Search Results (5,136)

We study in detail the critical points of Bohmian flow, both in the inertial frame of reference (Y-points) and in the frames centered at the moving nodal points of the guiding wavefunction (X-points), and analyze their role in the onset of chaos in a system of two entangled qubits. We find the distances between these critical points and a moving Bohmian particle at varying levels of entanglement, with particular emphasis on the times at which chaos arises. Then, we find why some trajectories are ordered, without any chaos. Finally, we examine numerically how the Lyapunov Characteristic Number ($LCN$) depends on the degree of quantum entanglement. Our results indicate that increasing entanglement reduces the convergence time of the finite-time $LCN$ of the chaotic trajectories toward its final positive value. Full article

Background and Significances: In patients with Epstein–Barr virus-driven hemophagocytic lymphohistiocytosis (EBV-HLH), identifying the underlying cause poses a significant diagnostic challenge. HLH may precede overt disease, and early directed treatment for HLH can obscure histopathological findings. A liquid biopsy enables the detection of tumor-derived DNA from various sources, including cell-free DNA, circulating tumor cells, extracellular vesicles, and tumor-educated platelets, and might aid in this setting. Case Presentation: This case presents a young patient with EBV-HLH, in which genomic analysis of tumor-derived DNA from circulating tumor cells led to the diagnosis of an EBV-positive NK/T-cell lymphoma—where conventional tissue biopsies had failed. Conclusions: This report underscores the potential of the liquid biopsy as a valuable diagnostic tool in complex cases of EBV-HLH. Full article

Human cutaneous leishmaniasis (CL) caused by Leishmania (Viannia) braziliensis is a complex parasitic disease marked by dynamic host–parasite interactions and immunomodulation. Extracellular vesicles (EV) derived from immune cells have emerged as key mediators of intercellular communication and potential biomarkers in infectious diseases. In this study, we combined a modified lymphocyte proliferation assay with nano-flow cytometry to quantify and phenotype EV released by CD4⁺, CD8⁺, and CD14⁺ cells in PBMC cultures from CL patients at different clinical stages: before treatment (PBT), during treatment (PDT), and post-treatment (PET) with antimonial. Healthy individuals (HI) were included as physiological controls. Upon stimulation with L. (V.) braziliensis antigens, we observed a distinct modulation of EV subsets. In the PBT group, CD4⁺ and CD14⁺ EV were significantly reduced, while CD8⁺ EV remained elevated. During PDT and PET, EV concentrations were restored across all subsets. These findings suggest that L. (V.) braziliensis selectively modulates the release of immune cell–derived EV, possibly as an immune evasion mechanism. The restoration of EV release following antimonial therapy highlights their potential as sensitive biomarkers for disease activity and treatment monitoring. This study offers novel insights into the immunoregulatory roles of EV in CL and underscores their relevance in host–parasite interactions. Full article

Background: Inherited thrombophilia is increasingly recognized as a contributing factor to placental vascular pathology and adverse pregnancy outcomes. While the clinical implications are well-established, fewer studies have systematically explored the histopathological changes associated with specific genetic mutations in thrombophilic pregnancies. Materials and Methods: This retrospective observational study included two cohorts of placental samples collected between September 2020 and September 2024 at a tertiary maternity hospital. Group 1 included women diagnosed with hereditary thrombophilia, and Group 2 served as controls without known maternal pathology. Placentas were examined macroscopically and histologically, with pathologists blinded to group allocation. Histological lesions were classified according to the Amsterdam Consensus and quantified using a composite score (0–5) based on five key vascular features. Results: Placental lesions associated with maternal vascular malperfusion—including infarctions, intervillous thrombosis, stromal fibrosis, villous stasis, and acute atherosis—were significantly more frequent in the thrombophilia group (p < 0.05 for most lesions). A combination of well-established thrombophilic mutations (Factor V Leiden, Prothrombin G20210A) and other genetic polymorphisms with uncertain clinical relevance (MTHFR C677T, PAI-1 4G/4G) showed moderate-to-strong correlations with histopathological markers of placental vascular injury. A composite histological score ≥3 was significantly associated with thrombophilia (p < 0.001). Umbilical cord abnormalities, particularly altered coiling and hypertwisting, were also more prevalent in thrombophilic cases. Conclusions: Thrombophilia is associated with distinct and quantifiable placental vascular lesions, even in pregnancies without overt clinical complications. The use of a histological scoring system may aid in the retrospective identification of thrombophilia-related placental pathology and support the integration of genetic and histologic data in perinatal risk assessment. Full article

