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IMPORTANCE: In the last 25 years, functional magnetic resonance imaging drug cue reactivity (FDCR) studies have characterized some core aspects in the neurobiology of drug addiction. However, no FDCR-derived biomarkers have been approved for treatment development or clinical adoption. Traversing this translational gap requires a systematic assessment of the FDCR literature evidence, its heterogeneity, and an evaluation of possible clinical uses of FDCR-derived biomarkers. OBJECTIVE: To summarize the state of the field of FDCR, assess their potential for biomarker development, and outline a clear process for biomarker qualification to guide future research and validation efforts. EVIDENCE REVIEW: The PubMed and Medline databases were searched for every original FDCR investigation published from database inception until December 2022. Collected data covered study design, participant characteristics, FDCR task design, and whether each study provided evidence that might potentially help develop susceptibility, diagnostic, response, prognostic, predictive, or severity biomarkers for 1 or more addictive disorders. FINDINGS: There were 415 FDCR studies published between 1998 and 2022. Most focused on nicotine (122 [29.6%]), alcohol (120 [29.2%]), or cocaine (46 [11.1%]), and most used visual cues (354 [85.3%]). Together, these studies recruited 19 311 participants, including 13 812 individuals with past or current substance use disorders. Most studies could potentially support biomarker development, including diagnostic (143 [32.7%]), treatment response (141 [32.3%]), severity (84 [19.2%]), prognostic (30 [6.9%]), predictive (25 [5.7%]), monitoring (12 [2.7%]), and susceptibility (2 [0.5%]) biomarkers. A total of 155 interventional studies used FDCR, mostly to investigate pharmacological (67 [43.2%]) or cognitive/behavioral (51 [32.9%]) interventions; 141 studies used FDCR as a response measure, of which 125 (88.7%) reported significant interventional FDCR alterations; and 25 studies used FDCR as an intervention outcome predictor, with 24 (96%) finding significant associations between FDCR markers and treatment outcomes. CONCLUSIONS AND RELEVANCE: Based on this systematic review and the proposed biomarker development framework, there is a pathway for the development and regulatory qualification of FDCR-based biomarkers of addiction and recovery. Further validation could support the use of FDCR-derived measures, potentially accelerating treatment development and improving diagnostic, prognostic, and predictive clinical judgments.

Copper (Cu) is essential for respiration, neurotransmitter synthesis, oxidative stress response, and transcription regulation, with imbalances leading to neurological, cognitive, and muscular disorders. Here we show the role of a novel Cu-binding protein (Cu-BP) in mammalian transcriptional regulation, specifically on skeletal muscle differentiation using murine primary myoblasts. Utilizing synchrotron X-ray fluorescence-mass spectrometry, we identified murine cysteine-rich intestinal protein 2 (mCrip2) as a key Cu-BP abundant in both nuclear and cytosolic fractions. mCrip2 binds two to four Cu+ ions with high affinity and presents limited redox potential. CRISPR/Cas9-mediated deletion of mCrip2 impaired myogenesis, likely due to Cu accumulation in cells. CUT&RUN and transcriptome analyses revealed its association with gene promoters, including MyoD1 and metallothioneins, suggesting a novel Cu-responsive regulatory role for mCrip2. Our work describes the significance of mCrip2 in skeletal muscle differentiation and metal homeostasis, expanding understanding of the Cu-network in myoblasts. Copper (Cu) is essential for various cellular processes, including respiration and stress response, but imbalances can cause serious health issues. This study reveals a new Cu-binding protein (Cu-BP) involved in muscle development in primary myoblasts. Using unbiased metalloproteomic techniques and high throughput sequencing, we identified mCrip2 as a key Cu-BP found in cell nuclei and cytoplasm. mCrip2 binds up to four Cu+ ions and has a limited redox potential. Deleting mCrip2 using CRISPR/Cas9 disrupted muscle formation due to Cu accumulation. Further analyses showed that mCrip2 regulates the expression of genes like MyoD1, essential for muscle differentiation, and metallothioneins in response to copper supplementation. This research highlights the importance of mCrip2 in muscle development and metal homeostasis, providing new insights into the Cu-network in cells.

