To develop a predictive model based on inflammatory gene mRNA expression in conjunctival cells of graft versus host disease (GvHD)-associated dry eye (DE) patients, as well as to find meaningful ...correlations between gene signals and clinical signs.
Twenty GvHD-DE patients and 14 healthy controls were recruited. Patients discontinued medications for 1 week before examination. Dry eye-related symptoms and signs were recorded, and conjunctival epithelial cells were collected by impression cytology after spending 20 minutes under standard conditions within a Controlled Environmental Research Laboratory. Gene expression of inflammatory molecules was determined by polymerase chain reaction, and the results were correlated with clinical signs. Shrinkage discriminant analysis, support vector machine, and k-nearest neighbor classifier methods were used to develop predictive models that were validated considering accuracy, calibration, and discriminant capability.
Out of the 84 genes analyzed, 34 showed significant differences in expression. IL-6, IL-9, CCL24, CCL18, IL-10, IFN-γ, and CCL2 were highly increased (>6-fold); 26 genes were moderately upregulated (2- to 6-fold), whereas EGFR was downregulated (2.63 fold) in GvHD-DE samples. A panel based on EGFR, IL-6, IL-9, and NAMPT had an area under the receiver operating characteristic curve of 0.994, a sensitivity of 100%, and a specificity of 92.9%. EGFR expression correlated negatively with ocular surface damage markers, while IL-6, IL-9, and NAMPT correlated positively with these tests.
EGFR, IL-6, IL-9, and NAMPT have the greatest potential as diagnostic biomarkers, with excellent sensitivity, specificity, and clinical relevance to the ocular surface status of GvHD.
Purpose
The purpose of this paper is to analyse student performance and perceptions when a flipped classroom setting is used, in comparison with the traditional model.
Design/methodology/approach
The ...inverted learning model or “flipped classroom” is a pedagogical approach that attempts to reverse the traditional teaching and learning process, making the student the protagonist of their own learning, and is characterised by the theoretical contents being taught “outside the classroom”, allowing students to spend more class time carrying out other types of more practical activities that encourage much more active learning, such as enquiry exercises, problem solving, collaborative projects and so on. The study was conducted on a biology course of the Primary Education Bachelor’s Degree during the 2017/2018 academic year (n = 240).
Findings
The results revealed that better learning outcomes were achieved by students when the flipped classroom methodology was proposed. It has also been found that student perceptions of the teaching approach were more positive when the flipped model was followed. The flipped classroom methodology also seems to foster student participation and motivation more effectively than traditional teaching formats, mainly because the active learning activities that are carried out in this new educative approach manage to involve the students in their own learning processes.
Originality/value
Despite the enhanced popularity of flipped classroom research in multiple educational contexts and the growing number of studies published in recent years, there is little empirical evidence regarding the effect of the flipped classroom on learning outcomes and satisfaction in pre-service teachers.
Display omitted
Mortality risk prediction for Intermediate Respiratory Care Unit's (IRCU) patients can facilitate optimal treatment in high-risk patients. While Intensive Care Units (ICUs) have a ...long term experience in using algorithms for this purpose, due to the special features of the IRCUs, the same strategics are not applicable. The aim of this study is to develop an IRCU specific mortality predictor tool using machine learning methods.
Vital signs of patients were recorded from 1966 patients admitted from 2007 to 2017 in the Jiménez Díaz Foundation University Hospital's IRCU. A neural network was used to select the variables that better predict mortality status. Multivariate logistic regression provided us cut-off points that best discriminated the mortality status for each of the parameters. A new guideline for risk assessment was applied and mortality was recorded during one year.
Our algorithm shows that thrombocytopenia, metabolic acidosis, anemia, tachypnea, age, sodium levels, hypoxemia, leukocytopenia and hyperkalemia are the most relevant parameters associated with mortality. First year with this decision scene showed a decrease in failure rate of a 50%.
