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Cyclic fluctuations in hypothalamic-pituitary-gonadal axis (HPG-axis) hormones exert powerful behavioral, structural, and functional effects through actions on the mammalian central nervous system. Yet, very little is known about how these fluctuations alter the structural nodes and information highways of the human brain. In a study of 30 naturally cycling women, we employed multidimensional diffusion and T1-weighted imaging during three estimated menstrual cycle phases (menses, ovulation, and mid-luteal) to investigate whether HPG-axis hormone concentrations co-fluctuate with alterations in white matter (WM) microstructure, cortical thickness (CT), and brain volume. Across the whole brain, 17β-estradiol and luteinizing hormone (LH) concentrations were directly proportional to diffusion anisotropy (μFA; 17β-estradiol: β1 = 0.145, highest density interval (HDI) = [0.211, 0.4]; LH: β1 = 0.111, HDI = [0.157, 0.364]), while follicle-stimulating hormone (FSH) was directly proportional to CT (β1 = 0 .162, HDI = [0.115, 0.678]). Within several individual regions, FSH and progesterone demonstrated opposing relationships with mean diffusivity (Diso) and CT. These regions mainly reside within the temporal and occipital lobes, with functional implications for the limbic and visual systems. Finally, progesterone was associated with increased tissue (β1 = 0.66, HDI = [0.607, 15.845]) and decreased cerebrospinal fluid (CSF; β1 = -0.749, HDI = [-11.604, -0.903]) volumes, with total brain volume remaining unchanged. These results are the first to report simultaneous brain-wide changes in human WM microstructure and CT coinciding with menstrual cycle-driven hormone rhythms. Effects were observed in both classically known HPG-axis receptor-dense regions (medial temporal lobe, prefrontal cortex) and in other regions located across frontal, occipital, temporal, and parietal lobes. Our results suggest that HPG-axis hormone fluctuations may have significant structural impacts across the entire brain.

BACKGROUND: The risk of recurrence is overestimated by the Kaplan-Meier method when competing events, such as death without recurrence, are present. Such overestimation can be avoided by using the Aalen-Johansen method, which is a direct extension of Kaplan-Meier that accounts for competing events. Meningiomas commonly occur in older individuals and have slow-growing properties, thereby warranting competing risk analysis. The extent to which competing events are considered in meningioma literature is unknown, and the consequences of using incorrect methodologies in meningioma recurrence risk analysis have not been investigated. METHODS: We surveyed articles indexed on PubMed since 2020 to assess the usage of competing risk analysis in recent meningioma literature. To compare recurrence risk estimates obtained through Kaplan-Meier and Aalen-Johansen methods, we applied our international database comprising ~ 8,000 patients with a primary meningioma collected from 42 institutions. RESULTS: Of 513 articles, 169 were eligible for full-text screening. There were 6,537 eligible cases from our PERNS database. The discrepancy between the results obtained by Kaplan-Meier and Aalen-Johansen was negligible among low-grade lesions and younger individuals. The discrepancy increased substantially in the patient groups associated with higher rates of competing events (older patients with high-grade lesions). CONCLUSION: The importance of considering competing events in recurrence risk analysis is poorly recognized as only 6% of the studies we surveyed employed Aalen-Johansen analyses. Consequently, most of the previous literature has overestimated the risk of recurrence. The overestimation was negligible for studies involving low-grade lesions in younger individuals; however, overestimation might have been substantial for studies on high-grade lesions.