Network monitoring systems can struggle to detect the full sequence of actions in a multi-step cyber attack, frequently resulting in multiple alerts (some of which are false positive (FP)) and missed actions. The challenge of easing the job of security analysts by triggering a single and accurate alert per attack requires developing and evaluating advanced event correlation techniques and models that have the potential to devise relationships between the different observed events/alerts.This work introduces a flexible architecture designed for hierarchical and iterative correlation of alerts and events. Its key feature is the sequential correlation of operations targeting specific attack episodes or aspects. This architecture utilizes IDS alerts or similar cybersecurity sensors, storing events and alerts in a non-relational database. Modules designed for knowledge creation then query these stored items to generate meta-alerts, also stored in the database. This approach facilitates creating a more refined knowledge that can be built on top of existing one by creating specialized modules. For illustrative purposes, we make a case study where we use this architectural approach to explore the feasibility of monitoring the progress of attacks of increased complexity by increasing the levels of the hyperalerts defined, including a case of a multi-step attack that adheres to the ATT&CK model. Although the mapping between the observations and the model components (i.e., techniques and tactics) is challenging, we could fully monitor the progress of two attacks and up to 5 out of 6 steps of the most complex attack by building up to three specialized modules. Despite some limitations due to the sensors and attack scenarios tested, the results indicate the architecture’s potential for enhancing the detection of complex cyber attacks, offering a promising direction for future cybersecurity research.

Resumen: Introducción: La identificación de los factores que determinan el éxito académico puede ayudar a diseñar estrategias efectivas para su mejora. El objetivo de este trabajo fue identificar predictores asociados al éxito académico en estudiantes de pregrado de Nutrición y Dietética de la Pontificia Universidad Católica de Chile (PUC). Métodos: Estudio retrospectivo utilizando la base de datos institucional. La variable dependiente primaria fue el éxito académico, considerando dos índices: i) promedio ponderado acumulado final (PPA-f) y; ii) graduación oportuna, definida como graduarse en ≤10 semestres. Las variables predictoras fueron: edad, sexo, región de origen, tipo de establecimiento escolar, puntaje en la Prueba de Selección Universitaria (PSU), vía de admisión y posición de preferencia de admisión. Para identificar los predictores del PPA-f se utilizó regresión lineal por pasos y para las variables asociadas a la graduación oportuna se utilizó regresión logística binaria. Resultados: El puntaje PSU fue el único predictor del PPA-f, explicando 24% de la varianza. Las probabilidades (OR [IC 95%]) de tener una graduación oportuna estuvieron influenciadas por puntaje PSU (1,017 [1,003–1,031]) y vía de admisión (PSU 1,00 [Referencia], Equidad 0,30 [0,10–0,96], Especial 0,46 [0,13–1,57]). Conclusiones e implicancias: El puntaje PSU predice parcialmente el éxito académico de estudiantes de Nutrición y Dietética PUC. Además, los estudiantes que ingresaron mediante la vía de admisión equidad tuvieron menores probabilidades de graduarse oportunamente. Debido a que las desigualdades educativas pueden afectar el éxito académico, es necesario abordar el proceso de enseñanza y aprendizaje con estrategias específicas para estos estudiantes, asegurando así su éxito académico. Abstract: Introduction: Identifying the factors that determine academic success can help design strategies focused on increasing academic success. We aimed to identify predictors associated with academic success in undergraduate students of the Nutrition and Dietetics Program of the Pontificia Universidad Católica de Chile (PUC). Methods: Retrospective study using the institutional database. Academic success was the main outcome, including two indexes: i) final grade point average (GPA-f) and; ii) timely graduation, defined as graduating in ≤10 semesters. Candidate predictors were: age, sex, region of origin, school attended, score at the university selection test (PSU-score), admission route, and preference for the program. Stepwise linear regression was used to identify predictors of GPA-f. Binary logistic regression was used to identify variables associated with timely graduation. Results: PSU-score was the only predictor of GPA, explaining 24% of its variance. The odds (OR [95%CI]) for a timely graduation were influenced by PSU-score (1.017 [1.003–1.031]) and admission route (PSU 1.00 [Reference], Inclusive 0.30 [0.10–0.96], Special 0.46 [0.13–1.57]). Conclusions and implications: PSU-score partially predicts the academic success of Nutrition and Dietetics students. In addition, students who accessed the program by the equity admission had lower odds of a timely graduation. As educational inequalities may affect academic success, the teaching and learning process needs to be addressed with specific strategies for these students to ensure academic success.

