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Abstract Background CD155 is a transmembrane protein that inhibits antitumor immune response and represents a predictor of worse prognosis in non-small-cell lung cancer (NSCLC). However, it remains unexplored its association with clinical characteristics and genomic status of Latin American patients. This study characterizes the CD155 expression and its clinical implications in this population. Methods Tissue biopsies from 86 patients with locally-advanced or metastatic NSCLC were assessed for CD155 protein expression, ALK rearrangements and EGFR mutations. Cutoff values for high CD155 expression (CD155high) were determined from receiver operating characteristic (ROC) curves according to 2-year survival. It was evaluated its association with clinicopathological features, median progression-free survival (mPFS) and overall survival (mOS). Results the cutoff score for CD155high was 155 in the entire cohort and in patients without oncogenic alterations, and it was 110 in patients with oncogenic alterations. Eighty-four patients (97.7%) were CD155 positive, of which fifty-six (65.0%) had CD155high. EGFR L858R mutation related to lower CD155 IHC score than exon 19 deletion. Individuals with CD155high showed a shorter mOS (13.0 vs. 30.8 months; HR: 1.96 [95% CI, 1.15–3.35]; p = 0.014). Patients without oncogenic alterations having a CD155high displayed shorter mPFS (1.6 vs. 6.4 months, HR: 2.09 [95% CI, 1.06–4.20]; p = 0.034) and mOS (2.9 vs. 23.1 months; HR: 1.27 [95% CI, 1.07– 4.42]; p = 0.032). Patients with oncogenic alterations having CD155high only showed a trend to shorter mOS (26.3 vs. 52.0 months; HR: 2.39 [95% CI, 0.98–5.83]; p = 0.058). Conclusion CD155high is a predictor of worse outcomes in patients with advanced NSCLC, predominantly among those without oncogenic alterations. CD155 could be a potential biomarker and a molecular target in patients with poor responses to current therapies.

Abstract The early identification of individuals with radiologically isolated syndrome (RIS) who are at an elevated risk of progressing to multiple sclerosis (MS) is essential for making informed treatment decisions. This study aimed to evaluate the predictive potential of multifocal Visual Evoked Potentials (mfVEP) measures in individuals with RIS with respect to their conversion to MS. A prospective observational cohort study was conducted, involving 21 individuals with RIS recruited from a MS center. Baseline assessments, including mfVEP, magnetic resonance imaging (MRI), and clinical examinations, were performed, and participants were longitudinally followed for up to 24 months. The primary outcome measures were the conversion to MS. Over a clinical follow-up period of 24 months, five individuals (5/21) with RIS progressed to MS. MfVEP amplitude responses (interocular and monocular probability analysis) demonstrated abnormal cluster visual field defects in 47.6% of RIS eyes at baseline, whereas multifocal VEP latency analysis showed significant delays in 38.4%. A reduction in interocular amplitude [OR = 0.036, (95% CI 0.003–0.503); P = 0.014], monocular amplitude [OR = 0.083, (95% CI 0.007–0.982); P = 0.048], and a prolonged interocular latency [OR = 0.095, (95% CI 0.009–0.972); P = 0.047] were associated with a higher relative risk of clinical conversion at the 2-year follow-up. Multifocal VEP may serve as a novel and independent risk factor for predicting the conversion to MS in individuals with Radiologically Isolated Syndrome.

There is still a debate on the influence and effectiveness of pedagogical agents in a learning environment, especially on the means these agents employ for enhancing students’ academic performance. The current study aims at measuring the effectiveness of cognitive and affective feedback (CaAF) types that a human teacher and a virtual Affective Pedagogical Tutor (APT) used in their groups of students (control and experimental groups respectively) in an authentic long-term learning situation. Participants were a sample of 115 students carrying out collaborative activities in a “web design” course. Our findings showed that APT cognitive feedback (CF) significantly increased students’ learning outcomes compared to the human teacher’s feedback, whereas APT affective feedback (AF) only achieved partial success. Nevertheless, the study has some limitations: it is based on a single course and a specific academic context, limiting the generalizability of its findings. Additionally, while cognitive feedback demonstrated a clear impact, the analysis of affective feedback was less conclusive, and its design requires further refinement. Finally, the cross-sectional design of the study restricts the ability to assess whether improvements in learning outcomes persist over time. Future research directions include exploring the generalizability of results across diverse disciplines, deepening the analysis of affective feedback, and incorporating longitudinal studies to evaluate the durability of the observed effects.

