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Background Microbial Keratitis (MK) is a leading cause of corneal blindness due to infection and its consequences, with a higher incidence in resource-limited nations. Hospital-based patient records from different parts of Nepal suggest patients often use traditional eye medicine to treat MK. Traditional healers (TH) within the community are often the first point of care for MK management. Little is known of their practice, perceptions, and knowledge around MK management. We aimed to understand the role of traditional healers in the management of MK in south-eastern Nepal. Methods A cross-sectional, mixed method, descriptive study was conducted in the Siraha district of Nepal. A total of 109 traditional healers consented to participate in a survey of knowledge, attitude, and practices. Some participants were also invited to participate in in-depth interviews and focus group discussions. Interviews and focus groups were conducted and recorded in the Maithili language by a native speaking interviewer and transcribed into English. Descriptive analysis was performed for the survey. Data saturation was considered the endpoint for qualitative data collection, and a thematic was analysis applied. Results Traditional healers believe that infection of the eye can be caused by trauma, conjunctivitis, or evil spirits. They were unclear about differentiating MK from other eye conditions. They provided various types of treatment. Some were confident that they could treat severe ulcers that had not responded to medical therapy, while others thought treating larger diameter ulcers would be difficult. Although there were mixed responses in referring patients with MK, the majority of TH were willing to refer. Conclusion In a weak health system, traditional healers may help address barriers to healthcare access and reduce delays to definitive care, upon integration into the formal health system and referral pathway.

BackgroundLabeling color fundus photos (CFP) is an important step in the development of artificial intelligence screening algorithms for the detection of diabetic retinopathy (DR). Most studies use the International Classification of Diabetic Retinopathy (ICDR) to assign labels to CFP, plus the presence or absence of macular edema (ME). Images can be grouped as referrable or nonreferrable according to these classifications. There is little guidance in the literature about how to collect and use metadata as a part of the CFP labeling process. ObjectiveThis study aimed to improve the quality of the Multimodal Database of Retinal Images in Africa (MoDRIA) by determining whether the availability of metadata during the image labeling process influences the accuracy, sensitivity, and specificity of image labels. MoDRIA was developed as one of the inaugural research projects of the Mbarara University Data Science Research Hub, part of the Data Science for Health Discovery and Innovation in Africa (DS-I Africa) initiative. MethodsThis is a crossover assessment with 2 groups and 2 phases. Each group had 10 randomly assigned labelers who provided an ICDR score and the presence or absence of ME for each of the 50 CFP in a test image with and without metadata including blood pressure, visual acuity, glucose, and medical history. Specificity and sensitivity of referable retinopathy were based on ICDR scores, and ME was calculated using a 2-sided t test. Comparison of sensitivity and specificity for ICDR scores and ME with and without metadata for each participant was calculated using the Wilcoxon signed rank test. Statistical significance was set at P

Abstract To develop and assess a deep learning (DL) pipeline to learn dynamic MR image reconstruction from publicly available natural videos (Inter4K). Learning was performed for a range of DL architectures (VarNet, 3D UNet, FastDVDNet) and corresponding sampling patterns (Cartesian, radial, spiral) either from true multi-coil cardiac MR data (N = 692) or from synthetic MR data simulated from Inter4K natural videos (N = 588). Real-time undersampled dynamic MR images were reconstructed using DL networks trained with cardiac data and natural videos, and compressed sensing (CS). Differences were assessed in simulations (N = 104 datasets) in terms of MSE, PSNR, and SSIM and prospectively for cardiac cine (short axis, four chambers, N = 20) and speech cine (N = 10) data in terms of subjective image quality ranking, SNR and Edge sharpness. Friedman Chi Square tests with post-hoc Nemenyi analysis were performed to assess statistical significance. In simulated data, DL networks trained with cardiac data outperformed DL networks trained with natural videos, both of which outperformed CS (p

Abstract Background To assess the prevalence of low corneal endothelial cell density and correlates of corneal endothelial cell density among adults attending Mbarara University and Referral Hospital Eye Centre in Uganda. Methods In this hospital-based cross-sectional study, participants 18 years and older, were enrolled. We obtained informed consent, and basic demographic data. We also conducted visual acuity, a detailed slit lamp examination, intra-ocular pressure, corneal diameter, tear-film break-up time, keratometry, A-scan, and pachymetry on all participants. A confocal microscope Heidelberg HRT3 was used to examine the central cornea and to obtain the mean cell density (cells/mm2). To calculate the proportion of low endothelial cell density, descriptive statistics were used, whereas correlates of endothelial cell density were assessed, using linear regression analyses. Results We evaluated a total of 798 eyes of 404 participants aged between 18 and 90 years (males = 187, females = 217). The average endothelial cell density was 2763.6 cells/mm2, and there was a decrease in endothelial cell density with increasing age, irrespective of gender. There was no significant difference in endothelial cell density between males and females. Increasing age (adjusted coefficient − 10.1, p

