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The cornea, the transparent part of the anterior eye, is vital for light refraction and vision. This review examines the intricate chemical and biochemical interactions essential for maintaining corneal transparency and highlights significant advancements in corneal biology. The cornea comprises five layers: the epithelium, Bowman's layer, stroma, Descemet's membrane, and endothelium, each contributing uniquely to its structure and function. The epithelium, maintained by limbal stem cells, serves as a barrier and interacts with the tear film to maintain ocular surface health. The stroma, abundant in organized collagen fibrils and regulated by proteoglycans, is crucial for corneal clarity and biomechanical integrity, whereas the endothelium regulates corneal hydration and nutrition. Recent imaging advances have improved visualization of these molecular structures, enhancing our understanding of collagen organization and cross-linking. Proteoglycans such as decorin and lumican regulate collagen spacing and hydration, directly influencing corneal clarity. Biochemical processes within the cornea involve signaling molecules, growth factors, and cytokines, which are essential for wound healing, inflammation, and injury response. Despite progress, questions remain regarding corneal wound healing mechanisms, the impact of oxidative stress, and the roles of microRNAs. This review synthesizes recent discoveries to advance our understanding of corneal physiology and biochemical functions., (© 2024 Wiley‐VHCA AG, Zurich, Switzerland.)

Mg alloy corrosion susceptibility is a major issue that limits its wide industrial application in transport, energy and medical sectors. A corrosion-resistant layer containing crystalline MgCO 3 was formed on the surface of AZ91D Mg alloy by Li salt loading and thermal CO 2 treatment. Compared to the uncoated AZ91D surface, the surface layer exhibited up to a ∼15-fold increase in corrosion resistance according to the electrochemical results in 3.5 wt% NaCl solution and ∼32% decrease in wear rate compared to untreated AZ91D. The improved corrosion resistance is attributed to the formation of a <10 μm thick dense layer containing Mg, O, C and Li with crystalline MgCO 3 phases. The initial step was to form a porous MgO layer on the surface of AZ91D Mg alloy, followed by loading an alkali metal salt ( i.e. , LiNO 3 ) onto the MgO surface. The porous MgO surface was then reconstructed into a dense insulation layer containing Mg carbonate through CO 2 absorption facilitated by molten Li salt during thermal CO 2 treatment at 350 °C. As a potential method to utilize excessive CO 2 for beneficial outcomes, the formation of the carbonate-containing film introduced in this study opens a new pathway for protecting various existing Mg alloys for diverse industrial applications., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Purpose: This paper aims to describe the clinical presentation and demographic distribution of keratoconus (KCN) in India by analyzing the electronic medical records (EMR) of patients presenting at a multitier ophthalmology hospital network., Methods: This cross-sectional hospital-based study included the data of 2,384,523 patients presenting between January 2012 and March 2020. Data were collected from an EMR system. Patients with a clinical diagnosis of KCN in at least one eye were included in this study. Univariate analysis was performed to identify the prevalence of KCN. A multiple logistic regression analysis was performed using R software (version 3.5.1), and the odds ratios are reported., Results: Data were obtained for 14,749 (0.62%) patients with 27,703 eyes diagnosed with KCN and used for the analysis. The median age of the patients was 22 (inter-quartile range (IQR): 17-27). In total, 76.64% of adults (odds ratio = 8.77; P = <0.001) were affected the most. The majority of patients were male (61.25%), and bilateral (87.83%) affliction was the most common presentation. A significant proportion of the patients were students (63.98%). Most eyes had mild or no visual impairment (<20/70; 61.42%). Corneal signs included ectasia (41.35%), Fleischer ring (44.52%), prominent corneal nerves (45.75%), corneal scarring (13.60%), Vogts striae (18.97%), and hydrops (0.71%). Only 7.85% showed an association with allergic conjunctivitis. A contact lens clinic assessment was administered to 47.87% of patients. Overall, 10.23% of the eyes affected with KCN underwent a surgical procedure. the most common surgery was collagen cross-linking (8.05%), followed by deep anterior lamellar keratoplasty (1.13%) and penetrating keratoplasty (0.88%)., Conclusion: KCN is usually bilateral and predominantly affects males. It commonly presents in the second and third decade of life, and only a tenth of the affected eyes require surgical treatment., (Copyright © 2023 Copyright: © 2023 Indian Journal of Ophthalmology.)

