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Background: The immunomodulatory oligodeoxynucleotide (ODN) IMT504 might harbor antifibrotic properties within the liver. Methods: Fibrosis models were induced in mice through thioacetamide (TAA) administration and bile-duct ligation. Cre-loxP mice were utilized to identify GLAST + Wnt1 + bone marrow stromal progenitors (BMSPs) and to examine their contribution with cells in the liver. In vivo and in vitro assays; flow-cytometry, immunohistochemistry, and qPCR were conducted. Results: IMT504 demonstrated significant inhibition of liver fibrogenesis progression and reversal of established fibrosis. Early responses to IMT504 involved the suppression of profibrogenic and proinflammatory markers, coupled with an augmentation of hepatocyte proliferation. Additionally, this ODN stimulated the proliferation and mobilization of GLAST + Wnt1 + BMSPs, likely amplifying their contribution with endothelial- and hepatocytes-like cells. Moreover, IMT504 significantly modulated the expression levels of Wnt ligands and signaling pathway/target genes specifically within GLAST + Wnt1 + BMSPs, with minimal impact on other BMSPs. Intriguingly, both IMT504 and conditioned media from IMT504-pre-treated GLAST + Wnt1 + BMSPs shifted the phenotype of fibrotic macrophages, hepatic stellate cells, and hepatocytes, consistent with the potent antifibrotic effects observed. Conclusion: In summary, our findings identify IMT504 as a promising candidate molecule with potent antifibrotic properties, operating through both direct and indirect mechanisms, including the activation of GLAST + Wnt1 + BMSPs. [ABSTRACT FROM AUTHOR]

Background: Telemedicine is a means of providing efficient treatment for children with complex chronic conditions and/or subsidiary palliative paediatric care. Aim: To evaluate how satisfied families and healthcare professionals are with a telemedicine programme. Methodology: This is a qualitative study of narrative design. Ten interviews were conducted with family members and professionals who had been using telemedicine for a year. Sampling was intentional and a discourse and content analysis was conducted. Results: Six thematic categories emerged from the analysis of the interviews: degree of satisfaction; usefulness; benefits according to patient needs and attention; technical and human difficulties; and implantation of the system and proposals for improvement. Conclusions: The study shows that telemedicine is a very useful complementary tool for healthcare professionals in a palliative care context. It is necessary to take into account the perception and needs of both families and healthcare professionals with regard to this tool since it can improve patient care. [ABSTRACT FROM AUTHOR]