Abstract Background Existing plasmid systems offer a fundamental foundation for gene expression in Cupriavidus necator; however, their applicability is constrained by the limitations of conjugation. Low segregational stabilities and plasmid copy numbers, particularly in the absence of selection pressure, pose challenges. Phytases, recognized for their widespread application as supplements in animal feed to enhance phosphate availability, present an intriguing prospect for heterologous production in C. necator. The establishment of stable, high-copy number plasmid that can be electroporated would support the utilization of C. necator for the production of single-cell protein from CO2. Results In this study, we introduce a novel class of expression plasmids specifically designed for electroporation. These plasmids contain partitioning systems to boost segregation stability, eliminating the need for selection pressure. As a proof of concept, we successfully produced Escherichia coli derived AppA phytase in C. necator H16 PHB− 4 using these improved plasmids. Expression was directed by seven distinct promoters, encompassing the constitutive j5 promoter, hydrogenase promoters, and those governing the Calvin-Benson-Bassham cycle. The phytase activities observed in recombinant C. necator H16 strains ranged from 2 to 50 U/mg of total protein, contingent upon the choice of promoter and the mode of cell cultivation - heterotrophic or autotrophic. Further, an upscaling experiment conducted in a 1 l fed-batch gas fermentation system resulted in the attainment of the theoretical biomass. Phytase activity reached levels of up to 22 U/ml. Conclusion The new expression system presented in this study offers a highly efficient platform for protein production and a wide array of synthetic biology applications. It incorporates robust promoters that exhibit either constitutive activity or can be selectively activated when cells transition from heterotrophic to autotrophic growth. This versatility makes it a powerful tool for tailored gene expression. Moreover, the potential to generate active phytases within C. necator H16 holds promising implications for the valorization of CO2 in the feed industry.

Objective A comparison of cryoneurolysis or radio frequency (RF) with placebo in patients with facetogenic chronic low back pain (LBP) for patient global impression of change (PGIC), pain intensity, function and quality of life, with 1-year follow-up.Design Single-centre, single-blinded placebo-controlled randomised controlled trial.Setting Single-centre study.Participants Inclusion from March 2020 to September 2022: consenting adults over 18 years of age, LBP>3 months, average Numeric Rating Scale LBP≥4 average last 14 days and a positive response to a diagnostic medial branch block (>50% pain reduction after 60 min).Interventions 120 patients were block randomised 1:1:1 to cryoneurolysis, RF or placebo of the medial branch nerves. Physical therapy was added after 4 weeks for all groups.Main outcome measures Primary outcome was PGIC 4 weeks after the intervention. Secondary outcomes included pain intensity (Numeric Rating Scale, NRS), quality of life (Short Form 36, EQ-5D-5L), disability (Oswestry Disability Index), depression (Major Depression Inventory) and catastrophising (Pain Catastrophising Scale). Outcomes were measured at 4 weeks, 3, 6 and 12 months.Results There was no statistically significant difference in PGIC at 4 weeks between cryoneurolysis and placebo (risk ratio (RR) 2; 95% CI 0.75 to 5.33, p=0.17) and RF and placebo (RR 1.6; 95% CI 0.57 to 4.49, p=0.37), except PGIC for cryoneurolysis at 6-month follow-up (RR 5.1; 95% CI 1.20 to 22.03, p=0.03). No statistically significant differences were found in secondary follow-up endpoints.Conclusions Denervation of the medial branch nerve by either cryoneurolysis or RF compared with placebo did not demonstrate significant improvement in PGIC, pain intensity, function and quality of life in patients with facetogenic chronic LBP at short-term or long-term follow-up.Trial registration number NCT04786145.

