Brain signal variability and executive functions across the life span.

Neural variability is thought to facilitate survival through flexible adaptation to changing environmental demands. In humans, such capacity for flexible adaptation may manifest as fluid reasoning, inhibition of automatic responses, and mental set-switching-skills falling under the broad domain of executive functions that fluctuate over the life span. Neural variability can be quantified via the BOLD signal in resting-state fMRI. Variability of large-scale brain networks is posited to underpin complex cognitive activities requiring interactions between multiple brain regions. Few studies have examined the extent to which network-level brain signal variability across the life span maps onto high-level processes under the umbrella of executive functions. The present study leveraged a large publicly available neuroimaging dataset to investigate the relationship between signal variability and executive functions across the life span. Associations between brain signal variability and executive functions shifted as a function of age. Limbic-specific variability was consistently associated with greater performance across subcomponents of executive functions. Associations between executive function subcomponents and network-level variability of the default mode and central executive networks, as well as whole-brain variability, varied across the life span. Findings suggest that brain signal variability may help to explain to age-related differences in executive functions across the life span.

Traditionally, regional variability in brain signals has been viewed as a source of noise in human neuroimaging research. Our study demonstrates that brain signal variability may contain meaningful information related to psychological processes. We demonstrate that brain signal variability, particularly whole-brain variability, may serve as a reliable indicator of cognitive functions across the life span. Global variability and network-level variability play differing roles in supporting executive functions. Findings suggest that brain signal variability serves as a meaningful indicator of development and cognitive aging.

Machine Learning-Based Prediction of Changes in the Clinical Condition of Patients With Complex Chronic Diseases: 2-Phase Pilot Prospective Single-Center Observational Study.

BACKGROUND: Functional impairment is one of the most decisive prognostic factors in patients with complex chronic diseases. A more significant functional impairment indicates that the disease is progressing, which requires implementing diagnostic and therapeutic actions that stop the exacerbation of the disease. OBJECTIVE: This study aimed to predict alterations in the clinical condition of patients with complex chronic diseases by predicting the Barthel Index (BI), to assess their clinical and functional status using an artificial intelligence model and data collected through an internet of things mobility device. METHODS: A 2-phase pilot prospective single-center observational study was designed. During both phases, patients were recruited, and a wearable activity tracker was allocated to gather physical activity data. Patients were categorized into class A (BI≤20; total dependence), class B (2060; moderate or mild dependence, or independent). Data preprocessing and machine learning techniques were used to analyze mobility data. A decision tree was used to achieve a robust and interpretable model. To assess the quality of the predictions, several metrics including the mean absolute error, median absolute error, and root mean squared error were considered. Statistical analysis was performed using SPSS and Python for the machine learning modeling. RESULTS: Overall, 90 patients with complex chronic diseases were included: 50 during phase 1 (class A: n=10; class B: n=20; and class C: n=20) and 40 during phase 2 (class B: n=20 and class C: n=20). Most patients (n=85, 94%) had a caregiver. The mean value of the BI was 58.31 (SD 24.5). Concerning mobility aids, 60% (n=52) of patients required no aids, whereas the others required walkers (n=18, 20%), wheelchairs (n=15, 17%), canes (n=4, 7%), and crutches (n=1, 1%). Regarding clinical complexity, 85% (n=76) met patient with polypathology criteria with a mean of 2.7 (SD 1.25) categories, 69% (n=61) met the frailty criteria, and 21% (n=19) met the patients with complex chronic diseases criteria. The most characteristic symptoms were dyspnea (n=73, 82%), chronic pain (n=63, 70%), asthenia (n=62, 68%), and anxiety (n=41, 46%). Polypharmacy was presented in 87% (n=78) of patients. The most important variables for predicting the BI were identified as the maximum step count during evening and morning periods and the absence of a mobility device. The model exhibited consistency in the median prediction error with a median absolute error close to 5 in the training, validation, and production-like test sets. The model accuracy for identifying the BI class was 91%, 88%, and 90% in the training, validation, and test sets, respectively. CONCLUSIONS: Using commercially available mobility recording devices makes it possible to identify different mobility patterns and relate them to functional capacity in patients with polypathology according to the BI without using clinical parameters.

Privacy-preserving federated machine learning on FAIR health data: A real-world application.

