OSCA: a comprehensive open-access system of analysis of posterior capsular opacification

BACKGROUND: This paper presents and tests a comprehensive computerised system of analysis of digital images of posterior capsule opacification (PCO). It updates and expands significantly on a previous presentation to include facilities for selecting user defined central areas and for registering and subsequent merging of images for artefact removal. Also, the program is compiled and thus eliminates the need for specialised additional software. The system is referred to in this paper as the open-access systematic capsule assessment (OSCA). The system is designed to be evidence based, objective and openly available, improving on current systems of analysis. METHODS: Principal features of the OSCA system of analysis are discussed. Flash artefacts are automatically located in two PCO images and the images merged to produce a composite free from these artefacts. For this to be possible the second image has to be manipulated with a registration technique to bring it into alignment with the first. Further image processing and analysis steps use a location-sensitive entropy based texture analysis of PCO. Validity of measuring PCO progression of the whole new system is assessed along with visual significance of scores. Reliability of the system is assessed. RESULTS: Analysis of PCO by the system shows ability to detect early progression of PCO, as well as detection of more visually significant PCO. Images with no clinical PCO produce very low scores in the analysis. Reliability of the system of analysis is demonstrated. CONCLUSION: This system of PCO analysis is evidence-based, objective and clinically useful. It incorporates flash detection and removal as well as location sensitive texture analysis. It provides features and benefits not previously available to most researchers or clinicians. Substantial evidence is provided for this system's validity and reliability

Prevalence of Australians exposed to potentially cardiotoxic cancer medicines: a population-based cohort study

Background: Cardiovascular disease (CVD) and cancer are leading causes of death and people with cancer are at higher risk of developing CVD than the general population. Many cancer medicines have cardiotoxic effects but the size of the population exposed to these potentially cardiotoxic medicines is not known. We aimed to determine the prevalence of exposure to potentially cardiotoxic cancer medicines in Australia. Methods: We identified potentially cardiotoxic systemic cancer medicines through searching the literature and registered product information documents. We conducted a retrospective cohort study of Australians dispensed potentially cardiotoxic cancer medicines between 2005 and 2021, calculating age-standardised annual prevalence rates of people alive with exposure to a potentially cardiotoxic medicine during or prior to each year of the study period. Findings: We identified 108,175 people dispensed at least one potentially cardiotoxic cancer medicine; median age, 64 (IQR: 52–74); 57% female. Overall prevalence increased from 49 (95%CI: 48.7–49.3)/10,000 to 232 (95%CI: 231.4–232.6)/10,000 over the study period; 61 (95%CI: 60.5–61.5)/10,000 to 293 (95%CI: 292.1–293.9)/10,000 for females; and 39 (95%CI: 38.6–39.4)/10,000 to 169 (95%CI: 168.3–169.7)/10,000 for males. People alive five years following first exposure increased from 29 (95%CI: 28.8–29.2)/10,000 to 134 (95%CI: 133.6–134.4)/10,000; and from 22 (95%CI: 21.8–22.2)/10,000 to 76 (95%CI: 75.7–76.3)/10,000 for those alive at least 10 years following first exposure. Most people were exposed to only one potentially cardiotoxic medicine, rates of which increased from 39 (95%CI: 38.7–39.3)/10,000 in 2005 to 131 (95%CI: 130.6–131.4)/10,000 in 2021. Interpretation: The number of people exposed to efficacious yet potentially cardiotoxic cancer medicines in Australia is growing. Our findings can support the development of service planning and create awareness about the magnitude of cancer treatment-related cardiotoxicities. Funding: NHMRC Centre for Research Excellence in Medicines Intelligence, Cancer Institute NSW Early Career Fellowship

A freely accessible, evidence based, objective system of analysis of posterior capsular opacification ; Evidence for its validity and reliability

BACKGROUND: The aim of this study was to develop a system of computerised analysis of digital images of posterior capsule opacification (PCO) that is evidence based, objective and freely available. The paper will present evidence for the reliability and validity of the developed system. METHODS: The system of PCO analysis was developed considering current published evidence on visual significance of PCO and additional investigative analysis of PCO images. Details of the image processing and analysis steps are discussed and a final system that measures an entropy score weighted toward proximity to central areas is described. In order to assess validity, the systems ability to measure PCO progression is assessed along with the visual significance of its final computerised scores. Reliability of the system is also assessed. RESULTS: The final system runs successfully and is simple to use. Analyses of PCO by the system show an ability to detect early progression of PCO as well as detection of visually significant PCO. Images with no clinical PCO produce very low scores in the analysis. Reliability of the system of analysis is shown to be satisfactory. CONCLUSION: This paper presents a system of PCO analysis that is evidence based, objective and clinically useful. Substantial evidence is provided for its validity and reliability

Get Your Foes Fooled: Proximal Gradient Split Learning for Defense Against Model Inversion Attacks on IoMT Data

