Miracle-dz/UniFAR-FTUs huggingface dataset:
From bench to behaviour: The role of lifestyle factors on intraocular pressure, neuroprotection, and disease progression in glaucoma

Current glaucoma management centres on intraocular pressure (IOP) reduction through pharmacological and surgical therapy. Despite broad interest in active management of glaucoma through lifestyle modifications, such recommendations have yet to be incorporated into standards of treatment. In this review, noteworthy preclinical studies and their translations in clinical populations are discussed to evaluate the roles of lifestyle factors in lowering IOP, offering neuroprotection, and/or slowing disease progression in those with open‐angle glaucoma. Current literature suggests that aerobic exercise may be associated with neuroprotection and decreased disease progression. Mindfulness is associated with IOP reductions and neuroprotection. Caffeine is associated with mild, transient IOP elevations of uncertain significance. Nicotinamide supplementation is associated with neuroprotection and short‐term visual function improvement. This review also highlights knowledge gaps regarding these factors and opportunities to strengthen our understanding of their role in glaucoma, including future preclinical studies that elucidate underlying mechanisms and clinical studies with additional functional endpoints and longer follow‐up.
Plasmodium schizogony, a chronology of the parasite’s cell cycle in the blood stage

Malaria remains a significant threat to global health, and despite concerted efforts to curb the disease, malaria-related morbidity and mortality increased in recent years. Malaria is caused by unicellular eukaryotes of the genus Plasmodium, and all clinical manifestations occur during asexual proliferation of the parasite inside host erythrocytes. In the blood stage, Plasmodium proliferates through an unusual cell cycle mode called schizogony. Contrary to most studied eukaryotes, which divide by binary fission, the parasite undergoes several rounds of DNA replication and nuclear division that are not directly followed by cytokinesis, resulting in multinucleated cells. Moreover, despite sharing a common cytoplasm, these nuclei multiply asynchronously. Schizogony challenges our current models of cell cycle regulation and, at the same time, offers targets for therapeutic interventions. Over the recent years, the adaptation of advanced molecular and cell biological techniques have given us deeper insight how DNA replication, nuclear division, and cytokinesis are coordinated. Here, we review our current understanding of the chronological events that characterize the unusual cell division cycle of P. falciparum in the clinically relevant blood stage of infection.
Longitudinal association between dietary protein intake and survival in peritoneal dialysis patients

Abstract Background Decreased dietary protein intake (DPI) may lead to protein-energy malnutrition and may be associated with increased mortality risk. We hypothesized that longitudinal changes in dietary protein intake have independent associations with survival in peritoneal dialysis (PD) patients. Methods 668 stable PD patients were selected in the study from January 2006 to January 2018 and were followed up until December 2019. Their three-day dietary records were collected at the baseline (the sixth month after PD) and thereafter every 3 months for two and a half years. The latent class mixed models (LCMM) were used to identify subgroups of PD patients with similar longitudinal trajectories of DPI. The relation between DPI (baseline and longitudinal data) and survival was examined using Cox model to estimate death hazard ratios. Meanwhile, different formulae were used to assess nitrogen balance. Results The results showed that baseline DPI ≤ 0.60g/kg/day was associated with the worst outcome in PD patients. Patients with DPI 0.80–0.99g/kg/day and DPI ≥ 1.0g/kg/day both presented positive nitrogen balance; patients with DPI 0.61–0.79g/kg/day presented obviously negative nitrogen balance. Longitudinal association between time-dependent DPI and survival was found in PD patients. The consistently low DPI' (0.61–0.79g/kg/d) group was correlated with increased death risk as compared with the 'consistently median DPI' group (0.80–0.99g/kg/d, HR = 1.59, p = 0.008), whereas there was no difference in survival between 'consistently median DPI' group and 'high-level DPI' group (≥1.0 g/kg/d, p > 0.05). Conclusion Our study revealed that DPI ≥ 0.8 g/kg/day was beneficial to the long-term outcome for the PD population.
Effects of Endogenous Task Complexity and the Endowed Bundle on Stated Choice

