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Objective: The fragility index (FI) of a meta-analysis evaluates the extent that the statistical significance can be changed by modifying the event status of individuals from included trials. Understanding the FI improves the interpretation of the results of meta-analyses and can help to inform changes to clinical practice. This review determined the fragility of ophthalmology-related meta-analyses., Methods: Meta-analyses of randomized controlled trials with binary outcomes published in a journal classified as 'Ophthalmology' according to the Journal Citation Report or an Ophthalmology-related Cochrane Review were included. An iterative process determined the FI of each meta-analysis. Multivariable linear regression modeling evaluated the relationship between the FI and potential predictive factors in statistically significant and non-significant meta-analyses., Results: 175 meta-analyses were included. The median FI was 6 (Q1-Q3: 3-12). This meant that moving 6 outcomes from one group to another would reverse the study's findings. The FI was 1 for 18 (10.2%) of the included meta-analyses and was ≤5 for 75 (42.4%) of the included meta-analyses. The number of events (p < 0.001) and the p-value (p < 0.001) were the best predictors of the FI in both significant and non-significant meta-analyses., Conclusion: The statistical significance of meta-analyses in ophthalmology often hinges on the outcome of a few patients. The number of events and the p-value are the most important factors in determining the fragility of the evidence. The FI is an easily interpretable measure that can supplement the reader's understanding of the strength of the evidence being presented., Prospero Registration: CRD42022377589., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Hypertension is a significant public health concern and a modifiable risk factor for increased mortality worldwide. It is reported to be influenced by gene-environment interactions and micronutrient intake. This study aims to understand the relationship between global DNA methylation levels and hypertension, independently and in the context of micronutrient status, among rural population in Punjab, India. A total of 2300 individuals, aged 30-75 years, (54.9% females) were screened for blood pressure. Of 2300 screened individuals, 900 (age sex matched 450 cases and 450 controls of hypertension) individuals were selected to examine the relationship between hypertension, global DNA methylation (5mC), and biochemicals (Folate, Vitamin B12, and Homocysteine). Folate, vitamin B12, and homocysteine levels were estimated using chemiluminescence technique. The ELISA-based colorimetric technique was used for performing peripheral blood leucocyte (PBL) global DNA methylation (5mC). Statistical analyses were performed using SPSS version 22.0. Hypertensives were found to have significantly lower levels of global DNA methylation than normotensives (0.65 vs. 0.72 respectively; p-value = 0.01*). Individuals in the 1st quartile of 5mC were at significantly (OR: 1.671; 95% CI: 1.206-2.315; p-value = 0.01*) increased risk for hypertension in comparison to those in the 4th quartile (reference). Further hypertensives on medication with controlled blood pressure (BP) were significantly hypermethylated as compared to hypertensives on medication with uncontrolled BP (0.70 vs. 0.62 respectively; p-value = 0.04*). Folate appeared to mediate global DNA methylation among hypertensives on medication-controlled BP. Further hypertension driven hypomethylation hints towards accelerated biological aging among younger hypertensives. Hypertension may be associated with Global DNA hypomethylation in the studied rural population of Punjab, India. Folate sufficiency may prove to be an aid in improving the methylation levels among the cases of hypertension who were on medication and had controlled BP., (© 2024. The Author(s).)

Practice patterns for neovascular age-related macular degeneration (nAMD) have evolved from the landmark registration trials of vascular endothelial growth factor (VEGF) inhibitors. Non-monthly regimens like treat-and-extend (T&E) have become popular due to their effectiveness in clinical practice. T&E regimens attempt to limit the burden of visits and treatments by allowing progressively longer treatment intervals, but in so doing, are potentially associated with the expense of treating quiescent disease. This is acceptable to many patients and their ophthalmologists but can still be problematic in the real-world. Recent studies have further refined the T&E approach by allowing for quicker and longer extension of treatment intervals when less severe disease is detected. With newer drugs offering increased durability, a shift to longer regular intervals may emerge as a new practice pattern for VEGF inhibitor therapy. This review aims to consolidate the current literature on the most effective treatment patterns and update treatment guidelines based on options that are now available. It also summarises new aspects of nAMD management that may help to further refine current practice., (© 2024. The Author(s).)

