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Digital tools to support postpartum recovery: a systematic review
No full textIntroduction: Returning to physical activity (PA) postpartum is challenging due to physical,
psychological and socio-cultural barriers. Successful return is associated with physical
and mental health benefits. Advancements in digital technology access, and a digital
focus for providers offer potential areas to improve PA, however current strategies and
their efficacy have not been described in the literature.
Methods and analysis: A systematic review of studies evaluating digital technologies in
returning postpartum women to PA was completed according to Preferred Reporting
Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Electronic
databases: Web of Science, SCOPUS, Embase, APA Psycnet and PubMed were
searched from inception until 24 July 2022. Primary objectives were return to PA
postpartum when utilising digital technologies and secondary objectives included patient
satisfaction and confidence towards returning to physical activity.
Results: The review returned 14 eligible studies (n=2714), using digital technologies such
as pedometers, text messaging and smartphone applications. Outcome measures were
patient questionnaires, although some used activity trackers. Statistically significant
differences in PA were seen in 7 studies with an average intervention increase of
approximately 108%. Secondary outcomes of perceived reduction in barriers, increased
satisfaction and self-reported confidence towards engaging in physical activity were
investigated in 6 of the studies with 4 studies reporting an increase in physical
activity.
Conclusion: Digital interventions may play a role in supporting return to physical activity
after childbirth, particularly as part of a multi-modal strategy. However, further research
randomising participants into digital and standard arms is needed to quantify the specific
contribution of digital tools
High-areal-capacity Na-ion battery electrode with high energy and power densities by simultaneous electrospinning-spraying fabrication
No full textSodium-ion batteries (SIBs) are cost-effective alternatives to lithium-ion batteries (LIBs), but their low energy density remains a challenge. Current electrode designs fail to simultaneously achieve high areal loading, high active content, and superior performance. In response, this work introduces an ideal electrode structure, featuring a continuous conductive network with active particles securely trapped in the absence of binder, fabricated using a universal technique that combines electrospinning and electrospraying (co-ESP). We found that the particle size must be larger than the network's pores for optimised performance, an aspect overlooked in previous research. The free-standing co-ESP Na2V3(PO4)3 (NVP) cathodes demonstrated state-of-the-art 296 mg cm−2 areal loading with 97.5 wt% active content, as well as remarkable rate-performance and cycling stability. Co-ESP full cells showed uncompromised energy and power densities (231.6 W h kg−1/7152.6 W kg−1), leading among reported SIBs with industry-relevant areal loadings. The structural merit is analysed using multi-scale X-ray computed tomography, providing valuable design insights. Finally, the superior performance is validated in the pouch cells, highlighting the electrode's scalability and potential for commercial application
Discovery and validation of a novel class of necroptosis inhibitors targeting RIPK1
No full textNecroptosis is a form of programmed cell death that, when dysregulated, is associated with cancer and inflammatory and neurodegenerative diseases. Here, starting from hits identified from a phenotypic high-throughput screen for inhibitors of necroptosis, we synthesized a library of compounds containing a 7-phenylquinoline motif and validated their anti-necroptotic activity in a novel live-cell assay. Based on these data, we designed an optimized photoaffinity probe for target engagement studies and through biochemical and cell-based assays established receptor-interacting kinase 1 (RIPK1) as the cellular target, with inhibition of necroptosis arising from the prevention of RIPK1 autophosphorylation and activation. X-ray crystallography and mass spectrometry revealed that these compounds bind at the hinge region of the active conformation of RIPK1, establishing them as type I kinase inhibitors. In addition, we demonstrated in vitro synergy with type III kinase inhibitors, such as necrostatin-1 and found that lead compounds protected mice against acute inflammation in necroptosis models in vivo. Overall, we present a novel pharmacophore for inhibition of human RIPK1, a key protein involved in necroptosis, and provide a photoaffinity probe to explore RIPK1 target engagement in cells
Urban heat island and the risk of schizophrenia spectrum disorders in middle-aged and older adults