Conventionally, studies examining the impacts of choice complexity only consider complexity introduced exogenously from the tasks respondents face. In the context of a stated conjoint survey, this article establishes endogenous complexity measures through decision-makers' experience known as the endowed bundle before the survey. Results show that complexity should not only be defined exogenously. Endogenous complexity measures are important in determining the utility associated with an alternative and the decision of whether to participate in the market. In addition, some of these complexity effects are nonlinear. We also show that exogenous complexity simultaneous affects the choice consistency.
Optimal design of ultrabroadband tellurite fiber Raman amplifier for wavelength-division multiplexing transmission systems

We present a complete analysis on improving the gain flatness of ultrabroadband tellurite fiber Raman amplifiers (TFRAs) by optimizing the parameters of multiwavelength pumps. Compared to conventional TFRAs, our amplifier has low gain ripple despite the ultrawide amplification bandwidth: well below 3.78% (5.66%, 11.98%) with respect to the average net gain 10 dB over a 120-nm (140-, 160-nm) bandwidth. In addition, we investigate the fractional gain contribution from each pump wavelength for the optimal 140-nm TFRA, and observe that the configuration is effective in equalizing the peculiar dual-peak gain spectra produced by multiple pumps. Finally, we calculate the noise figure for the 140-nm TFRA with a vibration less than 3 dB.
Cell composition inference and identification of layer-specific spatial transcriptional profiles with POLARIS

Spatial transcriptomics (ST) technology, providing spatially resolved transcriptional profiles, facilitates advanced understanding of key biological processes related to health and disease. Sequencing-based ST technologies provide whole-transcriptome profiles, but are limited by the non-single cell level resolution. Lack of knowledge in the number of cells or cell type composition at each spot can lead to invalid downstream analysis, which is a critical issue recognized in ST data analysis. Methods developed, however, tend to under-utilize histological images, which conceptually provide important and complementary information including anatomical structure and distribution of cells. To fill in the gaps, we present POLARIS, a versatile ST analysis method that can perform cell type deconvolution, identify anatomical or functional layer-wise differentially expressed (LDE) genes and enable cell composition inference from histology images. Applied to four tissues, POLARIS demonstrates high deconvolution accuracy, accurately predicts cell composition solely from images, and identifies LDE genes that are biologically relevant and meaningful.
Antibiotic resistance, pathotypes, and pathogen-host interactions in Escherichia coli from hospital wastewater in Bulawayo, Zimbabwe

This study aimed to characterise E. coli strains isolated from hospital wastewater effluent in Bulawayo, Zimbabwe, using both molecular and cytological approaches. Wastewater samples were aseptically collected from the sewerage mains of a major public referral hospital in Bulawayo province weekly for one month. A total of 94 isolates were isolated and confirmed as E. coli through biotyping and PCR targeting the uidA housekeeping gene. A total of 7 genes (eagg, eaeA, stx, flicH7, ipaH, lt, and st genes) coding for virulence in diarrheagenic E. coli were targeted. Antibiotic susceptibility of E. coli was determined against a panel of 12 antibiotics through the disk diffusion assay. The infectivity status of the observed pathotypes was investigated using HeLa cells through adherence, invasion, and intracellular assay. None of the 94 isolates tested positive for the ipaH and flicH7genes. However, 48 (53.3%) isolates were enterotoxigenic E. coli (ETEC) (lt gene positive), 2 (2.13%) isolates were enteroaggregative E. coli (EAEC) (eagg gene), and 1 (1.06%) isolate was enterohaemorrhagic E. coli (EHEC) (stx and eaeA). A high level of sensitivity was observed in E. coli against ertapenem (98.9%), and Azithromycin (75.5%). The highest resistance was against ampicillin (92.6%) and sulphamethoxazole—trimethoprim (90.4%). Seventy-nine (84%) E. coli isolates exhibited multidrug resistance. The infectivity study results indicated that environmentally isolated pathotypes were as infective as the clinically isolated pathotypes for all three parameters. No adherent cells were observed using ETEC, and no cells were observed in the intracellular survival assay using EAEC. This study revealed that hospital wastewater is a hotspot for pathogenic E. coli and that the environmentally isolated pathotypes maintained their ability to colonise and infect mammalian cells.
Pseudomonas aeruginosa Keratitis in Rats: Study of the Effect of Topical 5% Hesperidin Practice on Healing