PURPOSETargeted therapies are indicated for patients with non–small cell lung cancer (NSCLC) and driver tumor mutations. However, real-world studies on the survival benefits of these agents are limited. This study aimed to evaluate the effect of targeted therapies matched to a genomic alteration on the survival of patients with NSCLC.METHODSThis retrospective study included 446 patients with advanced NSCLC who underwent next-generation sequencing between 2016 and 2023 at the Instituto Nacional de Cancerología in Mexico. The primary outcomes were progression-free survival (PFS) and overall survival (OS).RESULTSFor the entire cohort, the PFS and OS were 10.71 months (95% CI, 9.35 to 12.06) and 47.77 months (95% CI, 29.67 to 65.86). PFS was significantly longer in patients with actionable mutations treated with targeted therapies (19.41 months [95% CI, 14.27 to 24.55]; P < .001) than in patients without actionable mutations (6.4 months [95% CI, 4.4 to 8.4]) or not treated with targeted therapies (6.6 months [95% CI, 5.3 to 7.89]). Similarly, OS was significantly longer in patients with actionable mutations treated with targeted therapies (89.69 months [95% CI, 45.54 to 133.84]; P < .001) than in patients without actionable mutations (17.11 months [95% CI, 8.65 to 25.57]) or not treated with targeted therapies (22.3 months [95% CI, 12.48 to 32.1]). Survival gains were driven by significant improvements in PFS and OS in patients with EGFR and ALK mutations.CONCLUSIONThis real-world data analysis demonstrated that targeted therapies improve the survival of patients with NSCLC with actionable mutations, which supports a recommendation for widening access to broad-based genomic testing and targeted therapies.

Despite advances in educational technology, the specific ways in which Generative Artificial Intelligence (GAI) and Large Language Models cater to learners’ nuanced cognitive and emotional needs are not fully understood. This mini-review methodically describes GAI’s practical implementations and limitations in meeting these needs. It included journal and conference papers from 2019 to 2024, focusing on empirical studies that employ GAI tools in educational contexts while addressing their practical utility and ethical considerations. The selection criteria excluded non-English studies, non-empirical research, and works published before 2019. From the dataset obtained from Scopus and Web of Science as of June 18, 2024, four significant studies were reviewed. These studies involved tools like ChatGPT and emphasized their effectiveness in boosting student engagement and emotional regulation through interactive learning environments with instant feedback. Nonetheless, the review reveals substantial deficiencies in GAI’s capacity to promote critical thinking and maintain response accuracy, potentially leading to learner confusion. Moreover, the ability of these tools to tailor learning experiences and offer emotional support remains limited, often not satisfying individual learner requirements. The findings from the included studies suggest limited generalizability beyond specific GAI versions, with studies being cross-sectional and involving small participant pools. Practical implications underscore the need to develop teaching strategies leveraging GAI to enhance critical thinking. There is also a need to improve the accuracy of GAI tools’ responses. Lastly, deep analysis of intervention approval is needed in cases where GAI does not meet acceptable error margins to mitigate potential negative impacts on learning experiences.

Abstract Mantle cell lymphoma (MCL) is an incurable B-cell neoplasm characterized by an aggressive behavior, short responses to conventional therapies and SOX11 overexpression, which is associated with aggressive disease features and inferior clinical outcome of patients. Oxidative stress is known to induce tumorigenesis and tumor progression, whereas high expression levels of antioxidant genes have been associated with chemoresistance in different cancers. However, the role of oxidative stress in MCL pathogenesis and the involvement of SOX11 regulating redox homeostasis in MCL cells are largely unknown. Here, by integrating gene set enrichment analysis of two independent series of MCL, we observed that SOX11+ MCL had higher reactive oxygen species (ROS) levels compared to SOX11− MCL primary tumors and increased expression of Peredoxine2 (PRDX2), which upregulation significantly correlated with SOX11 overexpression, higher ROS production and worse overall survival of patients. SOX11 knockout (SOX11KO) significantly reduced PRDX2 expression, and SOX11KO and PRDX2 knockdown (PRDX2KD) had increased ROS levels and ROS-mediated tumor cell death upon treatment with drugs, compared to control MCL cell lines. Our results suggest an aberrant redox homeostasis associated with chemoresistance in aggressive MCL through SOX11-mediated PRDX2 upregulation, highlighting PRDX2 as promising target for new therapeutic strategies to overcome chemoresistance in aggressive MCLs.