Background: Delivering effective feedback to large groups of students represents a challenge for the academic staff at universities. Research suggests that undergraduate students often ignore the Elaborated Feedback (EF) received via digital learning environments. This may be because instructors provide feedback in written format instead of using more engaging channels (e.g., audiovisual). Objectives: This quasi‐experimental study examines the extent to which feedback format (video vs. written) influences students' perceptions of feedback, their decision to access EF messages related to high‐stakes assignments in digital environments, and its impact on academic performance, while considering the effect of their academic engagement. Methods: A total of 171 undergraduate students received generic EF messages through a learning platform the day after submitting each course assignment. 78 students received EF in written format and 93 in video format. Results and Conclusions: Our results showed that feedback format influenced students' decision to access EF and their academic performance, but not their feedback perceptions. Students in the written‐feedback group accessed EF messages more often, but students who received video‐feedback performed better than their counterparts in the written‐feedback group. Moderation analysis showed that the relationship between the feedback format and students' academic performance was moderated by their academic engagement, suggesting that students with lower levels of academic engagement may benefit from video‐feedback. Takeaways: The results reveal that using video feedback in digital environments may influence students' decisions to process EF and their academic achievement, especially when it comes to students with lower levels of academic engagement. Lay Description: What is currently known about the subject matter: Delivering Elaborated Feedback (EF) to large groups of students represents a challenge for instructors.Undergraduate students often ignore the EF received via digital learning environments.Students usually prefer audiovisual formats to receive feedback compared to the written format.Results in regard to whether video‐feedback is best for learning are inconclusive. What this paper adds: A quasi‐experimental study to compare two feedback formats (video and written) in an ecologically valid setup.Data of students' voluntary decisions to process EF related to high‐stakes assignments.The moderating effect of students' academic engagement on the relationship between feedback format and academic performance. The implications of study findings for practitioners: Students positively value the EF received in both video and written formats.Students may not engage with EF as expected even when provided in audiovisual formats.Students may access written‐EF more frequently than video‐EF.Video‐EF may positively influence academic performance when students have low levels of academic engagement. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stromal cells (MSCs) tropism for tumours allows their use as carriers of antitumoural factors and in vitro transcribed mRNA (IVT mRNA) is a promising tool for effective transient expression without insertional mutagenesis risk. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine with antitumor properties by stimulating the specific immune response. The aim of this work was to generate modified MSCs by IVT mRNA transfection to overexpress GM-CSF and determine their therapeutic effect alone or in combination with doxorubicin (Dox) in a murine model of hepatocellular carcinoma (HCC). Methods: DsRed or GM-CSF IVT mRNAs were generated from a cDNA template designed with specific primers followed by reverse transcription. Lipofectamine was used to transfect MSCs with DsRed (MSC/DsRed) or GM-CSF IVT mRNA (MSC/GM-CSF). Gene expression and cell surface markers were determined by flow cytometry. GM-CSF secretion was determined by ELISA. For in vitro experiments, the J774 macrophage line and bone marrow monocytes from mice were used to test GM-CSF function. An HCC model was developed by subcutaneous inoculation (s.c.) of Hepa129 cells into C3H/HeN mice. After s.c. injection of MSC/GM-CSF, Dox, or their combination, tumour size and mouse survival were evaluated. Tumour samples were collected for mRNA analysis and flow cytometry. Results: DsRed expression by MSCs was observed from 2 h to 15 days after IVT mRNA transfection. Tumour growth remained unaltered after the administration of DsRed-expressing MSCs in a murine model of HCC and MSCs expressing GM-CSF maintained their phenotypic characteristic and migration capability. GM-CSF secreted by modified MSCs induced the differentiation of murine monocytes to dendritic cells and promoted a proinflammatory phenotype in the J774 macrophage cell line. In vivo, MSC/GM-CSF in combination with Dox strongly reduced HCC tumour growth in C3H/HeN mice and extended mouse survival in comparison with individual treatments. In addition, the tumours in the MSC/GM-CSF + Dox treated group exhibited elevated expression of proinflammatory genes and increased infiltration of CD8 + T cells and macrophages. Conclusions: Our results showed that IVT mRNA transfection is a suitable strategy for obtaining modified MSCs for therapeutic purposes. MSC/GM-CSF in combination with low doses of Dox led to a synergistic effect by increasing the proinflammatory tumour microenvironment, enhancing the antitumoural response in HCC. [ABSTRACT FROM AUTHOR]

Objective: Aging produces changes in emotional reactivity and the retrieval of autobiographical memories. The main aim of this study was to assess age-related differences, comparing emotion induction and autobiographical memory recall using photos from the International Affective Picture System (IAPS) that are thematically related to childhood. Method: A cross-sectional observational study was conducted, with the participation of 327 individuals (168 young adults and 159 older adults) with no cognitive impairment and aged between 18 and 88  years. We showed the participants a set of five pictures from the IAPS, the affective content of which was related to childhood. Two of these were considered to be positive images, two negative and one neutral, according to the valence of these pictures in the literature. The main study variables were the reactions associated with emotional valence or pleasure, arousal and dominance, after viewing the photos, and the autobiographical memories retrieved by the participants. Results: The younger adults retrieved a larger number of memories than their older counterparts. As regards the responses to the five affective pictures (IAPS) on valence, arousal and dominance (IAPS), statistically significant differences were only found for pictures 2,345 (BlackEye), with a more positive valence in the group of older adults and higher arousal in the young ones, and 2,312 (Mother), with a more positive valence in the group of older persons. A greater number of memories were retrieved for the photos that generated higher levels of pleasure, greater relaxation and greater emotional control. Conclusion: Of the variables that may be associated with the elicitation of involuntary autobiographical memories, the most significant are age and a positive stimulus. [ABSTRACT FROM AUTHOR]