Corneal scarring and opacification are a significant cause of blindness affecting millions worldwide. The current standard of care for corneal blindness is corneal transplantation, which suffers from several drawbacks. One alternative approach that has shown promise is the use of xenogeneic corneal extracellular matrix (ECM), but its clinical applicability is challenging due to safety concerns. This study reports the innovative use of human cornea-derived ECM to prevent post-traumatic corneal scarring. About 30 - 40% of corneas donated to the eye banks do not meet the standards defined for clinical use and are generally discarded, although they are completely screened for their safety. In this study, human cornea-derived decellularized ECM hydrogel was prepared from the non-transplantation grade human cadaveric corneas obtained from an accredited eye-bank. The prepared hydrogel was screened for its efficacy against corneal opacification following an injury in an animal model. Our in vivo study revealed that, the control collagen-treated group developed corneal opacification, while the prophylactic application of human cornea-derived hydrogel effectively prevented corneal scarring and opacification. The human hydrogel-treated corneas were indistinguishable from healthy corneas and comparable to those treated with the xenogeneic bovine corneal hydrogel. We also demonstrated that the application of the hydrogel retained the biological milieu including cell behavior, protein components, optical properties, curvature, and nerve regeneration by remodeling the corneal wound after injury. The hydrogel application is also sutureless, resulting in faster corneal healing. We envision that this human cornea-derived ECM-based hydrogel has potential clinical application in preventing scarring from corneal wounding. STATEMENT OF SIGNIFICANCE: There are significant challenges surrounding corneal regeneration after injury due to extensive scarring. Although there is substantial research on corneal regeneration, much of it uses synthetic materials with chemical cross-linking methods or xenogeneic tissue-based material devices which have to undergo exhaustive safety analysis before clinical trials. Herein, we demonstrate the potential application of a human corneal extracellular matrix hydrogel without any additional materials for scarless corneal tissue regeneration, and a method to reduce the wasting of donated allogenic corneal tissue from eye banks. We found no difference in efficacy between the usage of human tissues compared to xenogeneic sources. This may help ease clinical translation and can be used topically without sutures as an outpatient procedure., Competing Interests: Declaration of Competing of Interests The data will be used for the commercial purpose initiated by the authors Shibu Chameettachal and Falguni Pati. Shibu Chameettachal and Falguni Pati are named inventors on Indian Patent Application No 201841009835, dated March 17, 2018, Decellularized corneal matrix-based hydrogel, bioink formulation and methods thereof which was assigned to the Indian Institute of Technology Hyderabad (IITH), and subsequently IITH and Hyderabad Eye Research Foundation joined together, wherein the patent application has been filed in the United States 16/981,957 dated September 17, 2020. The authors declare that they have no other competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In this work, we have developed a unique in situ multimodal corrosion system that is capable of acquiring electrochemical data, sample imaging/visualization and hydrogen collection, simultaneously. Each of these modalities yield valuable information pertaining to the ongoing corrosion process. Combining them can yield holistic information on the role of microstructure, processing history, presence of coatings, etc., on the sequence of steps occurring during the corrosion process, and how they correlate with the acquired electrochemical data. Four materials systems, namely AA6061-T6 aluminum alloy, AZ91 magnesium alloy, galvanized DP590 steel, and pure Zn, were investigated under open circuit potential and under potentiodynamic polarization. The multimodal corrosion system was utilized to observe processes such as surface passivation and dissolution, pit and filiform corrosion initiation and propagation, and was correlated with location and magnitude of hydrogen evolution. This approach is shown to yield a truly multimodal understanding of the ongoing corrosion processes., (© 2023. Springer Nature Limited.)

