Endocrinologic Dysfunctions and Neuropsychiatric Sequelae in Pediatric Patients With a History of Central Nervous System Infection (ENDLESS):A Prospective Monocentric Study

Introduction: Central nervous system (CNS) infections represent some of the most critical pediatric health challenges, characterized by high mortality rates and a notable risk of long-term complications. Despite their significance, standardized guidelines for endocrinological follow-up of CNS infection survivors are lacking, leading to reliance on the expertise of individual centers and clinicians. Materials and Methods: Prospective monocentric observational study conducted at the Fondazione Policlinico Universitario Agostino Gemelli in Rome, Italy. It included patients with a history of CNS infection, admitted to various pediatric departments of the hospital. The participants were selected based on a coded diagnosis of CNS infection and had completed their follow-up at the Pediatric Endocrinology Day Hospital after October 2019. Results: Eighty participants were included, comprising 53 patients with a prior CNS infection and 27 healthy controls, with a median age of 7.4 years (range 3.6–12.3 years). Endocrinologic alterations were detected in 13 patients, with 8 cases in those who had meningitis, 4 in encephalitis survivors, and 1 in a patient with a cerebral abscess. Patients with a history of CNS infections were shorter compared with healthy controls (P = 0.027). Moreover, those who had meningitis exhibited an increased risk of developing epilepsy (P = 0.01), neurosensory disabilities (P = 0.034) and the need for ventriculoperitoneal shunt insertion (P = 0.006). Patients with bacterial CNS infections were more prone to neurosensory and endocrine dysfunctions compared to those with viral or other infections. Significant differences were observed in hormone levels between previously infected patients and controls, specifically in TSH (P &lt; 0.001), ACTH (P = &lt;0.001), and cortisol (P = 0.019). IGF-1 levels were considerably lower in the infection group, both in absolute terms and when adjusted for sex and age (P &lt; 0.001). The regression analysis suggested that the reduction in IGF-1 was more pronounced the earlier the CNS infection occurred, irrespective of infection type. Conclusions: Our study found several endocrinologic imbalances in children who survived CNS infections.</p

Epigallocatechin-3-gallate binds tandem RNA recognition motifs of TDP-43 and inhibits its aggregation

Transactive response DNA-binding Protein 43 (TDP-43) aggregation is a key pathological feature in Amyotrophic Lateral Sclerosis and related neurodegenerative diseases. This study investigates the inhibitory effects of Epigallocatechin-3-gallate (EGCG), a polyphenol found in green tea, on TDP-43 aggregation. Using a combination of fluorescence assays, NMR spectroscopy, and computational modeling, we demonstrate that Epigallocatechin-3-gallate significantly delays the nucleation phase of TDP-43 aggregation process, thus inhibiting the formation of TDP-43 aggregates in vitro. Additionally, we proved a direct interaction of the compound with the RNA recognition motifs of TDP-43 and modeled the mechanism of interaction. Our findings reveal that EGCG stabilizes the RRM domains, counteracting aggregation by interfering with the early stages of the amyloidogenic pathway. Furthermore, EGCG's stability under experimental conditions was ensured using reducing agents, highlighting the importance of maintaining its reduced form for reproducible results. These insights underscore the therapeutic potential of EGCG in TDP-43 proteinopathies and provide a foundation for developing targeted treatments for ALS and related disorders.</p

Post-COVID-19 Condition Prediction in Hospitalised Cancer Patients:A Machine Learning-Based Approach

BACKGROUND: The COVID-19 pandemic has led to widespread long-term complications, known as post-COVID conditions (PCC), particularly affecting vulnerable populations such as cancer patients. This study aims to predict the incidence of PCC in hospitalised cancer patients using the data from a longitudinal cohort study conducted in four major university hospitals in Moscow, Russia.METHODS: Clinical data have been collected during the acute phase and follow-ups at 6 and 12 months post-discharge. A total of 49 clinical features were evaluated, and machine learning classifiers including logistic regression, random forest, support vector machine (SVM), k-nearest neighbours (KNN), and neural network were applied to predict PCC.RESULTS: Model performance was assessed using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. KNN demonstrated the highest predictive performance, with an AUC of 0.80, sensitivity of 0.73, and specificity of 0.69. Severe COVID-19 and pre-existing comorbidities were significant predictors of PCC.CONCLUSIONS: Machine learning models, particularly KNN, showed some promise in predicting PCC in cancer patients, offering the potential for early intervention and personalised care. These findings emphasise the importance of long-term monitoring for cancer patients recovering from COVID-19 to mitigate PCC impact.</p

Fatigue-creep design of transpiration cooled nickel gas turbine blades via low order aerothermal-stress and crystal plasticity finite element modelling