Objective: This paper introduces a privacy-preserving federated machine learning (ML) architecture built upon Findable, Accessible, Interoperable, and Reusable (FAIR) health data. It aims to devise an architecture for executing classification algorithms in a federated manner, enabling collaborative model-building among health data owners without sharing their datasets. Materials and methods: Utilizing an agent-based architecture, a privacy-preserving federated ML algorithm was developed to create a global predictive model from various local models. This involved formally defining the algorithm in two steps: data preparation and federated model training on FAIR health data and constructing the architecture with multiple components facilitating algorithm execution. The solution was validated by five healthcare organizations using their specific health datasets. Results: Five organizations transformed their datasets into Health Level 7 Fast Healthcare Interoperability Resources via a common FAIRification workflow and software set, thereby generating FAIR datasets. Each organization deployed a Federated ML Agent within its secure network, connected to a cloud-based Federated ML Manager. System testing was conducted on a use case aiming to predict 30-day readmission risk for chronic obstructive pulmonary disease patients and the federated model achieved an accuracy rate of 87%. Discussion: The paper demonstrated a practical application of privacy-preserving federated ML among five distinct healthcare entities, highlighting the value of FAIR health data in machine learning when utilized in a federated manner that ensures privacy protection without sharing data. Conclusion: This solution effectively leverages FAIR datasets from multiple healthcare organizations for federated ML while safeguarding sensitive health datasets, meeting legislative privacy and security requirements.

Promotion of structural plasticity in area V2 of visual cortex prevents against object recognition memory deficits in aging and Alzheimer's disease rodents.

JOURNAL/nrgr/04.03/01300535-202408000-00038/figure1/v/2023-12-16T180322Z/r/image-tiff Memory deficit, which is often associated with aging and many psychiatric, neurological, and neurodegenerative diseases, has been a challenging issue for treatment. Up till now, all potential drug candidates have failed to produce satisfactory effects. Therefore, in the search for a solution, we found that a treatment with the gene corresponding to the RGS14414 protein in visual area V2, a brain area connected with brain circuits of the ventral stream and the medial temporal lobe, which is crucial for object recognition memory (ORM), can induce enhancement of ORM. In this study, we demonstrated that the same treatment with RGS14414 in visual area V2, which is relatively unaffected in neurodegenerative diseases such as Alzheimer's disease, produced long-lasting enhancement of ORM in young animals and prevent ORM deficits in rodent models of aging and Alzheimer's disease. Furthermore, we found that the prevention of memory deficits was mediated through the upregulation of neuronal arborization and spine density, as well as an increase in brain-derived neurotrophic factor (BDNF). A knockdown of BDNF gene in RGS14414-treated aging rats and Alzheimer's disease model mice caused complete loss in the upregulation of neuronal structural plasticity and in the prevention of ORM deficits. These findings suggest that BDNF-mediated neuronal structural plasticity in area V2 is crucial in the prevention of memory deficits in RGS14414-treated rodent models of aging and Alzheimer's disease. Therefore, our findings of RGS14414 gene-mediated activation of neuronal circuits in visual area V2 have therapeutic relevance in the treatment of memory deficits.

Pre-pandemic Executive Function Protects Against Pandemic Anxiety in Children with and Without Autism Spectrum Disorder.

The COVID-19 pandemic may have exacerbated depression, anxiety, and executive function (EF) difficulties in children with autism spectrum disorder (ASD). EF skills have been positively associated with mental health outcomes. Here, we probed the psychosocial impacts of pandemic responses in children with and without ASD by relating pre-pandemic EF assessments with anxiety and depression symptoms several months into the pandemic. We found that pre-pandemic inhibition and shifting difficulties, measured by the Behavior Rating Inventory of Executive Function, predicted higher risk of anxiety symptoms. These findings are critical for promoting community recovery and maximizing clinical preparedness to support children at increased risk for adverse psychosocial outcomes.

A prospective observational concordance study to evaluate computational model-driven clinical practice guidelines for Type 2 diabetes mellitus.