Developing strategies to prevent corrosion at the interface of dissimilar metal alloys is challenging because of the presence of heterogenous distribution of galvanic couples and microstructural features that significantly change the corrosion rate. Devising strategies to mitigate this interfacial corrosion requires quantitative and correlative understanding of its surface electrochemical reaction. In this work, scanning electrochemical cell impedance microscopy (SECCIM) was employed to study location-specific corrosion in the interfacial region of dissimilar alloys, such as AZ31 (magnesium alloy) and DP590 (steel) welded using the Friction-stir Assisted Scribe Technique (FAST) processes. Herein, SECCM and SECCIM were used to perform correlative mapping of the local electrochemical impedance spectroscopic and potentiodynamic polarization to measure the effect of electronic and microstructural changes in the welded interfacial region on corrosion kinetics. Microstructural characterization including scanning electron microscopy and electron backscatter diffraction was performed to correlate changes in microstructural features and chemistry with the corresponding electronic properties that affect corrosion behavior. The variations in corrosion potential, corrosion current density, and electrochemical impedance spectroscopy behavior across the interface provide deeper insights on the interfacial region-which is chemically and microstructurally distinct from both bare AZ31 and DP590 that can help prevent corrosion in dissimilar metal structures., (© 2023. Springer Nature Limited.)

Purpose: To explore the relationship between the density, depth, and surface irregularity of superficial corneal opacities and vision., Methods: This prospective imaging study included 19 patients with unilateral superficial corneal opacification due to scarring post-microbial keratitis. Each eye underwent an assessment of uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), contact lens corrected visual acuity (CLCVA), and Scheimpflug and anterior segment optical tomography imaging. Regression analysis was performed to detect the association between density, depth of scarring, and the surface irregularity in terms of higher order aberrations (HOA), and keratometry and UCVA, CLCVA, and the difference between BSCVA and CLCVA., Results: The mean logMAR UCVA, BSCVA, and CLCVA were 0.76, 0.35, and 0.28, respectively. The corneal scars had a mean thickness of 158.7 ± 61 µ and density of 65.73 ± 24.46 GSU. Bivariate analysis model for UCVA showed an association with Z 4 2 secondary astigmatism ( p  = 0.02), Z 4 4 quadrafoil ( p  = 0.01), combined coma Z 3   ± 1 ( p  = 0.03), and combined HOA Z 3 -Z 6 ( p  = 0.045), out of which Z 4 4 Quadrafoil ( p  = 0.04) was most significant with multivariate analysis. Bivariate analysis for BCVA-CLVA showed association with Z 3 1 coma horizontal ( p  = 0.04), Z 3 3 oblique trefoil ( p  = 0.02), Z 4 0 primary spherical aberration ( p  = 0.008), and Z 5   - 5 ( p  = 0.007), out of which Z 3 1 horizontal coma ( p  = 0.04) and Z 4 0 spherical aberration ( p  = 0.009) were significant on multivariate analysis. Change in densitometry, corneal thickness, epithelial:stromal reflectivity ratio, scar depth, and keratometry did not show any significant association with UCVA, BSCVA-CLCVA, or CLCVA., Conclusion: In superficial corneal stromal scarring, deranged surface irregularity parameters like higher-order aberrations affect the final visual acuity more than the depth or density of the opacity.

Definitive treatment of dry eye disease (DED), one of the commonest ocular surface disorders, has remained elusive despite several recent advances in better diagnostics and the introduction of newer therapeutic molecules. The current treatment paradigms rely heavily on lubricating eye drops and anti-inflammatory agents that may need to be used long-term and are mainly palliative. Research is ongoing not only for a curative treatment option but also to improve the potency and efficacy of existing drug molecules through better formulations and delivery platforms. In the past two decades, significant advancement has been made in terms of preservative-free formulations, biomaterials such as nanosystems and hydrogels, stem cell therapy, and creation of a bioengineered lacrimal gland. This review comprehensively summarizes the newer approaches to DED treatment, which are biomaterials such as nanosystems, hydrogels, and contact lenses for drug delivery, cell and tissue-based regenerative therapy for damaged lacrimal gland and ocular surface, and tissue engineering for developing artificial lacrimal gland. Also, their potential efficacies in animal models or in vitro studies and possible limitations are discussed. The ongoing research looks promising and needs to be supported with clinical efficacy and safety studies for human use., Competing Interests: None