The past decade has seen a rapid adoption of Artificial Intelligence (AI), specifically the deep learning networks, in Internet of Medical Things (IoMT) ecosystem. However, it has been shown recently that the deep learning networks can be exploited by adversarial attacks that not only make IoMT vulnerable to the data theft but also to the manipulation of medical diagnosis. The existing studies consider adding noise to the raw IoMT data or model parameters which not only reduces the overall performance concerning medical inferences but also is ineffective to the likes of deep leakage from gradients method. In this work, we propose proximal gradient split learning (PSGL) method for defense against the model inversion attacks. The proposed method intentionally attacks the IoMT data when undergoing the deep neural network training process at client side. We propose the use of proximal gradient method to recover gradient maps and a decision-level fusion strategy to improve the recognition performance. Extensive analysis show that the PGSL not only provides effective defense mechanism against the model inversion attacks but also helps in improving the recognition performance on publicly available datasets. We report 14.0 % , 17.9 % , and 36.9 % gains in accuracy over reconstructed and adversarial attacked images, respectively

Pre-spliceosomal binding of U1 small nuclear ribonucleoprotein (RNP) and heterogenous nuclear RNP E1 is associated with suppression of a growth hormone receptor pseudoexon

Pseudoexons occur frequently in the human genome. This paper characterizes a pseudoexon in the GH receptor gene. Inappropriate activation of this pseudoexon causes Laron syndrome. Using in vitro splicing assays, pseudoexon silencing was shown to require a combination of a weak 5 ' pseudosplice- site and splicing silencing elements within the pseudoexon. Immunoprecipitation experiments showed that specific binding of heterogenous nuclear ribonucleoprotein E1 ( hnRNP E1) and U1 small nuclear ribonucleoprotein ( snRNP) in the pre- spliceosomal complex was associated with silencing of pseudoexon splicing. The possible role of hnRNP E1 was further supported by RNA interference experiments in cultured cells. Immunoprecipitation experiments with three other pseudoexons suggested that pre- spliceosomal binding of U1 snRNP is a potential general mechanism of suppression of pseudoexons

Tumor-educated Tregs drive organ-specific metastasis in breast cancer by impairing NK cells in the lymph node niche

Breast cancer is accompanied by systemic immunosuppression, which facilitates metastasis formation, but how this shapes organotropism of metastasis is poorly understood. Here, we investigate the impact of mammary tumorigenesis on regulatory T cells (Tregs) in distant organs and how this affects multi-organ metastatic disease. Using a preclinical mouse mammary tumor model that recapitulates human metastatic breast cancer, we observe systemic accumulation of activated, highly immunosuppressive Tregs during primary tumor growth. Tumor-educated Tregs show tissue-specific transcriptional rewiring in response to mammary tumorigenesis. This has functional consequences for organotropism of metastasis, as Treg depletion reduces metastasis to tumor-draining lymph nodes, but not to lungs. Mechanistically, we find that Tregs control natural killer (NK) cell activation in lymph nodes, thereby facilitating lymph node metastasis. In line, an increased Treg/NK cell ratio is observed in sentinel lymph nodes of breast cancer patients compared with healthy controls. This study highlights that immune regulation of metastatic disease is highly organ dependent

Phenolic Profile, Nutritional Composition, Functional Properties and Antioxidant Activity of Newly Grown Parthenocarpic and Normal Seeded Tomato

The aim of the study was to compare the physico-chemical parameters, sugar, vitamin C, and phenolic profiles in five genotypes of local indeterminate tunnel tomato hybrid (LITTH) (LITTH-778, LITTH-784, LITTH-786, LITTH-788 and LITTH-790) of natural parthenocarpic tomato (NPT) and normal seeded tomato (NST). Samples were collected from the experimental fields of Ayub Agricultural Research Institute, Faisalabad, Pakistan. Physical parameters (fruit shape, fruit weight, fruit length, fruit width, number of seeds per fruit, shelf life), chemical composition (moisture, ash, crude fat, crude fibre, total carbohydrate, crude protein, vitamin C), ofNPT and NST were analyzed by reported methods. The methanolic extracts of tomato pulp were prepared by shaking and extracts were assayed for antioxidant activity. Sugars contents and phenolic profile of NPT and NST were estimatedusing HPLC method.Weight and size of NPT were less and smaller than the NST. Moreover, NPT were seedless with longer shelf-life and had more phenolic and flavonoid contents than the NST.HPLC analysis revealed that chlorogenic acid, gallic acid, p-coumeric acid were major phenolics in methanol (polar solvent) extracts of NST whereas, caffeic acid, gallic acid, p-coumeric acid in NPT extract.NPT contained higher concentration of sugar contents, but lower concentration of vitamin C than NST. In 2,2-diphenyl-1-picrylhydrazyl(DPPH) free-radical-scavenging assay, NPT fruits extracts showed high scavenging activity with the 50% inhibitory concentration (IC50)value of 22.56 µg/mL than NSTfruit extracts having IC50 29.49 µg/mL. This study provided useful information for farmers and nutritionists

Mathematical Model of Plasmid-Mediated Resistance to Ceftiofur in Commensal Enteric Escherichia coli of Cattle

