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A pilot trial investigating feasibility and preliminary efficacy of a task-specific step training regimen to improve balance recovery among community-dwelling older adults
While a growing number of studies have shown positive effects of perturbation-based balance training on balance recovery after tripping, this training has employed specialized equipment that may pose a barrier for wider adoption. To address this, the purpose of this pilot trial was to evaluate the feasibility and preliminary efficacy of a novel, low-resource (i.e., not requiring specialized equipment) version of perturbation-based balance training referred to here as task-specific step training. Thirty community-dwelling older adults (mean (SD) age: 71.8 (4.4) years) were recruited and allocated to either step training ( n = 10), traditional treadmill perturbation-based balance training ( n = 10), or a control group involving no training ( n = 10). Participants were then exposed to two overground laboratory-induced trips while walking on a walkway. Results showed the step training group exhibited an initial recovery step that was 9.0% body height longer ( p < 0.001) and 0.25 m/s faster ( p = 0.011) than the control group.The step training group also exhibited a 4.8% body height longer recovery step, and a fall rate that was 39% lower ( p = 0.037) when compared to the treadmill training group after lab-induced trips. While promising, these results should be interpreted with caution give the modest sample size and a potential bias between groups with respect to safety harness usage during laboratory-induced trips. A future trial with adequate statistical power to better evaluate efficacy and effectiveness of this step training on real-world trip and fall risk appears warranted. The study was registered on clinicaltrials.gov (NCT05734443).
The quantitative proteomics analysis of multi-stage gastric mucosal lesions associated with Helicobacter pylori infection
Background Helicobacter pylori ( H. pylori ) infection is the principal etiological factor for gastric cancer (GC), which ranks as the fourth leading cause of cancer-related mortality globally. Although the Correa cascade describes the stepwise progression from chronic gastritis to intestinal-type GC, the molecular events underlying this “inflammation-to-cancer” transition remain incompletely characterized. Objective This study aimed to delineate stage-specific proteomic alterations across H. pylori -associated gastric mucosal lesions and to identify candidate progression-associated biomarkers in GC. Methods Label-free quantitative proteomic analysis (LC-MS/MS) was performed on gastric tissue specimens from 22 patients stratified into four histopathological stages: H. pylori -negative chronic non-atrophic gastritis (HpN-CG), H. pylori -positive chronic non-atrophic gastritis (HpC-CG), H. pylori -positive chronic atrophic gastritis (HpC-CAG), and intestinal-type GC. Functional enrichment (GO, KEGG), temporal clustering (Mfuzz), and protein-protein interaction (PPI) network analyses were conducted. Key hub genes were externally assessed using GEPIA RNA-seq data from TCGA and GTEx. Results A total of 6,019 proteins were quantified. Differential expression analysis identified 771 DEPs between HpC-CG and HpN-CG, 101 DEPs between HpC-CAG and HpC-CG, and 535 DEPs between GC and HpC-CAG. Immune response pathways were up-regulated upon H. pylori infection, whereas oxidative phosphorylation was progressively suppressed throughout disease progression. Mfuzz clustering revealed that Cluster 4 ribosome-biogenesis proteins, including NIP7 and PDCD11 identified in the proteomic/PPI analysis, exhibited continuous up-regulation from precancerous stages to GC. External RNA-expression validation supported significant up-regulation of seven Cluster 4 hub genes, whereas Cluster 6 proteins did not show concordant transcript-level down-regulation. Conclusion This study provides a comprehensive proteomic landscape of H. pylori -driven gastric carcinogenesis. Cluster 4 ribosome-biogenesis proteins represent candidate progression-associated protein markers requiring further protein-level validation, while the progressive decline in oxidative phosphorylation underscores mitochondrial dysfunction as a hallmark of disease progression.
