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Changes in cognition and astrocytic reactivity in a female rodent model of chemotherapy-induced cognitive impairment are variable both acutely and chronically
Chemotherapy-induced cognitive impairment (CICI) affects female cancer survivors, with impairment recognised in populations such as breast cancer survivors, where 1 in 3 are affected. Impairments include issues with memory, learning, concentration, and processing speed, negatively impacting quality of life. Several mechanisms are proposed to drive these, with evidence implicating neuroinflammation as a key contributor. However, the time course over which impairments occur is less well-established, with fewer longer-term time-points investigated. This study aimed to understand the evolution of cognitive changes following methotrexate (MTX) or 5- fluorouracil (5-FU) chemotherapy, assessing three time-points: acute (96-hour), sub-acute (31-days) and chronic (93-days). Further, we investigated whether alterations in cognition were associated with concomitant changes in astrocytic reactivity. Female Sprague Dawley rats received two intraperitoneal injections of MTX, 5-FU or saline and were assessed on the novel object recognition, 5-choice serial reaction time task and Barnes maze. Hippocampal and prefrontal cortex tissue was examined for GFAP expression. Both MTX and 5-FU exposure were associated with spatial memory, task acquisition, and processing speed impairments at 31-days, with impairment ameliorated by 93-days. While both MTX and 5-FU induced changes in GFAP expression across various timepoints and regions, with most notable changes at 96-hours, 5-FU exhibited expression changes in the hippocampus consistently across all time-points. These results provide valuable insight into the complexity of a mediator of neuroinflammation in CICI. While neuroinflammation may be a promising therapeutic target, further markers should be assessed to elucidate the full neuroimmune response, and thus which aspects to target and when, to ensure optimal outcomes for cancer patients treated with chemotherapy.Olivia J. Haller, Ines Semendric, Lyndsey E. Collins-Praino, Alexandra L. Whittaker, Rebecca P. Georg
Adaptive Event-Triggered Heterogeneous Consensus of Leader-Following Multi-Agent Systems With Nonlinear Dynamic Topology
Date of Publication: 23 July 2024This paper is interested in the event-triggered leader-following consensus problem for discrete-time multi-agent systems subject to nonlinear dynamic topology. Considering that the on-board resources of each agent are generally limited, a novel adaptive event-triggered strategy is presented in this paper through establishing a nonlinear transformation law of consensus errors, which provides an effective way to weaken the impact of small fluctuations on triggering behaviors after the error systems converge. Then, an interval type-2 fuzzy model is introduced to describe the nonlinear dynamic topology where the dynamic characteristics contain both nonlinear time-varying law and uncertain parameter. In view of the discrepancies in adjacency relationships between different agents, the heterogeneous fuzzy-dependent controllers are employed to further decrease the consensus error. Meanwhile, some sufficient conditions are deduced to solve the designed controllers while ensuring that the consensus of multi-agent systems can be achieved with desired H∞ performance. Ultimately, advantages of the presented leader-following control strategy are illustrated by two examples.Zehui Xiao, Zijing Xiao, Jie Tao, Chang Liu, Peng Shi, and Imre J. Ruda
Transient inhibition of type I interferon enhances CD8+ T cell stemness and vaccine protection
Developing vaccines that promote CD8+ T cell memory is a challenge for infectious disease and cancer immunotherapy. TCF-1+ stem cell–like memory CD8+ T (TSCM) cells are important determinants of long-lived memory. Yet, the developmental requirements for TSCM cell formation are unclear. Here, we identify the temporal window for type I interferon receptor (IFNAR) blockade to drive TSCM cell generation following viral infection and mRNA–lipid nanoparticle vaccination. We reveal a reversible developmental trajectory where transcriptionally distinct TSCM cells emerged from a transitional precursor of exhausted T cellular state concomitant with viral clearance. TSCM cell differentiation correlated with T cell retention within the lymph node paracortex due to disrupted CXCR3 chemokine gradient formation. These effects were linked to increased antigen load and a counterintuitive increase in IFNγ, which controlled cell location. Vaccination with the IFNAR blockade promoted TSCM cell differentiation and enhanced protection against chronic infection. These findings propose an approach to vaccine design whereby modulation of inflammation promotes memory formation and function.Benjamin J. Broomfield, Chin Wee Tan, Raymond Z. Qin, Hanna Abberger, Brigette C. Duckworth, Carolina Alvarado, Lennard Dalit, CheeLengLee, Rekha Shandre Mugan, Zihnil A.I. Mazrad, HiromiMuramatsu, Liana Mackiewicz, Bailey E. Williams, JinjinChen, Asuka Takanashi, Stewart Fabb, Marc Pellegrini, Kelly L. Rogers, Woohyun J. Moon, Colin W. Pouton, Melissa J. Davis, Stephen L. Nutt, Norbert Pardi, Verena C. Wimmer, Joanna R. Groom
Manual wheelchair training programs: a scoping review of educational approaches and intended learning outcomes
