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Abstract In lung disease, persistence of KRT8-expressing aberrant basaloid cells in the alveolar epithelium is associated with impaired tissue regeneration and pathological tissue remodeling. We analyzed single cell RNA sequencing datasets of human interstitial lung disease and found the profibrotic Interleukin-11 (IL11) cytokine to be highly and specifically expressed in aberrant KRT8+ basaloid cells. IL11 is similarly expressed by KRT8+ alveolar epithelial cells lining fibrotic lesions in a mouse model of interstitial lung disease. Stimulation of alveolar epithelial cells with IL11 causes epithelial-to-mesenchymal transition and promotes a KRT8-high state, which stalls the beneficial differentiation of alveolar type 2 (AT2)-to-AT1 cells. Inhibition of IL11-signaling in AT2 cells in vivo prevents the accumulation of KRT8+ cells, enhances AT1 cell differentiation and blocks fibrogenesis, which is replicated by anti-IL11 therapy. These data show that IL11 inhibits reparative AT2-to-AT1 differentiation in the damaged lung to limit endogenous alveolar regeneration, resulting in fibrotic lung disease.

Objective To conduct a head-to-head comparative analysis of cataract surgery patient education material generated by Chat Generative Pre-trained Transformer (ChatGPT-4) and Google Bard.Methods and analysis 98 frequently asked questions on cataract surgery in English were taken in November 2023 from 5 trustworthy online patient information resources. 59 of these were curated (20 augmented for clarity and 39 duplicates excluded) and categorised into 3 domains: condition (n=15), preparation for surgery (n=21) and recovery after surgery (n=23). They were formulated into input prompts with ‘prompt engineering’. Using the Patient Education Materials Assessment Tool-Printable (PEMAT-P) Auto-Scoring Form, four ophthalmologists independently graded ChatGPT-4 and Google Bard responses. The readability of responses was evaluated using a Flesch-Kincaid calculator. Responses were also subjectively examined for any inaccurate or harmful information.Results Google Bard had a higher mean overall Flesch-Kincaid Level (8.02) compared with ChatGPT-4 (5.75) (p0.10). None of the generated material contained dangerous information.Conclusion In comparison to Google Bard, ChatGPT-4 fared better overall, scoring higher on the PEMAT-P understandability scale and exhibiting more faithfulness to the prompt engineering instruction. Since input prompts might vary from real-world patient searches, follow-up studies with patient participation are required.

Abstract The Consolidated Standards of Reporting Trials extension for Artificial Intelligence interventions (CONSORT-AI) was published in September 2020. Since its publication, several randomised controlled trials (RCTs) of AI interventions have been published but their completeness and transparency of reporting is unknown. This systematic review assesses the completeness of reporting of AI RCTs following publication of CONSORT-AI and provides a comprehensive summary of RCTs published in recent years. 65 RCTs were identified, mostly conducted in China (37%) and USA (18%). Median concordance with CONSORT-AI reporting was 90% (IQR 77–94%), although only 10 RCTs explicitly reported its use. Several items were consistently under-reported, including algorithm version, accessibility of the AI intervention or code, and references to a study protocol. Only 3 of 52 included journals explicitly endorsed or mandated CONSORT-AI. Despite a generally high concordance amongst recent AI RCTs, some AI-specific considerations remain systematically poorly reported. Further encouragement of CONSORT-AI adoption by journals and funders may enable more complete adoption of the full CONSORT-AI guidelines.

The Macao Government provides web-based streaming videos for the public to monitor live traffic and road conditions across the city. This allows individuals to review the latest road traffic conditions online before planning their travels. To let road user makes better and faster decisions, it is desirable to design an automated subsystem in an Intelligent Transportation System (ITS). And the subsystem should analyze available live video streams and recommend multiple travel routes, if possible, to each query instantly. In the paper, we propose a real-time road traffic condition evaluation system. Its design is based on a combination of deep learning models (YOLO and BoTSORT), and a modified Non-Maximum Suppression (mNMS) algorithm. The mNMS strategy removes the needs to manually tune the NMS parameters. By deploying YOLO with our mNMS, the object detection efficiency on live videos improves significantly. Together with the BoTSORT method, we can track the moving vehicles, create the corresponding motion trajectories, and identify traffic lanes with high correctness. The generated trajectory then operates as a filtering mechanism in assessing real-time road traffic conditions. By separating the lanes based on observation angles and using a per-lane status score independently, we further enhance the overall system performance. Through thorough experiments on the live videos, our design correctly estimates traffic status with high accuracy and without needing any manual parametric adjustments.

