Folate as a potential treatment for lethal ventricular arrhythmias in TANGO2-deficiency disorder.

TANGO2-deficiency disorder (TDD) is an autosomal-recessive genetic disease caused by biallelic loss-of-function variants in the TANGO2 gene. TDD-associated cardiac arrhythmias are recalcitrant to standard antiarrhythmic medications and constitute the leading cause of death. Disease modeling for TDD has been primarily carried out using human dermal fibroblast and, more recently, in Drosophila by multiple research groups. No human cardiomyocyte system has been reported, which greatly hinders the investigation and understanding of TDD-associated arrhythmias. Here, we established potentially novel patient-derived induced pluripotent stem cell differentiated cardiomyocyte (iPSC-CM) models that recapitulate key electrophysiological abnormalities in TDD. These electrophysiological abnormalities were rescued in iPSC-CMs with either adenoviral expression of WT-TANGO2 or correction of the pathogenic variant using CRISPR editing. Our natural history study in patients with TDD suggests that the intake of multivitamin/B complex greatly diminished the risk of cardiac crises in patients with TDD. In agreement with the clinical findings, we demonstrated that high-dose folate (vitamin B9) virtually abolishes arrhythmias in TDD iPSC-CMs and that folate's effect was blocked by the dihydrofolate reductase inhibitor methotrexate, supporting the need for intracellular folate to mediate antiarrhythmic effects. In summary, data from TDD iPSC-CM models together with clinical observations support the use of B vitamins to mitigate cardiac crises in patients with TDD, providing potentially life-saving treatment strategies during life-threatening events.

Extended haplotype with rs41524547-G defines the ancestral origin of SCA10.

Spinocerebellar ataxia type 10 (SCA10) is a rare autosomal dominant ataxia caused by a large expansion of the (ATTCT)n repeat in ATXN10. SCA10 was described in Native American and Asian individuals which prompted a search for an expanded haplotype to confirm a common ancestral origin for the expansion event. All patients with SCA10 expansions in our cohort share a single haplotype defined at the 5'-end by the minor allele of rs41524547, located ~35 kb upstream of the SCA10 expansion. Intriguingly, rs41524547 is located within the miRNA gene, MIR4762, within its DROSHA cleavage site and just outside the seed sequence for mir4792-5p. The world-wide frequency of rs41524547-G is less than 5% and found almost exclusively in the Americas and East Asia-a geographic distribution that mirrors reported SCA10 cases. We identified rs41524547-G(+) DNA from the 1000 Genomes/International Genome Sample Resource and our own general population samples and identified SCA10 repeat expansions in up to 25% of these samples. The reduced penetrance of these SCA10 expansions may be explained by a young (pre-onset) age at sample collection, a small repeat size, purity of repeat units, or the disruption of miR4762-5p function. We conclude that rs41524547-G is the most robust at-risk SNP allele for SCA10, is useful for screening of SCA10 expansions in population genetics studies and provides the most compelling evidence to date for a single, prehistoric origin of SCA10 expansions sometime prior to or during the migration of individuals across the Bering Land Bridge into the Americas.

Carbon footprint and employment generation produced by ICT networks for Internet deployment: A multi-regional input-output analysis.

Internet is widely regarded as a necessary resource for economic and social development. The availability of this technology requires the deployment of ICT networks which have implications not only on the natural surroundings but also on the human environment. Understanding the impact generated on key areas of socio-ecological concern such as carbon footprint and employment generation is essential to ensure well-informed decision-making. This investigation utilized multiregional environmentally extended input-output (MRIO) methodology to evaluate the carbon footprint and the employment generation associated with providing internet to six geo-demographic scenarios, from urban to remote rural, using Peru as a reference site. The results showed that most of the carbon emissions (289-340 kg CO2 eq./subs./yr.) and employment (7-8 jobs/subs./yr.) associated with larger ICT networks intended for urban and suburban areas was attributable to the manufacturing of end-user devices. The sustainability of smaller ICT networks for rural areas was dominated by the construction of shared infrastructures (mainly 4G LTE equipment), while the contribution of the energy consumed was in all cases limited. Although the analysis considered ICT networks deployed in Peru, most impacts were generated in China, where the manufacturing of the electronic components was assumed to take place. This analysis highlights the value of econometric methods for sustainability assessment such as MR-EEIO, which are complementary to the more conventional process-based E-LCA.

