Marker-free characterization of full-length transcriptomes of single live circulating tumor cells.

The identification and characterization of circulating tumor cells (CTCs) are important for gaining insights into the biology of metastatic cancers, monitoring disease progression, and medical management of the disease. The limiting factor in the enrichment of purified CTC populations is their sparse availability, heterogeneity, and altered phenotypes relative to the primary tumor. Intensive research both at the technical and molecular fronts led to the development of assays that ease CTC detection and identification from peripheral blood. Most CTC detection methods based on single-cell RNA sequencing (scRNA-seq) use a mix of size selection, marker-based white blood cell (WBC) depletion, and antibodies targeting tumor-associated antigens. However, the majority of these methods either miss out on atypical CTCs or suffer from WBC contamination. We present unCTC, an R package for unbiased identification and characterization of CTCs from single-cell transcriptomic data. unCTC features many standard and novel computational and statistical modules for various analyses. These include a novel method of scRNA-seq clustering, named deep dictionary learning using k-means clustering cost (DDLK), expression-based copy number variation (CNV) inference, and combinatorial, marker-based verification of the malignant phenotypes. DDLK enables robust segregation of CTCs and WBCs in the pathway space, as opposed to the gene expression space. We validated the utility of unCTC on scRNA-seq profiles of breast CTCs from six patients, captured and profiled using an integrated ClearCell FX and Polaris workflow that works by the principles of size-based separation of CTCs and marker-based WBC depletion.

Depth-Camera Based Energy Expenditure Estimation System for Physical Activity Using Posture Classification Algorithm.

Insufficient physical activity is common in modern society. By estimating the energy expenditure (EE) of different physical activities, people can develop suitable exercise plans to improve their lifestyle quality. However, several limitations still exist in the related works. Therefore, the aim of this study is to propose an accurate EE estimation model based on depth camera data with physical activity classification to solve the limitations in the previous research. To decide the best location and amount of cameras of the EE estimation, three depth cameras were set at three locations, namely the side, rear side, and rear views, to obtain the kinematic data and EE estimation. Support vector machine was used for physical activity classification. Three EE estimation models, namely linear regression, multilayer perceptron (MLP), and convolutional neural network (CNN) models, were compared and determined the model with optimal performance in different experimental settings. The results have shown that if only one depth camera is available, optimal EE estimation can be obtained using the side view and MLP model. The mean absolute error (MAE), mean square error (MSE), and root MSE (RMSE) of the classification results under the aforementioned settings were 0.55, 0.66, and 0.81, respectively. If higher accuracy is required, two depth cameras can be set at the side and rear views, the CNN model can be used for light-to-moderate activities, and the MLP model can be used for vigorous activities. The RMSEs for estimating the EEs of standing, walking, and running were 0.19, 0.57, and 0.96, respectively. By applying the different models on different amounts of cameras, the optimal performance can be obtained, and this is also the first study to discuss the issue.

Procrastination predicts online self-regulated learning and online learning ineffectiveness during the coronavirus lockdown.

During the lockdown due to SARS-CoV-2 (coronavirus lockdown), there has been a tremendous increase in the number of students taking online courses. Few studies, however, have examined the individual dispositions that influence self-regulated online learning during the coronavirus lockdown. To address this gap, the present study explored the ineffectiveness of online learning and examined how it can be predicted by self-regulated online learning and participants' procrastination disposition. Data of 433 participants were collected and subjected to confirmatory factor analysis with structural equation modeling. The results indicated that procrastination is negatively related to 6 sub-constructs of self-regulated online learning: task strategy, mood adjustment, self-evaluation, environmental structure, time management, and help-seeking. These sub-constructs were negatively related to the learners' perceived ineffectiveness of online learning. However, the relationship between perceived learning ineffectiveness and environmental structure or help-seeking was weaker than that with task strategy or mood adjustment, indicating that the latter two subtypes of self-regulated online learning should be considered before students engage in online learning.

Systems consequences of amplicon formation in human breast cancer.