ABSTRACT: Introduction: The incidence of breast cancer has risen in Chile, along with the complexity of diagnosis. For accurate diagnosis, it is necessary to complement the morphology assessed with hematoxylin and eosin with additional techniques to evaluate specific tumor markers. Evaluating the impact on costs, time, and productivity of automated techniques integrated with digital pathology solutions is crucial. Objectives: To estimate the impact on costs, time, and productivity of incorporating the automation of the HER2 in situ hybridization technique combined with integrative digital pathology (IDP) in breast cancer diagnosis in a Chilean public provider versus a manual technique. Methods: This economic evaluation adopted a health economics multi-method approach. A decision model was developed to represent the current manual fluorescence in situ hybridization (FISH) scenario versus an automated dual in situ hybridization (DISH) plus IDP in breast cancer diagnosis. Business process management (BPM) methodology was applied for capturing working time and latencies, in combination with a time-driven activity-based costing (TDABC) methodology for estimating direct, total, and average cost (2023 USD) for both scenarios for the following vectors: Human resources, supplies, and equipment, sorted by pre-analytical, analytical, and post-analytical phases. Indirect costs (2023 USD) were also retrieved. Both BPM and TDABC served to estimate labor productivity. Results: In the baseline scenario based on manual FISH, the turnaround time (TAT) was estimated at 1259 min, at an average total cost of $265.67, considering direct and indirect costs for all phases. An average of 20.5 FISH reports were submitted per pathologist monthly during the baseline. The automated DISH plus IDP scenario consumed 203 min per biopsy, at an average total cost of $231.08, considering direct and indirect costs for all phases; it also showed an average of 22.8 submitted reports per pathologist monthly. This represents a decrease of 13.02% in average total costs, an 83.86% decrease in TAT, and an average labor productivity increase of 11.29%. Conclusions: The incorporation of automated DISH plus IDP in the pathology department of this public provider has resulted in reductions in the time required to perform the in situ hybridization technique, a decrease in total costs, and increased productivity. Particular attention should be given to adopting new technologies to accelerate processing times and workflow.

La educación emocional gana presencia en el currículum escolar, mostrando que la Administración y los agentes educadores han desarrollado con el paso de los años una mayor sensibilidad sobre esta cuestión, considerada en la actualidad como un elemento central en la escuela. Las diferentes áreas realizan su aportación en estos procesos, dentro de los cuales emerge la figura de la autoestima como mejor conocimiento de uno mismo a partir de la interacción que se tiene con el medio que nos rodea. La Literatura Infantil, dentro de la Lengua y Literatura Castellanas, propone una gran cantidad de títulos dedicados al lector infantil. Entre ellos, se ha consolidado una corriente realista denominada psicoliteratura, que trata con sus tramas y personajes de aliviar aquellas angustias que inquietan a los niños. De este modo, temas como la muerte, el miedo a la oscuridad o la separación de los padres adquieren su espacio en las estanterías tratando de ayudar y aportar consuelo a sus lectores. El presente trabajo realiza un recorrido por los conceptos de educación emocional, inteligencia emocional y autoestima para llegar así a la psicoliteratura, desde la cual ofrecer el estudio de cinco obras recientes que tratan sobre la autoestima, con el objetivo de poner de manifiesto cómo la Literatura Infantil actual se preocupa también de la salud emocional de los menores.