HeNeCOn: An ontology for integrative research in Head and Neck cancer.

BACKGROUND: Head and Neck Cancer (HNC) has a high incidence and prevalence in the worldwide population. The broad terminology associated with these diseases and their multimodality treatments generates large amounts of heterogeneous clinical data, which motivates the construction of a high-quality harmonization model to standardize this multi-source clinical data in terms of format and semantics. The use of ontologies and semantic techniques is a well-known approach to face this challenge. OBJECTIVE: This work aims to provide a clinically reliable data model for HNC processes during all phases of the disease: prognosis, treatment, and follow-up. Therefore, we built the first ontology specifically focused on the HNC domain, named HeNeCOn (Head and Neck Cancer Ontology). METHODS: First, an annotated dataset was established to provide a formal reference description of HNC. Then, 170 clinical variables were organized into a taxonomy, and later expanded and mapped to formalize and integrate multiple databases into the HeNeCOn ontology. The outcomes of this iterative process were reviewed and validated by clinicians and statisticians. RESULTS: HeNeCOn is an ontology consisting of 502 classes, a taxonomy with a hierarchical structure, semantic definitions of 283 medical terms and detailed relations between them, which can be used as a tool for information extraction and knowledge management. CONCLUSION: HeNeCOn is a reusable, extendible and standardized ontology which establishes a reference data model for terminology structure and standard definitions in the Head and Neck Cancer domain. This ontology allows handling both current and newly generated knowledge in Head and Neck cancer research, by means of data linking and mapping with other public ontologies.

Innovation through the Quintuple Helix in living labs: lessons learned for a transformation from lab to ecosystem.

Introduction: In the process of growing societies, and especially in the digital era we live in, there is a need for a strong push for innovation that puts citizens at the center of the process from the beginning to build more resilient, cooperative and flexible communities. Different collaborative design approaches have emerged in recent decades, one of the most interesting being Living Labs, which involves user-centered design and co-creative innovation that bring together different actors and roles. However, although these new methodologies are harnessing creativity, some aspects of this new, more ecosystemic and complex vision are not clearly understood: possible barriers, how to facilitate local and operational solutions, overcoming institutional blockage, integrating new roles, etc. Methods: The incorporation of the Quintuple Helix as a driver to ensure greater coordinated participation of local actors has proven its usefulness and impact during the re-adaptation of LifeSpace (previously named Smart House Living Lab), managed by the Polytechnic University of Madrid (Spain), a transformation based on the experiences and lessons learned during the large-scale ACTIVAGE pilot funded by the European Commission, more specifically at the Madrid Deployment Site. It involved more than 350 older adult people and other stakeholders from different areas, including family members, formal and informal caregivers, hospital service managers, third-age associations, and public service providers, forming a sense of community, which was called MAHA. Results: The living lab infrastructure evolved from a single multi-purpose environment to incorporate three harmoniously competing environments: (1) THE LAB: Headquarters for planning, demonstration, initial design phases and entry point for newcomers to the process, (2) THE CLUB: Controlled interaction environment where returning users validate solutions, focusing mainly on AHA services (MAHA CLUB), such as exergames, social interaction applications, brain training activities, etc. (3) THE NEIGHBOURHOOD: Real-life environments for free and open interaction between actors and implementation of previously validated and tested solutions. Conclusion: The Quintuple Helix model applied in LifeSpace's new vision allows a coordinated involvement of a more diverse set of actors, beyond the end-users and especially those who are not traditionally part of research and innovation processes.