The retina offers a unique window into both ocular and systemic health, motivating the development of AI-based tools for disease screening and risk assessment. In this study, we present a comprehensive evaluation of six state-of-the-art deep neural networks, including convolutional neural networks and vision transformer architectures, on the Brazilian Multilabel Ophthalmological Dataset (BRSET), comprising 16,266 fundus images annotated for multiple clinical and demographic labels. We explored seven classification tasks: Diabetes, Diabetic Retinopathy (2-class), Diabetic Retinopathy (3-class), Hypertension, Hypertensive Retinopathy, Drusen, and Sex classification. Models were evaluated using precision, recall, F1-score, accuracy, and AUC. Among all models, the Swin-L generally delivered the best performance across scenarios for Diabetes (AUC = 0.88, weighted F1-score = 0.86), Diabetic Retinopathy (2-class) (AUC = 0.98, weighted F1-score = 0.95), Diabetic Retinopathy (3-class) (macro AUC = 0.98, weighted F1-score = 0.95), Hypertension (AUC = 0.85, weighted F1-score = 0.79), Hypertensive Retinopathy (AUC = 0.81, weighted F1-score = 0.97), Drusen detection (AUC = 0.93, weighted F1-score = 0.90), and Sex classification (AUC = 0.87, weighted F1-score = 0.80). These results reflect excellent to outstanding diagnostic performance. We also employed gradient-based saliency maps to enhance explainability and visualize decision-relevant retinal features. Our findings underscore the potential of deep learning, particularly vision transformer models, to deliver accurate, interpretable, and clinically meaningful screening tools for retinal and systemic disease detection. Full article

Background/Objectives: In many parts of the world, pharmacists hold the primary responsibility for providing safe and effective pharmacotherapy. A key aspect is the availability of appropriate medicines for each individual patient. When industrially manufactured medicines are unsuitable or unavailable, pharmacists can prepare tailor-made medicines. While this principle applies globally, practices vary between countries. In the Netherlands, the preparation of medicines in pharmacies is well-established and integrated into routine healthcare. This narrative review explores the role and significance of extemporaneous compounding, pharmacy preparations and related product care in the Netherlands. Methods: Pharmacists involved in pharmacy preparations across various professional sectors, including community and hospital pharmacies, central compounding facilities, academia, and the professional pharmacists’ organisation, provided detailed and expert insights based on the literature and policy documents while also sharing their critical perspectives. Results: We present arguments supporting the need for pharmacy preparations and examine their position and role in community and hospital pharmacies in the Netherlands. Additional topics are discussed, including the regulatory and legal framework, outsourcing, quality assurance, standardisation, education, and international context. Specific pharmacy preparation topics, often with a research component and a strong focus on product care, are highlighted, including paediatric dosage forms, swallowing difficulties and feeding tubes, hospital-at-home care, reconstitution of oncolytic drugs and biologicals, total parenteral nutrition (TPN), advanced therapy medicinal products (ATMPs), radiopharmaceuticals and optical tracers, clinical trial medication, robotisation in reconstitution, and patient-centric solid oral dosage forms. Conclusions: The widespread acceptance of pharmacy preparations in the Netherlands is the result of a unique combination of strict adherence to tailored regulations that ensure quality and safety, and patient-oriented flexibility in design, formulation, and production. This approach is further reinforced by the standardisation of a broad range of formulations and procedures across primary, secondary and tertiary care, as well as by continuous research-driven innovation to develop new medicines, formulations, and production methods. Full article