Escalating vector disease burdens pose significant global health risks, as such innovative tools for targeting mosquitoes are critical. CRISPR-Cas technologies have played a crucial role in developing powerful tools for genome manipulation in various eukaryotic organisms. Although considerable efforts have focused on utilizing class II type II CRISPR-Cas9 systems for DNA targeting, these modalities are unable to target RNA molecules, limiting their utility against RNA viruses. Recently, the Cas13 family has emerged as an efficient tool for RNA targeting; however, the application of this technique in mosquitoes, particularly Aedes aegypti, has yet to be fully realized. In this study, we engineered an antiviral strategy termed REAPER (vRNA Expression Activates Poisonous Effector Ribonuclease) that leverages the programmable RNA-targeting capabilities of CRISPR-Cas13 and its potent collateral activity. REAPER remains concealed within the mosquito until an infectious blood meal is uptaken. Upon target viral RNA infection, REAPER activates, triggering programmed destruction of its target arbovirus such as chikungunya. Consequently, Cas13-mediated RNA targeting significantly reduces viral replication and viral prevalence of infection, and its promiscuous collateral activity can even kill infected mosquitoes within a few days. This innovative REAPER technology adds to an arsenal of effective molecular genetic tools to combat mosquito virus transmission.

Abstract The International Institute of Intellectual Cooperation (IIIC) was an international organisation established post-World War I, aimed to foster intellectual relations for global peace. As this institution becomes centenary, the digitisation of archival records has democratised access, sparking renewed scholar interest and eventually enabling new research avenues. Here, we examine two letter collections from IIIC’s digitised funds, focusing on administrative and artistic/literary matters. By analysing recognisable sender-receiver pairs and their geographical origins, we construct networks revealing intricate international relationships. Notably, the community structures and roles differ between administrative and literary exchanges, suggesting distinct communication dynamics. Administrative matters depict a more egalitarian distribution. In contrast, relevant literary correspondents include Western European countries exclusively, reflecting the prominence of certain geocultural areas as well as potential geopolitical influence attempts, challenging the established historical narratives on centres and peripheries, inviting a revaluation of the IIIC’s geographical organisation and intellectual cooperation during the interwar period.

Percutaneous Osseointegrated Implants (POI) affix artificial limbs to the body after amputation. Several adverse events challenge mainstream uptake of this technology. This study aims to achieve a consensus regarding “the challenges and adverse events to POI integration and long-term fixation in limb amputation”. We sought a panel of clinical experts divided by profession into surgical, clinical, or clinical academic categories. We used a real time eDelphi method to develop consensus on both the challenges and adverse event items, enabling anonymity, iteration, controlled feedback, and statistical aggregation of group responses. The full panel agreed that the most impactful items are amongst 10 key challenges and eight adverse events. Panellists were in consensus regarding the five most impactful challenges, which were, in decreasing order: patient selection, absence of a multidisciplinary team, design of the implant, soft tissue stability and an experienced surgical team. Panellists considered the five most impactful adverse events, in decreasing order, to be the following: no biological fixation, deep infection, aseptic loosening, no mechanical fixation, and implant breakage. Consensus was obtained on implant breakage and deep infection items. The proportion of consensus from the whole panel across all items was in line with the literature, and we observed an improvement in consensus once the panel was stratified based on job, expertise and implant system.

Abstract Background Polyploidisation often results in genome rearrangements that may involve changes in both the single-copy sequences and the repetitive genome fraction. In this study, we performed a comprehensive comparative analysis of repetitive DNA, with a particular focus on ribosomal DNA (rDNA), in Brachypodium hybridum (2n = 4x = 30, subgenome composition DDSS), an allotetraploid resulting from a natural cross between two diploid species that resemble the modern B. distachyon (2n = 10; DD) and B. stacei (2n = 20; SS). Taking advantage of the recurrent origin of B. hybridum, we investigated two genotypes, Bhyb26 and ABR113, differing markedly in their evolutionary age (1.4 and 0.14 Mya, respectively) and which resulted from opposite cross directions. To identify the origin of rDNA loci we employed cytogenetic and molecular methods (FISH, gCAPS and Southern hybridisation), phylogenetic and genomic approaches. Results Unlike the general maintenance of doubled gene dosage in B. hybridum, the rRNA genes showed a remarkable tendency towards diploidisation at both locus and unit levels. While the partial elimination of 35S rDNA units occurred in the younger ABR113 lineage, unidirectional elimination of the entire locus was observed in the older Bhyb26 lineage. Additionally, a novel 5S rDNA family was amplified in Bhyb26 replacing the parental units. The 35S and 5S rDNA units were preferentially eliminated from the S- and D-subgenome, respectively. Thus, in the more ancient B. hybridum lineage, Bhyb26, 5S and 35S rRNA genes are likely expressed from different subgenomes, highlighting the complexity of polyploid regulatory networks. Conclusion Comparative analyses between two B. hybridum lineages of distinct evolutionary ages revealed that although the recent lineage ABR113 exhibited an additive pattern of rDNA loci distribution, the ancient lineage Bhyb26 demonstrated a pronounced tendency toward diploidisation manifested by the reduction in the number of both 35S and 5S loci. In conclusion, the age of the allopolyploid appears to be a decisive factor in rDNA turnover in B. hybridum.