Esta investigación explora el fenómeno de los agresores plurivictimizadores–victimización de tres o más mujeres– en violencia de género (VdG). Se emplearon datos de denuncias policiales de 69 agresores que en conjunto victimizaron a 217 mujeres. El diseño fue exploratorio y descriptivo, empleando variables de la dinámica temporal y de reincidencia, así como de la escalada de la violencia a lo largo de las diferentes víctimas. Los agresores plurivictimizadores persisten en la victimización hacia la misma víctima y también hacia diferentes mujeres, habiéndose hallado victimización solapada. Los agresores que incrementan la gravedad de la violencia a lo largo de las relaciones tienden a escalar de forma progresiva y no regresan a la “casilla de salida” al iniciar una nueva relación. Se propone abordar la reincidencia en VdG desde una perspectiva que incluya a los agresores plurivictimizadores, dada la refractariedad ante los recursos policiales y judiciales de gestión del riesgo.

Sascha Niclas Klimosch,1,&ast; Marbod Weber,1,&ast; Jordi Caballé-Serrano,2,3 Thomas Knorpp,1 Antonio Munar-Frau,2 Birgit Margareta Schaefer,4 Manfred Schmolz1 1HOT Screen GmbH, Reutlingen, Germany; 2Department of Oral and Maxillofacial Surgery, Universitat Internacional de Catalunya, Barcelona, Spain; 3Department of Periodontology, School of Dental Medicine - University of Bern, Bern, Switzerland; 4Geistlich Pharma AG, Wolhusen, Switzerland&ast;These authors contributed equally to this workCorrespondence: Manfred Schmolz, HOT Screen GmbH, Aspenhaustr. 25, Reutlingen, 72770, Germany, Tel +49 7121 628705-0, Fax +49 7121 628705-90, Email m.schmolz@hot-screen.deIntroduction: Common in vitro cell culture systems for testing implant material immune compatibility either rely on immortal human leukocyte cell lines or isolated primary cells. Compared to in vivo conditions, this generates an environment of substantially reduced complexity, often lacking important immune cell types, such as neutrophil granulocytes and others. The aim of this study was to establish a reliable test system for in vitro testing of implant materials under in vivo-like conditions.Methods: Test materials were incubated in closed, CO2-independent, tube-based culture vessels containing a proprietary cell culture medium and human whole blood in either a static or occasionally rotating system. Multiplex cytokine analysis was used to analyze immune cell reactions.Results: To demonstrate the applicability of the test system to implant materials, three commercially available barrier membranes (polytetrafluoroethylene (PTFE), polycaprolactone (PCL) and collagen) used for dental, trauma and maxillofacial surgery, were investigated for their potential interactions with immune cells. The results showed characteristic differences between the static and rotated incubation methods and in the overall activity profiles with very low immune cell responses to PTFE, intermediate ones to collagen and strong reactions to PCL.Conclusion: This in vitro human whole blood model, using a complex organotypic matrix, is an excellent, easily standardized tool for categorizing immune cell responses to implant materials. Compared to in vitro cell culture systems used for materials research, this new assay system provides a far more detailed picture of response patterns the immune system can develop when interacting with different types of materials and surfaces.Keywords: whole blood cultures, in vitro material testing, immune cells, cytokines, barrier membranes