Objective: The aim of this study is to investigate the effect of topical 5% hesperidin application on healing. Materials and Methods: After 48 rats were randomized and divided into 7 groups, on the first day, an epithelial defect was created in the center of the cornea with the help of microkeratome under intraperitoneal ketamine + xylazine and topical 5% proparacaine anesthesia for the groups to be infected with keratitis according to the groups mentioned below. An amount of 0.05 mL of the solution containing 108 colony-forming units/mL Pseudomonas aeruginosa (PA-ATC27853) will be taken and inoculated per rat. At the end of the 3 days incubation period, rats with keratitis will be added to the groups, and active substances and antibiotics will be given topically together with other groups for 10 days. At the end of the study, the ocular tissues of the rats will be removed and examined histopathologically. Results: A clinically significant reduction in inflammation was detected in the groups using hesperidin. No transforming growth factor-β1 staining was detected in the group in which keratitis + hesperidin was treated topically. In the group in which hesperidin toxicity was examined, mild inflammation and thickening of the corneal stroma layer were observed, and it was evaluated as a negative transforming growth factor-β1 expression in the lacrimal gland tissue. Corneal epithelial damage was minimal in the keratitis group, and the toxicity group was treated with only hesperidin when compared to the other groups. Conclusion: Topical hesperidin drops may be an important therapeutic factor in tissue healing and in the fight against inflammation in the treatment of keratitis.
Long-term and rapid evolution in powdery mildew fungi.

The powdery mildew fungi (Erysiphaceae) are globally distributed plant pathogens with a range of more than 10,000 plant hosts. In this review, we discuss the long- and short-term evolution of these obligate biotrophic fungi and outline their diversity with respect to morphology, lifestyle, and host range. We highlight their remarkable ability to rapidly overcome plant immunity, evolve fungicide resistance, and broaden their host range, e.g., through adaptation and hybridization. Recent advances in genomics and proteomics, particularly in cereal powdery mildews (genus Blumeria), provided first insights into mechanisms of genomic adaptation in these fungi. Transposable elements play key roles in shaping their genomes, where even close relatives exhibit diversified patterns of recent and ongoing transposon activity. These transposons are ubiquitously distributed in the powdery mildew genomes, resulting in a highly adaptive genome architecture lacking obvious regions of conserved gene space. Transposons can also be neo-functionalized to encode novel virulence factors, particularly candidate secreted effector proteins, which may undermine the plant immune system. In cereals like barley and wheat, some of these effectors are recognized by plant immune receptors encoded by resistance genes with numerous allelic variants. These effectors determine incompatibility ("avirulence") and evolve rapidly through sequence diversification and copy number variation. Altogether, powdery mildew fungi possess plastic genomes that enable their fast evolutionary adaptation towards overcoming plant immunity, host barriers, and chemical stress such as fungicides, foreshadowing future outbreaks, host range shifts and expansions as well as potential pandemics by these pathogens.
A Survey of Recent Results in Differential Equations

The purpose of this paper is to present the main ideas of some recent research in the theory of ordinary differential equations to an audience not necessarily consisting of researchers in the field. The topics covered are : the Kolomogorov–Arnold–Mosey theorem with an application to the restricted three-body problem ; the Smale–Easton classification of invarient manifolds in the planar three-body problem; structural stability, Moser’s method of linearizing a homeomorphism with an application to proving Hartman’s theorem; a brief idea of Conley’s theory of isolating blocks; a brief discussion of the status of functional differential equations, and lastly generalized differential equations and several vector fields on a manifold with an illustration of the interplay between this theory and the work of Stroock and Varadan on strong maximum principles for degenerate parabolic equations.
Oral liposomal delivery of an activatable budesonide prodrug reduces colitis in experimental mice