Frontal brain activity assessment during basic life support skill acquisition and transfer in serious game based learning environments
Basic Life Support (BLS) is a crucial life-saving skill, and the effectiveness of different training methods for acquiring and transferring BLS knowledge and skills remains an important area of investigation. Traditional methods, such as lectures, may be less engaging and lack the practical application necessary for optimal skill transfer. New training modalities, including serious games on tablets and in virtual reality (VR) environments, offer interactive experiences, enable personalized feedback, and repetitive practice, potentially enhancing the learning process. However, the effectiveness of these newer training delivery methods on skill acquisition, transfer, and the underlying neurophysiological mechanisms needs further investigation. Hence, this study explores the effectiveness of various BLS training modalities, including traditional lecture-based instruction, tablet-based serious gaming, and VR-based serious gaming. A wearable functional near-infrared spectroscopy (fNIRS) sensory system is used to monitor prefrontal cortex (PFC) activity during training and subsequent hands-on testing. A total of 51 participants, who were randomly assigned to one of three training groups (lecture, tablet, VR), were analyzed. These participants underwent fNIRS monitoring during the training sessions and a final hands-on exam. Our findings revealed that while all three training modalities led to comparable hands-on exam performance, there were notable differences in neural activation patterns. VR-based training appeared to elicit neural responses indicative of more efficient use of cognitive resources during the hands-on test, suggesting its potential effectiveness as a practice mode for skill acquisition and transfer. These findings highlight the importance of considering both behavioral and neurophysiological metrics when assessing the efficacy of educational interventions.
Implementation, enforcement, and monitoring of tobacco advertising, promotion, and sponsorship (TAPS) laws in Ethiopia: Insights from a qualitative study
Background Tobacco advertising and promotion remain major drivers of tobacco use, particularly at points of sale (PoS). Ethiopia has enacted comprehensive tobacco control laws, including bans on TAPS at PoS. However, little is known about how these laws are implemented, monitored, and enforced in practice. This study explored the facilitators and barriers to implementing, monitoring compliance with, and enforcing TAPS laws at PoS in Ethiopia. Methods Qualitative interviews with 41 key informants were conducted between December 2022 and January 2023 across 10 purposively selected cities. Participants included policy implementers and stakeholders from government agencies, civil society organizations (CSOs), and international partners. Participants were purposively selected from national and sub-national actors involved in tobacco control, including government agencies (MoH, EFDA, Ministry of Trade, regional health and trade authorities, regulatory bodies, and research institutions) and non-governmental stakeholders (WHO Ethiopia, professional associations, and CSOs). Semi-structured interview guides were developed and administered in local languages. Interviews were audio-recorded, transcribed verbatim, translated into English, and analyzed thematically using ATLAS.ti software. Results Key facilitators included strong tobacco control laws (Proclamation No. 1112/2019), federal-level political commitment, and the national tobacco control committee (NTCC). Barriers included the absence of EFDA structures at lower administrative levels, a lack of regionally adapted tobacco control laws, limited dedicated tobacco control departments, unclear enforcement mandates, advertisement of illicit tobacco products, not being a prioritized agenda, low awareness among non-health departments and retailers, tobacco industry interference, and, in some areas, a culture that normalizes tobacco smoking. Conclusions Strong legislation banning 100% of TAPS and the presence of a national tobacco control committee support implementation; however, enforcement remains limited by structural, operational, and socio-cultural challenges. Enhancing compliance requires strengthening regional regulations, establishing clear institutional frameworks, raising stakeholder awareness about the tactics of the tobacco industry, and ensuring adequate allocation of human and financial resources, particularly in regions with a high prevalence of illicit tobacco products, to achieve the intended public health impact of TAPS laws in Ethiopia.