Background: Posttraumatic stress disorder (PTSD) is a mental health condition triggered by exposure to traumatic events in an individual's life. Patients with PTSD are also at a higher risk for comorbidities. However, it is not well understood how PTSD affects human health and/or promotes the risk for comorbidities. Nevertheless, patients with PTSD harbor a proinflammatory milieu and dysbiotic gut microbiota. Gut barrier integrity helps to maintain normal gut homeostasis and its dysregulation promotes gut dysbiosis and inflammation., Methods: We used a mouse model of repeated social defeat stress (RSDS), a preclinical model of PTSD. Behavioral studies, metagenomics analysis of the microbiome, gut permeability assay (on mouse colon, using an Ussing chamber), immunoblotting, and immunohistochemical analyses were performed. Polarized intestinal epithelial cells and 3-dimensional crypt cultures were used for mechanistic analysis., Results: The RSDS mice harbor a heightened proinflammatory gut environment and microbiota dysbiosis. The RSDS mice further showed significant dysregulation of gut barrier functions, including transepithelial electrical resistance, mucin homeostasis, and antimicrobial responses. RSDS mice also showed a specific increase in intestinal expression of claudin-2, a tight junction protein, and epinephrine, a stress-induced neurotransmitter. Treating intestinal epithelial cells or 3-dimensional cultured crypts with norepinephrine or intestinal luminal contents (fecal contents) upregulated claudin-2 expression and inhibited transepithelial electrical resistance., Conclusions: Traumatic stress induces dysregulation of gut barrier functions, which may underlie the observed gut microbiota changes and proinflammatory gut milieu, all of which may have an interdependent effect on the health and increased risk of comorbidities in patients with PTSD., (© 2023 The Authors.)

A female patient in her 20s presented with a bulbar conjunctival mass lesion that was diagnosed as nodular scleritis. It was treated with topical and oral steroids in another hospital. Imaging was done using anterior segment optical coherence tomography and ultrasound biomicroscopy, which helped to rule out scleritis and subconjunctival cysticercosis. Histopathology of the excision biopsy specimen revealed fungal filaments. Topical antifungals were started, and the condition resolved without recurrence after therapy. Although rare, infections should be considered in the differential diagnosis of conjunctival mass lesions. Imaging can help to rule out other entities and guide towards appropriate management., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Nucleic acid (NA) therapy has gained importance over the past decade due to its high degree of selectivity and minimal toxic effects over conventional drugs. Currently, intravenous (IV) or intramuscular (IM) formulations constitute majority of the marketed formulations containing nucleic acids. However, oral administration is traditionally preferred due to ease of administration as well as higher patient compliance. To leverage the benefits of oral delivery for NA therapy, the NA of interest must be delivered to the target site avoiding all degrading and inhibiting factors during its transition through the gastrointestinal tract. The oral route presents myriad of challenges to NA delivery, making formulation development challenging. Researchers in the last few decades have formulated various delivery systems to overcome such challenges and several reviews summarize and discuss these strategies in detail. However, there is a need to differentiate between the approaches based on target so that in future, delivery strategies can be developed according to the goal of the study and for efficient delivery to the desired site. The goal of this review is to summarize the mechanisms for target specific delivery, list and discuss the formulation strategies used for oral delivery of NA therapies and delineate the similarities and differences between local and systemic targeting oral delivery systems and current challenges., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: This review aims to evaluate and simplify the recent literature on preoperative surgical planning, intraoperative considerations, postoperative surprises, and their management in patients with keratoconus undergoing cataract surgery., Methods: A review of the literature was done to analyze all the pertinent articles on Keratoconus and cataract surgery., Results: The surgical planning of cataracts in eyes with keratoconus needs a multifaceted approach. Preoperatively, techniques such as cross-linking or the use of intra-corneal rings help stabilize the progression. Unreliable biometric measurements are a significant problem in keratoconus patients, especially in an advanced stage of the disease. It is better to consider actual K readings if the K value is less than 55D but for a K value, more than 55D using standard K values will prevent postoperative refractive surprises. For calculation of K values, an elevation-based device like pentacam gives better repeatability in mild to moderate cases whereas for advanced keratoconus none of the keratometers is reliable. Recently, the Kane keratoconus formula performed better in all stages of disease whereas previous studies showed good results with SRK/T formula is a mild and moderate disease. Monofocal intraocular lenses are a better choice in these patients. Toric lenses can be used in mild and stable keratoconus. Intraoperatively, the use of a customized RGP lens can overcome the challenge of image distortion and loss of visual perspective. Despite taking necessary measures, postoperative refractive surprise can occur and can be managed with IOL exchange or Secondary IOLs., Conclusion: There is a spectrum of challenges in managing cataracts in keratoconus which makes thorough preoperative planning important for good surgical outcomes. Despite the measures, there might be post-operative surprises and the patients need to be informed regarding the same.