Traditional robot navigation passively plans/replans to avoid any contact with obstacles in the scene. This limits the obtained solutions to the collision‐free space and leads to failures if the path to the goal is obstructed. In contrast, humans actively modify their environment by repositioning objects if it assists locomotion. This article aims to bring robots closer to such abilities by providing a framework to detect and clear movable obstacles to continue navigation. The approach leverages a multimodal robot skin that provides both local proximity and tactile feedback regarding physical interactions with the surroundings. This multimodal contact feedback is employed to adapt the robot's behavior when interacting with object surfaces and regulating applied forces. This enables the robot to remove bulky obstacles from its path and solves otherwise infeasible navigation problems. The system's ability is demonstrated in simulation and real‐world scenarios involving movable and nonmovable obstacles.

Abstract The identification and characterization of enzyme function is largely lacking behind the rapidly increasing availability of large numbers of sequences and associated high-resolution structures. This is often hampered by lack of knowledge on in vivo relevant substrates. Here, we present a case study of a high-resolution structure of an unusual orphan lipase in complex with an endogenous C18 monoacylglycerol ester reaction intermediate from the expression host, which is insoluble under aqueous conditions and thus not accessible for studies in solution. The data allowed its functional characterization as a prototypic long-chain monoacylglycerol lipase, which uses a minimal lid domain to position the substrate through a hydrophobic tunnel directly to the enzyme’s active site. Knowledge about the molecular details of the substrate binding site allowed us to modulate the enzymatic activity by adjusting protein/substrate interactions, demonstrating the potential of our findings for future biotechnology applications.

Anthropocentrism centralizes the role of humans and human impact on the environment. In folktales, the anthropocentric nuance is amplified by the moral messages delivered after telling the tales. The moral messages are usually for the betterment of humans. This paper intends to offer an alternative reading of a folktale by shifting the focal perspective slightly from human to nature and supernatural beings and their power. The object of this paper is a folktale from Vietnamese culture titled The Celestial King Phu Dong and the Iron Horse. In the tale, the human character could defeat the monster since they had supernatural power. This paper employs three tools to foreground the roles of nature and supernatural power. The folktale's plot is analyzed by its tale elements proposed by Booker (2004). The power relation of the actants is analyzed using Greimas' actantial analysis, and the clause structure is examined by Systemic Functional Linguistic's thematic structure analysis. The result shows that the plot is built upon the opposition between human and nonhuman characters. The actantial analysis indicates that in opposing the nonhuman character, the human character needs help from nature and supernatural power. The thematic patterns structure the delivery of the power relation and the human character dependency. This paper concludes that human character is depicted as dependent on nature and supernatural power in solving problems and obstacles. It foregrounds the agency of objects surrounding humans.

Abstract Lytic polysaccharide monooxygenases (LPMOs) are taxonomically widespread copper-enzymes boosting biopolymers conversion (e.g. cellulose, chitin) in Nature. White-rot Polyporales, which are major fungal wood decayers, may possess up to 60 LPMO-encoding genes belonging to the auxiliary activities family 9 (AA9). Yet, the functional relevance of such multiplicity remains to be uncovered. Previous comparative transcriptomic studies of six Polyporales fungi grown on cellulosic substrates had shown the overexpression of numerous AA9-encoding genes, including some holding a C-terminal domain of unknown function (“X282”). Here, after carrying out structural predictions and phylogenetic analyses, we selected and characterized six AA9-X282s with different C-term modularities and atypical features hitherto unreported. Unexpectedly, after screening a large array of conditions, these AA9-X282s showed only weak binding properties to cellulose, and low to no cellulolytic oxidative activity. Strikingly, proteomic analysis revealed the presence of multiple phosphorylated residues at the surface of these AA9-X282s, including a conserved residue next to the copper site. Further analyses focusing on a 9 residues glycine-rich C-term extension suggested that it could hold phosphate-binding properties. Our results question the involvement of these AA9 proteins in the degradation of plant cell wall and open new avenues as to the divergence of function of some AA9 members.

Objective – This study delves into the perspectives of teenagers regarding their desired teen space within a small rural public library in the United States. Methods – To capture the richness of their thoughts, a visual data collection method was employed, wherein 27 8th-grade participants engaged in a drawing activity during an art class at a local middle school. Two additional teens were recruited for individual semi-structured interviews. Results – Through this creative exercise, the study unveiled the various library activities, amenities, books, and visual designs that resonated with the teens, as they envisioned their ideal teen space. Conclusion – The study’s findings hold practical implications for librarians working with this population, offering valuable insights to enhance and optimize teen services at the library. By aligning the library’s offerings with the desires of the young patrons, the potential for a thriving and engaging teen community within the library is enhanced.