GATEKEEPER's Strategy for the Multinational Large-Scale Piloting of an eHealth Platform: Tutorial on How to Identify Relevant Settings and Use Cases.

BACKGROUND: The World Health Organization's strategy toward healthy aging fosters person-centered integrated care sustained by eHealth systems. However, there is a need for standardized frameworks or platforms accommodating and interconnecting multiple of these systems while ensuring secure, relevant, fair, trust-based data sharing and use. The H2020 project GATEKEEPER aims to implement and test an open-source, European, standard-based, interoperable, and secure framework serving broad populations of aging citizens with heterogeneous health needs. OBJECTIVE: We aim to describe the rationale for the selection of an optimal group of settings for the multinational large-scale piloting of the GATEKEEPER platform. METHODS: The selection of implementation sites and reference use cases (RUCs) was based on the adoption of a double stratification pyramid reflecting the overall health of target populations and the intensity of proposed interventions; the identification of a principles guiding implementation site selection; and the elaboration of guidelines for RUC selection, ensuring clinical relevance and scientific excellence while covering the whole spectrum of citizen complexities and intervention intensities. RESULTS: Seven European countries were selected, covering Europe's geographical and socioeconomic heterogeneity: Cyprus, Germany, Greece, Italy, Poland, Spain, and the United Kingdom. These were complemented by the following 3 Asian pilots: Hong Kong, Singapore, and Taiwan. Implementation sites consisted of local ecosystems, including health care organizations and partners from industry, civil society, academia, and government, prioritizing the highly rated European Innovation Partnership on Active and Healthy Aging reference sites. RUCs covered the whole spectrum of chronic diseases, citizen complexities, and intervention intensities while privileging clinical relevance and scientific rigor. These included lifestyle-related early detection and interventions, using artificial intelligence-based digital coaches to promote healthy lifestyle and delay the onset or worsening of chronic diseases in healthy citizens; chronic obstructive pulmonary disease and heart failure decompensations management, proposing integrated care management based on advanced wearable monitoring and machine learning (ML) to predict decompensations; management of glycemic status in diabetes mellitus, based on beat to beat monitoring and short-term ML-based prediction of glycemic dynamics; treatment decision support systems for Parkinson disease, continuously monitoring motor and nonmotor complications to trigger enhanced treatment strategies; primary and secondary stroke prevention, using a coaching app and educational simulations with virtual and augmented reality; management of multimorbid older patients or patients with cancer, exploring novel chronic care models based on digital coaching, and advanced monitoring and ML; high blood pressure management, with ML-based predictions based on different intensities of monitoring through self-managed apps; and COVID-19 management, with integrated management tools limiting physical contact among actors. CONCLUSIONS: This paper provides a methodology for selecting adequate settings for the large-scale piloting of eHealth frameworks and exemplifies with the decisions taken in GATEKEEPER the current views of the WHO and European Commission while moving forward toward a European Data Space.

Feasibility study of a clinical decision support system for polymedicated patients in primary care.

Age-related changes in pharmacokinetics and pharmacodynamics, multimorbidity, frailty, and cognitive impairment represent challenges for drug treatments. Moreover, older adults are commonly exposed to polypharmacy, leading to increased risk of drug interactions and related adverse events, and higher costs for the healthcare systems. Thus, the complex task of prescribing medications to older polymedicated patients encourages the use of Clinical Decision Support Systems (CDSS). This paper evaluates the CDSS miniQ for identifying potentially inappropriate prescribing in poly-medicated older adults and assesses the usability and acceptability of the system in health care professionals, patients, and caregivers. The results of the study demonstrate that the miniQ system was useful for Primary Care physicians in significantly improving prescription, thereby reducing potentially inappropriate medication prescriptions for elderly patients. Additionally, the system was found to be beneficial for patients and their caregivers in understanding their medications, as well as usable and acceptable among healthcare professionals, patients, and caregivers, highlighting the potential to improve the prescription process and reduce errors, and enhancing the quality of care for elderly patients with polypharmacy, reducing adverse drug events, and improving medication management.