Chromosomal structural variations play an important role in determining the transcriptional landscape of human breast cancers. To assess the nature of these structural variations, we analyzed eight breast tumor samples with a focus on regions of gene amplification using mate-pair sequencing of long-insert genomic DNA with matched transcriptome profiling. We found that tandem duplications appear to be early events in tumor evolution, especially in the genesis of amplicons. In a detailed reconstruction of events on chromosome 17, we found large unpaired inversions and deletions connect a tandemly duplicated ERBB2 with neighboring 17q21.3 amplicons while simultaneously deleting the intervening BRCA1 tumor suppressor locus. This series of events appeared to be unusually common when examined in larger genomic data sets of breast cancers albeit using approaches with lesser resolution. Using siRNAs in breast cancer cell lines, we showed that the 17q21.3 amplicon harbored a significant number of weak oncogenes that appeared consistently coamplified in primary tumors. Down-regulation of BRCA1 expression augmented the cell proliferation in ERBB2-transfected human normal mammary epithelial cells. Coamplification of other functionally tested oncogenic elements in other breast tumors examined, such as RIPK2 and MYC on chromosome 8, also parallel these findings. Our analyses suggest that structural variations efficiently orchestrate the gain and loss of cancer gene cassettes that engage many oncogenic pathways simultaneously and that such oncogenic cassettes are favored during the evolution of a cancer.

Modeling the economic burden of postpartum hemorrhage due to substandard uterotonics in Ghana.

Uterotonics are essential in preventing postpartum hemorrhage (PPH), the leading direct cause of maternal death worldwide. However, uterotonics are often substandard in low- and middle-income countries, contributing to poor maternal health outcomes. This study examines the health and economic impact of substandard uterotonics in Ghana. A decision-tree model was built to simulate vaginal and cesarean section births across health facilities, uterotonic quality and utilization, PPH risk and diagnosis, and resulting health and economic outcomes. We utilized delivery data from Ghana's maternal health survey, risks of health outcomes from a Cochrane review, and E-MOTIVE trial data for health outcomes related to oxytocin quality. We compared scenarios with and without substandard uterotonics, as well as scenarios altering uterotonic use and care-seeking behaviors. We found that substandard uterotonic use contributes to $18.8 million in economic burden annually, including $6.3 million and $4.8 million in out-of-pocket expenditures in public and private sectors, respectively. Annually, the National Health Insurance Scheme bears $1.6 million in costs due to substandard uterotonic use. Substandard uterotonics contribute to $6 million in long-term productivity losses from maternal mortality annually. Improving the quality of uterotonics could reduce 20,000 (11%) PPH cases, 5,000 (11%) severe PPH cases, and 100 (11%) deaths due to PPH annually in Ghana. Ensuring the quality of uterotonics would result in millions of dollars in cost savings and improve maternal health outcomes for the government and families in Ghana. Cost savings from improving uterotonic quality would provide financial protection and help Ghana advance toward Universal Health Coverage.

Replacing the postoperative week 1 visit after routine phacoemulsification with a telephone consult.

OBJECTIVE: To assess the safety of replacing the postoperative week 1 (POW1) clinic visit with a nurse-conducted telephone call. DESIGN: Retrospective observational study that included cases from January 2019 to June 2021. PARTICIPANTS: Patients who had undergone uncomplicated phacoemulsification surgery with an unremarkable postoperative day 1 (POD1) examination. METHODS: All patients were seen in clinic on POD1 by an ophthalmologist. They then had a telephone conversation with a nurse at POW1 and subsequently an in-person postoperative month 1 (POM1) clinic consultation with an ophthalmologist. Main outcome measure was the incidence of unexpected management changes related to cataract surgery within POM1. Data also were collected on the reasons for unscheduled patient-initiated visits, additional procedures or medications, and postoperative visual acuity worse than 6/12 at POM1. RESULTS: Of the 20,475 patients, 541 patients (2.64%) had an unexpected management change within POM1. There were 565 patients (2.76%) who had self-initiated unscheduled visits between POD1 to POM1. There were 23 patients (0.11%) who required additional surgery within POM1 and 1 patient (0.005%) with endophthalmitis. The most common indication for additional surgical procedures was retained lens material (7 patients, 30.43%). Visual acuity was worse than 6/12 in 1,199 patients (6.22%), with the most common causes attributed to preexisting ocular conditions. CONCLUSIONS: These results suggest that replacing the POW1 visit with a nurse-conducted telephone consult for patients who have undergone uncomplicated phacoemulsification surgery and had a normal POD1 consultation is safe.