The sensitivity of phase-sensitive detectors, such as piezoelectric detectors, becomes increasingly directional as the detector element size increases. In contrast, pyroelectric sensors, which are phase-insensitive, retain their omni-directionality even for large element sizes, although they have significantly poorer temporal resolution. This study uses numerical models to examine whether phase-insensitive detectors can be used advantageously in ultrasound tomography, specifically absorption tomography, when the number of detectors is sparse. We present measurement models for phase-sensitive and phase-insensitive sensors and compare the quality of the absorption reconstructions between these sensor types based on relative error and image contrast metrics. We perform the inversion using synthetic data with a Jacobian-based linearized matrix inversion approach.

Abstract Background Non‐traumatic spinal cord hemorrhage (NTSH) is an uncommon cause of myelopathy in dogs. Objectives Describe the clinical characteristics, concurrent medical conditions and underlying causes, magnetic resonance imaging (MRI) findings and outcome in dogs with NTSH. Animals Dogs diagnosed with NTSH using gradient echo T2‐weighted (GRE) sequences with or without histopathological confirmation of hemorrhage were included. Dogs with a traumatic cause were excluded, including those with compressive intervertebral disc extrusion. Methods Retrospective descriptive study; the databases of 2 referral hospitals were searched between 2013 and 2021. Results Twenty‐three dogs met inclusion criteria. The onset of signs was acute and progressive in 70% of cases; spinal hyperesthesia was variable (48%). Hemorrhage was identified in the thoracolumbar spinal segments in 65% of dogs. An underlying cause was identified in 65% of cases. Angiostrongylus vasorum represented 18% of the total cohort, followed by steroid‐responsive meningitis arteritis (SRMA; 13%). Overall, 64% of dogs had a good or excellent outcome, regardless of cause; which was increased to 100% for SRMA, 75% for A. vasorum and 75% for idiopathic NTSH. Outcome was not associated with neurological severity. Recovery rate was 67% and 50% for nociception‐intact and nociception‐negative dogs, respectively. Conclusions Larger prospective studies would be required to define prognostic factors for dogs with NTSH, but outcome appeared to be most influenced by the underlying cause, as opposed to neurological severity at presentation.

“Family” in The Song of Silver Frond (TSOSF) functions as a site of gender and class struggles to challenge the Chinese yin-yang and nei-wai tradition. Continuities and transformations in Chinese familial practices result from complex socio-cultural-generational dynamics. "Family" becomes a battleground of gender and class struggles for the preservation and transformation of those familial traditions. Moreover, the dynamic of ethnicity also intersects with gender and class relations. The traditional Chinese familial practices follow two fundamental Confucian gender foundations: yin-yang and nei-wai. The yin-yang delineation privileges man versus woman. Meanwhile, the private/public distinction of nei-wai relegates the woman's place to the domestic sphere. By employing Post-Structural feminist perspectives focusing on gender intersectionality, this article examines how "family" becomes the site of ethnic-gender-class struggles in TSOSF. The articles revealed that some family members, both men, and women, continue to apply the traditional Confucian rules from generation to generation. However, other members challenge those traditional practices to contest gender and class inequalities to adapt to different sociocultural dynamics in Southeast Asian Society. Thus, this article has articulated the way TSOSF displays "family" as a site of gender and class struggle in Chinese familial practices.

A computational mechanistic viral infection model and trial simulation advocates for adaptation of respiratory disease clinical trials whose chances of success and interpretability are being degraded under COVID-19 pandemic mitigation measures.

Abstract Background Fatty acid-based substances play an important role in many products, from food supplements to pharmaceutical products and biofuels. The production of fatty acids, mainly in their esterified form as triacylglycerol (TAG), has been intensively studied in oleaginous yeasts, whereas much less effort has been invested into non-oleaginous species. In the present work, we engineered the model yeast Saccharomyces cerevisiae, which is commonly regarded as non-oleaginous, for the storage of high amounts of TAG, comparable to the contents achieved in oleaginous yeasts. Results We investigated the effects of several mutations with regard to increased TAG accumulation and identified six of them as important for this phenotype: a point mutation in the acetyl-CoA carboxylase Acc1p, overexpression of the diacylglycerol acyltransferase Dga1p, deletions of genes coding for enzymes involved in the competing pathways glycogen and steryl ester synthesis and TAG hydrolysis, and a deletion of CKB1, the gene coding for one of the regulatory subunits of casein kinase 2. With the combination of these mutations in a S. cerevisiae strain with a relatively high neutral lipid level already in the non-engineered state, we achieved a TAG content of 65% in the dry biomass. High TAG levels were not only obtained under conditions that favor lipid accumulation, but also in defined standard carbon-limited media. Conclusions Baker's yeast, which is usually regarded as inefficient in the storage of TAG, can be converted into a highly oleaginous strain that could be useful in processes aiming at the synthesis of fatty acid-based products. This work emphasizes the importance of strain selection in combination with metabolic engineering to obtain high product levels.