Antimicrobial use in food animals may contribute to antimicrobial resistance in bacteria of animals and humans. Commensal bacteria of animal intestine may serve as a reservoir of resistance-genes. To understand the dynamics of plasmid-mediated resistance to cephalosporin ceftiofur in enteric commensals of cattle, we developed a deterministic mathematical model of the dynamics of ceftiofur-sensitive and resistant commensal enteric Escherichia coli (E. coli) in the absence of and during parenteral therapy with ceftiofur. The most common treatment scenarios including those using a sustained-release drug formulation were simulated; the model outputs were in agreement with the available experimental data. The model indicated that a low but stable fraction of resistant enteric E. coli could persist in the absence of immediate ceftiofur pressure, being sustained by horizontal and vertical transfers of plasmids carrying resistance-genes, and ingestion of resistant E. coli. During parenteral therapy with ceftiofur, resistant enteric E. coli expanded in absolute number and relative frequency. This expansion was most influenced by parameters of antimicrobial action of ceftiofur against E. coli. After treatment (>5 weeks from start of therapy) the fraction of ceftiofur-resistant cells among enteric E. coli, similar to that in the absence of treatment, was most influenced by the parameters of ecology of enteric E. coli, such as the frequency of transfer of plasmids carrying resistance-genes, the rate of replacement of enteric E. coli by ingested E. coli, and the frequency of ceftiofur resistance in the latter

Tracking Antigen-Specific T-Cells during Clinical Tolerance Induction in Humans

Allergen immunotherapy presents an opportunity to define mechanisms of induction of clinical tolerance in humans. Significant progress has been made in our understanding of changes in T cell responses during immunotherapy, but existing work has largely been based on functional T cell assays. HLA-peptide-tetrameric complexes allow the tracking of antigen-specific T-cell populations based on the presence of specific T-cell receptors and when combined with functional assays allow a closer assessment of the potential roles of T-cell anergy and clonotype evolution. We sought to develop tools to facilitate tracking of antigen-specific T-cell populations during wasp-venom immunotherapy in people with wasp-venom allergy. We first defined dominant immunogenic regions within Ves v 5, a constituent of wasp venom that is known to represent a target antigen for T-cells. We next identified HLA-DRB1*1501 restricted epitopes and used HLA class II tetrameric complexes alongside cytokine responses to Ves v 5 to track T-cell responses during immunotherapy. In contrast to previous reports, we show that there was a significant initial induction of IL-4 producing antigen-specific T-cells within the first 3–5 weeks of immunotherapy which was followed by reduction of circulating effector antigen-specific T-cells despite escalation of wasp-venom dosage. However, there was sustained induction of IL-10-producing and FOXP3 positive antigen-specific T cells. We observed that these IL-10 producing cells could share a common precursor with IL-4-producing T cells specific for the same epitope. Clinical tolerance induction in humans is associated with dynamic changes in frequencies of antigen-specific T-cells, with a marked loss of IL-4-producing T-cells and the acquisition of IL-10-producing and FOXP3-positive antigen-specific CD4+ T-cells that can derive from a common shared precursor to pre-treatment effector T-cells. The development of new approaches to track antigen specific T-cell responses during immunotherapy can provide novel insights into mechanisms of tolerance induction in humans and identify new potential treatment targets

Cohort profile: design and methods in the eye and vision consortium of UK Biobank

PURPOSE: To describe the rationale, methods and research potential of eye and vision measures available in UK Biobank. PARTICIPANTS: UK Biobank is a large, multisite, prospective cohort study. Extensive lifestyle and health questionnaires, a range of physical measures and collection of biological specimens are collected. The scope of UK Biobank was extended midway through data collection to include assessments of other measures of health, including eyes and vision. The eye assessment at baseline included questionnaires detailing past ophthalmic and family history, measurement of visual acuity, refractive error and keratometry, intraocular pressure (IOP), corneal biomechanics, spectral domain optical coherence tomography (OCT) of the macula and a disc-macula fundus photograph. Since recruitment, UK Biobank has collected accelerometer data and begun multimodal imaging data (including brain, heart and abdominal MRI) in 100 000 participants. Dense genotypic data and a panel of 20 biochemistry measures are available, and linkage to medical health records for the full cohort has begun. FINDINGS TO DATE: A total of 502 665 people aged between 40 and 69 were recruited to participate in UK Biobank. Of these, 117 175 took part in baseline assessment of vision, IOP, refraction and keratometry. A subgroup of 67 321 underwent OCT and retinal photography. The introduction of eye and vision measures in UK Biobank was accompanied by intensive training, support and a data monitoring quality control process. FUTURE PLANS: UK Biobank is one of the largest prospective cohorts worldwide with extensive data on ophthalmic diseases and conditions. Data collection is an ongoing process and a repeat of the baseline assessment including the questionnaires, measurements and sample collection will be performed in subsets of 25 000 participants every 2-3 years. The depth and breadth of this dataset, coupled with its open-access policy, will create a powerful resource for all researchers to investigate the eye diseases in later life