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Engineering a dimeric single-domain antibody for improved detection and neutralization of amyloid-β oligomers
No full textSoluble Aβ oligomers are regarded as major neurotoxic agents in Alzheimer’s disease. Several monoclonal antibodies have been developed to target Aβ oligomers, but most of them show limited specificity binding also to monomers and fibrils. To generate an antibody with high specificity for the oligomers, we aimed to increase the efficiency and sensitivity of a humanized Aβ-oligomer specific single domain antibody, called DesAb-O. We engineered a dimeric DesAb-O variant, DiDesAb-O, which showed significantly higher binding affinity for Aβ oligomers as compared to the monomeric sdAb. DiDesAb-O selectively detected Aβ42 oligomers not only in vitro and in cultured cells using synthetic preparations, but also in the cerebrospinal fluid from Alzheimer's patients. Moreover, it inhibited the binding of these toxic species to cellular membranes and neutralized their neurotoxicity both in cells and in patient-derived cerebrospinal fluid at lower concentrations compared to DesAb-O. These results indicate that rational dimerization of single domain antibodies can substantially enhance target engagement and functional efficacy, providing a promising strategy for the development of improved diagnostic and therapeutic molecules for Alzheimer’s disease
The dynamic inducing magnetic field signal at Triton
No full textTriton, Neptune's largest moon, is suspected of harboring a subsurface ocean. Detecting sub-surface oceans requires measuring the ocean's induced magnetic field, typically exploiting common frequencies at which the field environment of the moon changes, in this case Triton's path through Neptune's magnetosphere. Triton's orbit around Neptune, whilst nearly completely circular, is highly inclined, with an inclination of approximately 157° to Neptune's equator. This results in a rotation signal strength and frequency which has significant orbital dependence, unlike at other ocean worlds. The work conducted in this study highlights how the inducing signal at Triton is dynamic in both power and frequency caused by Triton's high inclination. This means that there is a richer set of frequency signals than previously thought, that may be useful for induction studies. This work quantifies the effect that Triton's inclination has on the inducing signal, and rules out other potential sources of signal disruption
Preservation of the human ovary
No full textStudy 1a assessed oncological safety of fertility-sparing surgery (FSS) in 172 women with borderline ovarian tumours (BOTs). FSS was performed in 52.3% of cases and associated with higher recurrence than non-FSS (25.6% vs 7.7%). However, no invasive recurrences occurred following FSS, whereas all recurrences after radical surgery were invasive low-grade serous carcinomas. Ultrasound-guided ovarian wedge resection (UGOWR) was introduced as a novel FSS technique, showing comparable recurrence rates to established approaches, with postoperative ultrasound surveillance enabling early detection.
Study 1b compared BOT recurrence in women pursuing spontaneous pregnancy (SP) or fertility treatment (FT) following FSS versus non-exposed women. Recurrence risk did not differ significantly overall (22.2% vs 20%). While FT combined with successful SP was associated with increased recurrence risk, all recurrences were non-invasive, supporting the oncological safety of fertility treatment.
Study 2 surveyed 415 UK healthcare professionals and identified major deficits in fertility preservation (FP) education: 87% had no formal training, 39.5% never discussed FP with patients, and over half lacked counselling confidence, demonstrating system-wide barriers to effective FP provision.
Study 3’s randomized trial comparing laparoscopic cystectomy with ultrasound-guided ovarian cystectomy (UGLOC) found no significant differences in postoperative ovarian reserve (AMH, AFC) at six months, though UGLOC resulted in less excised ovarian tissue, suggesting potential benefit for women with diminished baseline reserve.
Study 4a surveyed 5,482 UK women and revealed pervasive misinformation on fertility decline, miscarriage risk, elective oocyte cryopreservation (EOC) timing and costs. Study 4b evaluated outcomes from EOC cycles: live birth occurred in 26.8% of thaw cycles, with no livebirths demonstrated among women ≥40.