Abstract Understanding the mechanisms underlying a stable polarization at the surface of ferroelectric thin films is of particular importance both from a fundamental point of view and to achieve control of the surface polarization itself. In this study, we demonstrate that the X-ray standing wave technique allows the surface polarization profile of a ferroelectric thin film, as opposed to the average film polarity, to be probed directly. The X-ray standing wave technique provides the average Ti and Ba atomic positions, along the out-of-plane direction, near the surface of three differently strained $$\mathrm {BaTiO_3}$$ thin films. This technique gives direct access to the local ferroelectric polarization at and below the surface. By employing X-ray photoelectron spectroscopy, a detailed overview of the oxygen-containing species adsorbed on the surface is obtained. The different amplitude and orientation of the local ferroelectric polarizations are associated with surface charges attributed to different type, amount and spatial distribution of the oxygen-containing adsorbates.

Early-life stages play a key role in the dynamics of bipartite life cycle marine fish populations. Difficult to monitor, observations of these stages are often scattered in space and time. While Mediterranean coastlines have often been surveyed, no effort has been made to assemble historical observations. Here we build an exhaustive compilation of dispersal traits for coastal fish species, considering in situ observations and growth models (Di Stefano et al., 2023; https://doi.org/10.17882/91148). Our database contains over 110 000 entries collected from 1993 to 2021 in various subregions. All observations are harmonized to provide information on dates and geolocations of both spawning and settlement, along with pelagic larval durations. When applicable, missing data and associated confidence intervals are reconstructed from dynamic energy budget theory. Statistical analyses allow traits’ variability to be revisited and sampling biases to be revealed across taxa, space and time, hence providing recommendations for future studies and sampling. Comparison of observed and modelled entries provides suggestions to improve the feed of observations into models. Overall, this extensive database is a crucial step to investigate how marine fish populations respond to global changes across environmental gradients.

Abstract Background Opicapone is a third-generation catechol-O-methyl-transferase inhibitor currently used for the treatment of motor fluctuations in Parkinson’s disease. Its benefit and safety have been established by clinical trials; however, data about its use in a real-life context, and particularly in an Italian population of patients with Parkinson’s disease, are missing. Objectives We aimed to gather data about the real-life tolerability/safety of opicapone when used for the treatment of Parkinson’s disease-related motor fluctuations. Methods We enrolled 152 consecutive patients with Parkinson’s disease and followed them for 2 years after opicapone introduction. We obtained baseline clinical and demographical information, including disease duration, stage, phenotype, as well as axial and non-motor symptoms. We collected the reasons for any treatment interruption and adverse events emerging after opicapone introduction. Results Eighty-nine (58%) patients reported adverse events and 46 (30%) patients discontinued the treatment. Adverse events occurred less frequently in “earlier” patients accordingly to the disease course and l-Dopa treatment pathway; a motor fluctuation duration ≥12 months and Hoehn and Yahr scale score ≥2.5 were the main predictors of therapy withdrawal. Conclusions This study confirms the good tolerability/safety profile of opicapone in a real-life setting and provides country-specific data for Italian patients with Parkinson’s disease.