We have generated a neural network model capable of identifying and classifying mortality predictors in the IRCU of a general hospital. Combined with multivariate regression analysis, it has provided us with an useful tool for the real-time monitoring of patients to detect specific mortality risks. The overall algorithm can be scaled to any type of unit offering personalized results and will increase accuracy over time when more patients are included to the cohorts.
La predicción del riesgo de mortalidad de los pacientes en la unidad de cuidados respiratorios intermedios (UCRI) puede facilitar un tratamiento óptimo en pacientes de alto riesgo. Si bien las unidades de cuidados intensivos (UCI) tienen una experiencia a largo plazo en el uso de algoritmos para este propósito, debido a las características especiales de las UCRI, no se pueden aplicar las mismas estrategias. El objetivo de este estudio es desarrollar una herramienta de predicción de mortalidad específica para la UCRI utilizando métodos de aprendizaje automático.
Se registraron los signos vitales de 1.966 pacientes ingresados entre 2007 y 2017 en la UCRI del Hospital Universitario de la Fundación Jiménez Díaz. Se utilizó una red neuronal para seleccionar las variables que mejor predijeran el estado de mortalidad. La regresión logística multivariante nos proporcionó los puntos de corte que discriminaban mejor el estado de la mortalidad para cada uno de los parámetros. Se aplicó una nueva guía para la evaluación de riesgos, y se registró la mortalidad durante un año.
Nuestro algoritmo muestra que la trombocitopenia, la acidosis metabólica, la anemia, la taquipnea, la edad, los niveles de sodio, la hipoxemia, la leucocitopenia y la hipercalemia son los parámetros más relevantes asociados con la mortalidad. En el primer año con este escenario de decisión se mostró una disminución en la tasa de fracaso de un 50%.
Hemos generado un modelo de red neuronal capaz de identificar y clasificar predictores de mortalidad en la UCRI de un hospital general. Combinado con el análisis de regresión multivariante, nos ha proporcionado una herramienta útil para la monitorización en tiempo real de pacientes para detectar riesgos de mortalidad específicos. El algoritmo general se puede modificar a escala para cualquier tipo de unidad, lo que ofrecerá resultados personalizados, y su precisión aumentará con el tiempo, según se incluyan más pacientes en las cohortes.
The current view of cancer progression highlights that cancer cells must undergo through a post-translational regulation and metabolic reprogramming to progress in an unfriendly environment. In here, ...the importance of neddylation modification in liver cancer was investigated. We found that hepatic neddylation was specifically enriched in liver cancer patients with bad prognosis. In addition, the treatment with the neddylation inhibitor MLN4924 in Phb1-KO mice, an animal model of hepatocellular carcinoma showing elevated neddylation, reverted the malignant phenotype. Tumor cell death in vivo translating into liver tumor regression was associated with augmented phosphatidylcholine synthesis by the PEMT pathway, known as a liver-specific tumor suppressor, and restored mitochondrial function and TCA cycle flux. Otherwise, in protumoral hepatocytes, neddylation inhibition resulted in metabolic reprogramming rendering a decrease in oxidative phosphorylation and concomitant tumor cell apoptosis. Moreover, Akt and LKB1, hallmarks of proliferative metabolism, were altered in liver cancer being new targets of neddylation. Importantly, we show that neddylation-induced metabolic reprogramming and apoptosis were dependent on LKB1 and Akt stabilization. Overall, our results implicate neddylation/signaling/metabolism, partly mediated by LKB1 and Akt, in the development of liver cancer, paving the way for novel therapeutic approaches targeting neddylation in hepatocellular carcinoma.
Mathematical models of cardiac electrical activity are one of the most important tools for elucidating information about heart diagnostics. In this paper, we present an efficient mathematical ...formulation for this modeling simple enough to be easily parameterized and rich enough to provide realistic signals. It relies on a five dipole representation of the cardiac electric source, each one associated with the well-known waves of the electrocardiogram signal. Beyond the physical basis of the model, the parameters are physiologically interpretable as they characterize the wave shape, similar to what a physician would look for in signals, thus making them very useful in diagnosis. The model accurately reproduces the electrocardiogram signals of any diseased or healthy heart. This new discovery represents a significant advance in electrocardiography research. It is especially useful for diagnosis, patient follow-up or decision-making on new therapies; is also a promising tool for well-performing, transparent and interpretable AI approaches.