Abstract Inflammatory bowel disease (IBD) is one of the most common intestinal disorders, with increasing global incidence and prevalence. Numerous therapeutic drugs are available but require intravenous administration and are associated with high toxicity and insufficient patient compliance. Here, an oral liposome that entraps the activatable corticosteroid anti-inflammatory budesonide was developed for efficacious and safe IBD therapy. The prodrug was produced via the ligation of budesonide with linoleic acid linked by a hydrolytic ester bond, which was further constrained into lipid constituents to form colloidal stable nanoliposomes (termed budsomes). Chemical modification with linoleic acid augmented the compatibility and miscibility of the resulting prodrug in lipid bilayers to provide protection from the harsh environment of the gastrointestinal tract, while liposomal nanoformulation enables preferential accumulation to inflamed vasculature. Hence, when delivered orally, budsomes exhibited high stability with low drug release in the stomach in the presence of ultra-acidic pH but released active budesonide after accumulation in inflamed intestinal tissues. Notably, oral administration of budsomes demonstrated favorable anti-colitis effect with only ∼7% mouse body weight loss, whereas at least ∼16% weight loss was observed in other treatment groups. Overall, budsomes exhibited higher therapeutic efficiency than free budesonide treatment and potently induced remission of acute colitis without any adverse side effects. These data suggest a new and reliable approach for improving the efficacy of budesonide. Our in vivo preclinical data demonstrate the safety and increased efficacy of the budsome platform for IBD treatment, further supporting clinical evaluation of this orally efficacious budesonide therapeutic.
Daytime Overlapping Cloud Detection in MODIS Data

Current efforts to derive a global cloud climatology from satellite data generally suffer in situations involving multilayered clouds. In fact, cloud properties are inferred for each imager pixel assuming only one cloud layer is present. Currently available satellite cloud climatologies provide a horizontal distribution of clouds, but need improvement in the description of the vertical distribution of clouds. The single cloud layer assumption is unfortunate because surface observations show that clouds often occur in multiple layers simultaneously in a vertical column, i.e., cloud layers often overlap.
Vascular density and macular sensitivity in eyes after scleral buckling surgery for macula-on rhegmatogenous retinal detachment

Purpose To investigate the structure and function of the retina after scleral buckling (SB) surgery due to macula-on rhegmatogenous retinal detachment (RRD). Methods Twenty eyes with repaired macula-on RRD and 20 fellow eyes were included. All patients within 6–12 months of the procedure, were examined to evaluate retinal structure using spectral domain optical coherence tomography (SD-OCT) and vessel density (VD) by OCT angiography (OCTA). Best corrected visual acuity (BCVA) and microperimetry (MP) tests were used to assess retinal function. Results Analysis of the microvascular network using OCTA between the operated and healthy fellow eyes showed a significant reduction on VD in superficial vascular plexus (SVP), deep vascular plexus (DVP) and radial peripapillary capillaries (RPC) (p< 0.001, p = 0.019 and p = 0.008, respectively). Comparison of retinal structure in SD-OCT showed no significant differences on thickness in ganglion cell complex (GCC) and peripaillary retinal nerve fiber layer (pRNFL) (p> 0.05) between examined eyes. Retinal function analysis by MP examination showed a decrease of retinal sensitivity (p = 0.0013) whereas postoperative BCVA showed no differences (p = 0.62) in the operated eyes. Significant Pearson’s correlations were observed between retinal sensitivity and VD in SVP, RPC (p< 0.05). Conclusion In the eyes after SB surgery due to macula-on RRD, changes in retinal sensitivity were accompanied by impairment of the microvascular network assessed by the OCTA.
Video Ocular Counter-Roll (vOCR): Otolith-Ocular Function and Compensatory Effect of the Neck Following Vestibular Loss