This systematic review and meta-analysis investigated the impact of anti-vascular endothelial growth factor (VEGF) treatment in management of eyes with non-proliferative diabetic retinopathy (NPDR) without centre involving diabetic macular oedema (CI-DMO). We searched multiple databases for all randomised clinical trials (RCTs) that evaluated anti-VEGF treatment versus observation in eyes with NPDR without CI-DMO. Data was collected for six outcomes (best corrected visual acuity (BCVA) improvement, diabetic retinopathy severity score (DRSS), central subfield thickness, progression to vision threatening complications (VTCs), ocular adverse events and quality of life measures). Risk of bias was assessed using Cochrane risk-of-bias tool for randomised trials (RoB 2) and certainty of evidence was assessed using Grade of Recommendations, Assessment, Development and Evaluation (GRADE). We identified a total of 2 unique RCTs that compared aflibercept and sham to treat a total of 811 eyes. For BCVA change, there was a small, clinically insignificant benefit for aflibercept treatment at year 2 (MD 0.70, 95% CI 0.02-1.38, GRADE rating: MODERATE). DRSS demonstrated a statistically significant improvement with aflibercept use at year 2 (RR 3.76, 95% CI 2.75-5.13, GRADE rating: MODERATE). VTCs were significantly less in aflibercept arm at year 2 (RR 0.30, 95% CI 0.23-0.40, GRADE rating: MODERATE). In conclusion, aflibercept treatment versus observation in eyes with NPDR without CI-DMO can result in reduced risk of development of VTCs and regression of DRSS score over 2 years. Future trials are needed to increase the precision of the treatment effect and to provide data on quality-of-life metrics.PROSPERO Registration: CRD42021288608., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

This study aimed to compare efficacy and treatment burden of treat-and-extend (T&E) anti-VEGF against fixed and pro re nata (PRN) regimens for neovascular age-related macular degeneration (nAMD). MEDLINE, CENTRAL, and EMBASE were searched. Randomized-controlled trials and observational studies comparing T&E to PRN or fixed dosing for treatment-naïve AMD patients were included. Mean difference (MD) for visual acuity (VA) and number of injections are presented. Risk of bias was assessed according to Cochrane guidelines. Methodology was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). VA improvement was similar with T&E and fixed dosing at one (MD -0.08 letters, p = 0.95) and two years (MD 0.58 letters, p = 0.62). In contrast, VA improvements were significantly greater for T&E when compared against a PRN regimen at one (MD 3.95 letters, p < 0.0001) and two years (MD 4.08 letters, p < 0.001). Significantly fewer ranibizumab injections were administered in the T&E arm at one (MD -2.42 injections, p < 0.0001) and two years (MD -6.06 injections, p < 0.00001) relative to fixed dosing. Fewer aflibercept injections were likewise administered to patients on a T&E regimen versus fixed dosing at one year (MD -0.78 injections, p < 0.0001). Low-certainty evidence from the present synthesis implies that T&E preserves VA similar to fixed schedules with significantly fewer injections at one and two years. Also, patients with T&E dosing achieved better VA outcomes than those on PRN regimen but T&E dosing was associated with more injections., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Biofabrication of gold nanoparticles (AuNPs) using the aromatic essential oils is highlighted due to its simple, economical, low toxicity, and eco-friendly nature. Essential oil of Cymbopogon flexuosus (CF), an economically valuable medicinal plant, exhibits anti-inflammatory, anti-tumor, antioxidant, and antimicrobial activities. For the first time, this research accounts for the biosynthesis, physicochemical, photocatalytic, antifungal, antibacterial properties of biogenic AuNPs, fabricated using CF essential oil collected from different altitudes (S1-Palampur, S2-Haryana, S3-Dehradun). The altitudinal disparity in the phytochemical composition of essential oils is highlighted. The average crystallite size ranged from 10 to 32 nm and was influenced by CF samples used in the synthesis. The spectroscopic outcomes revealed the involvement of bioactive reagents from CF essential oil in the fabrication and stabilization of AuNPs. The fabricated AuNPs exhibited excellent antimicrobial activities against all tested strains (Staphyloccucs aureus, Escherichia coli, Fusarium oxysporum), showing their efficacy as an antimicrobial agent to treat infectious diseases. Moreover, AuNPs exhibited excellent photocatalytic efficacy of around 91.8% for the degradation of methylene blue under exposure of direct sunlight for 3 h without the assistance of an external reducing agent. The outcomes highlight a potential economic and environmentally friendly strategy to fabricate biogenic AuNPs for diversified industrial applications where antimicrobial and photocatalytic efficacies are the key requirements., (© 2022. The Author(s).)

