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Peripheral and CSF protein quantification in Parkinson’s disease and multiple system atrophy - the Nucleic acid Linked Immuno-Sandwich Assay
No full textThere are currently no validated peripheral biomarkers for the diagnosis, differentiation or progression of the neurodegenerative synucleinopathies, Parkinson’s disease (PD) and multiple system atrophy (MSA). Diagnostic biomarkers that reflect the disease mechanisms, or progression biomarkers that change with disease severity would be extremely valuable for assessing disease modifying therapies. Our objective was to explore putative protein biomarkers of PD and MSA, in relation to clinical disease severity, using Nucleic Acid Linked Immuno-Sandwich Assay (NULISA) central nervous system disease panel for biomarker quantification.
We used the NULISA CNS disease panel to test plasma from 161 PD patients collected at 3 timepoints (0, 48, 96 weeks) and serum from 43 MSA patients at 3 timepoints (0, 24, 48 weeks) and compared results to paired plasma and serum samples collected from (n=39) age matched healthy control (HC) individuals at a single timepoint. We also tested paired CSF samples collected on 2 occasions, separated by 96 weeks from a subgroup of PD (n=51) and after an interval of 48 weeks in a subgroup MSA (n=23) participants. All samples were taken contemporaneously with objective clinical assessments of disease severity. Biomarker comparisons were made across disease status, and in relation to disease severity using linear modelling.
Multiple proteins showed significantly different quantitative levels (False Discovery Rate (FDR) corrected p value <0.05) between peripheral samples from PD and HC, and MSA and HC. For PD, we identified three key classes of proteins that showed significant differences between PD and controls: (i) Amyloidogenic proteins, specifically, oligomeric alpha-synuclein was significantly higher in PD compared to controls. A number of other aggregating proteins also exhibited differences. (ii) Metabolic pathways, including the adipokine (Chemokine-like protein TAFA-5) were associated with PD diagnosis and (iii) Inflammatory pathways (Interleukin-7) were associated with PD diagnosis. Importantly, some of these same proteins were significantly associated with PD severity including oligomeric and phosphorylated forms of alpha-synuclein and Insulin-like Growth Factor-1 receptor. We also confirmed as expected that Neurofilament Light levels strongly distinguish MSA patients from HC, while also demonstrating that serum inflammatory proteins (Interleukin-6) as well as the phosphorylated alpha synuclein ratio are strongly associated with MSA severity.
These results from the NULISA multiplex platform provide additional insights into the complex pathogenetic mechanisms associated with alpha-synucleinopathy related neurodegeneration. Individual protein levels or the combination of multiple protein candidates may usefully serve as diagnostic biomarkers, or as biomarkers for disease progression in trials of potential disease modifying interventions
A multi-strain probiotic modulates gut microbiome composition, intestinal barrier integrity and inflammation in a multi-compartmental in vitro gut model of decompensated alcohol-related advanced chronic liver disease
No full textDecompensated advanced chronic liver disease (dACLD), which is defined by the onset and worsening of clinical complications that require hospitalisation and can lead to organ dysfunction, is patho-biologically characterised by an altered gut microbiome composition and function, intestinal barrier failure, immune dysfunction and systemic inflammation. The gut microbiome represents a promising therapeutic target in dACLD to prevent the onset of such life-threatening clinical complications. We investigated the effect of a live, multi-strain, aqueous probiotic suspension (Symprove™) on faecal material from three people with alcohol-related dACLD utilising an advanced in vitro gut model. We evaluated the impact of Symprove™ on mucosal and luminal bacterial microbiome diversity after 48 h by 16S rRNA gene sequencing. The effect on epithelial tight-junction (TJ) integrity was estimated using transepithelial electrical resistance measurement. We quantified metabolites, anti-inflammatory markers, chemokines and epithelial wound healing pre- and post-treatment in cell culture models. The relative proportions of the main bacterial phyla differed from those of healthy subjects studied previously: levels of Firmicutes decreased and Bacteroidetes increased. Dosing with Symprove™ resulted in faecal microbiome modulation over a 48-h period. Several other surrogate indicators of gut barrier integrity and mucosal immunity improved with Symprove™ exposure; estimated TJ integrity and epithelial wound healing improved. Short chain fatty acids and anti-inflammatory cytokine production (IL-6 and IL-10) increased, whilst pro-inflammatory chemokines (MCP-1 and IL-8) decreased. These data support SymproveTM as a potential microbiome-targeting therapeutic for patients with dACLD, to prevent clinical complications, and warrants further investigation
Inhalable Curcumin–Sodium Cholesteryl Sulfate (Cur–SCS) nanoparticles: A dry powder formulation for targeted lung cancer therapy