The quality of care for type 2 diabetes mellitus management in Malaysian primary health care settings: A scoping review of ABC (glycated haemoglobin A1c, blood pressure, and LDL-cholesterol)
Background Diabetes is a major health concern in Malaysia, yet no comprehensive review has assessed the quality of care for these patients. This study aims to systematically review published evidence on type 2 diabetes mellitus (T2DM) management in Malaysian primary health care (PHC), focusing on the achievement of glycated haemoglobin (HbA1c), blood pressure (BP), and LDL-cholesterol (LDL-C) targets (ABC control). Methods A scoping review was conducted, involving a comprehensive search of four databases (PubMed, Embase, Scopus, and MyMedR) and grey literature for publications up to December 2024. Studies were included if they reported on at least one ABC indicator among the general adult T2DM population in Malaysian PHC settings. The scoping review followed the Joanna Briggs Institute (JBI) methodology and PRISMA-ScR guidelines. EndNote was used for deduplication, and Rayyan was utilised for the screening process. Data were extracted and synthesised narratively. Results A total of 109 publications were included. Publications increased post-2010 but remained geographically concentrated in urban states. Large-scale studies heavily relied on the National Diabetes Registry. HbA1c was the most reported indicator. Findings revealed no evidence of improvement in HbA1c and BP control over two decades; achievement rates were 30–45% for HbA1c (<7.0%) and 20–50% for combined BP target (<130/80 mmHg). Conversely, LDL-C control (≤2.6 mmol/L) showed a modest improvement, with achievement rates rising from approximately 30% to 50% over a decade. Conclusion Despite a substantial increase in research, the HbA1c and BP control for T2DM in Malaysian PHC has remained static and suboptimal, highlighting a persistent gap between clinical guidelines and real-world outcomes. The modest improvement in LDL-C suggests that progress is achievable. These findings underscore the need for a balanced policy focus on all three ABC indicators, strategies to overcome systemic barriers, and continued investment in the national registry to guide evidence-based improvements in diabetes care.
From theory to practice: A case study on estimating the costs of improving animal welfare on Simmental alpine dairy farms
This case study estimates the economic implications of enhancing animal welfare (AW) in Alpine dairy farming, specifically focusing on Simmental cattle in both conventional (CON) and organic (ORG) farms. Given the increasing demand for higher welfare standards from consumers and policymakers, it is important to assess the economic feasibility of implementing these practices. The primary aim of this study is to develop a proof of concept for estimating the costs involved in meeting specific AW standards. Data were collected from 30 dairy farms (15 CON and 15 ORG), and AW scores were evaluated using both resource-based and animal-based indicators (total score of 90 points). Additionally, AW costs were assessed by calculating the cumulative additional costs, offset by potential benefits. Results show ORG farms achieve higher AW scores (73.99) compared to CON farms (70.28) but incur significantly higher production costs (€1.263/kg ECM for ORG vs. €0.977/kg ECM for CON), primarily due to the dilution effect caused by lower milk production on ORG farms. A nonlinear relationship between AW scores and AW costs was also observed, indicating that higher AW scores in initial farm conditions could, in some cases, lead to cost savings, particularly in larger and more efficient farms. The study emphasizes the need for clearly defined AW standards and a corresponding scoring system that reflects both the welfare impacts on animals and the economic feasibility for farmers. Further, we argue that the aggregation of AW scores should not merely categorize welfare on a simple best-to-worst continuum. Rather, it should account for the specific targets and conditions that policymakers and consumers are willing to support financially.
Molecular analysis and computational modeling reveal temporally separable responses triggered by DENV-induced soluble factors in endothelial cells
Dengue virus (DENV) represents a growing global health challenge with billions of people at risk. Severe Dengue (SD), a complication of DENV infection that involves generalized hemorrhage, is driven, at least in part, by endothelial dysfunction. Endothelial dysfunction refers to increased permeability due to inflammation, mechanical injury and/or modification of the genetic program of endothelial cells. Previous work showed that exposure of endothelial cells to conditioned media from DENV-infected cells (CMDV) increased permeability and cellular stiffness, repressed endothelial markers and induced mesenchymal genes. However, the generality, extent, mechanism and ultimate impact of these events in the onset of SD remain elusive. Here, we integrate analysis from in vitro treatment of endothelial cells with media containing UV-inactivated DENV with computational modeling to investigate the key features of CMDV-induced endothelial alterations and their potential impact on endothelial dysfunction. We found that CMDV increased SNA1 and CDH2 expression, while suppressing endothelial genes OCLN and CDH5 . Global transcriptomics analysis revealed that CMDV triggered a transient pro-inflammatory response, followed by induction of selected tissue repair genes and matrix remodeling. A non-directed asynchronous network model (NDAM-CMDV) identified IL6 and FN1 as central nodes of DENV-induced endothelial trans-differentiation, providing new molecular insights that predict the evolution of the disease and identify potential therapeutic targets.