Study 5a demonstrated that reduced ovarian reserve (low AMH/AFC) significantly increases miscarriage risk, particularly in women under 35. Study 5b found that blastocyst PGT-A modestly improves live birth and implantation rates while reducing miscarriage compared with morphology alone, although further validation is required.Open Acces
Coherent two dimensional electronic-X-ray spectroscopy
No full textUltrafast pump-probe time resolved X-ray spectroscopy carries information on the valence-core dynamics of molecular systems. Here, a coherent two-dimensional nonlinear electronic-X-ray spectroscopy (2DEX) application is proposed in order to reveal the frequency-frequency correlations for the valence and the core transition excitations. 2DEX is in the class of extreme-cross peak
correlation spectroscopy and is experimentally straightforward to measure as an adaptation of the
conventional optical pump – X-ray probe technique by creating a phase-locked pulse pair of the ultrafast laser for the valence excitation. Theoretical evaluation of the coherences and populations for several applications of ultrafast valence-core spectroscopy experiments is shown. Using a response function approach, 2DEX four wave signals are calculated and evaluated with respect to
frequency separation in the electronic and X-ray ranges as well as the lineshape characteristics. It is shown that stationary and oscillatory contributions to the rephasing, non-rephasing and absorptive signals can be resolved depending on pulse shaping and phase cycling, phase matching, X-ray spectrometer and material response parameters. Calculations are shown for examples that include the valence-core coherences for a vibrational monomer and for Frenkel and charge transfer (CT)
electronic exciton states, which in the X-ray absorption near-edge structure (XANES) spectral region have the potential to resolve the population and coherence contributions in the atomic localised basis
Improving care for Lynch syndrome patients: integrating surveillance into England’s national bowel cancer screening programme
No full textQuality assurance, timeliness and equity of access to colonoscopy for people with Lynch syndrome (LS) in England has historically been highly variable. The LS-Bowel Cancer Screening Programme (LS-BCSP) launched in July 2023, delivers high quality colonoscopy to the average-risk population, from colonoscopists who have undergone high-level accreditation, utilising the existing average-risk BCSP infrastructure. Eligible individuals have a genetic diagnosis of LS. Comprehensive retrospective diagnoses of LS in England (since the 1990s) were ascertained from 17 regional genetics services. The National Disease Registration Service (NDRS) developed a registry of eligible individuals, and a portal for prospectively diagnosed cases. An existing national screening IT framework was adapted to incorporate disease-specific clinical pathway information, linked to existing national guidelines. Nationally standardised training for BCSP teams was delivered to > 2000 staff from 64 national screening centres in 2023. By November 2024, 10,913 eligible individuals were identified, with 150–250 new diagnoses added each month. A historical backlog of > 1000 patients overdue colonoscopy surveillance was cleared by January 2024. Diagnostic outcomes of LS patients from the first two years of LS-BCSP will be available to facilitate evaluation of the successes and failures of the LS_BCSP. This evaluation will include diagnostic outcomes, stratified by demographic and socioeconomic status, genotype, measures of colonoscopy quality and regional variation. This novel programme includes complete ascertainment of the national LS population in England, without requirement for referral. Individuals with LS now have access to high-quality, timely colonoscopy through an accredited programme which is quality-assured along the entire pathway
Effect of probiotic yogurt on short-chain fatty acids, inflammation, and oxidative stress biomarkers: a systematic review and meta-analysis of randomized controlled trials
No full textShort-chain fatty acids (SCFAs) production by fermented foods is a promising health strategy regarding inflammation and oxidative stress regulation. However, there is uncertainty whether probiotic yogurt is truly superior to conventional yogurt. This systematic review and meta-analysis aimed to evaluate current evidence on the effect of probiotic yogurt on SCFAs, oxidative stress, and inflammatory biomarkers. A systematic literature search was performed up to December 2025 on PubMed, Scopus, Embase, Web of Science and LILACS. Only randomized controlled trials and crossover studies were included. A random-effects meta-analysis of standardized mean difference (SMD) was performed. A total of 15326 articles were selected. After full-text review, 33 trials were considered. Pooled analysis showed a statistically significant
increase in fecal acetate levels (SMD 0.29; 95% CI: 0.02; 0.57). No significant differences were found for propionate, butyrate, and total SCFAs. Subgroup analysis revealed significant differences between study design in acetate and butyrate. Similarly, no significant difference was found for C-reactive protein (SMD -0.61; 95% CI: -2.25; 1.03) and oxidative stress biomarkers. In contrast, interleukin-10 showed a significant increase (SMD 0.48; 95% CI: 0.15; 0.80). Current evidence comparing probiotic yogurt with conventional yogurt is very limited. Preliminary findings suggest increments of clinically uncertain relevance in fecal acetate levels and interleukin-10. However, due to the very low certainty of the evidence, superiority over conventional yogurt is uncertain. Further trials are needed to standardize follow-up time, doses and to address possible effect modification by study design
A custom force plate for quantifying the force applied by the finger during smartphone usage
No full textIntroduction: The increase in thumb activity due to smartphone use in recent years may be associated with an elevated risk of developing musculoskeletal disorders. Prior studies on hand biomechanics during touchscreen use have indicated that activities such as swiping and tapping lead to varying levels of muscle activation and ranges of motion. Currently, however, there is no device that can be used readily to measure finger forces accurately during smartphone use.
Method: This study presents the design of a portable force plate specifically developed to quantify fingertip forces during smartphone use. The device utilises a load-cell structure and foil strain gauges to measure applied force magnitude, direction, and location.
Results: The device achieved a force sensitivity of 0.15 N and a positional sensitivity of 2.5 mm, with a maximum measurable force capacity of 3 N.