Burn injuries are complex and require effective wound management strategies. Traditional treatments, such as dermal templates, are limited by simplified extracellular matrix (ECM) composition (e.g., collagen-elastin or collagen-glycosaminoglycan), sheet-based formats, and frequent use of animal-derived materials. These limitations can reduce wound conformity, biocompatibility, and integration with host tissue. Functional hydrogels are being explored as alternatives due to properties such as high water content, biodegradability, adhesiveness, antimicrobial activity, and support for angiogenesis. Unlike standard templates, hydrogels can adapt to irregular wound shapes as in burn wounds and reach deeper tissue layers, supporting moisture retention, cell migration, and controlled drug delivery. These features may improve the wound environment and support healing in burns of varying severity. This review outlines recent developments in functional hydrogel technologies and compares them to current clinical treatments for burn care. Emphasis is placed on the structural and biological features that influence performance, including material composition, bioactivity, and integration capacity. Through an exploration of key mechanisms of action and clinical applications, this review highlights the benefits and challenges associated with hydrogel technology, providing insights into its future role in burn care. Full article

Freezing of gait (FoG) impairs mobility and daily functioning and increases the risk of falls, leading to a reduced quality of life (QoL) in people with Parkinson’s disease (PD). The Cue2walk, a wearable smart cueing device, can detect FoG and hereupon provides rhythmic cues to help people with PD manage FoG in daily life. This study investigated the user experiences and device usage of the Cue2walk, and its impact on health-related QoL, FoG and daily activities. Twenty-five users of the Cue2walk were invited to fill out an online survey, which included a modified version of the EQ-5D-5L, tailored to the use of the Cue2walk, and its scale for health-related QoL, three FoG-related questions, and a question about customer satisfaction. Sixteen users of the Cue2walk completed the survey. Average device usage per day was 9 h (SD 4). Health-related QoL significantly increased from 5.2/10 (SD 1.3) to 6.2/10 (SD 1.3) (p = 0.005), with a large effect size (Cohen’s d = 0.83). A total of 13/16 respondents reported a positive effect on FoG duration, 12/16 on falls, and 10/16 on daily activities and self-confidence. Customer satisfaction was 7.8/10 (SD 1.7). This pilot study showed that Cue2walk usage per day is high and that 15/16 respondents experienced a variety of positive effects since using the device. To validate these findings, future studies should include a larger sample size and a more extensive set of questionnaires and physical measurements monitored over time. Full article

Cystinosis is a rare systemic disease characterized by the accumulation of cystine in tissues, leading to multi-organ damage. Infantile nephropathic cystinosis is the dominant and severe form of cystinosis with critical renal manifestations that require kidney transplantation at an early age if left untreated. Cysteamine, the lifelong cystine-depleting therapy, is the mainstay treatment of nephropathic cystinosis. Cysteamine prevents cystine crystal formation and delays disease progression. While the initially introduced cysteamine consists of an immediate-release (IR) formulation, a delayed-release (DR) formulation has been developed with a simplified dosing regimen (Q12H instead of Q6H) and an improved quality of life while maintaining comparable efficacy. Due to the rare incidence of the disease and lack of international guidelines, diagnosis and treatment initiation are oftentimes delayed, leading to a poor prognosis. Pediatric and adult nephrologists from Kuwait, Saudi Arabia, the United Arab Emirates (UAE), and Qatar, in addition to one international expert from Amsterdam, convened to share their clinical experience, reflecting on the challenges encountered and therapeutic approaches followed in the management of nephropathic cystinosis in the Gulf Cooperation Council (GCC) region. Experts completed a multiple-choice questionnaire and engaged in structured discussions, where they shed light on gaps and limitations with regard to diagnostic tests and criteria to ensure early diagnosis and timely treatment initiation. Based on available literature, experts suggested an algorithm to help guide nephropathic cystinosis management in the GCC. It is highly recommended for patients who do not tolerate IR-cysteamine and do not adhere to IR-cysteamine treatment to switch to DR-cysteamine. Given the systemic nature of the disease, a multi-disciplinary approach is required for optimal disease management. Full article

