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Pores in the retinal inner limited membrane formed by M\ufcller cell protrusions
No full textPURPOSE: To investigate the ultrastructure of inner limiting membrane (ILM) pores in whole-retina specimens, and to compare with surgically excised specimens from eyes with vitreo-maculopathies. METHODS: Ultrastructural analysis included 1) three-dimensional serial block-face scanning electron microscopy (3D SBF-SEM) of inner retinal layers from macular area of two human donor eyes and 2) transmission electron microscopy (TEM) of ILM specimens obtained from 25 eyes with tractional vitreo-maculopathies that tested positive for the presence of ILM pores. RESULTS: SBF-SEM analysis revealed circumscribed areas of ILM thinning and multiple retinal cell processes protruding into the ILM with or without ILM breakthrough. In the peri-pore regions, the ILM was thin and bulged toward the vitreous. M\ufcller cells had finger-like extensions through the ILM forming small individual breakthrough points. Surgically removed ILM specimens also showed regions with ILM thinning and protruding retinal cell fragments in the ILM but with no preexisting ILM breakthroughs. Epiretinal cells were found on the vitreal side of the ILM pore regions. CONCLUSION: There is evidence that ILM pores are newly formed by retinal M\ufcller cells, growing their processes through the ILM toward its vitreal side in health and disease. These pore regions may contribute to the formation of epiretinal membranes
Structure of the 30S translation initiation complex coupled to paused RNA polymerase and its potential for riboregulation
Full text link\ua9 The Author(s) 2025.In many bacterial species, transcription and translation can be coupled physically, with potential impact on the rates and efficiency of gene expression. Here, we present structural evidence from cryo-EM demonstrating that a bacterial RNA polymerase that is paused proximally to the promoter can associate with the pioneering 30S translation initiation complex (30S IC). These findings suggest that the physical link between transcription and translation can be established prior to commitment to protein synthesis. Although the mRNA is embedded in this ‘early expressome’ complex, it can nonetheless interact with small regulatory RNA (sRNA) and be targeted for cleavage in the protein-coding region by the RNA degradosome assembly in vitro. The potential tagging of transcripts with sRNA during pioneering and subsequent stages of translation initiation, when the 30S IC is at the 5′ end of a polyribosome, may in principle contribute to efficient and rapid termination of gene expression in response to regulatory signals
Motor unit magnetic resonance imaging (MUMRI) as a novel biomarker of muscle activity in spinal muscular atrophy
Full text link\ua9 2026 The Author(s)Motor unit MRI (MUMRI) non-invasively detects fasciculation, a common symptom of SMA and potential biomarker for clinical trials. We applied MUMRI in ten SMA III patients and ten controls comparing fasciculation rates. Images of the tongue, upper arm, paraspinal and thighs & lower legs were acquired using MUMRI and 3-point Dixon (fat fraction) sequences. Fasciculation rate (cm−3min−1) was significantly higher in SMA than controls for: paraspinal 0.15 \ub1 0.20 vs. 0.003 \ub1 0.006, p = 0.001, thighs 1.28 \ub1 1.76 vs. 0.008 \ub1 0.005, p = 0.002 and lower legs 0.53 \ub1 0.85 vs. 0.02 \ub1 0.02, p = 0.001, but not for the tongue 0.20 \ub1 0.20 vs. 0.06 \ub1 0.09, p = 0.082 or upper arm 0.45 \ub1 0.95 vs. 0.002 \ub1 0.004, p = 0.014. Fat fraction %, was significantly higher in SMA than controls for: upper arm 35.0 \ub1 25.4 vs. 4.2 \ub1 1.1, p<<0.001, paraspinal 41.4 \ub1 31.0 vs. 7.4 \ub1 4.5, p = 0.002, thighs 54.8 \ub1 23.8 vs. 5.7 \ub1 1.0, p<<0.001 and lower legs 29.6 \ub1 23.5 vs. 4.4 \ub1 0.9, p = 0.0003, but not for the tongue 13.9 \ub1 3.2 vs. 13.0 \ub1 3.3, p = 0.393. MUMRI is an attractive non-invasive biomarker, which could be used to monitor progression & response in SMA clinical trials
Development of nanoparticle-based Toll-like receptor agonists for respiratory immunotherapy
Full text link\ua9 2026, Leibniz Research Centre for Working Environment and Human Factors. All rights reserved. Respiratory diseases are global health challenges demanding innovative immunotherapy solutions. Toll-like receptors (TLRs) play a crucial role in immune responses, making them attractive therapeutic targets. This review examines nanoparticle-based Toll-like receptor agonists as a promising approach for respiratory immunotherapy. Nanoparticles offer targeted drug delivery and sustained release, ideal for enhancing TLR agonist efficacy. This article explores TLRs\u27 role in immunomodulation, nanoparticle applications, design considerations, preclinical efficacy, safety assessments, challenges, and future prospects. Promising results from animal studies suggest enhanced immunological responses and reduced inflammation compared to conventional treatments. Safety concerns are addressed with insights from toxicity studies. Challenges include regulatory hurdles and biocompatibility, with strategies proposed for optimization. Nanoparticle-based TLR agonists hold great potential to transform respiratory disease treatment, warranting further research and collaboration for successful clinical translation
Enhancing injury severity prediction in small sample scenarios: A novel TabNet-DAAN approach for transfer learning