Promoting Obesity Prevention and Healthy Habits in Childhood: The OCARIoT Experience.

OBJECTIVE: Long term behavioural disturbances and interventions in healthy habits (mainly eating and physical activity) are the primary cause of childhood obesity. Current approaches for obesity prevention based on health information extraction lack the integration of multi-modal datasets and the provision of a dedicated Decision Support System (DSS) for health behaviour assessment and coaching of children. METHODS: Continuous co-creation process has been applied in the frame of the Design Thinking Methodology, involving children, educators and healthcare professional in the whole process. Such considerations were used to derive the user needs and the technical requirements needed for the conception of the Internet of Things (IoT) platform based on microservices. RESULTS: To promote the adoption of healthy habits and the prevention of the obesity onset for children (9-12 years old), the proposed solution empowers children -including families and educators- in taking control of their health by collecting and following-up real-time information about nutrition, physical activity data coming from IoT devices, and interconnecting healthcare professionals to provide a personalised coaching solution. The validation has two phases involving +400 children (control/intervention group), on four schools in three countries: Spain, Greece and Brazil. The prevalence of obesity decreased in 75.5% from baseline levels in the intervention group. The proposed solution created a positive impression and satisfaction from the technology acceptance perspective. CONCLUSIONS: Main findings confirm that this ecosystem can assess behaviours of children, motivating and guiding them towards achieving personal goals. Clinical and Translational Impact Statement-This study presents Early Research on the adoption of a smart childhood obesity caring solution adopting a multidisciplinary approach; it involves researchers from biomedical engineering, medicine, computer science, ethics and education. The solution has the potential to decrease the obesity rates in children aiming to impact to get a better global health.

Shining a light on cultural neuroscience: Recommendations on the use of fNIRS to study how sociocultural contexts shape the brain.

Functional near-infrared spectroscopy (fNIRS) is a portable neuroimaging technique that may serve as a methodological tool for studying how sociocultural contexts can shape the human brain and impact cognition and behavior. The use of fNIRS in community-based research may (a) advance theoretical knowledge in psychology and neuroscience, particularly regarding underrepresented ethnic-racial communities; (b) increase diversity in samples; and (c) provide neurobiological evidence of sociocultural factors supporting human development. The review aims to introduce the use of fNIRS, including its practicalities and limitations, to new adopters inquiring how sociocultural inputs affect the brain. The review begins with an introduction to cultural neuroscience, and a review on the use of fNIRS follows. Next, benefits and guidelines to the design of fNIRS research in naturalistic environments (in the community or in the field) using a cultural lens are discussed. Strengths-based and community-based approaches in cultural neuroscience are recommended throughout. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Analysing associations between digitalization and the accomplishment of the Sustainable Development Goals.

Sustainability is a very complex concept made up of a multitude of interacting aspects that do not necessarily work synergistically with each other. The consequential outcome of cross-cutting drivers, such as digitalisation, is often difficult to assess, as the achievement of certain targets may also inadvertently hinder progress towards others. This investigation describes a comprehensive and systematic country-based analysis of statistical associations between digitalization and sustainability indicators operating at three different levels (i.e., index, goal and indicators). Results showed strong correlations between the composite indices for digitalization (IDI Development Index), sustainability (SDG Index from) and economic growth (GCI and GDP). However, the analysis of lower-level indicators provides a more ambiguous picture, with 2 of the sustainability goals and 22 % of the sustainability indicators included in the SDG Index showing negative associations with digitalisation. It appears that while synergies are generated in aspects related to economic and social sustainability, trade-offs occur in areas related to environmental protection such as climate change, depletion of natural resources and waste generation due to their negative associations with existing economic development models. These structural obstacles need to be acknowledged and adequately managed in order to ensuring harmonious and integral progress towards effective sustainability.