Isolation and characterization of Candida metapsilosis from foci of chronic pododermatitis in captive steppe eagles in Kazakhstan
Pododermatitis (bumblefoot) is a chronic, debilitating disease of the plantar surface of the foot that affects birds of prey kept in captivity worldwide. Although bacterial pathogens, especially Staphylococcus aureus , are most commonly considered as causative agents, the contribution of opportunistic yeasts to chronic, non-healing footpad lesions remains poorly characterized. Keratinophilic yeasts may sustain the disease process by degrading keratin in superficial tissues, impairing wound healing and, owing to their thermotolerance and minimal nutritional requirements, persisting in the environment of the bird’s enclosure. In this study, three captive steppe eagles ( Aquila nipalensis ) from a single aviary in Kazakhstan, all presenting with chronic pododermatitis unresponsive to antibacterial treatment, were investigated by integrated mycological, biochemical and molecular approaches. The yeast isolates were recovered from the deep footpad lesions and identified to species level by sequencing of the ITS1-5.8S-ITS2 rDNA region. All these isolates were assigned to Candida metapsilosis , and phylogenetic analysis confirmed their close clustering with reference C. metapsilosis sequences. Phenotypic characterization showed that all isolates were thermotolerant (growth at 8–37 °C), expressed strong urease and keratinolytic activity (the latter confirmed in vitro by the hair perforation test), high saccharolytic activity and selective, weak proteolytic activity. Disk diffusion screening showed susceptibility to azoles (ketoconazole, clotrimazole, fluconazole) and reduced susceptibility to polyenes (nystatin, amphotericin B). To our knowledge, this is the first report of C. metapsilosis isolated from chronic pododermatitis lesions in captive steppe eagles. Combined with the documented in vitro virulence-associated traits and the resolution of the lesions following targeted antifungal therapy, our findings support a contributory etiological role of C. metapsilosis as an opportunistic pathogen in raptor pododermatitis in immunocompromised birds maintained under suboptimal husbandry. Mycological work-up, including molecular identification, is therefore warranted in cases of chronic, non-resolving pododermatitis in captive birds of prey.
Integrated transcriptomic analysis of LMB2-induced podocyte injury identifies conserved inflammatory and adaptive stress responses
Podocyte injury is a central driver of progressive glomerular diseases, yet the temporal organization of podocyte-intrinsic responses remains incompletely defined. In this study, we performed an integrated re-analysis of two publicly available mouse transcriptomic datasets (GSE108629 and GSE151869) to identify conserved molecular responses to LMB2-induced podocyte injury across comparable post-injury time points. Differential expression analysis was conducted independently at Day 4 and Day 7 in each dataset, followed by cross-dataset integration at each time point by identifying shared differentially expressed genes (DEGs) with consistent directionality. The resulting Day 4 and Day 7 shared gene sets were subsequently combined to define a final pooled shared DEG set. Functional enrichment, network analysis, upstream regulator prediction, and gene set enrichment analysis (GSEA) were used to characterize conserved biological processes and regulatory features. We identified 1,418 and 1,401 shared DEGs at Day 4 and Day 7, respectively, with 725 genes defining the final pooled shared DEGs set. At Day 4, the transcriptional response was characterized by inflammatory signaling and adaptive stress-related pathways, including endoplasmic reticulum stress. By Day 7, this response expanded to include extracellular matrix remodeling, focal adhesion reorganization, sustained inflammatory signaling, and downregulation of autophagy–lysosome pathways, together with disruption of ER-to-Golgi trafficking. Network analysis highlighted RELA-centered regulatory modules alongside epigenetic- and kinase-associated regulators. Collectively, these findings support a conserved, cross-dataset biphasic transcriptional response to podocyte injury, characterized by an early adaptive inflammatory phase followed by a later maladaptive state involving extracellular remodeling and impaired proteostasis. This framework provides a reproducible, temporally organized injury signature and is consistent with stage-specific pathways as potential targets for future mechanistic and therapeutic studies.