No full text\ua9 2026 Taylor & Francis Group, LLC and The University of Tennessee.This study proposes a novel transfer learning framework, TabNet-Dynamic Adversarial Adaptation Networks (TabNet-DAAN), to address the challenge of inadequate and imbalanced traffic crash data in certain regions. By integrating TabNet’s robust feature extraction with the dynamic adversarial framework of DAAN, this approach enhances transfer learning effectiveness through automatic alignment of data distributions across different domains. Moreover, it integrates a Class-balanced Loss (CBLoss) algorithm to mitigate the adverse effects of data imbalance and further enhance the model’s robustness. The methodology was empirically validated using two-vehicle crash data (2018–2022) from Birmingham (7,432 crashes, source domain) and Leeds (3,275 crashes, target domain) in the UK. Results from ablation studies confirm the effectiveness of the CBLoss algorithm and TabNet module. Moreover, TabNet-DAAN demonstrates superior performance compared to other transfer and non-transfer learning algorithms in predicting injury severity of target domain data, exhibiting excellent generalization capabilities, particularly when using a 7:1 source-to-target data ratio in training. Additionally, feature importance analysis shows that TabNet-DAAN adaptively refines its feature selection, effectively identifying key predictors across domains. These findings highlight the model’s potential to improve predictions of injury severity in data-scarce regions, presenting profound implications for targeted traffic safety interventions
Provision of knee bracing for knee osteoarthritis (PROP OA): Multicentre, parallel group, superiority, statistician blinded, randomised controlled trial
Full text link\ua9 Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.Objective To determine whether adding compartment specific knee bracing with an adherence intervention to advice, written information, and exercise instruction (AIE+B) is superior to advice, written information, and exercise instruction (AIE) only in improving patient reported outcomes in people with knee osteoarthritis. Design Multicentre, parallel group, superiority, statistician blinded, randomised (1:1; block; stratified; centralised web based) controlled trial. Setting Recruitment through general practices and the community in Cheshire, Manchester, North Tyneside, and Staffordshire, England; enrolment 25 November 2019 to 16 September 2022. Participants 466 adults aged ≥45 years with symptoms of knee osteoarthritis. Interventions AIE was delivered in one in-person consultation by a trained physiotherapist. Individuals randomised to the AIE+B group were also fitted with a patellofemoral, tibiofemoral unloading, or neutral stabilising knee brace, according to their predominant compartmental distribution of knee osteoarthritis, and were offered a two week follow-up consultation. Brief motivational interviewing with targeted text reminders supported brace adherence. Main outcome measures The primary outcome was a composite patient reported Knee Osteoarthritis Outcomes Score (KOOS)-5 (0-100) at six months after randomisation. Key secondary outcomes were KOOS-5 at three and 12 months, KOOS-5 subscale scores, and pain on weight bearing activity at three, six, and 12 months. Results 466 participants (mean age 64 (standard deviation 9) years; 46% female participants) were randomised, with 401 (86%), 394 (85%), and 370 (79%) participants followed up with analysable data at three, six, and 12 months, respectively. At six months, greater improvement in KOOS-5 was seen in the AIE+B group than in the AIE group (adjusted mean difference 3.39, 95% confidence interval (CI) 0.96 to 5.82; effect size 0.24). Secondary outcomes showed the benefits of AIE+B over AIE that diminished over time. The largest effects observed were for pain reduction (KOOS pain (0-100) adjusted mean difference at six months 6.13, 95% CI 3.36 to 8.91; effect size 0.39). Adverse events were minor and expected. Conclusions Adding compartment specific knee bracing and an adherence intervention to advice, written information, and exercise instruction resulted in small improvements in patient reported outcomes among individuals with knee osteoarthritis. This safe intervention offers a potential treatment option for this common condition. Trial registration ISRCTN28555470
Modelling of Aerostatic Bearings with Micro-Hole Restriction
Full text link\ua9 2025 by the authors.Aerostatic bearings incorporating micro-hole restrictors with diameters on the order of tens of microns demonstrate superior static and dynamic stiffness characteristics, while significantly reducing air consumption, and are increasingly adopted in precision engineering applications. This paper investigates the modelling of aerostatic bearings with micro-hole restrictors. First, a refined discharge coefficient formula is developed, incorporating the orifice length-to-diameter ratio effect using the computational fluid dynamics (CFD) simulation results on a centrally fed circular aerostatic bearing. A numerical solution scheme is proposed using the developed discharge coefficients to enable more accurate and efficient prediction of the bearing performance and flow characteristics. Finally, the proposed numerical approach is implemented using the finite difference method (FDM) and demonstrated through a circular thrust air bearing case study. The results are validated against both CFD simulations and experimental measurements, showing excellent agreement and confirming the reliability of the FDM-based numerical model. Numerical and experimental investigations consistently demonstrate that micro-hole-restricted air bearings can achieve both high load capacity and high stiffness, having the potential for application in more complex air bearing designs and systems
Rethinking Mechanical Ventilation: Can Ventilation Mode Influence Long-Term Cognitive Outcomes in ICU Patients with COVID-19?