No full textLung cancer, particularly non-small cell lung cancer (NSCLC), remains a principal cause of cancer-related mortality worldwide. Despite advances in targeted and immunotherapeutic approaches, poor drug solubility, significant systemic toxicity, and emerging drug resistance continue to limit the effectiveness of currently available treatments. In this work, we sought to develop and characterize an inhalable dry powder formulation of curcumin complexed with sodium cholesteryl sulfate (Cur–SCS) to facilitate localized therapy against NSCLC. Curcumin was complexed with sodium cholesteryl sulfate at a 1:2 M ratio using a thin-film hydration method and was subsequently spray-dried in the presence of L-leucine and lactose to improve aerosolization properties. Physicochemical parameters, including particle size distribution, zeta potential and the fine particle fraction (FPF) following aerosolization, were measured, and in vitro cytotoxicity was assessed in A549 lung cancer cells. Solid-state characterization using X-ray diffraction (XRD), and differential scanning calorimetry (DSC) was also performed. The resulting Cur–SCS nanoparticles exhibited an average size of 175–186 nm, a zeta potential between −54 and −57 mV, and, when spray-dried with appropriate excipients, achieved an FPF of approximately 53.7 % and a mass median aerodynamic diameter (MMAD) of 2.38 μm—suitable for deep lung deposition. The aqueous solubility of curcumin was enhanced from less than 0.6 μg/mL to approximately 0.8 mg/mL, corresponding to an increase of over 1000-fold. Cytotoxicity studies revealed an IC50 of 28.7 μM against A549 cells, which was comparable to curcumin dissolved in DMSO (33.3 μM). XRD and DSC analyses indicated that curcumin adopted an amorphous or partially amorphous form in the complex, thereby favouring improved dispersibility. Collectively, these findings support the feasibility of Cur–SCS dry powder as an inhalable lung cancer therapy. Further in vivo studies are recommended to confirm pharmacokinetics, lung deposition, and efficacy
Bioimpedance-Driven Haptic Feedback for Human-Computer Interaction
No full textThis work presents a novel method for establishing a feedback loop in future human-computer interactions by using bioimpedance measurements to enhance the sense of physical engagement. The proposed system consists of a bioimpedance measurement unit, a vibration motor, an inertial measurement unit (IMU) and a Bluetooth wireless communication module. By measuring the bioimpedance of flexor digitorum muscles, the system estimates the hand's grasping angle and applied force independently. To address the drift commonly observed in long-term bioimpedance measurements, the rate of change in bioimpedance is used instead of absolute values. The bioimpedance change rate-based method achieved a linear coefficient of determination (R2) of 0.9845. Vibration motor rotational speed is then modulated in real time based on either the estimated hand grasping angle or force magnitude, depending on the application. The proposed haptic feedback bridges a key limitation of traditional vision-based interaction methods, which are unable to detect force, thereby enabling a more immersive interaction experience. The entire system is implemented as a wearable Bluetooth human interface device (HID), ensuring compatibility with a range of commercial consumer electronics
Quantum Skyshield: Quantum Key Distribution and Post-Quantum Authentication for Low-Altitude Wireless Networks in Adverse Skies
No full textRecently, low-altitude wireless networks (LAWNs) have emerged as a critical backbone for supporting the low-altitude economy, particularly with the densification of unmanned aerial vehicles (UAVs) and high-altitude platforms (HAPs). To meet growing data demands, some LAWN deployments incorporate free-space optical (FSO) links, which offer exceptional bandwidth and beam directivity. However, without strong security measures in place, both conventional radio frequency channels and FSO beams remain vulnerable to interception and spoofing, and FSO in particular can suffer from turbulence, misalignment, and weather-related attenuation. To address these challenges in the quantum era, a quantum-secure architecture called Quantum Skyshield is proposed to enable reliable communication between the base transceiver station (BTS) and LAWN. The proposed design integrates BB84 quantum key distribution (QKD) with post-quantum authentication mechanisms. Simulation results confirm the reliable generation of a 128-bit symmetric key when the quantum bit error rate (QBER) remains below the threshold of 11%. Authentication is enforced using Lamport one-time signatures and hash-based message authentication codes (HMAC) to ensure message integrity. A Grover-inspired threat detection mechanism identifies anomalies with up to 89% probability in a single iteration, enabling real-time trust evaluation. Lastly, future research challenges have also been identified and discussed to guide further development in this area
Longitudinal development and interrelations of motivation, ethnic identity, and self-perceived proficiency among adolescent Chinese heritage learners in Belgium