Background Training programs grounded in educational theory offer a systematic framework to facilitate learning and outcomes. This scoping review aims to map the educational approaches documented for manual wheelchair training and to record intended learning outcomes and any relationships between learning theories, instructional design and outcomes. Methods Eight databases; Cochrane’s Library, EMBASE, CINAHL, PubMed, Scopus, EmCare, Medline, ProQuest Nursing and Allied Health Database and grey literature were searched in September 2023, with citation chaining for relevant papers. Included papers related to manual wheelchair training programs/protocols describing intended wheelchair training outcomes for adults and/or caregivers. Data extracted included study characteristics, type of intervention, explicit learning theories, instructional design principles and intended learning outcomes. The International Classification of Functioning and Kirkpatrick’s evaluation framework were used to organise intended outcomes. Results Of the forty-four articles included in this review, only fourteen explicitly used a learning theory in the instructional design of training. Training outcomes most commonly related to changes in knowledge/skills of manual wheelchair users (Level 2b of Kirkpatrick’s evaluation (n = 43), with less emphasis on participatory outcomes. Training designs incorporating Social Cognitive Theory (n = 8) were more likely to explore long term training outcomes, compared with other training designs. Conclusion Wheelchair training programs that are designed using learning theory are more likely to produce learning outcomes that are retained and meaningfully applied. Such longer terms outcomes could have systemic cost and efficiency implications, such as reduction in wheelchair falls and readmissions to hospital. Deliberate integration of learning theory into manual wheelchair training design is recommended to support broad outcomes and longterm learning. This design could synergise different learning theories.Kimberly Charlton, Carolyn Murray, Natasha Layton, and Stacie Attril
3D Terahertz Confocal Imaging with Chromatic Metasurface
First published: 07 January 2025.
The copyright line for this article was changed on 15 January 2025 after original online publication.Terahertz confocal imaging allows 3D see-through of a non-metallic object with high resolution. Conventional methods acquiring 3D images of thick objects suffer from limited depth-of-field, constrained depth resolution, and/or inconsistent spatial resolution at different depths. To address these limitations, the intrinsic chromatic aberration of a typical focusing metasurface is exploited to achieve frequency-dependent focal lengths. An object located within this extended focal range can be readily 3D inspected by performing 2D raster scans. A rigorous analysis reveals that the focal spot maintains a constant waist diameter of 2.4 mm (equivalent to 2.20 at 275 GHz) and migrates 68.1 mm (equivalent to 62.40, or 16.4 times of Rayleigh length, or 1.4-fold of the designed focal length at 275 GHz) from 175 to 525 GHz, and thus achieving a consistent spatial resolution and a large depth-of-field for 3D imaging. Importantly, this large depth-of-field is achieved with a relatively high numerical aperture of around 0.42. Measurements conducted between 220 and 330 GHz exhibit close agreement with the calculation. To demonstrate its imaging functionality, two stacked papers with different texts, a mobile phone, and earphones concealed in a charging case are imaged, where a short-time Fourier transform is implemented in the time-domain terahertz images to enhance image contrast. The presented metasurface is technologically significant for imaging systems to rapidly inspect objects in 3D with exceptional resolutions. Its potential applications include in-situ defect detection and object identification in security screening.Xiaolong You, Rajour Tanyi Ako, Sharath Sriram, and Withawat Withayachumnanku
In situ Re–Os geochronology of Re-rich Palaeogene molybdenite by LA-ICP-MS/MS†
In situ Re–Os geochronology by LA-ICP-MS/MS was previously demonstrated by reacting Os with CH₄ or N₂O reaction gasses. However, for both reactions, a minor proportion of the Re parent isotope also reacts, potentially leading to significant isobaric interferences of ¹⁸⁷Re on ¹⁸⁷Os, especially for young samples with little radiogenic in-growth. Here we present an interlaboratory comparison and compare three reaction gas mixtures (CH₄ + H₂ + He, N₂O and N2O + He) with the aim to robustly date Palaeogene (66–23 Ma) molybdenite from the Bingham Canyon and Henderson deposits. CH₄ mixed with H₂ gas gives the highest sensitivity, while N₂O and He gas buffer Re reaction. On balance, the analytical method involving N₂O + He reaction gas is most suitable for dating Palaeogene molybdenite, resulting in age precision of 2.6% for Bingham and 5.8% for Henderson. For older, >1 Ga molybdenite, CH₄ + H₂ + He may give comparatively better age precision.Stijn Glorie, Jay M. Thompson, Sarah E. Gilbert and A. Kate Souder
Evaluating the Potential for Different Fabrics to Protect Grapes from Contamination by Smoke
Vineyard smoke exposure can lead to the accumulation of free and glycosylated volatile phenols (VPs) in grapes, negatively affecting wine quality. Activated carbon fibre (ACF) cloth has proven effective in mitigating smoke contamination of grapes, but its commercial use is hindered by low tensile strength and light transmission. This study therefore compared the efficacy of different fabrics (polyester, polypropylene, cotton and viscose) to mitigate the smoke contamination of grapes (benchmarking against ACF cloth), alongside their physical properties (i.e., tensile strength and air permeability). Polyester and polypropylene provided limited protection, whereas grapes enclosed in cotton or viscose had VP profiles that were comparable to grapes enclosed in ACF cloth (i.e., VP concentrations ≤ 5.3 µg/kg). In a subsequent trial, ACF cloth prevented the uptake of >90% of smoke-derived VPs during ten successive smoke treatments, but after repeated smoke exposure, VP concentrations had increased in grapes enclosed in cotton and viscose, presumably due to saturation. Washing and drying restored the protection afforded by cotton and viscose but resulted in the disintegration of the ACF cloth. However, the application of a non-woven fabric to one or both sides of the ACF cloth improved tensile strength, without significantly compromising air permeability. These findings demonstrate the potential for fabric coverings to be used to mitigate the occurrence of smoke taint in the vineyard, with ACF affording superior protection.Tingting Shi, Renata Ristic, Kerry Wilkinso
Role of gut microbiota disruption in prosthetic joint infection: a scoping review
Available online from 8 Sept 2025.