Transpiration Cooling (TC) systems can substantially improve the fuel efficiency of jet engines by allowing them to run much hotter than current designs allow. However, TC systems require radically new designs where large cyclic thermomechanical stresses and creep-plastic deformation can limit the life of core components. This can only be mitigated through integrated design approaches which simultaneously consider the aerothermal and mechanical performance. We develop here a low order aerothermal-stress model (LOM) which combines first order coolant flow and fluid-solid convective-conductive heat transfer calculations with stress calculations in the solid. The LOM provides rapid answers to crucial design questions: how much cooling air and how many cooling holes are required in gas turbine blades for them to operate safely at a given turbine inlet (hot gas) temperature? The LOM also narrows the range of conditions under which Crystal Plasticity Finite Element (CPFE) simulations may be required for fatigue-creep life assessment at final design stages. Our answer to previous pessimistic views on the practical use of TC is that TC systems can actually work thanks to the threefold benefit of cooling holes in reducing metal temperatures, temperature gradients and effective thermal stresses. CPFE simulations confirm this new conclusion, encouraging the wider use of our hybrid design strategy in turbomachines, hypersonic technologies and fusion reactors as well as the take-up of TC systems to deliver durable hydrogen-fuelled turbines for Net Zero.</p

The effects of recent stressful life events on outcomes in individuals at clinical high risk for psychosis:results from the longitudinal EU-GEI high-risk study

BACKGROUND: Recent stressful life events (SLE) are a risk factor for psychosis, but limited research has explored how SLEs affect individuals at clinical high risk (CHR) for psychosis. The current study investigated the longitudinal effects of SLEs on functioning and symptom severity in CHR individuals, where we hypothesized CHR would report more SLEs than healthy controls (HC), and SLEs would be associated with poorer outcomes.METHODS: The study used longitudinal data from the EU-GEI High Risk study. Data from 331 CHR participants were analyzed to examine the effects of SLEs on changes in functioning, positive and negative symptoms over a 2-year follow-up. We compared the prevalence of SLEs between CHR and HCs, and between CHR who did (CHR-T) and did not (CHR-NT) transition to psychosis.RESULTS: CHR reported 1.44 more SLEs than HC ( p &lt; 0.001), but there was no difference in SLEs between CHR-T and CHR-NT at baseline. Recent SLEs were associated with poorer functioning and more severe positive and negative symptoms in CHR individuals (all p &lt; 0.01) but did not reveal a significant interaction with time. CONCLUSIONS: CHR individuals who had experienced recent SLEs exhibited poorer functioning and more severe symptoms. However, as the interaction between SLEs and time was not significant, this suggests SLEs did not contribute to a worsening of symptoms and functioning over the study period. SLEs could be a key risk factor to becoming CHR for psychosis, however further work is required to inform when early intervention strategies mitigating against the effects of stress are most effective.</p

Association between Adverse Childhood Experiences and long-term outcomes in people at Clinical High-Risk for Psychosis

Adverse childhood experiences (ACEs) are common in people at clinical high-risk for psychosis (CHR), however, the relationship between ACEs and long-term clinical outcomes is still unclear. This study examined associations between ACEs and clinical outcomes in CHR individuals. 344 CHR individuals and 67 healthy controls (HC) were assessed using the Childhood Trauma Questionnaire (CTQ), the Bullying Questionnaire and the Childhood Experience of Care and Abuse (CECA). CHR were followed up for up to 5 years. Remission from the CHR state, transition to psychosis (both defined with the Comprehensive Assessment of an At Risk Mental State), and level of functioning (assessed with the Global Assessment of Functioning) were assessed. Stepwise and multilevel logistic regression models were used to investigate the relationship between ACEs and outcomes. ACEs were significantly more prevalent in CHR individuals than in HC. Within the CHR cohort, physical abuse was associated with a reduced likelihood of remission (OR = 3.64, p = 0.025). Separation from a parent was linked to an increased likelihood of both remission (OR = 0.32, p = 0.011) and higher level of functioning (OR = 1.77, p = 0.040). Death of a parent (OR = 1.87, p = 0.037) was associated with an increased risk of transitioning to psychosis. Physical abuse and death of a parent are related to adverse long-term outcomes in CHR. The counter-intuitive association between separation from a parent and outcomes may reflect the removal of a child from an adverse environment. Future studies should investigate whether interventions targeting the effect of specific ACEs might help to improve outcomes in this population.</p

Smartphone apps for mental health:systematic review of the literature and five recommendations for clinical translation