Investigation on the Photodegradation Stability of Acrylic Acid-Grafted Poly(butylene carbonate-co-terephthalate)/Organically Modified Layered Zinc Phenylphosphonate Composites.

The application efficiency of biodegradable polymers used in a natural environment requires improved resistance to ultraviolet (UV) photodegradation. In this report, 1,6-hexanediamine modified layered zinc phenylphosphonate (m-PPZn), utilized as a UV protection additive for acrylic acid-grafted poly(butylene carbonate-co-terephthalate) (g-PBCT), was successfully fabricated and compared to the solution mixing process. Experimental data of both wide-angle X-ray diffraction and transmission electron microscopy reveal that the g-PBCT polymer matrix was intercalated into the interlayer spacing of m-PPZn, which was approximately delaminated in the composite materials. The evolution of photodegradation behavior for g-PBCT/m-PPZn composites was identified using Fourier transform infrared spectroscopy and gel permeation chromatography after being artificially irradiated by a light source. The change of carboxyl group produced via photodegradation was used to show the enhanced UV protection ability of m-PPZn in the composite materials. All results indicate that the carbonyl index of the g-PBCT/m-PPZn composite materials after photodegradation for 4 weeks was extensively lower than that of the pure g-PBCT polymer matrix. These findings were also supported by the decrease in the molecular weight of g-PBCT after photodegradation for 4 weeks, from 20.76% to 8.21%, with the loading of 5 wt% m-PPZn content. Both observations were probably owing to the better UV reflection ability of m-PPZn. This investigation shows, through typical methodology, a significant advantage of fabricating the photodegradation stabilizer to enhance the UV photodegradation behavior of the biodegradable polymer using an m-PPZn compared to other UV stabilizer particles or additives.

Assessing Study Skill Needs for Information Technology and Computer Science Students in Technical and Vocational Universities.

Not a great deal is known about what study skills are essential for success in the science, technology, engineering, and mathematics' disciplines, particularly in information technology (IT) and computer science (CS) programs in the technical and vocational education (TVE) in Taiwanese higher education. Since TVE accounts for more than half of the post-secondary enrolments in the country, and with the increasing demand for IT and CS talents, we studied perceptions of the importance and competency of such skills to identify the students' needs and demographic factors influencing them. A survey was administered to 1398 students in IT and CS programs in Taiwanese TVE universities. General skills were seen as the most important one among the study skills examined, and students felt competent using them. The needs to manage time, perform quantitative/mathematical tasks, and delegate were identified and these needs were affected by institutional quality, gender, and academic achievement. The results might be useful for further investigation in this area and guiding future plan to improve student performance in TVE.

Three-year Outcomes of an Expanded Asynchronous Virtual Glaucoma Clinic in Singapore.

PURPOSE: Virtual glaucoma clinics can help increase health care capacity, easing the disease burden of glaucoma. This study assesses the safety, rate of glaucoma progression, time efficiency, and cost-savings of our expanded Glaucoma Observation Clinic (GLOC) at the Singapore National Eye Centre over 3 years. METHODS: All patients seen at GLOC between July 2018 and June 2021 were included. Visual acuity, intraocular pressure, and visual fields or optic nerve head imaging were recorded, followed by a virtual review of the data by an ophthalmologist. An objective review of the management of 100 patients was conducted by 2 senior consultants independently as a safety audit. Patient outcomes including the rate of instability (due to worsening of clinical parameters necessitating a conventional clinic visit), glaucoma progression, the consultation review time efficiency, and cost-savings of GLOC were measured. RESULTS: Of 3458 patients, 16% had glaucoma, and the others had risk factors for glaucoma. The safety audit demonstrated a 95% interobserver agreement. The rate of instability was 14.6%, of which true progression was observed in 3.12%. The time taken for a glaucoma specialist to review a GLOC patient was 5.75±0.75 minutes compared with 13.7±2.3 minutes in a conventional clinic. The per capita manpower cost per GLOC patient per visit was $36.77 compared with $65.62 in the conventional clinic. This translates to a cost-saving of $280.65 over the lifetime of a hypothetical patient. CONCLUSIONS: Our expanded virtual glaucoma clinic is a safe, time-efficient, and cost-effective model with low rates of glaucoma progression, which could allow for significant health care capacity expansion.