BackgroundThe aim of this study was to describe the health-seeking journey for patients with microbial keratitis (MK) in Nepal and identify factors associated with delay.MethodsProspective cohort study where MK patients attending a large, tertiary-referral eye hospital in south-eastern Nepal between June 2019 and November 2020 were recruited. We collected demographic details, clinical history, and examination findings. Care-seeking journey details were captured including places attended, number of journeys, time from symptom onset, and costs. We compared “direct” with “indirect” presenters, analyzing for predictors of delay.ResultsWe enrolled 643 patients with MK. The majority (96%) self-referred. “Direct” attenders accounted for only 23.6% (152/643) of patients, the majority of “indirect” patients initially presented to a pharmacy (255/491). Over half (328/643) of all cases presented after at least 7 days. The total cost of care increased with increasing numbers of facilities visited (p < 0.001). Those living furthest away were least likely to present directly (p < 0.001). Factors independently associated with delayed presentation included distance >50 km from the eye hospital [aOR 5.760 (95% CI 1.829–18.14, p = 0.003)], previous antifungal use [aOR 4.706 (95% CI 3.139–5.360)], and two or more previous journeys [aOR 1.442 (95% CI 1.111–3.255)].ConclusionsMost patients visited at least one facility prior to our institution, with time to presentation and costs increasing with the number of prior journeys. Distance to the eye hospital is a significant barrier to prompt, direct presentation. Based on these findings, improving access to eye care services, strengthening referral networks and encouraging early appropriate treatment are recommended to reduce delay, ultimately improving clinical outcomes.

Autocatalytic networks may have started evolution during the origin of life. Here, the authors establish a landscape of thousands of RNA networks by barcoded sequencing and microfluidics, and derive relationships between topology and Darwinian properties such as variation and differential reproduction.

The state-of-the art for solving the nonlinear material decomposition problem in spectral computed tomography is based on variational methods, but these are computationally slow and critically depend on the particular choice of the regularization functional. Convolutional neural networks have been proposed for addressing these issues. However, learning algorithms require large amounts of experimental data sets. We propose a deep learning strategy for solving the material decomposition problem based on a U-Net architecture and a Sim2Real transfer learning approach where the knowledge that we learn from synthetic data is transferred to a real-world scenario. In order for this approach to work, synthetic data must be realistic and representative of the experimental data. For this purpose, numerical phantoms are generated from human CT volumes of the KiTS19 Challenge dataset, segmented into specific materials (soft tissue and bone). These volumes are projected into sinogram space in order to simulate photon counting data, taking into account the energy response of the scanner. We compared projection- and image-based decomposition approaches where the network is trained to decompose the materials either in the projection or in the image domain. The proposed Sim2Real transfer strategies are compared to a regularized Gauss-Newton (RGN) method on synthetic data, experimental phantom data and human thorax data.

Abstract Background Three-dimensional, whole heart, balanced steady state free precession (WH-bSSFP) sequences provide delineation of intra-cardiac and vascular anatomy. However, they have long acquisition times. Here, we propose significant speed-ups using a deep-learning single volume super-resolution reconstruction, to recover high-resolution features from rapidly acquired low-resolution WH-bSSFP images. Methods A 3D residual U-Net was trained using synthetic data, created from a library of 500 high-resolution WH-bSSFP images by simulating 50% slice resolution and 50% phase resolution. The trained network was validated with 25 synthetic test data sets. Additionally, prospective low-resolution data and high-resolution data were acquired in 40 patients. In the prospective data, vessel diameters, quantitative and qualitative image quality, and diagnostic scoring was compared between the low-resolution, super-resolution and reference high-resolution WH-bSSFP data. Results The synthetic test data showed a significant increase in image quality of the low-resolution images after super-resolution reconstruction. Prospectively acquired low-resolution data was acquired ~× 3 faster than the prospective high-resolution data (173 s vs 488 s). Super-resolution reconstruction of the low-resolution data took