Display omitted
•A solid mathematical modeling of the cardiac electric activity•The model accurately reconstructs, and generates, 12-lead ECG signals•Three markers for the diagnosis of LBBB, CBBB, and HYP pathologies•An APP analyses and diagnoses ECGs for any heart condition
Artificial intelligence; Cardiovascular medicine; Computer-aided diagnosis method
For constructionism, language is the link among different levels of analysis of emotional events, from individual to interpersonal and macrosocial. The interaction among these emotional levels allows ...us to construe an emotional episode and label it with an emotion word, coordinate with the emotions perceived in others, and represent events as a society. Across two studies, we found similarities and differences among inner emotions experienced (individual level), emotions perceived in others (descriptive feeling rules, interpersonal level) and emotions shared on the internet (socioemotional conventions, macrosocial level), with all these emotional targets focused on the COVID–19 outbreak. The results indicate a similarity between the emotional meaning of COVID–19 in society and the descriptive feeling rules, whereas the reported inner emotions were clearly distinct: Joy was irrelevant at the interpersonal and macrosocial levels but clearly important at the individual level. A mismatch also appeared for fear and hope. While fear was the most predominant emotion at the interpersonal and macrosocial levels during most of the phases, it was moderately predominant at the individual level. Hope followed the opposite pattern, being the most relevant emotion at the individual level but less relevant at the interpersonal and macrosocial levels. Each level might have different consequences: Mixed emotions at the individual level might promote resilience; fear perceived in other people might motivate protective behaviors; and sadness socially shared during Christmas might generate greater empathy. These results support the complexity of emotional concepts and the suitability of exploring them at different levels of analysis.
Pneumonia is the leading cause of hospital admission and mortality in coronavirus disease 2019 (COVID-19). We aimed to identify the cytokines responsible for lung damage and mortality. We ...prospectively recruited 108 COVID-19 patients between March and April 2020 and divided them into four groups according to the severity of respiratory symptoms. Twenty-eight healthy volunteers were used for normalization of the results. Multiple cytokines showed statistically significant differences between mild and critical patients. High HGF levels were associated with the critical group (OR = 3.51; p < 0.001; 95%CI = 1.95–6.33). Moreover, high IL-1α (OR = 1.36; p = 0.01; 95%CI = 1.07–1.73) and low IL-27 (OR = 0.58; p < 0.005; 95%CI = 0.39–0.85) greatly increased the risk of ending up in the severe group. This model was especially sensitive in order to predict critical status (AUC = 0.794; specificity = 69.74%; sensitivity = 81.25%). Furthermore, high levels of HGF and IL-1α showed significant results in the survival analysis (p = 0.033 and p = 0.011, respectively). HGF, IL-1α, and IL 27 at hospital admission were strongly associated with severe/critical COVID-19 patients and therefore are excellent predictors of bad prognosis. HGF and IL-1α were also mortality biomarkers.
Neuropathic dry eye is one of the most frequently seen complications after corneal refractive surgery, however, its incidence decreases in a significant manner along the first six months ...postoperative, reaching between 10 and 45% incidence. However, little is known on the inflammatory status of the ocular surface during this recovery process. We aim to analyze the clinical and tear molecule concentration changes along six months after advanced surface ablation for myopia correction, in a prospective study including 18 eyes of 18 subjects who bilaterally underwent advanced surface ablation corneal refractive surgery. Clinical variables (uncorrected distance visual acuity, symptoms, conjunctival hyperemia, tear osmolarity, tear stability, corneal fluorescein staining, conjunctival lissamine staining, Schirmer test, and corneal esthesiometry) and a panel of 23 pro and anti-inflammatory cytokines/chemokines concentration in tears preoperatively and at 1, 3 and 6 months postoperatively were evaluated. We found that uncorrected distance visual acuity improved significantly from baseline at 1-month visit, symptoms improved and tear osmolarity decreased significantly from baseline at 3-month visit and there was a decrease in mechanical corneal threshold between 1-month and 3- and 6-month visits. Regarding tear molecules, IL-4, IL-5, IL-6, IL-13, IL-17A, and IFN-γ tear levels were significantly increased at all the three visits, compared to preoperative levels at V0; IL-2 and VEGF were also significantly increased at 1-month and 6-month visits, but not at 3-month visit, whereas IL-9 IL-10 and IL-12 were only significantly increased at 6-month visit. Although we found that there is a recovery in clinical variables at 6 months postoperatively (i.e. neuropathic dry eye was not developed in the sample), ocular surface homeostasis is not completely restored, as it can be seen by the changes in concentration of some pro and anti-inflammatory molecules measured in tears.