No full textThis study examines the longitudinal development and interrelations of motivation, ethnic identity, and self-perceived proficiency in Chinese among 46 adolescent Chinese heritage language learners attending Chinese language schools in Belgium. Using four waves of data collected over two academic years, the study first examined changes in the three constructs. Although group-level analyses showed overall stability, qualitative responses revealed meaningful individual-level fluctuations in both motivation and ethnic identity. Cross-lagged analyses then assessed how the constructs influenced one another over time. Motivation and ethnic identity demonstrated reciprocal longitudinal effects, indicating that each contributes to the other’s development. Motivation and self-perceived proficiency were connected mainly through concurrent associations, suggesting immediate but not lasting links. By contrast, ethnic identity and perceived proficiency showed moderately positive correlations without predictive effects. These findings provide the first longitudinal evidence from Europe-based Chinese language school contexts on how the three constructs evolve and interact. They underscore the importance of pedagogical practices that foster ethnic identity, sustain motivation, and build learners’ confidence in their heritage language proficiency, which together shape adolescents’ heritage language learning process
Urban forests but NIMBY (Not In My Backyard): Evidence from tree proximity, characteristics, and house values in Sydney, Australia
No full textThis study utilises a micro-level property sale dataset alongside detailed tree data from 2021 to 2024 in the City of Sydney, Australia, to investigate how the proximity and characteristics of public street and park trees, including their numbers, species, canopy size, height, and maturity, affect house sale prices. We find that public trees generally enhance property values, provided they are not located within 10 m of the parcel centroid. Specifically, more mature street and park trees with larger canopies and greater heights within 10–20 m increase house prices, while certain species such as Brush Box, London Plane, and Tuckeroo can reduce prices if planted too close (<10 m), but increase sale prices when situated further away within 10–20 m. Beyond 20 m, public trees show no significant effect on house prices. A novel contribution of this research is the detailed analysis of trees and properties, offering empirical evidence of NIMBY attitudes within urban forestry programs. More importantly, we provide precise estimates of the proximity at which such NIMBY effects emerge. This insight is essential for developing city-wide urban forestry strategies and targets, highlighting the potential for resistance to urban greening projects when cities facing population increase and urban intensification
Long-term outcomes of paediatric craniopharyngiomas: a comparison of two large international series
No full textPurpose
Adamantinomatous craniopharyngioma (ACP) is an uncommon and anatomically variable tumor in children. The balance between critical treatment objectives, including the pursuit of gross total surgical resection and the reduction of hypothalamic injury and tumor recurrence, remains difficult and controversial. In this retrospective observational study, we compare the management and outcome of ACP in two large paediatric neurosurgical centres to determine how variations in tumor characteristics and management influence long-term outcomes.
Methods
In this retrospective observational study, consecutive children (aged ≤ 18 years) diagnosed with primary ACP between 1997 and 2023 at two tertiary paediatric neurosurgical centres (Great Ormond Street Hospital (GOSH), United Kingdom, and Universidade de São Paulo (USP), Brazil) were evaluated. Functional outcomes related to pituitary function, hypothalamic injury, cognition, and vision were analysed. Scans were independently reviewed for tumor size, characteristics, and relationship to the optic apparatus and hypothalamus. Extent of surgery was documented.
Results
123 patients (USP = 52; GOSH = 71) were included. Mean follow-up was 10.1 ± 5.6 years at USP and 7.5 ± 4.8 years at GOSH. There were no demographic differences. Rates of growth hormone deficiency (USP = 62.5%; GOSH = 35%;
p
= 0.009) and visual deficits (
p
< 0.05) were higher in the USP cohort at initial presentation. Patients at GOSH presented with predominantly cystic lesions (
n
= 46/60; 76.7%) while at USP solid tumors (
n
= 24/32; 75%) (
p
= 0.05) were more prevalent. Paris grade for hypothalamic involvement was higher in the GOSH cohort (
p
= 0.01). Although gross total resection (GTR) was similar in the two groups, cyst aspiration plus radiotherapy was commoner at GOSH, whereas debulking was commoner at USP (
p
< 0.001). Post-treatment hypothalamic scores were better in the GOSH cohort (
p
< 0.04). Patients at GOSH had earlier recurrences (25.5 ± 32 months) compared to patients treated at USP (37.4 ± 59.5 months) (
p
= 0.01). In multivariate analysis, STR/GTR (OR 0.17; 95%CI:0.05–0.55,
p
< 0.01) and older age at diagnosis (OR 0.91, 95%CI:0.82–0.99,
p
= 0.04) were associated with longer progression-free survival.
Conclusion
Comparative analysis of two large series of ACP in children identified different paradigms of surgical management driven by distinct clinical–radiological presentations. While cyst aspiration plus radiotherapy protects against hypothalamic injury, this may occur at the cost of earlier tumour recurrence. Further studies to define this balance are urgently needed.
Previous presentations
21st International Symposium on Pediatric Neuro-Oncology.
June 29–July 2, 202