The severity of non-alcoholic fatty liver disease (NAFLD) ranges from simple steatosis to steatohepatitis, and it is not yet clearly understood which patients will progress to liver fibrosis or cirrhosis. SPARC (Secreted Protein Acidic and Rich in Cysteine) has been involved in NAFLD pathogenesis in mice and humans. The aim of this study was to investigate the role of SPARC in inflammasome activation, and to evaluate the relationship between the hepatic expression of inflammasome genes and the biochemical and histological characteristics of NAFLD in obese patients. In vitro studies were conducted in a macrophage cell line and primary hepatocyte cultures to assess the effect of SPARC on inflammasome. A NAFLD model was established in SPARC knockout (SPARC−/−) and SPARC+/+ mice to explore inflammasome activation. A hepatic RNAseq database from NAFLD patients was analyzed to identify genes associated with SPARC expression. The results were validated in a prospective cohort of 59 morbidly obese patients with NAFLD undergoing bariatric surgery. Our results reveal that SPARC alone or in combination with saturated fatty acids promoted IL-1β expression in cell cultures. SPARC−/− mice had reduced hepatic inflammasome activation during the progression of NAFLD. NAFLD patients showed increased expression of SPARC, NLRP3, CASP1, and IL-1β. Gene ontology analysis revealed that genes positively correlated with SPARC are linked to inflammasome-related pathways during the progression of the disease, enabling the differentiation of patients between steatosis and steatohepatitis. In conclusion, SPARC may play a role in hepatic inflammasome activation in NAFLD. [ABSTRACT FROM AUTHOR]

Parental behavior in interactions with children has been related to child language development. Our study contributes to the literature about relations between the characteristics of parent–child interactions during play and a child's language development in typically developing children at early ages, with data from mothers and fathers from the same families in Spain. Our aim was to analyze the relation between positive parenting behaviors assessed with the Spanish version of the Parenting Interactions with Children: Checklist of Observations Linked to Outcomes (PICCOLO) and child language development assessed with the Bayley-III scales. We controlled for some sociodemographic variables. The participants were 90 children aged 15–31 months and their mothers and fathers. Bivariate analysis showed significant positive relations between mothers' responsive, encouraging and teaching behaviors and a child's language scores. Relations were found between fathers' encouraging and teaching behaviors and a child's language. Regression models indicate that maternal and paternal encouraging behaviors predicted 18% of the variability in the child's receptive language, and maternal responsive and teaching behaviors predicted 16% of the variability in the child's expressive language and total language scores. The study provides new data that support the relevance of positive parental behaviors to improve a child's linguistic development. [ABSTRACT FROM AUTHOR]

The aims of this study were to compare the parenting behaviors of mothers and fathers when evaluated in a free play situation at home and to study how these behaviors were related to the sociodemographic variables of the family. The study included 155 mothers and 155 fathers from the same families in Spain. The children (90 boys and 65 girls) were typically developing and were aged between 10 and 47 months old. The parents completed a sociodemographic questionnaire, and parenting behaviors in four domains (Affection, Responsiveness, Encouragement, and Teaching) were assessed from self-recorded videotapes, in accordance with the Spanish version of the PICCOLO. Our results showed both commonalities and differences between the mothers and fathers. The mean scores for the four parenting domains followed a similar pattern in both mothers and fathers: the highest mean score was in the Responsiveness domain, followed by the Affection, Encouragement, and the Teaching domains. Regarding the second aim, no differences were observed in parenting according to the child's gender and the only domain related to the child's age was mother's Teaching. Mothers with a higher educational level scored higher on all parenting domains, except for Responsiveness. Family income was positively related to maternal Affection, Encouragement, and the total PICCOLO score, and to the father's score in the Teaching domain. This study provides evidence that Spanish mothers and fathers show very similar strengths for promoting children's development during interactions. These results are relevant to inform social public policies and family programs. [ABSTRACT FROM AUTHOR]