Background: Falls are a major public health issue among older adults, often related to postural or orthostatic hypotension (OH). The optimal timing and methods for measuring blood pressure (BP) to assess OH and its relationship with falls are uncertain. Methods: We analyzed data from two older cohorts: the PROHEALTH study (n = 30, aged ≥ 65 years) and the NILVAD-CBF trial (n = 58, aged ≥ 50 years). Continuous beat-to-beat BP was measured during active stand tests. We assessed orthostatic BP responses during sit-to-stand and supine-to-stand maneuvers and calculated the associations between orthostatic BP response variables and falls. Results: In the PROHEALTH cohort, participants with a history of falls exhibited a significantly lower baseline BP (115 ± 13/68 ± 10 vs. 142 ± 21/79 ± 11 mmHg; p = 0.004/0.018) and lower systolic BP (SBP) nadir (90 ± 22 vs. 112 ± 25 mmHg; p = 0.043) than non-fallers. SBP recovery within three minutes post-stand was delayed in fallers but rapid in non-fallers. A lower resting BP was associated with fall risk, and a lower BP nadir within 10 s after standing showed a trend toward a higher fall risk. No significant associations were found in the NILVAD-CBF cohort (prospective falls). Conclusions: Our findings demonstrate that a lower resting SBP and diastolic BP (DBP) are associated with an increased fall risk in older adults, with a lower SBP and DBP nadir after standing also showing a potential association. Persistent OH or delayed BP recovery is identified as a potentially relevant fall risk factor. The supine-to-stand test was more sensitive in detecting OH than the sit-to-stand test. Continuous BP monitoring provides the advantage of detecting pathophysiologic orthostatic BP responses for fall risk assessment in older adults. Further research with larger cohorts is warranted to validate our findings. Full article

Since the start of the energy crisis in 2020, the Dutch government has introduced various programmes aimed at alleviating energy poverty among low-income households. This research examines the effects of three specific interventions—energy coaching, home renovations, and white goods schemes—on a range of energy poverty-related aspects, including living comfort, physical and mental health, energy costs, financial concerns, social connection, neighbourhood involvement, and sustainable behaviour. While previous studies have mostly investigated these interventions in isolation, this research offers a comparative analysis to explore how their impacts differ and how they may complement one another. This research, comparing an intervention group and control, shows that energy coaches, renovations, and white goods schemes each have positive effects on various aspects of energy poverty. However, the nature and magnitude of these effects differ by type of support measure. Renovations are the most effective overall, significantly improving living comfort, physical health, and reducing energy costs. White goods schemes primarily reduce moisture and mould in dwellings and have a notable positive impact on mental health. Energy coaches contribute to improved living comfort, lower energy costs, and uniquely enhance community involvement. The complementary nature of these interventions highlights the potential added value of integrated or combined approaches to tackling energy poverty. Full article

Anthropogenic infrastructure, such as inland wind turbines commonly found in agricultural fields, has substantially increased subterranean vibratory noise in the past decades. Plants, being rooted in soil, are continuously exposed to these vibrations, yet we have little understanding of how vibrational noise affects plant development and, consequently, plant–insect interactions. Here, we examine the impact of windmill-like vibrational noise on the growth of Pisum sativum and its full-factorial interaction with the generalist herbivore Spodoptera exigua. Plants were exposed to either high or low vibrational noise from seed germination to the seed production stage. We recorded germination, flowering, fruiting time, and daily shoot length. Additionally, we measured herbivory intensity by Spodoptera exigua caterpillars placed on a subset of plants. Plants exposed to high vibrational noise grew significantly faster and taller than those in the low-noise treatment. Additionally, we found a marginally significant trend for earlier flowering in plants exposed to high noise. We did not find a significant effect of vibrational noise on herbivory. Our results suggest that underground vibrational noise can influence plant growth rates, which may potentially have ecological and agricultural implications. Faster growth may alter interspecific competition and shift trade-offs between growth and defense. Understanding these effects is important in assessing the broader ecological consequences of renewable energy infrastructure. Full article