Amid ongoing devastation due to Serve-Acute-Respiratory-Coronavirus2 (SARS-CoV-2), the global spatial and temporal variation in the pandemic spread has strongly anticipated the requirement of designing area-specific preventive strategies based on geographic and meteorological state-of-affairs. Epidemiological and regression models have strongly projected particulate matter (PM) as leading environmental-risk factor for the COVID-19 outbreak. Understanding the role of secondary environmental-factors like ammonia (NH 3 ) and relative humidity (RH), latency of missing data structuring, monotonous correlation remains obstacles to scheme conclusive outcomes. We mapped hotspots of airborne PM 2.5 , PM 10 , NH 3 , and RH concentrations, and COVID-19 cases and mortalities for January, 2021-July,2021 from combined data of 17 ground-monitoring stations across Delhi. Spearmen and Pearson coefficient correlation show strong association (p-value < 0.001) of COVID-19 cases and mortalities with PM 2.5 (r > 0.60) and PM 10 (r > 0.40), respectively. Interestingly, the COVID-19 spread shows significant dependence on RH (r > 0.5) and NH 3 (r = 0.4), anticipating their potential role in SARS-CoV-2 outbreak. We found systematic lockdown as a successful measure in combatting SARS-CoV-2 outbreak. These outcomes strongly demonstrate regional and temporal differences in COVID-19 severity with environmental-risk factors. The study lays the groundwork for designing and implementing regulatory strategies, and proper urban and transportation planning based on area-specific environmental conditions to control future infectious public health emergencies., (© 2022. The Author(s).)

Emergent application of antimicrobial strategies as symptomatic treatment in coronavirus disease (COVID-19) and linkage of severe acute respiratory syndrome coronavirus2 with microbial infections, has created colossal demand for antimicrobials. For the first time, this communication explore the physicochemical, antifungal, antibacterial, and photocatalytic properties of biogenic magnesium nanoparticles (MgNPs), synthesized using essential oil of Cymbopogon flexuosus's as an efficient multifunctional reducing and stabilizing/capping reagent. It is observed that MgNPs (ranging in size: 8-16 nm) of varying phytochemical compositions (MgS1, MgS2, MgS3) exhibited various useful physicochemical, antimicrobial, and photocatalytic properties. FTIR outcomes highlight the functional biomolecules-assisted reduction of Mg from Mg + to Mg 0 . Among all, MgS3-Nps owing to the smallest particle size exhibited superior photocatalytic efficacy (91.2%) for the methylene blue degradation upon direct exposure to the sunlight for 3 h without using any reducing agents. Fabricated MgNPs also exhibited excellent antifungal (against Fusarium oxysporum) and antibacterial (versus Staphylococcus aureus and Escherichia coli) efficacies compared to state-of-the-art antimicrobial agents deployed for the treatment of infectious diseases. Based on this investigated greener approach, imperative from economic and environmental viewpoint, such essential oil based-MgNPs can be a potential nanosystem for various industrial applications where photocatalytic, and biomedical attributes are the key requirements., (© 2022. The Author(s).)

A variety of high-performance materials are utilized in electrical, electronic, and mechanical systems. Such systems account for a significant fraction of the world's electricity consumption. The next generation of such systems urgently require new material compositions which possess a better combination of both structural and functional properties. Only accelerated methodologies can rapidly determine the required multiple property set. Hence, a range of iron-cobalt-nickel ternary alloy composition powders were chemically synthesized. Compositionally graded bulk materials libraries were prepared by spark plasma sintering of these powders. A multiple property set of the crystal structure, magnetic, mechanical, and electrical properties were determined for a range of compositions. This property set revealed that a good combination of magnetic and mechanical properties can be obtained from Fe 50 Co 40 Ni 10 , high electrical resistivity from Fe 54 Co 17 Ni 29 and high saturation magnetization as well as high hardness from Fe 57 Co 29 Ni 14 . Thus, this multiple property library, developed by accelerated methodologies, can be utilized to identify new ternary compositions satisfying diverse property sets relevant to next generation systems., (© 2022. The Author(s).)