Childhood maltreatment is a major risk factor for emotional problems in adolescence and adulthood and has deleterious effects on cognitive functions such as working memory. A key aspect in the study of the cognitive and affective consequences of maltreatment is autobiographical memory, especially regarding the difficulty retrieving specific memories, known as overgeneral memory. In this study, autobiographical memory tests, working memory, and a depressive symptom assessment were administered to 48 adolescents in care with a history of maltreatment (22 abused and 26 neglected) without mental disorder, who had been removed from their family and were living in residential child care, and to 61 adolescents nonmaltreated who had never been placed in care. The results show that adolescents with a history of maltreatment remember fewer specific events (Cohen d = 1.1–1.3) and that both working memory and depressive symptoms are involved in overgeneral memory (R 2 =.13–.26). Directions for future research include neuropsychological assessment and implementation of a training program to increase specific memory recall in this population. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS) is the most frequent malignant bone tumor, affecting predominantly children. Metastases represent a major clinical challenge and an estimated 80% would present undetectable micrometastases at diagnosis. The identification of metastatic traits and molecules would impact in micrometastasis management. We demonstrated that OS LM7 metastatic cells secretome was able to induce microvascular endothelium cell rearrangements, an angiogenic-related trait. A proteomic analysis indicated a gain in angiogenic-related pathways in these cells, as compared to their parental-non-metastatic OS SAOS2 cells counterpart. Further, factors with proangiogenic functions like VEGF and PDGF were upregulated in LM7 cells. However, no differential angiogenic response was induced by LM7 cells in vivo. Regulation of the Fas–FasL axis is key for OS cells to colonize the lungs in this model. Analysis of the proteomic data with emphasis in apoptosis pathways and related processes revealed that the percentage of genes associated with those, presented similar levels in SAOS2 and LM7 cells. Further, the balance of expression levels of proteins with pro- and antiapoptotic functions in both cell types was subtle. Interestingly and of relevance to the model, Fas associated Factor 1 (FAF1), which participates in Fas signaling, was present in LM7 cells and was not detected in SAOS2 cells. The subtle differences in apoptosis-related events and molecules, together with the reported cell-survival functions of the identified angiogenic factors and the increased survival features that we observed in LM7 cells, suggest that the gain in angiogenesis-related pathways in metastatic OS cells would relate to a prosurvival switch rather to an angiogenic switch as an advantage feature to colonize the lungs. OS metastatic cells also displayed higher adhesion towards microvascular endothelium cells suggesting an advantage for tissue colonization. A gain in angiogenesis pathways and molecules does not result in major angiogenic potential. Together, our results suggest that metastatic OS cells would elicit signaling associated to a prosurvival phenotype, allowing homing into the hostile site for metastasis. During the gain of metastatic traits process, cell populations displaying higher adhesive ability to microvascular endothelium, negative regulation of the Fas–FasL axis in the lung parenchyma and a prosurvival switch, would be selected. This opens a new scenario where antiangiogenic treatments would affect cell survival rather than angiogenesis, and provides a molecular panel of expression that may help in distinguishing OS cells with different metastatic potential. [ABSTRACT FROM AUTHOR]

One question of great practical importance for the parents, and especially the mother, after the birth of a baby, refers to how long the time during which they have to go with less and more fragmented sleep actually lasts. Most of the studies only explore this issue up to 6 months of the newborn's life, and less is known about the sleep problems the mothers may have after this initial period. The objective of this study is to examine the relationship between the sleep disruption and daytime sleepiness of mothers with infants until 2 years old compared to a group of women currently not at care of babies. To this end, a sample of 113 women, 67 currently bringing up a baby of under 2 years old, and the remainder without a baby at their care under 6 years old, reported sleep duration, sleep interruptions, sleep quality, and responded to questionnaires of sleep quality and daytime sleepiness. The relationship between the age of the children and the comparison between the groups was used to highlight the sleep problems of the mothers taking care of the infant. The results showed that there was a positive relationship between the age of the infant and the duration of the sleep of the mothers and that the duration of sleep for them was similar to those of the women in the control group about 6 months after the infant was born. However, fragmentation of sleep, daytime sleepiness, and sleep problems were still higher than in the control group for mothers with children between 6 and 12 months old. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) arises in the setting of advanced liver fibrosis, a dynamic and complex inflammatory disease. The tumor microenvironment (TME) is a mixture of cellular components including cancer cells, cancer stem cells (CSCs), tumor-associated macrophages (TAM), and dendritic cells (DCs), which might drive to tumor progression and resistance to therapies. In this work, we study the effects of 4-methylumbelliferone (4Mu) on TME and how this change could be exploited to promote a potent immune response against HCC. First, we observed that 4Mu therapy induced a switch of hepatic macrophages (Mϕ) towards an M1 type profile, and HCC cells (Hepa129 cells) exposed to conditioned medium (CM) derived from Mϕ treated with 4Mu showed reduced expression of several CSCs markers and aggressiveness. HCC cells incubated with CM derived from Mϕ treated with 4Mu grew in immunosuppressed mice while presented delayed tumor progression in immunocompetent mice. HCC cells treated with 4Mu were more susceptible to phagocytosis by DCs, and when DCs were pulsed with HCC cells previously treated with 4Mu displayed a potent antitumoral effect in therapeutic vaccination protocols. In conclusion, 4Mu has the ability to modulate TME into a less hostile milieu and to potentiate immunotherapeutic strategies against HCC. [ABSTRACT FROM AUTHOR]