BACKGROUND: Clinical Practice Guidelines (CPGs) provide healthcare professionals with performance and decision-making support during the treatment of patients. Sometimes, however, they are poorly implemented. The IDE4ICDS platform was developed and validated with CPGs for type 2 diabetes mellitus (T2DM). OBJECTIVE: The main objective of this paper is to present the results of the clinical validation of the IDE4ICDS platform in a real clinical environment at two health clinics in the Andalusian Public Health System (SSPA) in the southern Spanish region of Andalusia. METHODS: National and international knowledge sources on T2DM were selected and reviewed and used to define a diabetes CPG model on the IDE4ICDS platform. Once the diabetes CPG was configured and deployed, it was validated. A total of 506 patients were identified as meeting the inclusion criteria, of whom 130 could be recruited and 89 attended the appointment. RESULTS: A concordance analysis was performed with the kappa value. Overall agreement between the recommendations provided by the system and those recorded in each patient's EHR was good (0.61 - 0.80) with a total kappa index of 0.701, leading to the conclusion that the system provided appropriate recommendations for each patient and was therefore well-functioning. CONCLUSIONS: A series of possible improvements were identified based on the limitations for the recovery of variables related to the quality of these recolected variables, the detection of duplicate recommendations based on different input variables for the same patient, and clinical usability, such as the capacity to generate reports based on the recommendations generated. Nevertheless, the project resulted in the IDE4ICDS platform: a Clinical Decision Support System (CDSS) capable of providing appropriate recommendations for improving the management and quality of patient care and optimizing health outcomes. The result of this validation is a safe and effective pathway for developing and adopting digital transformation at the regional scale of the use of biomedical knowledge in real healthcare.

Health data hubs: an analysis of existing data governance features for research.

BACKGROUND: Digital transformation in healthcare and the growth of health data generation and collection are important challenges for the secondary use of healthcare records in the health research field. Likewise, due to the ethical and legal constraints for using sensitive data, understanding how health data are managed by dedicated infrastructures called data hubs is essential to facilitating data sharing and reuse. METHODS: To capture the different data governance behind health data hubs across Europe, a survey focused on analysing the feasibility of linking individual-level data between data collections and the generation of health data governance patterns was carried out. The target audience of this study was national, European, and global data hubs. In total, the designed survey was sent to a representative list of 99 health data hubs in January 2022. RESULTS: In total, 41 survey responses received until June 2022 were analysed. Stratification methods were performed to cover the different levels of granularity identified in some data hubs' characteristics. Firstly, a general pattern of data governance for data hubs was defined. Afterward, specific profiles were defined, generating specific data governance patterns through the stratifications in terms of the kind of organization (centralized versus decentralized) and role (data controller or data processor) of the health data hub respondents. CONCLUSIONS: The analysis of the responses from health data hub respondents across Europe provided a list of the most frequent aspects, which concluded with a set of specific best practices on data management and governance, taking into account the constraints of sensitive data. In summary, a data hub should work in a centralized way, providing a Data Processing Agreement and a formal procedure to identify data providers, as well as data quality control, data integrity and anonymization methods.

Desiderata for the Data Governance and FAIR Principles Adoption in Health Data Hubs.

The objective of this study, as part of the European HealthyCloud project, has been to analyse the data management mechanisms of representative data hubs in Europe and identify whether they comply with an adequate adoption of FAIR principles that will enable data discovery. A dedicated consultation survey was performed, and the analysis of the results allowed to generate a set of comprehensive recommendations and best practices so that these data hubs can be integrated into a data sharing ecosystem such as the future European Health Research and Innovation Cloud.

FAIR principles to improve the impact on health research management outcomes.

Background: The FAIR principles, under the open science paradigm, aim to improve the Findability, Accessibility, Interoperability and Reusability of digital data. In this sense, the FAIR4Health project aimed to apply the FAIR principles in the health research field. For this purpose, a workflow and a set of tools were developed to apply FAIR principles in health research datasets, and validated through the demonstration of the potential impact that this strategy has on health research management outcomes. Objective: This paper aims to describe the analysis of the impact on health research management outcomes of the FAIR4Health solution. Methods: To analyse the impact on health research management outcomes in terms of time and economic savings, a survey was designed and sent to experts on data management with expertise in the use of the FAIR4Health solution. Then, differences between the time and costs needed to perform the techniques with (i) standalone research, and (ii) using the proposed solution, were analyzed. Results: In the context of the health research management outcomes, the survey analysis concluded that 56.57% of the time and 16800 EUR per month could be saved if the FAIR4Health solution is used. Conclusions: Adopting principles in health research through the FAIR4Health solution saves time and, consequently, costs in the execution of research involving data management techniques.