La unidad magisterial en el asociacionismo docente es un concepto complejo, articulado a través de diversas interpretaciones y prácticas que reflejan cohesión y divisiones históricas entre el profesorado. A partir de 30 entrevistas a docentes afiliados en distintas asociaciones, se analizan las interpretaciones y estrategias que desarrollan para construir unidad. Los resultados muestran que la unidad se construye como una estrategia circunstancial, a menudo relacionada con un pasado idealizado de vinculación ciudadana. Sin embargo, hoy enfrenta tensiones y dilemas, debido a la diversidad ideológica y comprensiones del trabajo político. Esto discute las reconfiguraciones del asociacionismo en una trama política fractura.

Copper (Cu) is essential for respiration, neurotransmitter synthesis, oxidative stress response, and transcription regulation, with imbalances leading to neurological, cognitive, and muscular disorders. Here we show the role of a novel Cu-binding protein (Cu-BP) in mammalian transcriptional regulation, specifically on skeletal muscle differentiation using murine primary myoblasts. Utilizing synchrotron X-ray fluorescence-mass spectrometry, we identified murine cysteine-rich intestinal protein 2 (mCrip2) as a key Cu-BP abundant in both nuclear and cytosolic fractions. mCrip2 binds two to four Cu+ ions with high affinity and presents limited redox potential. CRISPR/Cas9-mediated deletion of mCrip2 impaired myogenesis, likely due to Cu accumulation in cells. CUT&RUN and transcriptome analyses revealed its association with gene promoters, including MyoD1 and metallothioneins, suggesting a novel Cu-responsive regulatory role for mCrip2. Our work describes the significance of mCrip2 in skeletal muscle differentiation and metal homeostasis, expanding understanding of the Cu-network in myoblasts. Copper (Cu) is essential for various cellular processes, including respiration and stress response, but imbalances can cause serious health issues. This study reveals a new Cu-binding protein (Cu-BP) involved in muscle development in primary myoblasts. Using unbiased metalloproteomic techniques and high throughput sequencing, we identified mCrip2 as a key Cu-BP found in cell nuclei and cytoplasm. mCrip2 binds up to four Cu+ ions and has a limited redox potential. Deleting mCrip2 using CRISPR/Cas9 disrupted muscle formation due to Cu accumulation. Further analyses showed that mCrip2 regulates the expression of genes like MyoD1, essential for muscle differentiation, and metallothioneins in response to copper supplementation. This research highlights the importance of mCrip2 in muscle development and metal homeostasis, providing new insights into the Cu-network in cells.

In 1980, in the middle of the dictatorship, Chilean playwriter Juan Radrigán presented Las Brutas, a play that imagined the last days of three indigenous sisters whose dead body had been found in the precordillera in 1974. Their death happened shortly after the government announced a new law that would prohibit the stockbreeding of goats. In 2013, Sebastián Sepúlveda recovered the story and adapted Radrigán’s play to the big screen. This paper wonders about Sepúlveda’s use of film language to expand the sensation of absurdism already installed in Radrigán’s work, which allows to explore new preoccupations.

Introduction The management of a chronic and frequent pathology, such as obstructive sleep apnoea (OSA), requires personalised programmes that implement new technology-based tools to improve the comprehensive treatment of the patient to reduce the morbidity associated with this disease. This study will evaluate the effectiveness of an eHealth tool in managing the pathophysiological consequences of OSA and how they impact the quality of life after 3 months of intervention among adults.Methods and analysis This is a mixed-method sequential exploratory study protocol. Participants will be≥18 years with a new diagnosis of moderate OSA and diagnosed with hypertension. The qualitative phase will consist of personal semistructured interviews. The quantitative phase will be a triple-blind randomised controlled trial. The experimental group (n=135) will receive an eHealth intervention using an electronic wrist device and a mobile application that will offer specific healthcare recommendations, physical activity indications and hygienic and dietary advice. These recommendations will be based on the information obtained in the qualitative phase. Those in the control group (n=135) will receive the usual educational materials from the sleep unit. The primary outcome will be blood pressure changes at 3 months. Secondary outcomes are subjective sleep quality, sleep apnoea-related parameters, daytime sleepiness, physical activity, empowerment and motivation for change, quality of life, anthropometry, cost–benefit and adherence.Ethics and dissemination Ethical approval for the study has been obtained from the Hospital Universitari Arnau de Vilanova (CEIC-2511). Results will be published in a peer-reviewed journal.Trial registration number ClinicalTrials.gov Identifier: NCT05380726.