Purpose: The purpose of this study was to report the long-term outcomes of Descemet membrane endothelial keratoplasty (DMEK) with goniosynechialysis in eyes with iridocorneal endothelial syndrome with an emphasis on the surgical technique., Methods: This was a retrospective series of 5 eyes of 5 patients undergoing a DMEK procedure at a tertiary eye care institute by a single surgeon. Modifications in the standard surgical technique, including the release of peripheral anterior synechiae, peripheral descemetorhexis, the release of adherent membranes, maneuvers in the anterior chamber with or without cataract extraction were logged. Long-term outcomes of the surgery in these patients are reported., Results: Five DMEK procedures were performed in 5 eyes of 5 patients. The average age of the patients was 48.2 ± 10.8 years, and the donor was 55.2 ± 3.2 years with a mean endothelial cell density (ECD) of 2784.6 ± 231 cells/mm 2 . After a mean follow-up period of 29.6 months (24-41 mo), all the 5 grafts remained clear; the mean BCVA at the last follow-up was 0.18 ± 0.17 logarithm of the minimum angle of resolution with a mean ECD of 1086.2 ± 338 cells/mm 2 with a 61.1% reduction in ECD. intra ocular pressure was normal in all the cases. None of the patients had graft detachments that required rebubbling, and all eyes had a clear graft at the last follow-up., Conclusions: DMEK can be performed successfully in a case with iridocorneal endothelial syndrome with good visual outcomes with modifications to the surgical technique, including peripheral anterior synechiae release and minimizing surgical manipulation., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To investigate a method to identification of early progression of keratoconus using deep learning neural networks., Methods: Retrospective evaluation of medical records of patients with progressive keratoconus and had more than one followup visits. Images extracted from the single scheimplug analyzer for analysis were captured during the patient visits. The baseline progression of keratoconus is detected by a change in flat or steep K of ≥1.0D which is labeled as keratometric progression (KP) and progression detected by image based deep learning convolutional neural network (CNN) models, is labeled as latent progression (LP). Patient data consisted of model data (385 eyes of 351patients) to train and test the learning models and prediction data (1331 eyes of 828 patients) to determine the LP based on the learning models., Results: The LP prediction model was able to identify progression at a mean of 11.1 months earlier than KP (p < 0.001). LP prediction model was able to identify progression earlier than KP irrespective of age category, gender, the severity of keratoconus, presenting visual acuity, astigmatism, and spherical equivalent (P < 0.001). When compared to the first visit the corrected distance visual acuity was more stable in 71% of the eyes at LP prediction visit compared to 50% at KP visit (p < 0.001)., Conclusion: Through this study, we propose a possible solution to address the shortcomings noted in the current approaches of detecting progression relying only on KP. Avoiding bias towards feature selection from tomography images as done in the current study aids in identifying very subtle changes on the images between visits.

Indole is an endogenous substance currently being evaluated as a biomarker for ulcerative colitis, irritable bowel syndrome, Crohn’s disease and non-alcoholic fatty liver disease. A novel, selective, and sensitive method using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was developed for quantitation of indole concentrations in mouse plasma and tissues. Samples were prepared by protein precipitation using ice-cold acetonitrile (ACN) followed by injecting the extracted analyte to LC-MS/MS system. Indole was separated using Synergi Fusion C18 (4 µm, 250 × 2.0 mm) column with mobile phase 0.1% aqueous formic acid (A) and methanol (B) using gradient flow with run time 12 min. The mass spectrometer was operated in atmospheric pressure chemical ionization (APCI) positive mode at unit resolution in multiple reaction monitoring (MRM) mode, using precursor ion > product ion combinations of 118.1 > 91.1 m/z for indole and 124.15 > 96.1 m/z for internal standard (IS) indole d7. The MS/MS response was linear over the range of indole concentrations (1−500 ng/mL). The validated method was applied for quantitation of indole concentrations range in mouse lungs (4.3−69.4 ng/g), serum (0.8−38.7 ng/mL) and cecum (1043.8−12,124.4 ng/g). This method would help investigate the role of indole as a biomarker and understand its implications in different disease states.