This work proposes and realizes a control architecture that can support the deployment of a large‐scale robot skin in a Human‐Robot Collaboration scenario. It is shown, how whole‐body tactile feedback can extend the capabilities of robots during dynamic interactions by providing information about multiple contacts across the robot's surface. Specifically, an uncalibrated skin system is used to implement stable force control while simultaneously handling the multi‐contact interactions of a user. The system formulates control tasks for force control, tactile guidance, collision avoidance, and compliance, and fuses them with a multi‐priority redundancy resolution strategy. The approach is evaluated on an omnidirectional mobile‐manipulator with dual arms covered with robot skin. Results are assessed under dynamic conditions, showing that multi‐modal tactile information enables robust force control while at the same time remaining responsive to a user's interactions.

Summary: Background: We undertook a Grand Challenges in Global Eye Health prioritisation exercise to identify the key issues that must be addressed to improve eye health in the context of an ageing population, to eliminate persistent inequities in health-care access, and to mitigate widespread resource limitations. Methods: Drawing on methods used in previous Grand Challenges studies, we used a multi-step recruitment strategy to assemble a diverse panel of individuals from a range of disciplines relevant to global eye health from all regions globally to participate in a three-round, online, Delphi-like, prioritisation process to nominate and rank challenges in global eye health. Through this process, we developed both global and regional priority lists. Findings: Between Sept 1 and Dec 12, 2019, 470 individuals complete round 1 of the process, of whom 336 completed all three rounds (round 2 between Feb 26 and March 18, 2020, and round 3 between April 2 and April 25, 2020) 156 (46%) of 336 were women, 180 (54%) were men. The proportion of participants who worked in each region ranged from 104 (31%) in sub-Saharan Africa to 21 (6%) in central Europe, eastern Europe, and in central Asia. Of 85 unique challenges identified after round 1, 16 challenges were prioritised at the global level; six focused on detection and treatment of conditions (cataract, refractive error, glaucoma, diabetic retinopathy, services for children and screening for early detection), two focused on addressing shortages in human resource capacity, five on other health service and policy factors (including strengthening policies, integration, health information systems, and budget allocation), and three on improving access to care and promoting equity. Interpretation: This list of Grand Challenges serves as a starting point for immediate action by funders to guide investment in research and innovation in eye health. It challenges researchers, clinicians, and policy makers to build collaborations to address specific challenges. Funding: The Queen Elizabeth Diamond Jubilee Trust, Moorfields Eye Charity, National Institute for Health Research Moorfields Biomedical Research Centre, Wellcome Trust, Sightsavers, The Fred Hollows Foundation, The Seva Foundation, British Council for the Prevention of Blindness, and Christian Blind Mission. Translations: For the French, Spanish, Chinese, Portuguese, Arabic and Persian translations of the abstract see Supplementary Materials section.

The human brain contains billions of neurons that flexibly interconnect to support local and global computational spans. As neuronal activity propagates through the neural medium, it approaches a critical state hedged between ordered and disordered system regimes. Recent work demonstrates that this criticality coincides with the small-world topology, a network arrangement that accommodates both local (subcritical) and global (supercritical) system properties. On one hand, operating near criticality is thought to offer several neurocomputational advantages, e.g., high-dynamic range, efficient information capacity, and information transfer fidelity. On the other hand, aberrations from the critical state have been linked to diverse pathologies of the brain, such as post-traumatic epileptiform seizures and disorders of consciousness. Modulation of brain activity, through neuromodulation, presents an attractive mode of treatment to alleviate such neurological disorders, but a tractable neural framework is needed to facilitate clinical progress. Using a variation on the generative small-world model of Watts and Strogatz and Kuramoto's model of coupled oscillators, we show that the topological and dynamical properties of the small-world network are divided into two functional domains based on the range of connectivity, and that these domains play distinct roles in shaping the behavior of the critical state. We demonstrate that short-range network connections shape the dynamics of the system, e.g., its volatility and metastability, whereas long-range connections drive the system state, e.g., a seizure. Together, these findings lend support to combinatorial neuromodulation approaches that synergistically normalize the system dynamic while mobilizing the system state.