A Data Transformation Methodology to Create Findable, Accessible, Interoperable, and Reusable Health Data: Software Design, Development, and Evaluation Study.

BACKGROUND: Sharing health data is challenging because of several technical, ethical, and regulatory issues. The Findable, Accessible, Interoperable, and Reusable (FAIR) guiding principles have been conceptualized to enable data interoperability. Many studies provide implementation guidelines, assessment metrics, and software to achieve FAIR-compliant data, especially for health data sets. Health Level 7 (HL7) Fast Healthcare Interoperability Resources (FHIR) is a health data content modeling and exchange standard. OBJECTIVE: Our goal was to devise a new methodology to extract, transform, and load existing health data sets into HL7 FHIR repositories in line with FAIR principles, develop a Data Curation Tool to implement the methodology, and evaluate it on health data sets from 2 different but complementary institutions. We aimed to increase the level of compliance with FAIR principles of existing health data sets through standardization and facilitate health data sharing by eliminating the associated technical barriers. METHODS: Our approach automatically processes the capabilities of a given FHIR end point and directs the user while configuring mappings according to the rules enforced by FHIR profile definitions. Code system mappings can be configured for terminology translations through automatic use of FHIR resources. The validity of the created FHIR resources can be automatically checked, and the software does not allow invalid resources to be persisted. At each stage of our data transformation methodology, we used particular FHIR-based techniques so that the resulting data set could be evaluated as FAIR. We performed a data-centric evaluation of our methodology on health data sets from 2 different institutions. RESULTS: Through an intuitive graphical user interface, users are prompted to configure the mappings into FHIR resource types with respect to the restrictions of selected profiles. Once the mappings are developed, our approach can syntactically and semantically transform existing health data sets into HL7 FHIR without loss of data utility according to our privacy-concerned criteria. In addition to the mapped resource types, behind the scenes, we create additional FHIR resources to satisfy several FAIR criteria. According to the data maturity indicators and evaluation methods of the FAIR Data Maturity Model, we achieved the maximum level (level 5) for being Findable, Accessible, and Interoperable and level 3 for being Reusable. CONCLUSIONS: We developed and extensively evaluated our data transformation approach to unlock the value of existing health data residing in disparate data silos to make them available for sharing according to the FAIR principles. We showed that our method can successfully transform existing health data sets into HL7 FHIR without loss of data utility, and the result is FAIR in terms of the FAIR Data Maturity Model. We support institutional migration to HL7 FHIR, which not only leads to FAIR data sharing but also eases the integration with different research networks.

Correction: A Personalized Ontology-Based Decision Support System for Complex Chronic Patients: Retrospective Observational Study.

[This corrects the article DOI: 10.2196/27990.].

Gemelos con convulsiones febriles: coincidencia en tiempo y etiología / Febrile seizures in siblings: coincidence in timing and aetiology

Las convulsiones febriles tienen alta prevalencia en la infancia y son un motivo de consulta frecuente en Urgencias, generando gran ansiedad en los cuidadores. La etiología es multifactorial y se ha descrito una agregación familiar (hasta el 25-40% de los niños con crisis febriles presentan antecedentes familiares de estas). Sin embargo, esta es la primera vez que se describen convulsiones febriles en hermanos al mismo tiempo y con el mismo hallazgo microbiológico. Presentamos dos parejas de hermanos gemelos de 23 y 33 meses, valorados en Urgencias por crisis febriles al mismo tiempo que su respectivo gemelo. La exploración física y el examen neurológico fueron normales en todos ellos. La PCR para enterovirus recogida en faringe y/o recto fue positiva. En todos los casos la recuperación fue completa, permitiendo el alta sin requerir otros estudios. En los últimos años, las infecciones por enterovirus están adquiriendo importancia creciente en el papel de las convulsiones. Ante casos de hermanos con crisis febriles al mismo tiempo debería tenerse en cuenta la posible infección por este agente. Establecer una etiología podría ser tranquilizador para los padres (AU)