Hot rolling and annealing are critical intermediate steps for controlling microstructures and thickness variations when fabricating uranium alloyed with 10% molybdenum (U-10Mo), which is highly relevant to worldwide nuclear non-proliferation efforts. This work proposes a machine-learning surrogate model combined with sensitivity analysis to identify and predict U-10Mo microstructure development during thermomechanical processing. Over 200 simulations were collected using physics-based microstructure models covering a wide range of thermomechanical processing routes and initial alloy grain features. Based on the sensitivity analysis, we determined that an increase in rolling reduction percentage at each processing pass has the strongest effect in reducing the grain size. Multi-pass rolling and annealing can significantly improve recrystallization regardless of the reduction percentage. With a volume fraction below 2%, uranium carbide particles were found to have marginal effects on the average grain size and distribution. The proposed stratified stacking ensemble surrogate predicts the U-10Mo grain size with a mean square error four times smaller than a standard single deep neural network. At the same time, with a significant speedup (1000×) compared to the physics-based model, the machine learning surrogate shows good potential for U-10Mo fabrication process optimization., (© 2022. The Author(s).)

To assess the utility of a universal smartphone attachment to capture images of the anterior segment of the eye, we conducted a retrospective analysis of 344 images captured using a smartphone by the patients to identify factors affecting image quality, such as lack of perspective, lack of focus, improper illumination, and resolution. Based on this analysis, a universal smartphone attachment named Grabi TM Lite and a protocol for anterior segment imaging were designed and validated in the first prospective arm of 60 patients. These images were then compared with the same eyes imaged on the gold standard slit-lamp photography. In the second prospective arm, nine patients were trained to use the Grabi TM Lite with the imaging protocol, and the images were assessed for utility in arriving at a diagnosis. A total of 178 images were analyzed using a questionnaire by masked observers. The images were evaluated based on their quality and suitability in clinical decision-making, risk stratification for triage for referral to a tertiary eye care centre. The quality of 344 images captured by patients using only their smartphone was rated as good 24 (7%), average 209 (60.8%), and poor in 111 (32.2%). Of these, 55 (16%) images were deemed suitable for clinical decision-making, and 224 (65.6%) images were adequate for risk stratification. Lack of perspective, focus, illumination, and resolution were seen in 167 (51.2%), 284 (87.1%), 226 (69.3%), and 126 (38.7%) images, respectively. These metrics improved in the next iteration of 178 images captured by patients using Grabi Lite + imaging protocol to good 103 (57%), average 58 (32.6%), and bad 17 (19.6%) ( p < .001 using chi-square test). Images deemed suitable for clinical decision-making, and risk stratification for triage also improved to 80 (45%), 158 (88.8%) ( p < .001 using chi-square test), respectively. Adherence to protocol was seen in 98 (55.5%) images, of which all were suitable for risk stratification, while of these images, 66 (67.3%) were eligible for clinical decision making. In comparison with slit-lamp photography, out of 120 responses by masked observers to images captured by Grabi TM Lite with the imaging protocol, 63 (52.85%) were suitable for clinical decision-making, and 68 (57%) were graded to be between 70 and 99% of the quality of the slit lamp photographs. The Grabi TM lite with imaging protocol training is an effective tool to improve anterior segment imaging, potentially allowing smartphone use for teleconsultations. This device may serve as a universal solution for all smartphones with the patient as the user and is of value in the future of tele-ophthalmology.

Objective: To describe the clinical features, risk factors and outcomes of Neisseria keratitis., Methods: This is a retrospective observational study wherein medical records of cases with microbiologically proven Neisseria keratitis were reviewed. Data pertaining to the underlying predisposing factors, clinical characteristics of the corneal ulcer, antibiotic susceptibility of the Neisseria species isolate from the corneal scraping, the treatment given, and outcomes were collected and analyzed., Results: Medical records of 60 patients (60 eyes) with Neisseria keratitis were reviewed. Among the causes of poor ocular surface as predisposing factor, vernal keratoconjunctivitis (n = 6 eyes), along with use of topical corticosteroids (n = 18 eyes) was the most common. The ulcer was characterized by a central infiltrate (31/60, 51.7%) involving up to the mid-stroma (43/60, 71.7%). Of the forty-four (73.3%) eyes with pure Neisseria keratitis, 31 eyes (72.1%) resolved with medical therapy alone while five eyes (11.6%) underwent therapeutic penetrating keratoplasty and in two (4.6%) eyes evisceration was performed. The other 5/44 (11.6%) patients were lost to follow-up. Resolution with medical therapy was found to be similar in cases with pure infection and mixed infection (p = 0.58)., Conclusions: Neisseria keratitis most commonly causes a mild form of keratitis and is often associated with the poor ocular surface or prior steroid use. In most cases medical therapy is sufficient for complete resolution of the keratitis., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