Full text link\ua9 2026 by the authors. Background: Long-term cognitive impairment is common among ICU patients who required invasive mechanical ventilation (IMV). Its etiology is likely multifactorial. This preregistered study examined the association between the duration of IMV and cognitive function post-ICU, as well as the moderating effects of age and cognitive reserve. Methods: A secondary analysis was conducted using data from a published study of COVID-19 ICU survivors. One year after discharge, participants underwent a neuropsychological assessment. Linear regression models were used to evaluate associations between the variables. Results: Among patients who received IMV via endotracheal intubation, ventilation duration was not significantly associated with cognitive performance. In contrast, among tracheostomized patients, longer IMV duration was associated with better cognitive outcomes (Cohen’s f2 = 0.21). Age had a small negative main effect; in combination with IMV duration, f2 increased to 0.31. Cognitive reserve showed a strong positive association with cognitive outcome; in combination with IMV duration, f2 increased to 0.67. The interaction terms were negligible in both cases. Conclusions: We hypothesize that, compared to endotracheal intubation, IMV via tracheostoma may not only reduce the need for sedation, but also provide a more efficient respiratory support, therefore contributing to positive cognitive outcomes. However, IMV via tracheostomy still represents a form of positive pressure ventilation (PPV), which carries risks, such as ventilator-induced lung injury and reduced cardiac output and brain perfusion. These concerns about PPV, combined with our findings, indicate that alternative, non-invasive modes, such as negative pressure ventilation (NPV), warrant evaluation in future trials
Management of OPTic disc pIt MAculopathy
No full text\ua9 2025 American Academy of Ophthalmology.Purpose To evaluate long-term anatomical and visual outcomes after pars plana vitrectomy (PPV) combined with internal limiting membrane (ILM) flap in the treatment of optic disc pit maculopathy (ODPM). Design Multicenter, retrospective cohort study. Participants Patients with congenital ODPM who underwent primary or revisional PPV with ILM flap, with a minimum follow-up of 12 months. Methods Clinical data were retrospectively collected, including baseline characteristics, surgical details, fluid distribution, central macular thickness (CMT), and best-corrected visual acuity (BCVA) at baseline and at 1, 6, and 12 months postoperatively, as well as at the final follow-up. Main Outcomes Measures The primary outcome was the rate of anatomical resolution (defined as complete reabsorption of intraretinal fluid and subretinal fluid [SRF]) at 12 months. Secondary outcomes included anatomical resolution at last follow-up, change in CMT and BCVA, fluid distribution patterns, and identification of predictors of treatment response. Results A total of 71 eyes from 71 patients were included. Complete resolution was achieved in 33.8% of cases at 12 months, increasing to 57.7% at a median follow-up of 24 months. An additional 19.7% showed anatomical improvement. Mean CMT decreased significantly (from 639.5 μ m to 316.7 μ m at 12 months and 297.2 μ m at final follow-up, P < .0001 for both), and median BCVA improved from 0.6 (20/80) to 0.3 (20/40) logarithm of the minimum angle of resolution (LogMAR) at both 12-month and final follow-up ( P < .001). Anatomical and visual outcomes were comparable between primary and revisional surgeries. Multivariate analysis revealed that female sex (odds ratio [OR] = 5.7, P = .008) and presence of SRF only (OR = 8.0, P = .005) were independent predictors of complete resolution. Subretinal fluid-only configuration was also significantly associated with ≥0.2 LogMAR (2 Snellen lines) visual gain (OR = 5.0, P = .038). Intraoperative laser to optic disc edge was negatively associated with visual improvement (OR = 3.5, P = .048). Conclusions Pars plana vitrectomy with ILM flap offers favorable long-term anatomical and functional outcomes for ODPM, thus representing an effective treatment, in particular in revision cases. The presence of isolated SRF appears to be a positive prognostic marker for both anatomical and visual recovery. In contrast, adjunctive laser photocoagulation may negatively impact visual recovery. Our findings support caution against unnecessary early reoperation. Financial Disclosure(s) The authors have no proprietary or commercial interest in any materials discussed in this article