The prevalence of febrile seizures is high in the paediatric population, and seizures are a frequent reason for emergency department (ED) visits, and a significant source of anxiety in caregivers. Their aetiology is multifactorial, and family aggregation has been described (as many as 25-40% of children with febrile seizures have a positive family history). However, this is the first time that febrile seizures have been described as occurring in siblings at the same time with identification of the same etiological agent.We present the cases of 2 pairs of twins, aged 23 months and 33 months, respectively, who presented at the ED with simple febrile seizures in both twins at the same time. The physical and neurological examination were normal in all of them. Polymerase chain reaction tests for enterovirus in pharyngeal and/or rectal swabs were positive. All of the patients recovered fully and were discharged home without requiring further diagnostic tests.In recent years, there has been a growing awareness of the important role of enterovirus infection in seizures. Therefore, enterovirus infection should be considered in the case of siblings presenting with febrile seizures at the same time. Establishing the aetiology of seizures may be reassuring to parents. (AU)

A Personalized Ontology-Based Decision Support System for Complex Chronic Patients: Retrospective Observational Study.

BACKGROUND: Due to an increase in life expectancy, the prevalence of chronic diseases is also on the rise. Clinical practice guidelines (CPGs) provide recommendations for suitable interventions regarding different chronic diseases, but a deficiency in the implementation of these CPGs has been identified. The PITeS-TiiSS (Telemedicine and eHealth Innovation Platform: Information Communications Technology for Research and Information Challenges in Health Services) tool, a personalized ontology-based clinical decision support system (CDSS), aims to reduce variability, prevent errors, and consider interactions between different CPG recommendations, among other benefits. OBJECTIVE: The aim of this study is to design, develop, and validate an ontology-based CDSS that provides personalized recommendations related to drug prescription. The target population is older adult patients with chronic diseases and polypharmacy, and the goal is to reduce complications related to these types of conditions while offering integrated care. METHODS: A study scenario about atrial fibrillation and treatment with anticoagulants was selected to validate the tool. After this, a series of knowledge sources were identified, including CPGs, PROFUND index, LESS/CHRON criteria, and STOPP/START criteria, to extract the information. Modeling was carried out using an ontology, and mapping was done with Health Level 7 Fast Healthcare Interoperability Resources (HL7 FHIR) and Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT; International Health Terminology Standards Development Organisation). Once the CDSS was developed, validation was carried out by using a retrospective case study. RESULTS: This project was funded in January 2015 and approved by the Virgen del Rocio University Hospital ethics committee on November 24, 2015. Two different tasks were carried out to test the functioning of the tool. First, retrospective data from a real patient who met the inclusion criteria were used. Second, the analysis of an adoption model was performed through the study of the requirements and characteristics that a CDSS must meet in order to be well accepted and used by health professionals. The results are favorable and allow the proposed research to continue to the next phase. CONCLUSIONS: An ontology-based CDSS was successfully designed, developed, and validated. However, in future work, validation in a real environment should be performed to ensure the tool is usable and reliable.

A Formal Model for the FAIR4Health Information Architecture.

In the EU project FAIR4Health, a ETL pipeline for the FAIRification of structured health data as well as an agent-based, distributed query platform for the analysis of research hypotheses and the training of machine learning models were developed. The system has been successfully tested in two clinical use cases with patient data from five university hospitals. Currently, the solution is also being considered for use in other hospitals. However, configuring the system and deploying it in the local IT architecture is non-trivial and meets with understandable concerns about security. This paper presents a model for describing the information architecture based on a formal approach, the 3LGM metamodel. The model was evaluated by the developers. As a result, the clear separation of tasks and the software components that implement them as well as the rich description of interactions via interfaces were positively emphasized.

Predicting 30-Day Readmission Risk for Patients With Chronic Obstructive Pulmonary Disease Through a Federated Machine Learning Architecture on Findable, Accessible, Interoperable, and Reusable (FAIR) Data: Development and Validation Study.