•Clinical variables completely restore after 6 months of ASA refractive surgery.•Some tear pro-inflammatory cytokines/chemokines do not recover their basal values.•Ocular surface homeostasis is not completely restored after 6 months of ASA surgery.
Conjunctiva-associated lymphoid tissue (CALT) plays a key role in protecting the eye surface by initiating and regulating immune responses. The aim of this study was to investigate in healthy ...children the proportion of intraepithelial lymphocytes (IELs), the degree of viability and/or apoptosis and cell proliferation in three different topographic areas of the conjunctiva. Superior tarsal, superior bulbar, and inferior tarsal-bulbarfornix conjunctival cells were collected by brush cytology (BC) from 24 healthy paediatric subjects (13 boys and 11 girls, mean age 6±2 years) who were to undergo strabismus correction surgery under general anaesthesia. Subsequently, these cells were analysed phenotypically and functionally by flow cytometry (FC). Flow cytometry analysis showed that not all the cells obtained by BC were of the epithelial lineage, but that there was a population of CD45+ cells (IELs) regularly present in the conjunctiva of healthy children. These IELs were mostly T-lymphocytes (CD3+) and B-lymphocytes (CD19+), with higher levels of T-lymphocytes (CD3+) in the upper areas than in the inferior tarsal-bulbar-fornix, where the highest levels of B-lymphocytes (CD19+) were found. In the apoptosis assay, two groups of cell populations were differentiated by cell size and complexity (cytoplasmic granularity), with more complex cells predominating in the upper areas of the conjunctiva and less complex cells being more abundant in the inferior tarsal-bulbar-fornix. Finally, the proliferative capacity of the conjunctival epithelium was significantly higher in the upper tarsal zone than in the rest of the zones analysed. These results suggest that the epithelial component and the IELs of CALT are also regularly present in the conjunctiva of the healthy child, varying in phenotype, viability and cell proliferation according to the different conjunctival regions analysed, which could lead us to believe that each conjunctival zone plays a different, specific role in the regulation of the immune response at the ocular level.
An automated tool for corneal nerve fiber tortuosity quantification from in vivo confocal microscopy (IVCM) is described and evaluated. The method is a multi-stage process based on the splitting of ...the corneal nerve fibers into individual segments, whose endpoints are an extreme or intersection of white pixels on a binarized image. Individual segment tortuosity is quantified in terms of the arc-chord ratio. Forty-three IVCM images from 43 laser-assisted in situ keratomileusis (LASIK) surgery patients were used for evaluation. Images from symptomatic dry eye disease (DED) post-LASIK patients, with (n=16) and without (n=7) ocular pain, and non-DED post-LASIK controls (n=20) were assessed. The automated tortuosity measure was compared to a manual grading one, obtaining a moderate correlation (Spearman’s rank correlation coefficient = 0.49, p=0.0008). The new tortuosity index was significantly higher in post-LASIK patients with ocular pain than in control patients (p=0.001), while no significant differences were detected with manual measurement (p>0.28). The tortuosity quantification was positively correlated with the ocular surface disease index (OSDI) and a numeric rating scale (NRS) assessing pain (p=0.0012 and p=0.0051, respectively). The results show good performance of the proposed automated methodology for the evaluation of corneal nerve tortuosity.
PDF