Eye-trackers are widely used to study nervous system dynamics and neuropathology. Despite this broad utility, eye-tracking remains expensive, hardware-intensive, and proprietary, limiting its use to high-resource facilities. It also does not easily allow for real-time analysis and closed-loop design to link eye movements to neural activity. To address these issues, we developed an open-source eye-tracker – EyeLoop – that uses a highly efficient vectorized pupil detection method to provide uninterrupted tracking and fast online analysis with high accuracy on par with popular eye tracking modules, such as DeepLabCut. This Python-based software easily integrates custom functions using code modules, tracks a multitude of eyes, including in rodents, humans, and non-human primates, and operates at more than 1,000 frames per second on consumer-grade hardware. In this paper, we demonstrate EyeLoop’s utility in an open-loop experiment and in biomedical disease identification, two common applications of eye-tracking. With a remarkably low cost and minimum setup steps, EyeLoop makes high-speed eye-tracking widely accessible.

Objective Fungal keratitis is a major ophthalmic public health problem, particularly in low-income and middle-income countries. The options for treating fungal keratitis are limited. Our study aimed to describe the outcomes of using chlorhexidine 0.2% eye-drops as additional treatment in the management of patients with recalcitrant fungal keratitis.Methods This study was nested within a large cohort study of people presenting with microbial keratitis in Uganda. We enrolled patients with recalcitrant fungal keratitis not improving with topical natamycin 5% and commenced chlorhexidine 0.2%. Follow-up was scheduled for 3 months and 1 year. The main outcome measures were healing, visual acuity and scar size at final follow-up.Results Thirteen patients were followed in this substudy. The patients were aged 27–73 years (median 43 years). Filamentous fungi were identified by microscopy of corneal scrape samples in all cases. Isolated organisms included Aspergillus spp, Fusarium spp, Candida spp, Bipolaris spp and Acremoninum spp. At the final follow-up, nine patients (75%) had healed; three had vision of better than 6/18. Three patients lost their eyes due to infection. In the remaining nine cases, corneal scarring was variable ranging from 4.6 to 9.4 mm (median 6.6 mm, IQR 5.9–8.0 mm); of these five had dense scars, three had moderate scars and one had a mild scar. None of the patients demonstrated signs of chlorhexidine toxicity during the follow-up.Conclusion Chlorhexidine 0.2% was found to be a useful sequential adjunctive topical antifungal in cases of fungal keratitis not responding to natamycin 5%, which warrants further evaluation.

Neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) are inflammatory diseases of the CNS. Overlap in the clinical and MRI features of NMOSD and MS means that distinguishing these conditions can be difficult. With the aim of evaluating the diagnostic utility of MRI features in distinguishing NMOSD from MS, we have conducted a cross-sectional analysis of imaging data and developed predictive models to distinguish the two conditions. NMOSD and MS MRI lesions were identified and defined through a literature search. Aquaporin-4 (AQP4) antibody positive NMOSD cases and age- and sex-matched MS cases were collected. MRI of orbits, brain and spine were reported by at least two blinded reviewers. MRI brain or spine was available for 166/168 (99%) of cases. Longitudinally extensive (OR = 203), “bright spotty” (OR = 93.8), whole (axial; OR = 57.8) or gadolinium (Gd) enhancing (OR = 28.6) spinal cord lesions, bilateral (OR = 31.3) or Gd-enhancing (OR = 15.4) optic nerve lesions, and nucleus tractus solitarius (OR = 19.2), periaqueductal (OR = 16.8) or hypothalamic (OR = 7.2) brain lesions were associated with NMOSD. Ovoid (OR = 0.029), Dawson's fingers (OR = 0.031), pyramidal corpus callosum (OR = 0.058), periventricular (OR = 0.136), temporal lobe (OR = 0.137) and T1 black holes (OR = 0.154) brain lesions were associated with MS. A score-based algorithm and a decision tree determined by machine learning accurately predicted more than 85% of both diagnoses using first available imaging alone. We have confirmed NMOSD and MS specific MRI features and combined these in predictive models that can accurately identify more than 85% of cases as either AQP4 seropositive NMOSD or MS.

Filamentous fungal infections of the cornea known as filamentous fungal keratitis (FK) are challenging to treat. Topical natamycin 5% is usually first-line treatment following the results of several landmark clinical trials. However, even when treated intensively, infections may progress to corneal perforation. Current topical antifungals are not always effective and are often unavailable. Alternatives topical therapies to natamycin include voriconazole, chlorhexidine, amphotericin B and econazole. Surgical therapy, typically in the form of therapeutic penetrating keratoplasty, may be required for severe cases or following corneal perforation. Alternative treatment strategies such as intrastromal or intracameral injections of antifungals may be used. However, there is often no clear treatment strategy and the evidence to guide therapy is often lacking. This review describes the different treatment options and their evidence and provides a pragmatic approach to the management of fungal keratitis, particularly for clinicians working in tropical, low-resource settings where fungal keratitis is most prevalent.