Objective. Assessment of recovery following vestibular loss has been limited by the lack of bedside measures in clinical settings. Here, we used the video ocular counter-roll (vOCR) test to study otolith-ocular function and compensatory effect of neck proprioception in patients at different stages of vestibular loss. Study Design. Case-control study. Setting. Tertiary care center. Methods. Fifty-six subjects were recruited including patients with acute (9 ± 2 days [mean ± standard error of mean]), subacute (61 ± 11 days), and chronic (1009 ± 266 days) unilateral loss of vestibular function, as well as a group of healthy controls. We used a video-oculography method based on tracking the iris for vOCR measurement. To examine the effect of neck inputs, vOCR was recorded during two simple tilt maneuvers in all subjects while seated: 30° head-on-body tilt and 30° head-and-body tilt. Results. The vOCR responses evolved at different stages following vestibular loss with improvement of the gains in the chronic stage. The deficit was more pronounced when the whole body was tilted (acute: 0.08 ± 0.01, subacute: 0.11 ± 0.01, chronic: 0.13 ± 0.02, healthy control: 0.18 ± 0.01), and the gain of vOCR improved when the head was tilted on the body (acute: 0.11 ± 0.01, subacute: 0.14 ± 0.01, chronic: 0.13 ± 0.02, healthy control: 0.17 ± 0.01). The time course of vOCR response was affected as well with reduced amplitude and slower response in the acute stage of vestibular loss. Conclusion. The vOCR test can be valuable as a clinical marker to measure vestibular recovery and compensatory effect of neck proprioception in patients at different stages following loss of vestibular function.
Drug Discovery Perspectives of Antisense Oligonucleotides

The era of innovative RNA therapies using antisense oligonucleotides (ASOs), siRNAs, and mRNAs is beginning. Since the emergence of the concept of ASOs in 1978, it took more than 20 years before they were developed into drugs for commercial use. Nine ASO drugs have been approved to date. However, they target only rare genetic diseases, and the number of chemistries and mechanisms of action of ASOs are limited. Nevertheless, ASOs are accepted as a powerful modality for next-generation medicines as they can theoretically target all disease-related RNAs, including (undruggable) protein-coding RNAs and non-coding RNAs. In addition, ASOs can not only downregulate but also upregulate gene expression through diverse mechanisms of action. This review summarizes the achievements in medicinal chemistry that enabled the translation of the ASO concept into real drugs, the molecular mechanisms of action of ASOs, the structure-activity relationship of ASO-protein binding, and the pharmacology, pharmacokinetics, and toxicology of ASOs. In addition, it discusses recent advances in medicinal chemistry in improving the therapeutic potential of ASOs by reducing their toxicity and enhancing their cellular uptake.
Topology Identification of General Dynamical Network with Distributed Time Delays

General dynamical networks with distributed time delays are studied. The topology of the networks are viewed as unknown parameters, which need to be identified. Some auxiliary systems (also called the network estimators) are designed to achieve this goal. Both linear feedback control and adaptive strategy are applied in designing these network estimators. Based on linear matrix inequalities and the Lyapunov function method, the sufficient condition for the achievement of topology identification is obtained. This method can also better monitor the switching topology of dynamical networks. Illustrative examples are provided to show the effectiveness of this method.
Electrostatic (plasmon) resonances in nanoparticles

A surface integral eigenvalue based technique for the direct calculation of resonance values of the permittivity of nanoparticles, and hence resonance frequencies, is discussed. General physical properties of electrostatic plasmon resonances are presented. Strong orthogonality properties of resonance modes, a twodimensional phenomenon of “twin” spectrum and explicit estimates of resonance frequencies in terms of geometrical characteristics of convex nanoparticles are reported. Second-order corrections for resonance values of the dielectric permittivity are derived. Tunability and optical controllability of plasmon resonances in semiconductor nanoparticles are discussed and, as a digression, a plausible plasmon resonance mechanism for nucleation and formation of ball lightning is outlined. An efficient numerical algorithm for the calculation of resonance frequencies is developed and illustrated by extensive computational results that are compared with theoretical results and available experimental data.
Compressed image quality and Zipf law

We point out the interest in using Zipf law in the wide field of image analysis. We show how it is possible to adapt it to image analysis. There are many applications; here we are concerned with image compression and focus on a new definition of quality measurement of an image obtained after a decompression process. First we propose a coding mode of an image using some neighborhood of each pixel and the Zipf law. Then some significant comparisons can be achieved between different images. A statistical study of the patterns present in the image allows a characterization of the information contained in the image so that a measurement of information modification is made possible. We define two quantitative parameters; one indicates the structure of the image whereas the second indicates high content information. The examples of the images of a landscape and of a female face are used to illustrate the influence of the compression rate.