No full textRapid urbanization and climate crisis amplified the adverse effects of urban heat, while it remained unclear about the long-term impacts of urban heat island (UHI) on mental disorders, especially schizophrenia spectrum disorders (SSD). This study included 393,507 participants from the UK Biobank to examine the impact of long-term exposure to UHI on the incidence risk of SSD and changes of brain structures. UHI exposure were quantified as surface UHI intensity and normalized land surface temperature from satellite data. Cox proportional hazard models and multiple linear regression models were used to examine associations of UHI effects with SSD and changes of brain structures. During a median follow-up of 13.8 years, there were 1112 (0.3 %) participants diagnosed with SSD and 367 (0.1 %) with schizophrenia. Every standard deviation increased surface UHI intensity was associated with a 17 % (HR, 1.17; [95 % CI, 1.07–1.28]) excess risk of SSD and a 26 % excess risk of schizophrenia (HR, 1.26; [95 % CI, 1.08–1.46]). These effects were more pronounced in individuals with a high genetic risk of schizophrenia and those aged <60 years. UHI exposure was also associated with brain macrostructure and microstructure, particularly in the frontal and temporal lobes, as well as white matter tracts. In this cohort study of middle-aged and older adults, UHI exposure was identified as a risk factor for the onset of SSD and schizophrenia. These findings highlight the need for implementing initiatives of UHI mitigation and heat resilience to improve mental health and sustainable development in urban communities worldwide
On the modeling of hydrocarbon combustion in external electric fields with reactive molecular dynamics
No full textThe use of electric fields may provide a mechanism to enable fuel-flexible technologies in aviation. The development of such technologies requires methodologies able to accurately quantify electric field effects on chemical reactions at the molecular level. This work provides a comprehensive assessment of methodologies used in the framework of reactive molecular dynamics (MD) with the reactive force field ReaxFF. The focus is on the computation of atomic charges, the method used for equilibration, and the use of global thermostats for hydrocarbon combustion in an external electric field. The charge equilibration method (QEq) and the charge transfer with polarization current equilibration method (QTPIE) were analyzed for the computation of atomic charges. For the fuel–oxygen system investigated, QEq leads to molecules with a sizable spurious net charge. QTPIE leads to more accurate molecular charges but at the cost of underestimating some atomic charges. This leads to faster combustion kinetics with QEq compared with QTPIE. A two-step equilibration procedure provides a more equilibrated system compared to widely used equilibration procedures. Furthermore, using a global thermostat with an external electric field results in an artificial reduction in fuel and oxygen first-order reaction rates. These artificial effects can be avoided by not using a thermostat, but at the expense of electric-field-induced heating. Applying an external electric field without a global thermostat accelerates combustion much more with QEq compared with QTPIE, due to the larger charges predicted by QEq. This study reveals several simulation artifacts that affect reactive MD of fuel combustion and contributes toward the more accurate modeling of fuel combustion in external electric fields
Subunit specialization in AAA+ proteins and substrate unfolding during transcription complex remodeling
No full textBacterial RNA polymerase (RNAP) is a multisubunit enzyme that copies DNA into RNA in a process known as transcription. Bacteria use σ factors to recruit RNAP to promoter regions of genes that need to be transcribed, with 60% bacteria containing at least one specialized σ factor, σ54. σ54 recruits RNAP to promoters of genes associated with stress responses and forms a stable closed complex that does not spontaneously isomerize to the open state where promoter DNA is melted out and competent for transcription. The σ54-mediated open complex formation requires specific AAA+ proteins (ATPases Associated with diverse cellular Activities) known as bacterial enhancer-binding proteins (bEBPs). We have now obtained structures of new intermediate states of bEBP-bound complexes during transcription initiation, which elucidate the mechanism of DNA melting driven by ATPase activity of bEBPs and suggest a mechanistic model that couples the Adenosine triphosphate (ATP) hydrolysis cycle within the bEBP hexamer with σ54 unfolding. Our data reveal that bEBP forms a nonplanar hexamer with the hydrolysis-ready subunit located at the furthest/highest point of the spiral hexamer relative to the RNAP. ATP hydrolysis induces conformational changes in bEBP that drives a vectoral transiting of the regulatory N terminus of σ54 into the bEBP hexamer central pore causing the partial unfolding of σ54, while forming specific bEBP contacts with promoter DNA. Furthermore, our data suggest a mechanism of the bEBP AAA+ protein that is distinct from the hand-over-hand mechanism proposed for many other AAA+ proteins, highlighting the versatile mechanisms utilized by the large protein family
A general probabilistic framework for impact localisation based on flexural wave propagation