Brain disease has become one of this century’s biggest health challenges, urging the development of novel, more effective treatments. To this end, neuromodulation represents an excellent method to modulate the activity of distinct neuronal regions to alleviate disease. Recently, the medical indications for neuromodulation therapy have expanded through the adoption of the idea that neurological disorders emerge from deficits in systems-level structures, such as brain waves and neural topology. Connections between neuronal regions are thought to fluidly form and dissolve again based on the patterns by which neuronal populations synchronize. Akin to a fire that may spread or die out, the brain’s activity may similarly hyper-synchronize and ignite, such as seizures, or dwindle out and go stale, as in a state of coma. Remarkably, however, the healthy brain remains hedged in between these extremes in a critical state around which neuronal activity maneuvers local and global operational modes. While it has been suggested that perturbations of this criticality could underlie neuropathologies, such as vegetative states, epilepsy, and schizophrenia, a major translational impact is yet to be made. In this hypothesis article, we dissect recent computational findings demonstrating that a neural network’s short- and long-range connections have distinct and tractable roles in sustaining the critical regime. While short-range connections shape the dynamics of neuronal activity, long-range connections determine the scope of the neuronal processes. Thus, to facilitate translational progress, we introduce topological and dynamical system concepts within the framework of criticality and discuss the implications and possibilities for therapeutic neuromodulation guided by topological decompositions.

Clinically diagnosing fungal keratitis (FK) is challenging; diagnosis can be assisted by investigations including in vivo confocal microscopy (IVCM), smear microscopy, and culture. The aim of this study was to estimate the sensitivity in detecting fungal keratitis (FK) using IVCM, smear microscopy, and culture in a setting with a high prevalence of FK. In this cross-sectional study nested within a prospective cohort study, consecutive microbial keratitis (MK) patients attending a tertiary-referral eye hospital in south-eastern Nepal between June 2019 and November 2020 were recruited. IVCM and corneal scrapes for smear microscopy and culture were performed using a standardised protocol. Smear microscopy was performed using potassium hydroxide (KOH), Gram stain, and calcofluor white. The primary outcomes were sensitivities with 95% confidence intervals [95% CI] for IVCM, smear microscopy and culture, and for each different microscopy stain independently, to detect FK compared to a composite referent. We enrolled 642 patients with MK; 468/642 (72.9%) were filamentous FK, 32/642 (5.0%) were bacterial keratitis and 64/642 (10.0%) were mixed bacterial-filamentous FK, with one yeast infection (0.16%). No organism was identified in 77/642 (12.0%). Smear microscopy had the highest sensitivity (90.7% [87.9–93.1%]), followed by IVCM (89.8% [86.9–92.3%]) and culture (75.7% [71.8–79.3%]). Of the three smear microscopy stains, KOH had the highest sensitivity (85.3% [81.9–88.4%]), followed by Gram stain (83.2% [79.7–86.4%]) and calcofluor white (79.1% [75.4–82.5%]). Smear microscopy and IVCM were the most sensitive tools for identifying FK in our cohort. In low-resource settings we recommend clinicians perform corneal scrapes for microscopy using KOH and Gram staining. Culture remains an important tool to diagnose bacterial infection, identify causative fungi and enable antimicrobial susceptibility testing.

A 35-year-old male presented with Candida keratitis in the left eye. He was HIV positive with a CD4 of 352 cells/µL. The eye quickly deteriorated, despite intensive antifungal treatment and was eviscerated. Five months later, he re-presented with Candida keratitis in his right eye. A focal source of Candida infection was suspected and a urine culture identified Candida spp, despite being asymptomatic for genitourinary candidiasis. He was subsequently treated with good outcome (max. 75 words) Keywords: Fungal keratitis, Candida keratitis, Genitourinary candidiasis, HIV, Uganda

In this manuscript, we present the first experience of evaluating donation after circulatory death (DCD) lungs, using the normothermic preservation Organ Care System (OCS) and subsequent successful transplantation. The OCS could be a useful tool for the evaluation of marginal lungs from DCD donors as it allows a proper recruitment and bronchoscopy in such donations in addition to continuous ex-vivo perfusion and assessment and treatment during transport. The OCS could potentially be a standard of care in the evaluation of marginal lungs from DCD. [ABSTRACT FROM PUBLISHER]