Abstract Background Systems that capture motion under laboratory conditions limit validity in real-world environments. Mobile motion capture solutions such as Inertial Measurement Units (IMUs) can progress our understanding of "real" human movement. IMU data must be validated in each application to interpret with clinical applicability; this is particularly true for diverse populations. Our IMU analysis method builds on the OpenSim IMU Inverse Kinematics toolkit integrating the Versatile Quaternion-based Filter and incorporates realistic constraints to the underlying biomechanical model. We validate our processing method against the reference standard optical motion capture in a case report with participants with transfemoral amputation fitted with a Percutaneous Osseointegrated Implant (POI) and without amputation walking over level ground. We hypothesis that by using this novel pipeline, we can validate IMU motion capture data, to a clinically acceptable degree. Results Average RMSE (across all joints) between the two systems from the participant with a unilateral transfemoral amputation (TFA) on the amputated and the intact sides were 2.35° (IQR = 1.45°) and 3.59° (IQR = 2.00°) respectively. Equivalent results in the non-amputated participant were 2.26° (IQR = 1.08°). Joint level average RMSE between the two systems from the TFA ranged from 1.66° to 3.82° and from 1.21° to 5.46° in the non-amputated participant. In plane average RMSE between the two systems from the TFA ranged from 2.17° (coronal) to 3.91° (sagittal) and from 1.96° (transverse) to 2.32° (sagittal) in the non-amputated participant. Coefficients of Multiple Correlation (CMC) results between the two systems in the TFA ranged from 0.74 to > 0.99 and from 0.72 to > 0.99 in the non-amputated participant and resulted in ‘excellent’ similarity in each data set average, in every plane and at all joint levels. Normalized RMSE between the two systems from the TFA ranged from 3.40% (knee level) to 54.54% (pelvis level) and from 2.18% to 36.01% in the non-amputated participant. Conclusions We offer a modular processing pipeline that enables the addition of extra layers, facilitates changes to the underlying biomechanical model, and can accept raw IMU data from any vendor. We successfully validate the pipeline using data, for the first time, from a TFA participant using a POI and have proved our hypothesis.

Abstract Eutrophication is a main threat to continental aquatic ecosystems. Prevention and amelioration actions have been taken under the assumption of a stable climate, which needs reconsideration. Here, we show that reduced precipitation can bring a lake ecosystem to a more productive regime even with a decline in nutrient external load. By analyzing time series of several decades in the largest lake of the Iberian Peninsula, we found autocorrelated changes in the variance of state variables (i.e., chlorophyll and oxygen) indicative of a transient situation towards a new ecosystem regime. Indeed, exceptional planktonic diatom blooms have occurred during the last few years, and the sediment record shows a shift in phytoplankton composition and an increase in nutrient retention. Reduced precipitation almost doubled the water residence time in the lake, enhancing the relevance of internal processes. This study demonstrates that ecological quality targets for aquatic ecosystems must be tailored to the changing climatic conditions for appropriate stewardship.

Abstract Artificial intelligence (AI) is revolutionizing the field of medical imaging, holding the potential to shift medicine from a reactive “sick-care” approach to a proactive focus on healthcare and prevention. The successful development of AI in this domain relies on access to large, comprehensive, and standardized real-world datasets that accurately represent diverse populations and diseases. However, images and data are sensitive, and as such, before using them in any way the data needs to be modified to protect the privacy of the patients. This paper explores the approaches in the domain of five EU projects working on the creation of ethically compliant and GDPR-regulated European medical imaging platforms, focused on cancer-related data. It presents the individual approaches to the de-identification of imaging data, and describes the problems and the solutions adopted in each case. Further, lessons learned are provided, enabling future projects to optimally handle the problem of data de-identification. Critical relevance statement This paper presents key approaches from five flagship EU projects for the de-identification of imaging and clinical data offering valuable insights and guidelines in the domain. Key Points ΑΙ models for health imaging require access to large amounts of data. Access to large imaging datasets requires an appropriate de-identification process. This paper provides de-identification guidelines from the AI for health imaging (AI4HI) projects.