Increasing diversity in developmental cognitive neuroscience: A roadmap for increasing representation in pediatric neuroimaging research.

Understanding of human brain development has advanced rapidly as the field of developmental cognitive neuroscience (DCN) has matured into an established scientific discipline. Despite substantial progress, DCN lags behind other related disciplines in terms of diverse representation, standardized reporting requirements for socio-demographic characteristics of participants in pediatric neuroimaging studies, and use of intentional sampling strategies to more accurately represent the socio-demographic, ethnic, and racial composition of the populations from which participants are sampled. Additional efforts are needed to shift DCN towards a more inclusive field that facilitates the study of individual differences across a variety of cultural and contextual experiences. In this commentary, we outline and discuss barriers within our current scientific practice (e.g., research methods) and beliefs (i.e., what constitutes good science, good scientists, and good research questions) that contribute to under-representation and limited diversity within pediatric neuroimaging studies and propose strategies to overcome those barriers. We discuss strategies to address barriers at intrapersonal, interpersonal, community, systemic, and structural levels. Highlighting strength-based models of inclusion and recognition of the value of diversity in DCN research, along with acknowledgement of the support needed to diversify the field is critical for advancing understanding of neurodevelopment and reducing health inequities.

Person-specific connectivity mapping uncovers differences of bilingual language experience on brain bases of attention in children.

Bilingualism influences children's cognition, yet bilinguals vary greatly in their dual-language experiences. To uncover sources of variation in bilingual and monolingual brain function, the present study used standard analysis and innovative person-specific connectivity models combined with a data-driven grouping algorithm. Children (ages 7-9; N = 52) completed a visuo-spatial attention task while undergoing functional near-infrared spectroscopy neuroimaging. Both bilingual and monolingual groups performed similarly, and engaged bilateral frontal and parietal regions. However, bilinguals showed greater brain activity than monolinguals in left frontal and parietal regions. Connectivity models revealed two empirically-derived subgroups. One subgroup was composed of monolinguals and bilinguals who were more English dominant, and showed left frontal-parietal connections. The other was composed of bilinguals who were balanced in their dual-language abilities and showed left frontal lobe connections. The findings inform how individual variation in early language experiences influences children's emerging cortical networks for executive function, and reveal efficacy of data-driven approaches.

Attentional orienting abilities in bilinguals: Evidence from a large infant sample.

A key question in studies of cognitive development is whether bilingual environments impact higher-cognitive functions. Inconclusive evidence in search of a "bilingual cognitive advantage" has sparked debates on the reliability of these findings. Few studies with infants have examined this question, but most of them include small samples. The current study presents evidence from a large sample of 6- and 10-month-old monolingual- and bilingual-exposed infants (N = 152), which includes a longitudinal subset (n = 31), who completed a cueing attentional orienting task. The results suggest bilingual infants showed significant developmental gains in latency performance during the condition that was most cognitively demanding (Incongruent). The results also revealed bilingual infants' performance was associated with their parents' dual-language switching behavior. Taken together, these results provide support that bilingual experiences (i.e., dual-language mixing) influence infants' shifting and orienting of attention.

Bilingualism alters infants' cortical organization for attentional orienting mechanisms.

A bilingual environment is associated with changes in the brain's structure and function. Some suggest that bilingualism also improves higher-cognitive functions in infants as young as 6-months, yet whether this effect is associated with changes in the infant brain remains unknown. In the present study, we measured brain activity using functional near-infrared spectroscopy in monolingual- and bilingual-raised 6- and 10-month-old infants. Infants completed an orienting attention task, in which a cue was presented prior to an object appearing on the same (Valid) or opposite (Invalid) side of a display. Task performance did not differ between the groups but neural activity did. At 6-months, both groups showed greater activity for Valid (> Invalid) trials in frontal regions (left hemisphere for bilinguals, right hemisphere for monolinguals). At 10-months, bilinguals showed greater activity for Invalid (> Valid) trials in bilateral frontal regions, while monolinguals showed greater brain activity for Valid (> Invalid) trials in left frontal regions. Bilinguals' brain activity trended with their parents' reporting of dual-language mixing when speaking to their child. These findings are the first to indicate how early (dual) language experience can alter the cortical organization underlying broader, non-linguistic cognitive functions during the first year of life.