Testing standards for AI-based scores in automated essay scoring
Recent developments in the field of artificial intelligence and machine learning allow the wide application of large language models for the evaluation of written text and other non-numerical data. When applied in the context of psychological and educational assessments, such models can be used for assigning scores to essays and other types of responses. In contrast to classical tests, essays do not consist of test items, which leads to specific challenges in the evaluation of testing standards for scores obtained from AI models that differ from those observed for classical ability tests and personality questionnaires. To address these challenges, we discuss the evaluation of validity, fairness, and reliability for scores obtained from models of artificial intelligence in the context of automated essay scoring. We review existing methods, propose new methods, and further illustrate the reviewed methods with an empirical example based on the Hewlett Foundation data set on automated essay scoring. By applying the proposed framework to an evaluation based on a DistilBERT model, we find the model to be robust with sufficiently high internal consistency (Spearman-Brown coefficients in the range from .77 to .92). We further found empirical evidence for the validity of the evaluation model, but also indications for violations of fairness when comparing the human and AI scores across different topics. This study provides a standardized, replicable toolkit for researchers and practitioners to evaluate the psychometric quality of AI-based assessments.
Barriers and levers to using an app for motor function assessment by therapists in hospitals: A qualitative study of the MFM-Play app
Background The Motor Function Measure (MFM) is an important evaluation tool used to monitor the progression of most neuromuscular diseases. However, the MFM is subject to inter-rater variability, and patients must produce their best effort, which can be difficult for children. In response to these issues, we developed a digital app named MFM-Play, designed to optimise completion of the MFM in a fun manner. The objective of this study was to explore barriers and levers to the MFM-Play’s use by therapists. Method We conducted a qualitative study with rehabilitation professionals who had tested the app in a previous reliability study. Individual interviews based on the Technology Acceptance Model were followed by a focus group based on the interview results. Thematic analysis was performed on transcripts. Results Seven therapists participated in the interviews and seven others in the focus group. The results revealed the multi-dimensional features related to adopting the MFM-Play app. Barriers related to ease of use, training and organisational constraints were identified, and were partly due to the additional mental burden of learning to use the technology. However, therapists who were at ease with the digital tool found it useful for their practice. The app also modified patient-therapist dynamics, fostering greater patient autonomy, but sometimes disrupted therapists’ habits, by calling into question assessment methods. Conclusion The MFM-Play app offers considerable practical and efficiency benefits; however, its successful adoption depends on overcoming technical, organisational, and user-specific barriers. This involves providing support for the change in the therapist’s stance within the triadic patient-therapist-tablet relationship.
Herbal medicine use disclosure, database-flagged potential herb-drug interactions, and inter – interaction database concordance among patients with non-communicable diseases in Vietnam: A multicenter cross-sectional study
Background The widespread use of herbal medicines in clinical practice, particularly in Southeast Asia, presents significant challenges for medication safety management, notably regarding interactions between herbs and conventional drugs. Current drug interaction screening tools demonstrate substantial gaps in documenting herb-drug interactions, especially for regionally specific medicinal plants, creating potential risks for patients receiving concurrent therapies. Aim (1) to identify the prevalence of potential herb–drug and herb–herb interactions and the disclosure rate of HM use in patients with NCDs; and (2) to assess the consistency of interaction information across commonly used drug interaction databases. Methods An observational study enrolled 658 patients with non-communicable diseases from two Vietnamese tertiary care facilities. Structured interviews captured herbal medicine utilization patterns, disclosure practices, and specific botanical preparations used. Potential herb-drug and herb-herb interactions were systematically evaluated using four databases: Micromedex®, UpToDate Lexicomp Drug Interactions, Medscape Drug Interaction Checker, and Stockley’s Herbal Medicines Interactions. Inter-database agreement was assessed using Fleiss’ kappa statistics. Results 48.6% of participants reported active herbal medicines use, with 96% failing to disclose this to their healthcare providers. Potential interactions were identified in 31.3% of herbal medicine users, representing 15.2% of the total cohort. Database concordance was remarkably poor, with only 0.7% of interactions consistently documented across all four resources (Fleiss’ κ = –0.0653; p < 0.001). Multiple indigenous medicinal plants commonly used by patients were absent from all evaluated databases. Conclusion The substantial prevalence of undisclosed herbal medicine use, alongside inadequate representation in drug interaction databases, represents a critical gap in medication safety infrastructure. These findings demonstrated the necessity for integrating herbal medicine assessment into routine care, enhanced provider training, and expansion of clinical decision support systems to include region-specific botanical data for populations using concurrent traditional and conventional therapies.