Discussion: The portable force plate enables the study of hand kinetics whilst allowing for physiological kinematics during smartphone use, with applications spanning musculoskeletal and finite-element model development of the hand, ergonomic risk assessment, smartphone interface evaluation, and musculoskeletal injury prevention
Hybrid process-based and deep learning for river nutrient prediction under limited monitoring data
No full textAccurate simulation of riverine nutrient dynamics remains challenging in catchments with limited monitoring data, where both process-based models (PBMs) and data-driven approaches face constraints. This study investigates hybrid modelling strategies that combine PBM simulations with long short-term memory (LSTM) networks to predict nitrogen and phosphorus concentrations at the outlet of Salmons Brook catchment, London, UK. We designed two scenario sets to evaluate (i) the role of extreme weather indices as input features and (ii) the value of integrating different outputs from the Water Systems Integrated Modelling framework (WSIMOD) into LSTM architectures. Results show that the selected hybrid PBM-LSTM models outperformed both empirical LSTM and standalone WSIMOD simulations. For phosphorus, incorporating extreme weather indices improved performance, reflecting its sensitivity to high air temperatures and intense precipitation, while nitrogen predictions degraded, suggesting that memory from past water quality observations carries more predictive value. Comparisons between hybrid designs further indicate that simulated pre-river nutrient loads provide stronger constraints for LSTM models than in-river nutrient processes. These findings emphasize the need for nutrient-specific observational inputs in LSTM frameworks and demonstrate that PBM-LSTM hybridization offers a promising pathway for improving predictions relative to standalone LSTM or PBM simulations. Moreover, the comparative performance of different modelling configurations offers insights into the types of signals LSTM networks retain or discard, thereby contributing to the interpretability of DL applications in river water quality prediction
Patient perceptions of eHealth interventions in surgery-A multi-method study
No full textIntroduction
eHealth plays a pivotal role in modern healthcare, providing patients with greater access to information, new methods of receiving care, and enhanced communication with healthcare providers. The way individuals perceive eHealth is influenced by demographic factors, life experiences, and cultural beliefs, all of which shape motivations and potential barriers to adoption. Understanding these key factors is essential for improving the uptake and acceptance of eHealth.
Aims
The principle aims of this thesis were to:
1. evaluate surgical patients' internet usage patterns, eHealth experiences, and preferences
2. assess the impact of eHealth literacy and individual patient factors on eHealth acceptance
3. explore the perceptions of patients and clinicians regarding eHealth technologies
4. identify key enablers and barriers to eHealth implementation
Methods
The following methods were used:
1. a systematic review
2. a patient survey assessing eHealth literacy and technology use
3. focus groups with surgical patients
4. in-depth interviews with clinicians
Results
Surgical patients are increasingly engaged with digital technologies but primarily for basic tasks. Higher eHealth literacy is associated with greater acceptance of digital health tools, yet significant disparities remain, particularly among older patients and those with lower educational attainment. Patients valued eHealth for empowerment and convenience but expressed concerns about accessibility, digital literacy, and privacy. Clinicians recognised the potential of eHealth but highlighted challenges related to IT infrastructure, integration into clinical workflows, and the need for clear implementation strategies.
Conclusion
Understanding patient factors and customising eHealth implementation and support are essential for its utilisation and acceptance. Enhancing clinician involvement and tackling infrastructure barriers are vital for optimising eHealth implementation in surgical care.Open Acces
Estimating population immunity against serotype-two poliomyelitis from the inactivated polio vaccine in routine immunization across 112 countries: a modelling study
No full textBackground: To mitigate the risk of outbreaks of serotype 2 poliomyelitis after withdrawal of this sero-
type from oral poliovirus vaccine (OPV) in 2016, inactivated poliovirus vaccine (IPV) was introduced into
the routine immunization (RI) programmes of all countries using OPV. Since 2022, WHO has recommended a 2-dose schedule, with a first dose at 14 weeks of age followed by a second dose at least 4 months later (e.g. 14-39 week schedule), although an earlier schedule may be adopted, despite lower immunogenicity, if vaccine coverage is low at older ages.
Methods and Findings: We combined published data on type-2 IPV seroconversion with age, national
RI coverage estimates, dose introduction dates, and country-specific schedules using a cohort model of population immunity to estimate IPV-induced immunity from 2024-2031 for 112 countries using either one or two doses of IPV. We projected immunity for current, 6-14, and 14-39 week schedules to find the optimal schedule and estimate the impact of interventions such as schedule changes and catch-ups. Under current schedules, estimated median serotype 2 population immunity in 2025 among children under five years of age is at 61% (IQR: 52%, 72%), rising to 71% (IQR: 57%, 80%) in 2031. The later 14-39 week schedule was optimal in all countries, with potential for the median immunity to rise to 78% (IQR: 66%, 85%) by 2031 if adopted by all countries in 2026. Eight countries would still have < 50% immunity, rising to 65%-72% if catch-up
campaigns with 80% coverage were implemented in 2030. The work is limited by the fact that IPV provides
only a partial picture of total immunity where there has been emergency type-two OPV use. Furthermore,
national estimates may mask subnational coverage differences and pockets of extremely low immunity.
Conclusions: Under these estimates, IPV schedules and coverage are suboptimal in many countries. Those with a single dose should introduce a second on the 14-39 week schedule; those on early schedules would benefit from adopting the 14-39 week schedule. IPV catch-up campaigns are recommended where RI coverage is low