Abstract Sensorimotor impairments, resulting from conditions like stroke and amputations, can profoundly impact an individual’s functional abilities and overall quality of life. Assistive and rehabilitation devices such as prostheses, exo-skeletons, and serious gaming in virtual environments can help to restore some degree of function and alleviate pain after sensorimotor impairments. Myoelectric pattern recognition (MPR) has gained popularity in the past decades as it provides superior control over said devices, and therefore efforts to facilitate and improve performance in MPR can result in better rehabilitation outcomes. One possibility to enhance MPR is to employ transcranial direct current stimulation (tDCS) to facilitate motor learning. Twelve healthy able-bodied individuals participated in this crossover study to determine the effect of tDCS on MPR performance. Baseline training was followed by two sessions of either sham or anodal tDCS using the dominant and non-dominant arms. Assignments were randomized, and the MPR task consisted of 11 different hand/wrist movements, including rest or no movement. Surface electrodes were used to record EMG and the MPR open-source platform, BioPatRec, was used for decoding motor volition in real-time. The motion test was used to evaluate performance. We hypothesized that using anodal tDCS to increase the excitability of the primary motor cortex associated with non-dominant side in able-bodied individuals, will improve motor learning and thus MPR performance. Overall, we found that tDCS enhanced MPR performance, particularly in the non-dominant side. We were able to reject the null hypothesis and improvements in the motion test’s completion rate during tDCS (28% change, p-value: 0.023) indicate its potential as an adjunctive tool to enhance MPR and motor learning. tDCS appears promising as a tool to enhance the learning phase of using assistive devices using MPR, such as myoelectric prostheses.

In this paper, we analyzed the local stability of three species in two fractional tritrophic systems, with Caputo's fractional derivative and Holling type Ⅱ and Ⅲ functional responses, when the prey density has a linear growth. To begin, we obtained the equilibria in the first octant under certain conditions for the parameters. Subsequently, through linearization and applying the Routh-Hurwitz Criterion, we concluded that only the system with Holling type Ⅲ exhibits an asymptotically stable equilibrium point, where the fractional derivative order belongs to the interval $ (0, 1] $. Finally, we obtained the solution of the system with the Holling type Ⅲ functional response, using the multistage homotopic perturbation method, and presented an example that shows the dynamics of the solutions around the stable equilibrium point.

Abstract The switching dynamics of antiferroelectric lead zirconate (PbZrO3) freestanding capacitors compared to their epitaxial counterparts is reported. Frequency dependence of hysteresis indicates that freestanding capacitors exhibit a lower dispersion of switching fields, lower residual polarization, and faster switching response as compared to epitaxially‐clamped capacitors. As a consequence, freestanding capacitor membranes exhibit better energy storage density and efficiency.