Superior passive cooling technologies are urgently required to tackle device overheating, consequent performance degradation, and service life reduction. Magnetic cooling, governed by the thermomagnetic convection of a ferrofluid, is a promising emerging passive heat transfer technology to meet these challenges. Hence, we studied the performance metrics, non-dimensional parameters, and thermomagnetic cooling performance of various ferrite and metal-based ferrofluids. The magnetic pressure, friction factor, power transfer, and exergy loss were determined to predict the performance of such cooling devices. We also investigated the significance of the magnetic properties of the nanoparticles used in the ferrofluid on cooling performance. γ-Fe 2 O 3 , Fe 3 O 4 , and CoFe 2 O 4 nanoparticles exhibited superior cooling performance among ferrite-based ferrofluids. FeCo nanoparticles had the best cooling performance for the case of metallic ferrofluids. The saturation magnetization of the magnetic nanoparticles is found to be a significant parameter to enhance heat transfer and heat load cooling. These results can be used to select the optimum magnetic nanoparticle-based ferrofluid for a specific magnetic cooling device application., (© 2021. The Author(s).)

Oil spills are a potential hazard, causing the deaths of millions of aquatic animals and this leaves a calamitous effect on the marine ecosystem. This research focuses on evaluating the potential of polarimetric parameters in discriminating the oil slick from water and also possible thicker/thinner zones within the slick. For this purpose, L-band UAVSAR quad-pol data of the Gulf of Mexico region is exploited. A total number of 19 polarimetric parameters are examined to study their behavior and ability in distinguishing oil slick from water and its own less or more oil accumulated zones. The simulation of compact-pol data from UAVSAR quad-pol data is carried out which has shown good performance in detection and discrimination of oil slick from water. To know the extent of separation between oil and water classes, a statistical separability analysis is carried out. The outcomes of each polarimetric parameter from separability analysis are then quantified with the radial basis function (RBF) supervised Support Vector Machine classifier followed with an accurate estimation of the results. Moreover, a comparison of the achieved and estimated accuracy has shown a significant drop in accuracy values. It has been observed that the highest accuracy is given by LHV compact-pol decomposition and coherency matrix with a classification accuracy of ~ 94.09% and ~ 94.60%, respectively. The proposed methodology has performed well in discriminating the oil slick by utilizing UAVSAR dataset for both quad-pol and compact-pol simulation.

Chimeric Antigen Receptor-T (CAR-T) cell immunotherapy has produced dramatic responses in hematologic malignancies. One of the challenges in the field is the lack of a simple assay for the detection of CARs on the surface of immune effector cells. In this study, we describe a novel luciferase-based assay, termed Topanga Assay, for the detection of CAR expression. The assay utilizes a recombinant fusion protein, called Topanga reagent, generated by joining the extra-cellular domain of a CAR-target in frame with one of the marine luciferases or their engineered derivatives. The assay involves incubation of CAR expressing cells with the Topanga reagent, a few washes and measurement of luminescence. The assay can detect CARs comprising either immunoglobulin- or non-immunoglobulin-based antigen binding domains. We further demonstrate that addition of epitope tags to the Topanga reagent not only allows its convenient one step purification but also extends its use for detection of CAR cells using flow cytometry. However, crude supernatant containing the secreted Topanga reagent can be directly used in both luminescence and flow-cytometry based assays without prior protein purification. Our results demonstrate that the Topanga assay is a highly sensitive, specific, convenient, economical and versatile assay for the detection of CARs.

While the AlCoFeNi high entropy alloy exhibits a single ordered B2 phase at high temperature, both the substitution of ferromagnetic Co with antiferromagnetic Cr, and lower annealing temperatures lead to a tendency for this system to decompose into a two-phase mixture of ordered B2 and disordered BCC solid solution. The length scale of this decomposition is determined by the combination of composition and annealing temperature, as demonstrated in this investigation by comparing and contrasting AlCoFeNi with the AlCo 0.5 Cr 0.5 FeNi alloy. The resulting phase stability has been rationalized based on solution thermodynamic predictions. Additionally, it is shown that replacement of Co by Cr in the AlCoFeNi alloy resulted in a substantial reduction in saturation magnetization and increase in coercivity. The microhardness is also strongly influenced by the composition and the length scale of B2 + BCC decomposition in these high entropy alloys.