Urate dysregulation (hyperuricemia and gout) among people living with HIV: A protocol for a systematic review and meta-analysis
Introduction Approximately 39.9 million people are living with HIV worldwide, most in sub-Saharan Africa. Effective antiretroviral therapy has shifted attention to metabolic comorbidities, and emerging evidence links integrase inhibitors such as dolutegravir to elevated serum uric acid, yet the global burden of hyperuricemia and gout in this population is unquantified. Methods and analysis This protocol describes a systematic review and meta-analysis of observational studies (cross-sectional, cohort, and case-control) published from inception to May 2026. We will search PubMed/MEDLINE, EMBASE, Web of Science, and CINAHL. Studies involving adults (≥18 years) living with HIV that report the prevalence or incidence of hyperuricemia or gout will be included. Two independent reviewers will screen studies, extract data, and assess risk of bias using the Joanna Briggs Institute Prevalence Critical Appraisal Checklist and the Newcastle-Ottawa Scale (NOS). Primary outcomes are the pooled prevalence of hyperuricemia and gout in PLHIV. Secondary outcomes include risk factors associated with urate dysregulation (ART regimen, Cluster of Differentiation 4 [CD4] count, viral load, metabolic comorbidities, and HIV duration), and gout as an immune reconstitution inflammatory syndrome (IRIS) manifestation. A random-effects meta-analysis using the DerSimonian-Laird method with Freeman-Tukey double-arcsine transformation for prevalence data will be performed in R software. Heterogeneity will be assessed using the I 2 statistic and Cochran’s Q test. Subgroup analyses will explore variation by ART class (pre-ART, PI, NNRTI, INSTI/dolutegravir era), geographic region, CD4 category, and study quality. PROSPERO Registration Number CRD420261360734.
Simulation study on matrix acidification of heterogeneous reservoirs based on seepage-acid etching coupled discrete virtual internal bond
Matrix acidification is one of the important means for carbonate reservoir modification and permeability increase, and the growth behavior of wormhole determines the effect of matrix acidification. In order to have a deeper understanding of the expansion law of acidified wormhole, this paper carried out numerical simulation of matrix acidification based on the seepage-acid etching coupled discrete virtual internal bond model, and analyzed the influence of matrix acidification on the growth and evolution of acid etched wormhole during matrix acidification in heterogeneous reservoirs. It was found that the enhancement of the heterogeneity of matrix porosity will lead to an increase in wormhole branches and complexity in the acidification process, and the corresponding acid breakthrough time will also become longer. When the anisotropy of the reservoir is strong, there are obvious master wormhole growing perpendicular to the anisotropic direction, and the wormhole morphology is relatively simple. Natural cracks have a strong guiding effect on acid etched wormhole. The results of this paper further reveal the growth law of acid etched wormhole pores, which provides a theoretical understanding for the construction of on-site matrix acidification.