BACKGROUND: Owing to the nature of health data, their sharing and reuse for research are limited by legal, technical, and ethical implications. In this sense, to address that challenge and facilitate and promote the discovery of scientific knowledge, the Findable, Accessible, Interoperable, and Reusable (FAIR) principles help organizations to share research data in a secure, appropriate, and useful way for other researchers. OBJECTIVE: The objective of this study was the FAIRification of existing health research data sets and applying a federated machine learning architecture on top of the FAIRified data sets of different health research performing organizations. The entire FAIR4Health solution was validated through the assessment of a federated model for real-time prediction of 30-day readmission risk in patients with chronic obstructive pulmonary disease (COPD). METHODS: The application of the FAIR principles on health research data sets in 3 different health care settings enabled a retrospective multicenter study for the development of specific federated machine learning models for the early prediction of 30-day readmission risk in patients with COPD. This predictive model was generated upon the FAIR4Health platform. Finally, an observational prospective study with 30 days follow-up was conducted in 2 health care centers from different countries. The same inclusion and exclusion criteria were used in both retrospective and prospective studies. RESULTS: Clinical validation was demonstrated through the implementation of federated machine learning models on top of the FAIRified data sets from different health research performing organizations. The federated model for predicting the 30-day hospital readmission risk was trained using retrospective data from 4.944 patients with COPD. The assessment of the predictive model was performed using the data of 100 recruited (22 from Spain and 78 from Serbia) out of 2070 observed (records viewed) patients during the observational prospective study, which was executed from April 2021 to September 2021. Significant accuracy (0.98) and precision (0.25) of the predictive model generated upon the FAIR4Health platform were observed. Therefore, the generated prediction of 30-day readmission risk was confirmed in 87% (87/100) of cases. CONCLUSIONS: Implementing a FAIR data policy in health research performing organizations to facilitate data sharing and reuse is relevant and needed, following the discovery, access, integration, and analysis of health research data. The FAIR4Health project proposes a technological solution in the health domain to facilitate alignment with the FAIR principles.

Hiperinfección por Strongyloides stercolaris de aparición temprana después del tratamiento corticosteroideo de un síndrome nefrótico / Hyperinfection on Strongyloides stercolaris of early appearance after corticosteroid treatment of a nephrotic syndrome

Strongyloides stercolaris es un parásito endémico de áreas tropicales que infecta a su huésped a través de la penetración transcutánea de sus larvas filariformes. Generalmente, la infección por S. stercolaris transcurre de forma asintomática; pero en un porcentaje de pacientes inmunodeprimidos puede acontecer el síndrome de hiperinfección con diversas manifestaciones. La asociación de S. stercolaris con la afectación glomerular es inusual. Se reporta el caso de una paciente de 42 años, que acudió a Urgencias por disnea y edemas. Los síntomas y hallazgos en los exámenes de laboratorio fueron compatibles con síndrome nefrótico. La paciente ingresó en Nefrología para recibir tratamiento corticoesteroideo intravenoso, así como la realización de una biopsia renal. Tras 10 días de tratamiento presentó mejoría clínica y se dio el alta a la espera de los resultados anatomopatológicos. Diez días más tarde acudió nuevamente por dolor abdominal intenso, deposiciones diarreicas y persistencia de la disnea. La paciente se diagnosticó con síndrome de hiperinfección por S. stercolaris secundario al tratamiento inmunosupresor recibido. Los síntomas se resolvieron con ivermectina y albendazol. Los resultados de la biopsia revelaron hallazgos compatibles con glomerulonefritis por cambios mínimos secundarios a la infección por S. stercolaris. Si bien la glomerulopatía suele manifestarse entre el primer y segundo mes de tratamiento inmunosupresor, en el presente trabajo se observó una aparición precoz de los síntomas respecto al resto de casos, que se manifestó en el día 21 de tratamiento corticoesteroideo(AU)

Strongyloides stercolaris is an endemic threadworm from tropical areas that infects its host through transcutaneous penetration of its filariform larvae. Generally, S. stercolaris infection is asymptomatic. However, in a percentage of immunosuppressed patients, the hyperinfection syndrome may occur, presenting constitutional symptoms, gastrointestinal, pulmonary and, sometimes, central nervous system symptoms. The association between S. stercolaris and glomerular damage is unusual. We report the case of a 42-year-old Bolivian patient, living in Spain, that came to the emergency room due to edema in lower limbs and dyspnea. Symptoms and laboratory test results were compatible with nephrotic syndrome, so she was admitted to Nephrology to receive treatment with intravenous corticosteroids, as well as a renal biopsy. After 10 days of treatment, she presented clinical improvement, so she was discharged waiting the anatomopathological results. Ten days later, she was readmitted due to severe abdominal pain, diarrhea, and persistent dyspnea. The patient was diagnosed with hyperinfection syndrome due to S. stercolaris secondary to the immunosuppressive treatment received. Symptoms resolved with ivermectin and albendazole. Biopsy results revealed findings consistent with minimal change disease secondary to S. stercolaris infection. Although glomerulopathy usually appears between the first and second month after immunosuppressive treatment, in the present study, an early appearance of symptoms was observed compared to the rest of the cases, appearing on day 21 of corticosteroid treatment(AU)