We explore orthogonal polynomials on the unit circle whose Schur parameters are {cαn}∞n=1, where 0 < ∣α∣, ∣c∣ < 1. Specifically, we derive two different generating functions. The first can be represented explicitly in terms of sums of a q-hypergeometric type and used to derive explicitly the underlying orthogonal polynomials, while the second obeys a functional differential equation and can be used to determine the asymptotic behaviour of these polynomials. Extending these constructs to orthogonal polynomials of the second kind, we are able to construct the Carathéodory function and examine the underlying orthogonality measure. [ABSTRACT FROM AUTHOR]

This study aimed to examine the relationship between maternal sensitivity and affect, as perceived by the child, and childhood creativity. Self-esteem and shyness were considered mediating factors. A total of 151 elementary school pupils were tested on verbal and pictorial creativity, self-esteem, and perceived maternal affect and sensitivity. Their teachers assessed each child’s shyness in their relations at school. A Multiple Indicators and Multiple Causes (MIMIC) model of the causal relationships among the study’s variables was tested. Results supported this theoretical model of causality. Maternal sensitivity had a significant, direct, positive effect on self-esteem, and a direct negative effect on shyness. In addition, self-esteem had a direct positive effect on verbal creativity and shyness had a negative direct effect on verbal and pictorial creativity. The indirect effect of maternal sensitivity on verbal creativity was significant via both self-esteem and shyness. The findings were discussed in terms of their implications for child development. [ABSTRACT FROM PUBLISHER]

In this paper we will discuss the problem of generation of sequences of orthogonal polynomials with respect to measures supported on the unit circle from a given sequence of orthogonal polynomials using a perturbation of a cubic sieved process. The basic tools are the Szeg $ o\kern -5pt \'{}\kern -1pt\'{} $ forward recurrence relation as well as the fact of the coprimality of orthogonal polynomials on the unit circle and their corresponding reverse polynomials. We also give the connection between the associated orthogonality measures. Finally, some examples of this cubic decomposition are shown. [ABSTRACT FROM AUTHOR]

Liver fibrosis results from many chronic injuries and may often progress to cirrhosis and hepatocellular carcinoma (HCC). In fact, up to 90% of HCC arise in a cirrhotic liver. Conversely, stress is implicated in liver damage, worsening disease outcome. Hence, stress could play a role in disrupting liver homeostasis, a concept that has not been fully explored. Here, in a murine model of TAA-induced liver fibrosis we identified nerve growth factor (NGF) to be a crucial regulator of the stress-induced fibrogenesis signaling pathway as it activates its receptor p75 neurotrophin receptor (p75NTR), increasing liver damage. Additionally, blocking the NGF decreased liver fibrosis whereas treatment with recombinant NGF accelerated the fibrotic process to a similar extent than stress challenge. We further show that the fibrogenesis induced by stress is characterized by specific changes in the hepatoglycocode (increased β1,6GlcNAc-branched complex N-glycans and decreased core 1 O-glycans expression) which are also observed in patients with advanced fibrosis compared to patients with a low level of fibrosis. Our study facilitates an understanding of stress-induced liver injury and identify NGF signaling pathway in early stages of the disease, which contributes to the established fibrogenesis. [ABSTRACT FROM AUTHOR]