Association of urate-lowering therapies with abdominal aortic aneurysm growth and clinical events in men: A population-based cohort study
Objective Abdominal aortic aneurysms (AAA) are potentially life-threatening if they rupture. Xanthine oxidase inhibitors have been suggested to reduce aneurysm growth via urate-lowering and antioxidative mechanisms, though their clinical efficacy remains uncertain. The primary objective of this prospective cohort study was to estimate potential associations between urate-lowering therapies and AAA growth, and secondarily risk of rupture, surgery, all-cause mortality, and major adverse cardiovascular events (MACE), in men aged 65–74. Design This population-based cohort study included data from two large cardiovascular screening trials. Methods The two Danish AAA male cohorts contributed with baseline characteristics, including AAA measurements through ultrasound and computed tomography scans. Participants were followed for five years through linkage with the Danish national health registries. Prescription records defined the exposure of urate-lowering therapies, and participants were categorised as users or non-users. Growth rate was examined using multivariate linear regression, and the secondary outcomes were evaluated using Cox regression. Results This study included 998 men, of whom 73 (7.3%) were exposed to urate-lowering therapies, with a mean defined daily dose of 0.377 per day. During 3 993 person-years, an insignificant mean difference of 0.28 mm/year (95%CI: −0.96–1.52, p = .66) in AAA growth was observed between users and non-users. No associations between urate-lowering therapies and risk of surgery, rupture, all-cause mortality, or MACE were observed. Conclusion The use of urate-lowering therapies was not associated with a reduction in AAA progression. These findings do not support a clinically meaningful effect of urate-lowering therapies on aneurysm progression in men with AAA.
Cardiovascular adjustments during experimentally induced retraction and locomotion in the invasive terrestrial snail Cornu aspersum (Müller, 1774)
The coupled function of physiology and behavior is crucial for generating survival responses. Generally, the cardiovascular system undergoes rapid adjustments during scape behavior to increase oxygen delivery to muscle tissues. In contrast, passive antipredator responses such as retraction in snails may impose mechanical constraints on the circulatory system. Here, we evaluated the cardiovascular response underlying the scape response (through induced retraction) and the physical activity in the invasive land snail Cornu aspersum . We quantified heart rate and heart rate variability in adult snails using laser optocardiography under the two conditions. We found that heart rate increased from retracted to the moving state and was accompanied by changes in heart rate variability and reduction of cardiac irregularities. Also, we found that locomotion intensity and body size did not influence these cardiac parameters. Our results suggest that metabolic demands, neural regulation and mechanical configuration collectively alter heart rate and heart rate variability. Thus, cardiovascular function is strongly dependent on behaviorally induced mechanical shifts in the circulatory system and on a “fight-or-flight”-like response.
Deep learning architectures for EEG-based classification of Dravet syndrome: A comparative study of pre-trained and non-pretrained hybrid CNN-LSTM models
Objective This study explores the potential of artificial intelligence (AI) using a hybrid deep learning Convolutional Neural Network–Long Short-Term Memory (CNN-LSTM) framework, for EEG-based classification and analysis of Dravet Syndrome (DS). Method The study cohort comprised nine pediatric patients with DS, confirmed through either a heterozygous pathogenic mutation in the SCN1A gene or a clinical diagnosis consistent with established diagnostic criteria. In addition, EEG recordings from age-matched healthy control subjects and pediatric patients with non-Dravet epilepsy (“abnormal” EEG) were included. Data on demographic information, seizure characteristics, developmental skills, cognitive functions, and genetic results were gathered from patient records. EEG recordings were analyzed using a subject-independent leave-one-subject-out validation strategy, spatial and temporal features by employing this model on preprocessed EEG data, effectively differentiating DS patients from Abnormal cases and healthy controls. Result Among the evaluated CNN-LSTM models, the pre-trained architecture achieved superior performance with improved stability across most subjects, with an overall accuracy of 85%, balanced accuracy of 85%, a macro-averaged F1-score of 0.85, and a macro-averaged ROC–AUC of 0.87, demonstrating stable performance for multi-class EEG classification of DS, Abnormal, and control subjects. The non-pretrained model showed reduced sensitivity and increased inter-class confusion, particularly for DS and Abnormal classes. Conclusion This study demonstrates that a pre-trained CNN-LSTM framework can support automated EEG-based classification of DS-related patterns as a proof-of-concept methodological approach, even in the context of limited subject availability. EEG-specific pretraining improves classification consistency and feature separability compared with training from scratch, highlighting the value of representation learning for rare epilepsy syndromes. Larger multi-center datasets and prospective validation will be required to assess robustness, generalizability, and clinical utility.