Psychosomatic response to acute emotional stress in healthy students.

The multidimensionality of the stress response has shown the complexity of this phenomenon and therefore the impossibility of finding a unique biomarker among the physiological variables related to stress. An experimental study was designed and performed to guarantee the correct synchronous and concurrent measure of psychometric tests, biochemical variables and physiological features related to acute emotional stress. The population studied corresponds to a group of 120 university students between 20 and 30 years of age, with healthy habits and without a diagnosis of chronic or psychiatric illnesses. Following the protocol of the experimental pilot, each participant reached a relaxing state and a stress state in two sessions of measurement for equivalent periods. Both states are correctly achieved evidenced by the psychometric test results and the biochemical variables. A Stress Reference Scale is proposed based on these two sets of variables. Then, aiming for a non-invasive and continuous approach, the Acute Stress Model correlated to the previous scale is also proposed, supported only by physiological signals. Preliminary results support the feasibility of measuring/quantifying the stress level. Although the results are limited to the population and stimulus type, the procedure and methodological analysis used for the assessment of acute stress in young people can be extrapolated to other populations and types of stress.

Definition and development of a digital system for the empowerment and activation of type 1 diabetic patient.

Health education is essential for type 1 diabetic patients to actively participate in the decision-making process about their disease. Under the framework of the INCAP project, a mobile application has been designed and developed with an easy-to-use interface for type 1 diabetic patients to improve their empowerment, activation and thus their self-control and improvement of their treatment adherence.

Data analytics for predicting quality of life changes in head and neck cancer survivors: a scoping review.

Head and neck cancer is the seventh most common cancer worldwide. The incidence of this cancer is increasing, but at the same time, the cancer-related mortality rate has decreased over time, leaving more head and neck cancer survivors. More emphasis is needed on quality-of-life research in the head and neck cancer field to improve their daily lives and reduce the disease and treatment response burden. To achieve this, we conducted a scoping review to find and learn which predictors and data analysis techniques have been used in previous studies. This work is undertaken in the context of the BD4QoL EU Research project.

Definition of a framework for the creation of a Living Labs network: the case of the European Living Labs and Test Beds Network focused on health care domain.

This paper describes the framework for the creation of a Living Labs network based on the experience of the setting up, growth and further consolidation of the European Living Labs and Test Beds Network focused on Health. The manuscript presents how to create an open innovation ecosystem through a network of Living Labs and Test Beds, introducing its value proposition and current status.

Culturally relevant stressors as moderators of intergenerational transmission of mother-adolescent executive function in Mexican immigrant families.

The intergenerational transmission of executive function may be enhanced or interrupted by culturally salient environmental stressors that shape the practice of executive function in the family. Building upon past research, the current study tests whether culturally relevant stressors such as economic stress and foreigner stress have a direct effect on adolescent executive function, as well as whether they modify the intergenerational transmission of mother-child executive function (i.e., working memory, inhibitory control, and shifting) in low-income Mexican immigrant families. The sample consists of 179 Mexican American adolescents (Mage = 17.03 years; SDage = 0.83; 58% females) and their Mexico-born mothers (Mage = 43.25 years; SDage = 5.90). Results show that mothers' perceived economic stress is associated with poor inhibitory control in adolescents. Low levels of mothers' perceived foreigner stress related to a stronger association between mothers' and adolescents' working memory, while high levels of mothers' perceived foreigner stress related to enhanced intergenerational transmission of poor shifting ability. Study findings demonstrate the prominence of perceived foreigner stress as a contextually relevant factor moderating the intergenerational transmission of mother-child executive function in low-income Mexican immigrant families.