No full textFlexural wave propagation-based impact localisation methods for composite structures face challenges in accurately estimating the group velocity profile (GVP) and quantifying localisation uncertainties due to wave dispersion. This paper introduces a two-step probabilistic framework to address these challenges. In the first step, a probabilistic model for GVP estimation is developed using Bayesian inference, leveraging wave dispersion relations from classical laminate theory to define the GVP probability space. Three GVP estimation methods depending on structural complexity and available knowledge are explored: physics-based, data-driven, and hybrid physics-data method. The estimated GVP facilitates multi-frequency probabilistic impact localisation in the second step, wherein the maximum likelihood impact location is identified solely using fast gradient-based optimisation. Experimental impact testing on laminated composite flat, stiffened, and sandwich panels validates the framework, demonstrating its efficiency, accuracy, and scalability in GVP estimation, impact localisation, and uncertainty quantification across diverse composite structures. The data-driven method notably requires only sparse reference impacts and a limited sensor network (each with no more than four) to accurately estimate GVPs for these structures
Macrocyclic peptide probes for immunomodulatory protein CD59: potent modulators of bacterial toxin activity and antibody-dependent cytotoxicity
No full textCD59 is an immunomodulatory cell surface receptor associated with human disease. Despite its importance in complement regulation and bacterial pathogenesis, CD59 remains a challenging therapeutic target. Research to date has focused on antibody or protein-based strategies. Here we present a new approach to target CD59 using macrocyclic peptides with low nanomolar affinity for CD59. Through X-ray crystallographic studies and structure-activity relationship (SAR) studies, we identify key interactions that are essential for binding and activity. We find that the macrocyclic peptide CP-06 adopts a beta-hairpin structure and binds CD59 through an intermolecular beta-sheet, mimicking protein–protein interactions of biologically relevant CD59 interaction partners. We create dimeric and lipidated macrocyclic peptide conjugates as enhanced cell-active CD59 inhibitors and show that these probes can be used to modulate both complement-mediated killing of human cells and lytic activity of bacterial virulence factors. Together, our data provide a starting point for future development of macrocyclic peptides to target CD59 activity in diverse cellular contexts
Experimental investigation of fatigue crack propagation under non-proportional multiaxial loading
No full textBlisks (bladed disks) are critical components in modern aero-engines that offer significant weight savings compared to conventional blade and disk rotor designs, resulting in improved fuel efficiency. However, due to their integrated design, blisks are susceptible to unique failure modes following foreign object damage (FOD) and crack initiation. Of particular interest is the trajectory of crack propagation from FOD sites, which determines whether failure will occur via a blade-off event or rupture of the blisk.
This work presents an experimental test setup which replicates the key features of non-proportional loading in a blisk. A novel feature of the test rig was the ability to apply loads independently in three axes using a biaxial machine equipped with only two hydraulic servo-actuators. A series of multiaxial fatigue tests were completed on notched cruciform specimens and a wide range of crack trajectories were achieved, validating the design of the test rig.
Crack trajectories produced by non-proportional load paths are not accurately predicted by conventional criteria, such as the maximum tensile stress criterion (MTS), when cracks are subject to high mean mode-II loads. The results of these experiments underscore the complexity of modelling non-proportionally loaded cracks and the acquired crack trajectory data is a useful tool for validating further models
AI-generated patient friendly MRI fistula summaries: a pilot randomised study
No full textPerianal fistulising Crohn’s disease (pfCD) affects 1 in 5 Crohn’s patients and requires frequent MRI monitoring. Standard radiology reports are written for clinicians using technical language often inaccessible to patients, which can cause anxiety and hinder engagement. This study evaluates the feasibility and safety of AI-generated patient-friendly MRI fistula summaries to improve patient understanding and shared decision-making. MRI fistula reports spanning healed to complex disease were identified and used to generate AI patient-friendly summaries via ChatGPT-4. Six de-identified MRI reports and corresponding AI summaries were assessed by clinicians for hallucinations and readability (Flesch-Kincaid score). Sixteen patients with perianal fistulas were randomized to review either AI summaries or original reports and rated them on readability, comprehensibility, utility, quality, follow-up questions, and trustworthiness using Likert scales. Patients rated AI summaries significantly higher in readability (median 5 vs. 2, p = 0.011), comprehensibility (5 vs. 2, p = 0.007), utility (5 vs. 3, p = 0.014), and overall quality (4.5 vs. 4, p = 0.013), with fewer follow-up questions (3 vs. 4, p = 0.018). Clinicians found AI summaries more readable (mean Flesch-Kincaid 54.6 vs. 32.2, p = 0.005) and free of hallucinations. No clinically significant inaccuracies were identified. AI-generated patient-friendly MRI summaries have potential to enhance patient communication and clinical workflow in pfCD. Larger studies are needed to validate clinical utility, hallucination rates, and acceptability