OBJECTIVES: Providing adequate access to mental health services is a global challenge. Smartphone apps offer a potentially cost-effective, available and accessible solution for monitoring, supporting and treating mental health conditions. This systematic review describes and evaluates the usage of smartphone apps across a wide range of mental health disorders in terms of clinical effectiveness, feasibility and acceptability.DESIGN: This is a systematic review of studies examining treatment, self-monitoring and multipurpose smartphone apps for mental health disorders.DATA SOURCES: Studies were identified through a comprehensive search of the Ovid and PubMed databases. Articles published up to 14 January 2024 were included based on predefined criteria.ELIGIBILITY CRITERIA: We included randomised controlled trials that compared mental health apps (single- or multipurpose) with treatment-as-usual or no treatment for clinical populations with mental health disorders. Studies were excluded if they focused on web-based interventions, combined apps with non-TAU treatments or targeted physical health apps.DATA EXTRACTION AND SYNTHESIS: Two independent reviewers screened and selected studies, with a third reviewer resolving inconsistencies. Extracted data included study details, participant characteristics, app information and outcome measures related to effectiveness, feasibility and acceptability. A risk-of-bias assessment for each study was conducted.RESULTS: Out of 4153 non-duplicate articles screened, 31 studies met full-text eligibility criteria. These included 6 studies on treatment apps, 4 on self-monitoring apps and 21 on multipurpose apps for a range of mental health disorders. Fifteen were identified as having between some and high concern on the risk-of-bias assessment. While smartphone apps were generally effective and acceptable, their feasibility appeared to decline over time.CONCLUSIONS: Smartphone apps are promising tools for mental healthcare, demonstrating effectiveness and acceptability. However, challenges such as reduced feasibility over time, potential biases and underrepresented demographics require further research. This review proposes five recommendations for improving clinical translation in future studies.</p

A vaccine central in A(H5) influenza antigenic space confers broad immunity

Highly pathogenic avian influenza A(H5) viruses globally impact wild and domestic birds, and have caused severe infections in mammals, including humans, underscoring their pandemic potential1, 2, 3, 4–5. The antigenic evolution of the A(H5) haemagglutinin (HA) poses challenges for pandemic preparedness and vaccine design6. Here the global antigenic evolution of the A(H5) HA was captured in a high-resolution antigenic map. The map was used to design immunogenic and antigenically central vaccine HA antigens, eliciting antibody responses that broadly cover the A(H5) antigenic space. In ferrets, a central antigen protected as well as homologous vaccines against heterologous infection with two antigenically distinct viruses. This work showcases the rational design of subtype-wide influenza A(H5) pre-pandemic vaccines and demonstrates the value of antigenic maps for the evaluation of vaccine-induced immune responses through antibody profiles.</p

Introduction:Beyond public reason

This introduction situates the special issue within longstanding debates on liberal public reason, tracing its Enlightenment roots through Habermas and Rawls to contemporary political dilemmas. It highlights how anthropology has revealed the exclusions embedded in public reason's universalist claims, particularly for those marginalized by culture, race, gender, class, or religion. We argue that liberal public reason has become both a hegemonic philosophy and a globalized pedagogical tool of governance, yet its assumptions about rationality, abstraction, and secularism often obscure or delegitimize alternative modes of political communication and ethical life. This introduction outlines how the essays collected here explore immanent social projects that do not merely critique liberalism from its margins but enact alternative public reasoning grounded in vernacular, embodied, and relational practices. These projects arise both within and beyond liberal institutions, offering political horizons not overdetermined by liberal assumptions. The authors advocate moving beyond frameworks that juxtapose liberalism with its ‘illiberal’ others, emphasizing anthropology's potential to illuminate diverse forms of public deliberation that exceed these binaries. Finally, the introduction argues that by attending ethnographically to these alternative practices, from community organizing to legal reasoning, from embodied solidarity to spiritual claims, we can rethink public reason as plural, situated, and capable of addressing deep difference without demanding assimilation to liberal norms.</p

Telecommuting and division of domestic work:the role of gender role attitudes in Germany

Telecommuting is often portrayed as a work-life balance measure. Though, in theory, telecommuting can provide workers with more time for leisure and family, due to the boundary blurring between work and life spheres, it can exacerbate gender inequalities by pushing women to carry out more domestic work while increasing men’s time in paid work. Empirically, the evidence is mixed. We extend the debate by exploring how individuals’ gender role attitudes (GRA) moderate the relationship between telecommuting and the division of domestic work. We apply hybrid models to the German Family Panel data. The data covers the timespan from 2008 to 2021, which includes the unique COVID-19 pandemic. Results show that GRA matter. When getting access to telecommuting, egalitarian men increased their contribution to childcare, while traditional men did not. Similarly, telecommuting traditional women increased their childcare contribution. The pattern remained the same during the expansion of telecommuting due to the COVID-19 pandemic: only telecommuting traditional women and telecommuting egalitarian men increased their childcare contribution. The results of this study suggest that telecommuting has the potential to serve as a ‘great equaliser’. However, achieving this requires actively promoting more egalitarian views on gender roles.<br/