VPS13A disease and Huntington’s disease (HD) are two basal ganglia disorders that may be difficult to distinguish clinically because they have similar symptoms, neuropathological features, and cellular dysfunctions with selective degeneration of the medium spiny neurons of the striatum. However, their etiology is different. VPS13A disease is caused by a mutation in the VPS13A gene leading to a lack of protein in the cells, while HD is due to an expansion of CAG repeat in the huntingtin (Htt) gene, leading to aberrant accumulation of mutant Htt. Considering the similarities of both diseases regarding the selective degeneration of striatal medium spiny neurons, the involvement of VPS13A in the molecular mechanisms of HD pathophysiology cannot be discarded. We analyzed the VPS13A distribution in the striatum, cortex, hippocampus, and cerebellum of a transgenic mouse model of HD. We also quantified the VPS13A levels in the human cortex and putamen nucleus; and compared data on mutant Htt-induced changes in VPS13A expression from differential expression datasets. We found that VPS13A brain distribution or expression was unaltered in most situations with a decrease in the putamen of HD patients and small mRNA changes in the striatum and cerebellum of HD mice. We concluded that the selective susceptibility of the striatum in VPS13A disease and HD may be a consequence of disturbances in different cellular processes with convergent molecular mechanisms already to be elucidated.

Este trabajo constituye un análisis comparativo enfocado en los patrones de aprendizaje adoptados por dos generaciones distintas de estudiantes: Millennials y Centennials. La noción de "patrones de aprendizaje" se centra en la organización que las personas emplean para acceder al conocimiento y abordar tanto tareas académicas como cotidianas. En la investigación han participado 315 estudiantes universitarios del ámbito educativo, quienes fueron sometidos a un análisis mediante la prueba U de Mann Whitney. Los resultados obtenidos revelan diferencias significativas entre ambas generaciones. En particular, los Millennials exhiben una mayor inclinación hacia la búsqueda y posesión de información detallada, contrastando con los Centennials, quienes presentan valores estadísticamente más elevados al emplear patrones asociados al trabajo autónomo. Esta disparidad sugiere que, en los últimos quince años, el estudiantado ha forjado enfoques de aprendizaje distintos, probablemente influenciados por diversos factores, tales como avances tecnológicos, cambios en el modelo educativo y situaciones derivadas de la pandemia. Este fenómeno plantea la necesidad imperante de reflexionar sobre la realidad social experimentada en estos últimos años y sobre cómo la acción docente debe adaptarse a estos cambios. Este estudio contribuye al entendimiento de estos cambios y brinda una base sólida para la toma de decisiones pedagógicas.

Summary: Chromatin-associated RNAs (cRNAs) are a poorly characterized fraction of cellular RNAs that co-purify with chromatin. Their full complexity and the mechanisms regulating their packaging and chromatin association remain poorly understood. Here, we address these questions in Drosophila. We find that cRNAs constitute a heterogeneous group of RNA species that is abundant in heterochromatic transcripts. We show that heterochromatic cRNAs interact with the heterogeneous nuclear ribonucleoproteins (hnRNP) hrp36/hrp48 and that depletion of linker histone dH1 impairs this interaction. dH1 depletion induces the accumulation of RNA::DNA hybrids (R-loops) in heterochromatin and, as a consequence, increases retention of heterochromatic cRNAs. These effects correlate with increased RNA polymerase II (RNAPII) occupancy at heterochromatin. Notably, impairing cRNA assembly by depletion of hrp36/hrp48 mimics heterochromatic R-loop accumulation induced by dH1 depletion. We also show that dH1 depletion alters nucleosome organization, increasing accessibility of heterochromatin. Altogether, these perturbations facilitate annealing of cRNAs to the DNA template, enhancing R-loop formation and cRNA retention at heterochromatin.

Abstract Background Gene-wise differential expression is usually the first major step in the statistical analysis of high-throughput data obtained from techniques such as microarrays or RNA-sequencing. The analysis at gene level is often complemented by interrogating the data in a broader biological context that considers as unit of measure groups of genes that may have a common function or biological trait. Among the vast number of publications about gene set analysis (GSA), the rotation test for gene set analysis, also referred to as roast, is a general sample randomization approach that maintains the integrity of the intra-gene set correlation structure in defining the null distribution of the test. Results We present roastgsa, an R package that contains several enrichment score functions that feed the roast algorithm for hypothesis testing. These implemented methods are evaluated using both simulated and benchmarking data in microarray and RNA-seq datasets. We find that computationally intensive measures based on Kolmogorov-Smirnov (KS) statistics fail to improve the rates of simpler measures of GSA like mean and maxmean scores. We also show the importance of accounting for the gene linear dependence structure of the testing set, which is linked to the loss of effective signature size. Complete graphical representation of the results, including an approximation for the effective signature size, can be obtained as part of the roastgsa output. Conclusions We encourage the usage of the absmean (non-directional), mean (directional) and maxmean (directional) scores for roast GSA analysis as these are simple measures of enrichment that have presented dominant results in all provided analyses in comparison to the more complex KS measures.