A 27-year-old woman had foggy vision and photophobia since 10 months after implantation of implantable collamer lens (ICL STAAR Surgical AG, Nidau, Switzerland) with evidence of corneal decompensation and no cataract formation. Descemet membrane endothelial keratoplasty in phakic eyes is challenging, considering presence of posterior chamber phakic intraocular lens (IOL), decreasing the space available in anterior chamber to manoeuvre the graft. Need of inferior peripheral iridotomy in presence of central hole technology in ICL depends on the dynamics of full chamber air bubble. At 8 months, vision had improved to 20/20 and normal IOP with well-attached graft, stable phakic IOL and clear lens., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To validate an animal model of corneal stromal opacity by using objective vision-independent in vivo imaging metrics., Methods: This was a prospective study, with two arms: (i) observational human arm which included 14 patients with healed unilateral ulcerative keratitis; and (ii) experimental rabbit arm, which included 6 New Zealand white rabbits. A 3-mm central wound was created in the left eye of the rabbits by manually removing 200-250 μm of the superficial stroma, followed by rotating-burr application. Both groups underwent photography, high-resolution anterior segment optical coherence tomography, and Scheimpflug imaging using similar diagnostic platforms and standardized image capturing protocols. Parameters studied were relative change in (i) corneal thickness; (ii) corneal epithelial: stromal (E:S) reflectivity ratio; (iii) corneal stromal light scattering using densitometry; and (iv) central corneal keratometry., Results: In the experimental arm, there was a significant decrease in corneal thickness (273 ± 51.3 vs. 407.3 ± 10.3 μm, p = 0.0038), E:S reflectivity ratio (0.71 ± 0.09 vs. 0.99 ± 0.06, p = 0.0018), and keratometry (40.4 ± 2.3 vs. 45.8 ± 0.9D, p = 0.0033) and increase in densitometry (54.2 ± 11.65 vs.18.7 ± 3.8 GSU, p = 0.0001) from baseline, which stabilized at 4 to 8-weeks post-wounding (p > 0.3632). At 8-weeks, the relative change from baseline in corneal thickness (28.4 ± 13.5% vs.22.4 ± 13%, p = 0.368), E:S reflectivity ratio (28.1 ± 11.5% vs. 30.6 ± 8.9%, p = 0.603), corneal densitometry (204.17 ± 97.3% vs. 304.9 ± 113.6%, p = 0.1113), and central corneal keratometry (13.6 ± 6.9% vs. 18.9 ± 7.4%, p = 0.1738) in rabbits was similar to human corneal scars., Conclusion: The animal model of corneal opacification was objectively comparable to human post-keratitis scars and can be valuable for in vivo evaluation of emerging therapies for corneal opacities., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Spatially resolved analysis of uranium (U) isotopes in small volumes of actinide-bearing materials is critical for a variety of technical disciplines, including earth and planetary sciences, environmental monitoring, bioremediation, and the nuclear fuel cycle. However, achieving subnanometer-scale spatial resolution for such isotopic analysis is currently a challenge. By using atom probe tomography-a three-dimensional nanoscale characterisation technique-we demonstrate unprecedented nanoscale mapping of U isotopic enrichment with high sensitivity across various microstructural interfaces within small volumes (~100 nm 3 ) of depleted and low-enriched U alloyed with 10 wt% molybdenum that has different nominal enrichments of 0.20 and 19.75% 235 U, respectively. We map enrichment in various morphologies of a U carbide phase, the adjacent γ-UMo matrix, and across interfaces (e.g., carbide/matrix, grain boundary). Results indicate the U carbides were formed during casting, rather than retained from either highly enriched or depleted U feedstock materials. The approach presented here can be applied to study nanoscale variations of isotopic abundances in the broad class of actinide-bearing materials, providing unique insights into their origins and thermomechanical processing routes.