Introduction: This study aims to create an artificial intelligence (AI) based machine learning (ML) model capable of predicting a spirometric obstructive pattern using variables with the highest predictive power derived from an active case-finding program for COPD in primary care. Material and methods: A total of 1190 smokers, aged 30–80 years old with no prior history of respiratory disease, underwent spirometry with bronchodilation. The sample was analyzed using AI tools. Based on an exploratory data analysis (EDA), independent variables (according to mutual information analysis) were trained using a gradient boosting algorithm (GBT) and validated through cross-validation. Results: With an area under the curve close to unity, the model predicted a spirometric obstructive pattern using variables with the highest predictive power: FEV1_theoretical_pre values. Sensitivity: 93%. Positive predictive value: 94%. Specificity: 97%. Negative predictive value: 96%. Accuracy: 95%. Precision: 94%. Conclusion: An ML model can predict the presence of an obstructive pattern in spirometry in a primary care smoking population with no prior diagnosis of respiratory disease using the FEV1_theoretical_pre values with an accuracy and precision exceeding 90%. Further studies including clinical data and strategies for integrating AI into clinical workflow are needed. Resumen: Introducción: Este estudio tiene como objetivo crear un modelo de aprendizaje automático (ML) basado en inteligencia artificial (IA) capaz de predecir un patrón obstructivo espirométrico utilizando variables con el mayor poder predictivo derivado de un programa activo de búsqueda de casos de enfermedad pulmonar obstructiva crónica (EPOC) en Atención Primaria. Materiales y métodos: Un total de 1.190 fumadores, de entre 30 y 80 años, sin antecedentes de enfermedad respiratoria, fueron sometidos a espirometría con IA artificial. Sobre la base de un análisis de datos exploratorio (EDA), las variables independientes (según el análisis de información mutua) se entrenaron utilizando un algoritmo de gradiente de aumento (GBT) y se validaron mediante validación cruzada. Resultados: Con un área bajo la curva cercana a la unidad, el modelo predijo un patrón obstructivo espirométrico utilizando los valores del FEV1 prebroncodilatador. Sensibilidad: 93%. Valor predictivo positivo: 94%. Especificidad: 97%. Valor predictivo negativo: 96%. Precisión: 95%. Precisión: 94%. Conclusión: Un modelo ML puede predecir la presencia de un patrón obstructivo en la espirometría en una población fumadora de atención primaria sin diagnóstico previo de enfermedad respiratoria utilizando los valores FEV1 prebroncodilatadores con una exactitud y precisión superiores al 90%. Se necesitan más estudios que incluyan datos clínicos y estrategias para integrar la IA en el flujo de trabajo clínico.

BackgroundFNDs mimicking a stroke represent a growing challenge in the emergency department (ED). A comprehensive diagnostic approach involving clinical evaluation and neuroimaging is essential to differentiate stroke from mimics. The safety profile of thrombolysis justifies its use where FNDs cannot be ruled out. This approach highlights the need for more precise diagnostic tools and protocols to improve patient care and reduce unnecessary treatments. Distinguishing FNDs from actual cerebrovascular events is critical yet difficult, particularly under time constraints. Given the urgency and potential severity of strokes, intravenous thrombolysis is frequently administered even when FNDs cannot be definitively excluded.MethodsThis retrospective study analyzed data of participants admitted to the Trieste University Hospital Stroke Unit between January 2018 and December 2022, focusing on those presenting with sudden-onset focal neurological deficits mimicking a stroke, with some presenting within the reperfusion treatment window (

Despite the functional impact of cognitive deficit in people with psychosis, objective cognitive assessment is not typically part of routine clinical care. This is partly due to the length of traditional assessments and the need for a highly trained administrator. Brief, automated computerised assessments could help to address this issue. We present data from an evaluation of PsyCog, a computerised, non-verbal, mini battery of cognitive tests. Healthy Control (HC) (N = 135), Clinical High Risk (CHR) (N = 233), and First Episode Psychosis (FEP) (N = 301) participants from a multi-centre prospective study were assessed at baseline, 6 months, and 12 months. PsyCog was used to assess cognitive performance at baseline and at up to two follow-up timepoints. Mean total testing time was 35.95 min (SD = 2.87). Relative to HCs, effect sizes of performance impairments were medium to large in FEP patients (composite score G = 1.21, subtest range = 0.52–0.88) and small to medium in CHR patients (composite score G = 0.59, subtest range = 0.18–0.49). Site effects were minimal, and test-retest reliability of the PsyCog composite was good (ICC = 0.82–0.89), though some practice effects and differences in data completion between groups were found. The present implementation of PsyCog shows it to be a useful tool for assessing cognitive function in people with psychosis. Computerised cognitive assessments have the potential to facilitate the evaluation of cognition in psychosis in both research and in clinical care, though caution should still be taken in terms of implementation and study design.