded graphic processing unit (GPU) devices. Moreover, state-of-the-art evaluations usually do not consider model optimization techniques, being that it is unknown what is the current potential on embedded GPU devices. In this work, we evaluate two state-of-the-art models on three different embedded GPU devices, with and without optimization methods, presenting performance results that illustrate the actual capabilities of embedded GPU devices for stereo depth estimation. More importantly, based on our evaluation, we propose the use of a U-Net like architecture for postprocessing the cost-volume, instead of a typical sequence of 3D convolutions, drastically augmenting the runtime speed of current models. In our experiments, we achieve real-time inference speed, in the range of 5-32 ms, for 1216 × 368 input stereo images on the Jetson TX2, Jetson Xavier, and Jetson Nano embedded devices.

In this work, we explore the use of images from different spectral bands to classify defects in melamine faced panels, which could appear through the production process. Through experimental evaluation, we evaluate the use of images from the visible (VS), near-infrared (NIR), and long wavelength infrared (LWIR), to classify the defects using a feature descriptor learning approach together with a support vector machine classifier. Two descriptors were evaluated, Extended Local Binary Patterns (E-LBP) and SURF using a Bag of Words (BoW) representation. The evaluation was carried on with an image set obtained during this work, which contained five different defect categories that currently occurs in the industry. Results show that using images from beyond the visual spectrum helps to improve classification performance in contrast with a single visible spectrum solution.

This paper presents a novel CNN-based architecture, referred to as Q-Net, to learn local feature descriptors that are useful for matching image patches from two different spectral bands. Given correctly matched and non-matching cross-spectral image pairs, a quadruplet network is trained to map input image patches to a common Euclidean space, regardless of the input spectral band. Our approach is inspired by the recent success of triplet networks in the visible spectrum, but adapted for cross-spectral scenarios, where, for each matching pair, there are always two possible non-matching patches: one for each spectrum. Experimental evaluations on a public cross-spectral VIS-NIR dataset shows that the proposed approach improves the state-of-the-art. Moreover, the proposed technique can also be used in mono-spectral settings, obtaining a similar performance to triplet network descriptors, but requiring less training data.