OnlinePublProsthetic joint infection (PJI) is a serious complication of joint replacement surgery. Emerging evidence suggests that gut dysbiosis (characterised by reduced microbial diversity, altered immune responses, and increased intestinal permeability) could facilitate bacterial translocation from the gut to prosthetic joints and contribute to the development of PJI. In this scoping review, we analysed eight studies (three preclinical and five clinical) that investigated the potential link between gut microbiota alteration (dysbiosis) and PJIs. Preclinical models indicated that animals experiencing gut dysbiosis had higher rates of PJI, with a study testing the Trojan horse hypothesis showing that neutrophils carrying viable meticillin-resistant Staphylococcus aureus from the gut seeded the prosthetic joints without detectable bloodstream infection. Clinical research identified higher levels of zonulin (a marker of intestinal barrier integrity) and inflammatory markers, decreased gut microbial diversity, and presence of gut commensals within the joint tissues of patients with PJI. However, few studies used stool sequencing or adhered to microbiome research guidelines, thereby restricting conclusions. This Review highlights the need for future research that includes gut microbiota profiling, tight junction biomarker characterisation, and intervention trials (eg, testing the effect of probiotic use) to elucidate the role of gut dysbiosis in PJI. Investigating the gut microbiota before arthroplasty and incorporating suitable control groups could help to identify any causative relationships. The findings of this Review suggest that gut dysbiosis could be a modifiable risk factor for PJI, warranting the exploration of osteomicrobiology and gut–joint axis mechanisms in arthroplasty outcomes.Boopalan Ramasamy, Deepti K. Sharma, Stuart A. Callary, Balamurugan Ramadass, Lucian Bogdan Solomon, Gerald J. Atkin
Molecular phylogenetics illuminates the evolutionary history and hidden diversity of Australian cave crickets (Orthoptera: Rhaphidophoridae)
OnlinePublCave crickets (Orthoptera: Rhaphidophoridae) are a globally distributed group of insects found in dark, humid microhabitats including natural caves, alpine scree, and forest litter. Ten extant subfamilies are currently recognised, of which Macropathinae, which comprises the entirety of the fauna in South America, South Africa, Australia, and New Zealand, is thought to be the most ancient. New Zealand comprises high phylogenetic diversity of Rhaphidophoridae throughout its mesic zone, with most species occurring above ground. In contrast, the Australian fauna is poorly known and contains an apparently greater relative proportion of species utilising caves as refugia. A robust phylogenetic framework is needed to underpin future taxonomic work on the group and uncover potentially contrasting patterns of taxonomic diversity. Here, we performed fossil-calibrated phylogenetic analysis using whole mitochondrial genomes and nuclear markers to reconstruct the evolutionary history of Macropathinae with a focus on the Australian fauna. By dramatically increasing taxon sampling relative to past studies, we recovered the Australian fauna as rampantly polyphyletic, with the remaining Macropathinae nested among six distinct Australian lineages. Deep divergences between major clades imply additional Australian lineages remain undetected, either due to extinction or sampling bias, and have likely confounded past biogeographic signal. We inferred the radiation of Macropathinae began during the Lower Cretaceous prior to the fragmentation of Gondwana with a potential Pangaean origin for Rhaphidophoridae. Finally, we found evidence for several undescribed species and genera of Australian Macropathinae, all of which qualify as shortrange endemics, and discuss the conservation implications of these restricted distributions.Perry G. Beasley-Hall, Steven A. Trewick, Stefan M. Eberhard, Andreas Zwick, Elizabeth H. Reed, Steven J. B. Cooper, Andrew D. Austi
Universal Design for Learning for Mathematics Education
In this first paper of the Symposium: Strategies that promote inclusive mathematics education, we introduce the Universal Design for Learning (UDL) guidelines through a mathematics lens. Using a rapid review, empirical studies on mathematics and UDL in early years, primary, or secondary school settings were sought. Six research papers were identified from school settings with no results for early years research, thus, the Early Years Learning Framework was used to identify connections to mathematics in this context. Findings highlighted the potential of UDL to enhance mathematics education for all students creating a flexible and accessible curriculum.Lorraine Gaunt, Kate Quane, Belinda Trewartha, Tom Port