A simple, accurate, sensitive and robust assay that can rapidly and specifically measure the death of target cells would have applications in many areas of biomedicine and particularly for the development of novel cellular- and immune-therapeutics. In this study, we describe a novel cytotoxicity assay, termed the Matador assay, which takes advantage of the extreme brightness, stability and glow-like characteristics of recently discovered novel marine luciferases and their engineered derivatives. The assay involves expression of a luciferase of interest in target cells in a manner so that it is preferentially retained within the healthy cells but is either released from dead and dying cells or whose activity can be preferentially measured in dead and dying cells. We demonstrate that this assay is highly sensitive, specific, rapid, and can be performed in a single-step manner without the need for any expensive equipment. We further validate this assay by demonstrating its ability to detect cytotoxicity induced by several cellular and immune-therapeutic agents including antibodies, natural killer cells, chimeric antigen receptor expressing T cells and a bispecific T cell engager.

Low cost, earth abundant, rare earth free magnetocaloric nanoparticles have attracted an enormous amount of attention for green, energy efficient, active near room temperature thermal management. Hence, we investigated the magnetocaloric properties of transition metal based (Fe 70 Ni 30 ) 100-x Cr x (x = 1, 3, 5, 6 and 7) nanoparticles. The influence of Cr additions on the Curie temperature (T C ) was studied. Only 5% of Cr can reduce the T C from ~438 K to 258 K. These alloys exhibit broad entropy v/s temperature curves, which is useful to enhance relative cooling power (RCP). For a field change of 5 T, the RCP for (Fe 70 Ni 30 ) 99 Cr 1 nanoparticles was found to be 548 J-kg -1 . Tunable T C in broad range, good RCP, low cost, high corrosion resistance and earth abundance make these nanoparticles suitable for low-grade waste heat recovery as well as near room temperature active cooling applications.

Plants form belowground associations with mycorrhizal fungi in one of the most common symbioses on Earth. However, few large-scale generalizations exist for the structure and function of mycorrhizal symbioses, as the nature of this relationship varies from mutualistic to parasitic and is largely context-dependent. We announce the public release of MycoDB, a database of 4,010 studies (from 438 unique publications) to aid in multi-factor meta-analyses elucidating the ecological and evolutionary context in which mycorrhizal fungi alter plant productivity. Over 10 years with nearly 80 collaborators, we compiled data on the response of plant biomass to mycorrhizal fungal inoculation, including meta-analysis metrics and 24 additional explanatory variables that describe the biotic and abiotic context of each study. We also include phylogenetic trees for all plants and fungi in the database. To our knowledge, MycoDB is the largest ecological meta-analysis database. We aim to share these data to highlight significant gaps in mycorrhizal research and encourage synthesis to explore the ecological and evolutionary generalities that govern mycorrhizal functioning in ecosystems.

Antibodies and growth factors have been chemically coupled to different toxins to produce cytotoxic molecules that selectively kill cells bearing appropriate antigens or receptors. Antibody-toxin conjugates (immunotoxins) produced using conventional chemical coupling techniques have several undesirable characteristics. The smallest binding unit of an antibody is an Fv fragment which consists of a light and heavy chain variable domain. Recently, active single chain Fv fragments of antibodies have been produced in Escherichia coli by attaching the light and heavy chain variable domains together with a peptide linker. Here we describe the construction and expression in E. coli of a single chain antibody toxin fusion protein, anti-Tac(Fv)-PE40, in which the variable regions of anti-Tac, a monoclonal antibody to the p55 subunit of the human interleukin-2 receptor, are joined in peptide linkage to PE40, a modified form of Pseudomonas exotoxin lacking its binding domain. Anti-Tac(Fv)-PE40 was very cytotoxic to two interleukin-2 receptor-bearing human cell lines but was not cytotoxic to receptor-negative cells.

It is projected that in the absence of effective therapy, most individuals infected with human immunodeficiency virus (HIV) will develop acquired immune deficiency syndrome (AIDS) and ultimately succumb to a combination of opportunistic microbial infections, malignancies and direct pathogenic effects of the virus. Anti-viral agents, immunomodulators, and inhibitors of specific HIV functions are being tested as potential treatments to alleviate the high morbidity and mortality. An alternative therapeutic concept involves the development of cytotoxic agents that are targeted to kill HIV-infected cells. Here we describe the purification and characterization of a recombinant protein produced in Escherichia coli that contains the HIV-binding portion of the human CD4 molecule linked to active regions of Pseudomonas exotoxin A. This hybrid protein displays selective toxicity toward cells expressing the HIV envelope glycoprotein and thus represents a promising novel therapeutic agent for the treatment of AIDS.