Lightweighting of automobiles by use of novel low-cost, high strength-to-weight ratio structural materials can reduce the consumption of fossil fuels and in turn CO2 emission. Working towards this goal we achieved high strength in a low cost β-titanium alloy, Ti-1Al-8V-5Fe (Ti185), by hierarchical nanostructure consisting of homogenous distribution of micron-scale and nanoscale α-phase precipitates within the β-phase matrix. The sequence of phase transformation leading to this hierarchical nanostructure is explored using electron microscopy and atom probe tomography. Our results suggest that the high number density of nanoscale α-phase precipitates in the β-phase matrix is due to ω assisted nucleation of α resulting in high tensile strength, greater than any current commercial titanium alloy. Thus hierarchical nanostructured Ti185 serves as an excellent candidate for replacing costlier titanium alloys and other structural alloys for cost-effective lightweighting applications.

We sought to analyze how the number and quality of publications predict clinical trial success for a set of gene-disease associations. Limiting the scope of our analysis to genes in the protein kinase family and to oncology indications, we extracted gene-disease relationships from more than 12 million article titles and abstracts published between 1992 and 2012. We integrated these data with clinical trial information for FDA-approved kinase inhibitors and kinase inhibitors that failed owing to lack of efficacy. We found that, up until the year when a compound enters clinical trials, the cumulative number of publications about a gene-disease relationship corresponding to the compound's mechanism of action is, at the median, 30 for approved compounds but only four for failed compounds., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Cluster analysis methods have been extensively researched, but the adoption of new methods is often hindered by technical barriers in their implementation and use. WebGimm is a free cluster analysis web-service, and an open source general purpose clustering web-server infrastructure designed to facilitate easy deployment of integrated cluster analysis servers based on clustering and functional annotation algorithms implemented in R. Integrated functional analyses and interactive browsing of both, clustering structure and functional annotations provides a complete analytical environment for cluster analysis and interpretation of results. The Java Web Start client-based interface is modeled after the familiar cluster/treeview packages making its use intuitive to a wide array of biomedical researchers. For biomedical researchers, WebGimm provides an avenue to access state of the art clustering procedures. For Bioinformatics methods developers, WebGimm offers a convenient avenue to deploy their newly developed clustering methods. WebGimm server, software and manuals can be freely accessed at http://ClusterAnalysis.org/.

Background: Integration of biological knowledge encoded in various lists of functionally related genes has become one of the most important aspects of analyzing genome-wide functional genomics data. In the context of cluster analysis, functional coherence of clusters established through such analyses have been used to identify biologically meaningful clusters, compare clustering algorithms and identify biological pathways associated with the biological process under investigation., Results: We developed a computational framework for analytically and visually integrating knowledge-based functional categories with the cluster analysis of genomics data. The framework is based on the simple, conceptually appealing, and biologically interpretable gene-specific functional coherence score (CLEAN score). The score is derived by correlating the clustering structure as a whole with functional categories of interest. We directly demonstrate that integrating biological knowledge in this way improves the reproducibility of conclusions derived from cluster analysis. The CLEAN score differentiates between the levels of functional coherence for genes within the same cluster based on their membership in enriched functional categories. We show that this aspect results in higher reproducibility across independent datasets and produces more informative genes for distinguishing different sample types than the scores based on the traditional cluster-wide analysis. We also demonstrate the utility of the CLEAN framework in comparing clusterings produced by different algorithms. CLEAN was implemented as an add-on R package and can be downloaded at http://Clusteranalysis.org. The package integrates routines for calculating gene specific functional coherence scores and the open source interactive Java-based viewer Functional TreeView (FTreeView)., Conclusion: Our results indicate that using the gene-specific functional coherence score improves the reproducibility of the conclusions made about clusters of co-expressed genes over using the traditional cluster-wide scores. Using gene-specific coherence scores also simplifies the comparisons of clusterings produced by different clustering algorithms and provides a simple tool for selecting genes with a "functionally coherent" expression profile.