IntroductionThe regimen with daratumumab, bortezomib, melphalan, and prednisone (D-VMP) is one of the recommended treatments for newly diagnosed multiple myeloma (NDMM) non-transplant eligible due to the results described in the ALCYONE trial. However, real-life outcomes with this regimen are limited. This study assesses the real-life effectiveness and safety of this regimen.MethodsWe retrospectively analyzed the data on efficacy, safety, and survival parameters of D-VMP regimen in 112 patients with NDMM not eligible for autologous stem-cell transplantation with attention to the effect of age, R2-ISS, high-risk cytogenetic abnormalities (CA), and depth of response.ResultsPatients aged ≥75 years constituted 70% of our cohort. Fifty-two percent had R2-ISS 3-4, and 60% had high-risk CA. Twenty-three percent of patients would have been excluded from the ALCYONE trial. After a median follow-up of 31.4 months, all patients had completed induction, with a median number of cycles of 9 (IQR 6-9). The overall response rate was 95%, and 72% achieved very good partial response (VGPR) or better. The median progression-free survival (PFS) was 41.5 (95% CI, 34.3 to NE), and the median overall survival (OS) was not reached. The most frequent adverse event (AE) was neuropathy (27%), followed by gastrointestinal symptoms (13%) and hematological AE (10%). Age did not negatively impact survival outcomes. Patients with ≥2 high-risk CA or those who achieved

The massive arrival of pelagic Sargassum on the coasts of several countries of the Atlantic Ocean began in 2011 and to date continues to generate social and environmental challenges for the region. Therefore, knowing the distribution and quantity of Sargassum in the ocean, coasts, and beaches is necessary to understand the phenomenon and develop protocols for its management, use, and final disposal. In this context, the present study proposes a methodology to calculate the area Sargassum occupies on beaches in square meters, based on the semantic segmentation of aerial images using the pix2pix architecture. For training and testing the algorithm, a unique dataset was built from scratch, consisting of 15,268 aerial images segmented into three classes. The images correspond to beaches in the cities of Mahahual and Puerto Morelos, located in Quintana Roo, Mexico. To analyze the results the fβ-score metric was used. The results for the Sargassum class indicate that there is a balance between false positives and false negatives, with a slight bias towards false negatives, which means that the algorithm tends to underestimate the Sargassum pixels in the images. To know the confidence intervals within which the algorithm performs better, the results of the f0.5-score metric were resampled by bootstrapping considering all classes and considering only the Sargassum class. From the above, we found that the algorithm offers better performance when segmenting Sargassum images on the sand. From the results, maps showing the Sargassum coverage area along the beach were designed to complement the previous ones and provide insight into the field of study.

Este artículo pretende explorar el hecho religioso como factor de paz o de conflicto. Partiendo del propio concepto de persona humana y de la realidad religiosa y social y mostrando el abandono o desprecio por lo religioso a partir de la exploración de una serie elementos o procesos disgregadores como el propio proceso de secularización de la sociedad occidental, la construcción del concepto de Estado, la globalización o la instrumentalización religiosa por razones geopolíticas o de relaciones internacionales que han contribuido a conformar una imagen negativa de la religión, constriñendo su propia área de acción e impidiendo la apertura de espacios de diálogo interreligioso y cultural en la resolución de conflictos a través de la construcción de ámbitos pacíficos y de conocimiento mutuo entre comunidades y pueblos.