Global, Regional, and National Burden of chronic kidney disease in older adults from 1990 to 2021: Results from the Global Burden of Disease Study 2021
Background Drawing on data from the Global Burden of Disease (GBD) 2021 study, this research provides the first systematic assessment of the burden and trends of chronic kidney disease (CKD) among the global population aged 75 years and over between 1990 and 2021. Unlike previous studies covering the entire age spectrum, this study focuses on the age group with the highest concentration of disease burden and the greatest health vulnerability, with the aim of revealing the unique epidemiological patterns specific to this population. Methods The study methodology involved extracting data on the prevalence, incidence, mortality and disability-adjusted life years (DALYs) for chronic kidney disease (CKD) among people aged 75 years and over in 204 countries and territories from the GBD 2021 database. All reported rates are age-standardized. We calculated estimated annual percentage changes (EAPCs) to analyze trends and examined the association between the disease burden and the Sociodemographic Index (SDI). Results The study found that in 2021, approximately 127 million people aged 75 years and over worldwide were living with CKD. Between 1990 and 2021, the age-standardized prevalence declined slightly (EAPC = −0.06%; 95% UI: −0.09% – −0.03%), whilst incidence, mortality and DALY rates all rose significantly (EAPCs of 0.50%; 95% UI: 0.47%–0.53%, 1.55%; 95% UI: 1.48%–1.61% and 1.07%; 95% UI: 1.02%–1.12%, respectively), demonstrating the key phenomenon of ‘prevalence–mortality trend divergence’. The relationship between the burden of disease and socio-economic development is complex: regions with low SDI bear the heaviest burden of mortality, whilst regions with high SDI have experienced the fastest growth in mortality rates. The study also revealed significant heterogeneity in the burden across age, gender and geographical regions. Conclusions The burden of chronic kidney disease (CKD) among the global older adult population is rapidly shifting from a pattern of ‘high prevalence’ to one characterised by ‘high incidence, high mortality and high disability’, with the underlying drivers exhibiting fundamental differences across regions at various stages of development. This necessitates that public health strategies move beyond a ‘one-size-fits-all’ approach and instead develop highly age-specific and contextually tailored interventions. This study provides a detailed map for understanding the epidemiology of CKD in the context of extreme population ageing, and offers crucial evidence for the allocation of resources and the formulation of policies.
Cognitive-behavioral therapy focused on inhibitory learning, for adults with avoidant/restrictive food intake disorder (ARFID): Study protocol of a prospective study
Objective Currently, there are no evidence-based treatments available for adults with avoidant/restrictive food intake disorder (ARFID). The present paper describes the design of a study evaluating a cognitive-behavioral therapy (CBT) protocol for adults with ARFID, with a focus on exposure using inhibitory learning principles. Method This multicenter study uses a prospective, uncontrolled, repeated-measures design. A total of 120 adults (aged ≥ 18 years) with ARFID will be included via 11 participating treatment centers throughout the Netherlands. Participants will receive a manualized treatment of 25 weekly sessions. Assessments will be conducted at baseline, post-treatment, and at 1- and 12-month follow-ups. The primary outcome is ARFID severity, measured by the Pica, ARFID, and Rumination Disorder Interview (PARDI). Session-level measures of fear and expectancies will be collected throughout the treatment to explore potential mechanisms of change. Treatment effects will be examined across ARFID profiles and comorbid disorders. Discussion This is the first large-scale study to investigate an outpatient CBT program for adults with ARFID. By examining outcomes across ARFID profiles and exploring underlying mechanisms of change, the findings are expected to inform treatment refinement and provide a foundation for future controlled trials. The study has been preregistered in AsPredicted (#212,212) and the trial was registered in the Overview of Medical Research in the Netherlands (NL-OMON6121).