Intravitreal Antibiotics versus Early Vitrectomy plus Intravitreal Antibiotics for Post-Injection Endophthalmitis: an IRIS® Registry (Intelligent Research in Sight).

PURPOSE: To determine if intravitreal injection of antibiotics alone versus early pars plana vitrectomy (PPV) plus injection of intravitreal antibiotics predicted better or worse visual outcomes for patients with endophthalmitis after anti-vascular endothelial growth factor (anti-VEGF) injections. DESIGN: Retrospective cohort study PARTICIPANTS: Patients developing endophthalmitis after receiving an intravitreal anti-VEGF injection from the American Academy of Ophthalmology IRIS® Registry between 2016 and 2020. METHODS: Inclusion criteria were endophthalmitis diagnosis within 1 to 28 days after anti-VEGF injection and a recorded visual acuity (VA) at baseline, on the day of diagnosis, and post-treatment. Patients in the Injection Only group underwent intravitreal injection of antibiotics alone and in the Early Vitrectomy group received PPV with intravitreal antibiotics or intravitreal injection followed by PPV within 2 days of diagnosis. Patients were excluded if they had cataract surgery during the study, intravitreal steroids before endophthalmitis, or intermediate/posterior uveitis or cystoid macular edema. The study created a 1:1 matched cohort using Mahalanobis Distance Matching, accounting for the differences in VA at baseline and diagnosis. MAIN OUTCOME MEASURES: Post-treatment logMAR VA RESULTS: 1,044 patients diagnosed with post-injection endophthalmitis met the inclusion and exclusion criteria. In the unmatched cohort, there were 935 patients in the Injection Only and 109 in the Early Vitrectomy group. In 1:1 matched cohort 218 patients (109 in each group) were included; the median logMAR VAs were 0.32 [20/40-20/50] at baseline, 0.88 [∼20/150] at diagnosis, and 0.57 [20/70-20/80] post-treatment. There were no statistically significant differences in the visual outcomes between the two matched treatment groups (b = 0.05, p = 0.23); including the subgroup of patients with VA worse than 1.0 logMAR (b = 0.05, p = 0.452). CONCLUSIONS: There was no significant difference in final VA outcomes between patients receiving Injection Only and those treated with Early Vitrectomy for post-injection endophthalmitis. The findings support the use of either treatment strategy.

ChatGPT for digital pathology research.

The rapid evolution of generative artificial intelligence (AI) models including OpenAI's ChatGPT signals a promising era for medical research. In this Viewpoint, we explore the integration and challenges of large language models (LLMs) in digital pathology, a rapidly evolving domain demanding intricate contextual understanding. The restricted domain-specific efficiency of LLMs necessitates the advent of tailored AI tools, as illustrated by advancements seen in the last few years including FrugalGPT and BioBERT. Our initiative in digital pathology emphasises the potential of domain-specific AI tools, where a curated literature database coupled with a user-interactive web application facilitates precise, referenced information retrieval. Motivated by the success of this initiative, we discuss how domain-specific approaches substantially minimise the risk of inaccurate responses, enhancing the reliability and accuracy of information extraction. We also highlight the broader implications of such tools, particularly in streamlining access to scientific research and democratising access to computational pathology techniques for scientists with little coding experience. This Viewpoint calls for an enhanced integration of domain-specific text-generation AI tools in academic settings to facilitate continuous learning and adaptation to the dynamically evolving landscape of medical research.

Emergent properties of coupled bistable switches.

Understanding the dynamical hallmarks of network motifs is one of the fundamental aspects of systems biology. Positive feedback loops constituting one or two nodes - self-activation, toggle switch, and double activation loops - are the commonly observed motifs in regulatory networks underlying cell-fate decision systems. Their individual dynamics are well studied; they are capable of exhibiting bistability. However, studies across various biological systems suggest that such positive feedback loops are interconnected with one another, and design principles of coupled bistable motifs remain unclear. What happens to the bistability or multistability traits and the phenotypic space (collection of phenotypes exhibited by a system) due to the couplings? In this study, we explore a set of such interactions using discrete and continuous simulation methods. Our results suggest that the most frequent states in coupled networks follow the 'rules' within a motif (double activation, toggle switch) and those across the two motifs in terms of how the two motifs have been coupled. Moreover, 'hybrid' states can be observed, too, where one of the above-mentioned 'rules' can be compromised, leading to a more diverse phenotypic repertoire. Furthermore, adding direct and indirect selfactivations to these coupled networks can increase the frequency of multistability. Thus, our observations revealed specific dynamical traits exhibited by various coupled bistable motifs.

Landscape of epithelial-mesenchymal plasticity as an emergent property of coordinated teams in regulatory networks.

Elucidating the design principles of regulatory networks driving cellular decision-making has fundamental implications in mapping and eventually controlling cell-fate decisions. Despite being complex, these regulatory networks often only give rise to a few phenotypes. Previously, we identified two 'teams' of nodes in a small cell lung cancer regulatory network that constrained the phenotypic repertoire and aligned strongly with the dominant phenotypes obtained from network simulations (Chauhan et al., 2021). However, it remained elusive whether these 'teams' exist in other networks, and how do they shape the phenotypic landscape. Here, we demonstrate that five different networks of varying sizes governing epithelial-mesenchymal plasticity comprised of two 'teams' of players - one comprised of canonical drivers of epithelial phenotype and the other containing the mesenchymal inducers. These 'teams' are specific to the topology of these regulatory networks and orchestrate a bimodal phenotypic landscape with the epithelial and mesenchymal phenotypes being more frequent and dynamically robust to perturbations, relative to the intermediary/hybrid epithelial/mesenchymal ones. Our analysis reveals that network topology alone can contain information about corresponding phenotypic distributions, thus obviating the need to simulate them. We propose 'teams' of nodes as a network design principle that can drive cell-fate canalization in diverse decision-making processes.

PrISM: precision for integrative structural models.

MOTIVATION: A single-precision value is currently reported for an integrative model. However, precision may vary for different regions of an integrative model owing to varying amounts of input information. RESULTS: We develop PrISM (Precision for Integrative Structural Models) to efficiently identify high- and low-precision regions for integrative models. AVAILABILITY AND IMPLEMENTATION: PrISM is written in Python and available under the GNU General Public License v3.0 at https://github.com/isblab/prism; benchmark data used in this paper are available at doi:10.5281/zenodo.6241200. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Fungal biodegradation of low-density polyethylene using consortium of Aspergillus species under controlled conditions.

Low-Density polyethylene is subject to biodegradation using a fungal consortium comprising of Aspergillus niger, Aspergillus flavus and Aspergillus oryzae under laboratory conditions. The extent of biodegradation has been compared with the use of potato dextrose broth and czapek dox broth media and also in the presence and absence of Tween 80 additive. Biodegradation was performed replacing the sucrose in czapek dox broth with shredded Low-Density polyethylene as well. The biodegradation was carried out for a period of 55 days. The degree of biodegradation has been analyzed using the loss of weight, FT-IR, and SEM analysis. A maximum weight loss of 26.15% was obtained by using potato dextrose broth over a period of 55 days.