To enhance social interaction of residents living with dementia and their (in)formal carers in nursing homes, we examined the effects of a digital, person-centred, Photo-Activity (PA) versus a conversation activity (control). An explorative randomized controlled trial was conducted in 81 resident-informal carer (IC) dyads and 51 formal carers (FC) with three measurements (pre/post-test, 2-week follow-up). Intervention effects were tested using Mann–Whitney U’s, and ANCOVA’s with pre-test scores as covariates. Interaction effects were examined between dementia severity (DS; less/more) and condition (PA/control). A post-test effect was observed in social interaction (INTERACT-subscale: Mood [p = 0.037, ηp² = 0.07]), with PA residents showing better mood than controls. Residents with less DS showed more positive effects of PA than residents with more DS (interaction effects: INTERACT-subscales Mood [p = 0.017, ηp² = 0.092], Stimulation Level [p = 0.011, ηp² = 0.106], and Need for Prompting [p = 0.013, ηp² = 0.099]). Higher QUALIDEM Positive Affect scores were observed in the PA group, post-test (p = 0.025, ηp² = 0.082), and follow-up (p = 0.042, d = 0.39). PA FC showed less empathy (IRI; p = 0.006, ηp² = 0.185;) than controls, but reported getting to know the residents better (p = 0.035, r = 0.299). PA improved mood and positive affect of residents with dementia and led to FC knowing the residents better. Less empathy was observed in FC providing PA, requiring further investigation. Full article

Background/Objectives: Miscarriage is an increasingly common event worldwide arising from various factors, and identifying its etiology is important for planning and managing any future pregnancies. It is estimated that about half of early pregnancy loss cases are caused by genetic abnormalities, while a significantly lower rate is found in late pregnancy loss. Multiplex ligation-dependent probe amplification (MLPA) can detect small changes within a gene with precise breakpoints at the level of a single exon. The aim of our study was to identify the rate of copy number variations (CNVs) in spontaneous pregnancy loss samples after having previously tested them via quantitative fluorescence PCR (QF-PCR), with no abnormal findings. Methods: DNA was extracted from product-of-conception tissue samples, followed by the use of an MLPA kit for the detection of 31 microdeletion/microduplication syndromes (SALSA^® MLPA^® Probemix P245 Microdeletion Syndromes-1A, MRC-Holland, Amsterdam, The Netherlands). Results: A total of 11 (13.1%) out of the 84 successfully tested samples showed CNVs. Duplications accounted for 9.5% of the analyzed samples (eight cases), while heterozygous or hemizygous deletions were present in three cases (3.6%). Among all the detected CNVs, only three were certainly pathogenic (3.6%), with two deletions associated with DiGeorge-2 syndrome and Rett syndrome, respectively, and a 2q23.1 microduplication syndrome, all detected in early pregnancy loss samples. For the remaining cases, additional genetic tests (e.g., aCGH/SNP microarray) are required to establish CNV size and gene content and therefore their pathogenicity. Conclusions: MLPA assays seem to have limited value in detecting supplementary chromosomal abnormalities in miscarriages. Full article

Hospital layouts play a critical role in supporting efficient care processes, which are continually evolving. While care processes adapt over time, the spatial needs of care professionals are expected to remain relatively stable. This study proposes an evaluation framework combining cognitive mapping and space syntax analysis (SSA) to assess how hospital layouts align with these spatial needs. The framework is applied to a real-world emergency department (ED) with two distinct layout configurations. Cognitive mapping captures spatial needs from the perspective of care professionals, while SSA evaluates how the layout supports or constrains these needs. Drawing on the open building approach, we interpret layout adaptability through a layered system of primary (rigid), secondary (adaptable), and tertiary (care process) levels. Our results show that the choices in primary and secondary system designs can limit the functionality of the tertiary system. This approach supports informed decision-making by addressing multiple spatial needs simultaneously, offering insights into the coherence between spatial configuration and care delivery, and enabling quantitative comparison across different layout designs. Full article