Faricimab is a newly approved bispecific antibody for neovascular age-related macular degeneration (nAMD). Our study aims to evaluate clinical outcomes of faricimab switching in patients with treatment-refractory nAMD; determine parameters that predict these outcomes; and obtain patient subjective experience on this new injection. This is a retrospective case review with clinical and imaging data from a tertiary referral unit (Birmingham and Midland Eye Centre, UK), involving patients who were switched to faricimab between 1 January and 1 December 2023. In all, 63 eyes (54 patients) with a mean age of 79.2 ± 7.8 and mean of 41.5 ± 22.4 previous anti-VEGF injections were analysed. With a mean of 4.81 ± 1.16 faricimab injections over 6.98 ± 1.75 months, post-treatment visual acuity was logMAR 0.49 ± 0.36 and central macular thickness (CMT) was 320.3 ± 97.9 µm. After first dose, 39.1% achieved complete dryness and 89.1% had anatomical improvement. Presence of subretinal fluid was a predictor of better functional outcomes (p = 0.001, β = −0.182), while initial CMT predicted better anatomical outcomes (p = 0.001, β = 0.688). Compared to their experiences of previous anti-VEGF injections, 89% of patients reported no more discomfort and 87.0% experienced no more floaters, photopsia, or bubbles post-injection. Faricimab switching has anatomical efficacy but limited functional improvement in treatment-refractory AMD. Patient experiences of faricimab compared to previous injections were overall positive.

Rabies, a fatal viral zoonotic disease, has become a public health concern in Sarawak, Malaysia. Despite pre-exposure and post-exposure prophylaxis being available, there has been limited progress in developing treatments for rabies, emphasising the pressing need for productive solutions. We present a laboratory-confirmed human rabies case in which the patient survived without neurological sequelae after receiving intrathecal rabies immunoglobulin. [ABSTRACT FROM AUTHOR]

Abstract Parkinson’s disease (PD) is a debilitating neurodegenerative disease characterized by the loss of midbrain dopaminergic neurons (DaNs) and the abnormal accumulation of α-Synuclein (α-Syn) protein. Currently, no treatment can slow nor halt the progression of PD. Multiplications and mutations of the α-Syn gene (SNCA) cause PD-associated syndromes and animal models that overexpress α-Syn replicate several features of PD. Decreasing total α-Syn levels, therefore, is an attractive approach to slow down neurodegeneration in patients with synucleinopathy. We previously performed a genetic screen for modifiers of α-Syn levels and identified CDK14, a kinase of largely unknown function as a regulator of α-Syn. To test the potential therapeutic effects of CDK14 reduction in PD, we ablated Cdk14 in the α-Syn preformed fibrils (PFF)-induced PD mouse model. We found that loss of Cdk14 mitigates the grip strength deficit of PFF-treated mice and ameliorates PFF-induced cortical α-Syn pathology, indicated by reduced numbers of pS129 α-Syn-containing cells. In primary neurons, we found that Cdk14 depletion protects against the propagation of toxic α-Syn species. We further validated these findings on pS129 α-Syn levels in PD patient neurons. Finally, we leveraged the recent discovery of a covalent inhibitor of CDK14 to determine whether this target is pharmacologically tractable in vitro and in vivo. We found that CDK14 inhibition decreases total and pathologically aggregated α-Syn in human neurons, in PFF-challenged rat neurons and in the brains of α-Syn-humanized mice. In summary, we suggest that CDK14 represents a novel therapeutic target for PD-associated synucleinopathy.

The Babouri-Figuil and Mayo Oulo-Lere basins located in Northern Cameroon are small elongated sedimentary asymmetric half-grabens associated with the development of the West and Central African Rift System (WCARS). The evolution of these basins began during the Precambrian pre-rift period and continued through the Late Jurassic - Early Cretaceous periods, although details of their development remain unclear. The aim of this study is to understand the evolution and development of the border faults and their control on syn-rift geometry, accommodation space, and the resulting stratigraphic architecture. Using a combination of multiples surface and subsurface well logs data, we demonstrate the relationship and evolution of various stages of rifting and the associated sedimentary architecture. The basin is composed of an alluvial to lacustrine succession that developed during its tectonic evolution. A 3-stage tectonic model is proposed for the evolution of the basin that uses fault propagation analysis to describe the sedimentary architecture and evolution of basin geometry. The three stages of the model are the early rift, rift climax, and late rift; here, the early rifting phase is marked by the reactivation of faults in the Lower Cretaceous. The rift climax phase resulted in the interconnection of small segmented border faults leading to the high rate of activation of major border faults and to the development of the half graben structure of the basins. The late rift stage is marked by a decrease in border fault activity and accommodation. Sediment distribution and the facies architecture are controlled by tectonic subsidence created throughout the rifting phases. The stratigraphic signature of the Babouri-Figuil and Mayo Oulo-Lere basins are punctuated by the lacustrine water transgression-regression cycles, and controlled by the balance between the rate of sediment supply and tectonic accommodation. The progressive change between overfilled to starved sedimentary architecture is illustrated by this stratigraphic succession. Additional age assessment and sub-surface data in future work could help confirm the structures identified on the surface.