In recent years, the integration of "new media literacies" and, consequently, strategies such as transmedia learning in the teaching-learning processes has been a topic of interest among various types of national and international institutions and governments. In this sense, the current article deals with the abilities and habits that Italian students of "licei classici" have in order to face these new formative contexts that are coming. For this purpose, two quantitative instruments (one referring to digital attitudes and skills and the other corresponding to transmedia attitudes) were administered to 400 students. The results obtained show that the majority of young people have access to devices and that they prefer mobile phones. Furthermore, although they are inclined towards transmedia practices, they have certain difficulties in becoming the creative part that collaborates in a digital citizenship.

This study analysed the level of digital competence of 910 university teachers at one Spanish and one Polish university, using a self-perception questionnaire based on the DigCompEdu framework. For this purpose, a quantitative methodology was used with the aim of finding out the situation at both institutions through focusing on gender, professional category, and areas of knowledge of the participants. The results showed that the university teachers generally perceived themselves as having an intermediate level of digital competence. In this sense, it was observed that the elements selected for analysis (university, gender, and professional category) can have direct implications for the results and that there are significant differences depending on the group to which they belong.

In this section called ‘postcards from abroad’ we propose to diversify and open up the understandings and practices of repair itself, engaging material repair in conversation with other types of repair, coming from fields of creation and knowledge other than design. Although there could be many other ‘postcards’ from different reparative places, here we invited: DNA repair in the field of genetics; soil bioremediation from the perspective of edaphology; psychotherapy as a form of emotional and psychological ‘repair’; memory repair from the field of restorative justice and human rights; home maintenance and cleaning as a form of domestic infrastructure repair and care; repair of electrical and electronic devices by activist collectives for waste prevention; repair of scientific observation instruments in the field of astronomy; and neuro-rehabilitation and physical rehabilitation from the first-person experience of long COVID. We hope these postcards provide a plurality of visions and actions on repair that might lead to resonances, inspirations, and cross-fertilizations among the various forms of repair.

BackgroundDifferent prognostic scales exist in patients with brain metastasis, particularly in lung cancer. The Graded Prognostic Assessment for lung cancer using molecular markers (Lung-molGPA index) for brain metastases is a powerful prognostic tool that effectively identifies patients at different risks. However, these scales do not include perilesional edema diameter (PED) associated with brain metastasis. Current evidence suggests that PED might compromise the delivery and efficacy of radiotherapy to treat BM. This study explored the association between radiotherapy efficacy, PED extent, and gross tumor diameter (GTD).AimThe aim of this study was to evaluate the intracranial response (iORR), intracranial progression-free survival (iPFS), and overall survival (OS) according to the extent of PED and GT.MethodsOut of 114 patients with BM at baseline or throughout the disease, 65 were eligible for the response assessment. The GTD and PED sum were measured at BM diagnosis and after radiotherapy treatment. According to a receiver operating characteristic (ROC) curve analysis, cutoff values were set at 27 mm and 17 mm for PED and GT, respectively.ResultsMinor PED was independently associated with a better iORR [78.8% vs. 50%, OR 3.71 (95% CI 1.26–10.99); p = 0.018] to brain radiotherapy. Median iPFS was significantly shorter in patients with major PED [6.9 vs. 11.8 months, HR 2.9 (95% CI 1.7–4.4); p < 0.001] independently of other prognostic variables like the Lung-molGPA and GTD. A major PED also negatively impacted the median OS [18.4 vs. 7.9 months, HR 2.1 (95% CI 1.4–3.3); p = 0.001].ConclusionHigher PED was associated with an increased risk of intracranial progression and a lesser probability of responding to brain radiotherapy in patients with metastatic lung cancer. We encourage prospective studies to confirm our findings.

Laboratory Medicine is a crucial discipline that contributes to the diagnosis, management and monitoring of patients. This branch of medicine faces two major challenges: New technologies and increased demand. There is limited information available of the state of affairs in Laboratory Medicine in Spain. This study provides a picture of clinical laboratories and clinical laboratory professionals.