Applying the FAIR4Health Solution to Identify Multimorbidity Patterns and Their Association with Mortality through a Frequent Pattern Growth Association Algorithm.

The current availability of electronic health records represents an excellent research opportunity on multimorbidity, one of the most relevant public health problems nowadays. However, it also poses a methodological challenge due to the current lack of tools to access, harmonize and reuse research datasets. In FAIR4Health, a European Horizon 2020 project, a workflow to implement the FAIR (findability, accessibility, interoperability and reusability) principles on health datasets was developed, as well as two tools aimed at facilitating the transformation of raw datasets into FAIR ones and the preservation of data privacy. As part of this project, we conducted a multicentric retrospective observational study to apply the aforementioned FAIR implementation workflow and tools to five European health datasets for research on multimorbidity. We applied a federated frequent pattern growth association algorithm to identify the most frequent combinations of chronic diseases and their association with mortality risk. We identified several multimorbidity patterns clinically plausible and consistent with the bibliography, some of which were strongly associated with mortality. Our results show the usefulness of the solution developed in FAIR4Health to overcome the difficulties in data management and highlight the importance of implementing a FAIR data policy to accelerate responsible health research.

FAIR4Health: Findable, Accessible, Interoperable and Reusable data to foster Health Research.

Due to the nature of health data, its sharing and reuse for research are limited by ethical, legal and technical barriers. The FAIR4Health project facilitated and promoted the application of FAIR principles in health research data, derived from the publicly funded health research initiatives to make them Findable, Accessible, Interoperable, and Reusable (FAIR). To confirm the feasibility of the FAIR4Health solution, we performed two pathfinder case studies to carry out federated machine learning algorithms on FAIRified datasets from five health research organizations. The case studies demonstrated the potential impact of the developed FAIR4Health solution on health outcomes and social care research. Finally, we promoted the FAIRified data to share and reuse in the European Union Health Research community, defining an effective EU-wide strategy for the use of FAIR principles in health research and preparing the ground for a roadmap for health research institutions. This scientific report presents a general overview of the FAIR4Health solution: from the FAIRification workflow design to translate raw data/metadata to FAIR data/metadata in the health research domain to the FAIR4Health demonstrators' performance.

RGS14414-Mediated Activation of the 14-3-3ζ in Rodent Perirhinal Cortex Induces Dendritic Arborization, an Increase in Spine Number, Long-Lasting Memory Enhancement, and the Prevention of Memory Deficits.

The remedy of memory deficits has been inadequate, as all potential candidates studied thus far have shown limited to no effects and a search for an effective strategy is ongoing. Here, we show that an expression of RGS14414 in rat perirhinal cortex (PRh) produced long-lasting object recognition memory (ORM) enhancement and that this effect was mediated through the upregulation of 14-3-3ζ, which caused a boost in BDNF protein levels and increase in pyramidal neuron dendritic arborization and dendritic spine number. A knockdown of the 14-3-3ζ gene in rat or the deletion of the BDNF gene in mice caused complete loss in ORM enhancement and increase in BDNF protein levels and neuronal plasticity, indicating that 14-3-3ζ-BDNF pathway-mediated structural plasticity is an essential step in RGS14414-induced memory enhancement. We further observed that RGS14414 treatment was able to prevent deficits in recognition, spatial, and temporal memory, which are types of memory that are particularly affected in patients with memory dysfunctions, in rodent models of aging and Alzheimer's disease. These results suggest that 14-3-3ζ-BDNF pathway might play an important role in the maintenance of the synaptic structures in PRh that support memory functions and that RGS14414-mediated activation of this pathway could serve as a remedy to treat memory deficits.