How to increase and maintain high immunization coverage: Vaccination Demand Resilience (VDR) framework.

BACKGROUND: Resilience in vaccination demand is ever more critical as the COVID-19 pandemic has increased our understanding of the importance of vaccines on health and well-being. Yet timid demand for COVID-19 vaccines where available and reduced uptake of routine immunizations globally further raise the urgent need to build vaccination resilience. We demonstrate the complexity of vaccination demand and resilience in a framework where relevant dimensions are intertwined, fluid, and contextual. METHODS: We developed the Vaccination Demand Resilience (VDR) framework based on a literature review on vaccination demand and expert consultation. The matrix framework builds on three main axes: 1) vaccination attitudes and beliefs; 2) vaccination seeking behavior; and 3) vaccination status. The matrix generated eight quadrants, which can help explain people's levels of vaccination demand and resilience. We selected four scenarios as examples to demonstrate different interventions that could move people across quadrants and build vaccination resilience. RESULTS: Incongruence between individuals' attitudes and beliefs, vaccination behavior, and vaccination status can arise. For example, an individual can be vaccinated due to mandates but reject vaccination benefits and otherwise avoid seeking vaccination. Such incongruence could be altered by interventions to build resilience in vaccination demand. These interventions include information, education and communication to change individuals' vaccination attitudes and beliefs, incentive programs and reminder-recalls to facilitate vaccination seeking, or by strengthening healthcare provider communications to reduce missed opportunities. CONCLUSIONS: Vaccination decision-making is complex. Individuals can be vaccinated without necessarily accepting the benefits of vaccination or seeking vaccination, threatening resilience in vaccination demand. The VDR framework can provide a useful lens for program managers and policy makers considering interventions and policies to improve vaccination resilience. This would help build and sustain confidence and demand for vaccinations, and help to continue to prevent disease, disability, and death from vaccine-preventable diseases.

JMJD6 is a driver of cellular proliferation and motility and a marker of poor prognosis in breast cancer.

INTRODUCTION: We developed an analytic strategy that correlates gene expression and clinical outcomes as a means to identify novel candidate oncogenes operative in breast cancer. This analysis, followed by functional characterization, resulted in the identification of Jumonji Domain Containing 6 (JMJD6) protein as a novel driver of oncogenic properties in breast cancer. METHODS: Through microarray informatics, Cox proportional hazards regression was used to analyze the correlation between gene expression and distant metastasis-free survival (DMFS) of patients in 14 independent breast cancer cohorts. JMJD6 emerged as a top candidate gene robustly associated with poor patient survival. Immunohistochemistry, siRNA-mediated silencing, and forced overexpression of JMJD6 in cell-based assays elucidated molecular mechanisms of JMJD6 action in breast cancer progression and shed light on the clinical breast cancer subtypes relevant to JMJD6 action. RESULTS: JMJD6 was expressed at highest levels in tumors associated with worse outcomes, including ER- and basal-like, Claudin-low, Her2-enriched, and ER+ Luminal B tumors. High nuclear JMJD6 protein was associated with ER negativity, advanced grade, and poor differentiation in tissue microarrays. Separation of ER+/LN- patients that received endocrine monotherapy indicated that JMJD6 is predictive of poor outcome in treatment-specific subgroups. In breast cancer cell lines, loss of JMJD6 consistently resulted in suppressed proliferation but not apoptosis, whereas forced stable overexpression increased growth. In addition, knockdown of JMJD6 in invasive cell lines, such as MDA-MB231, decreased motility and invasion, whereas overexpression in MCF-7 cells slightly promoted motility but did not confer invasive growth. Microarray analysis showed that the most significant transcriptional changes occurred in cell-proliferation genes and genes of the TGF-ß tumor-suppressor pathway. High proliferation was characterized by constitutively high cyclin E protein levels. The inverse relation of JMJD6 expression with TGF-ß2 could be extrapolated to the breast cancer cohorts, suggesting that JMJD6 may affect similar pathways in primary breast cancer. CONCLUSIONS: JMJD6 is a novel biomarker of tumor aggressiveness with functional implications in breast cancer growth and migration.

Knowledge Sharing Types as Predictors of Job Performance Mediated by Problem-Solving Self-Efficacy in the Information System Integration Service Industry.

Knowledge sharing is an essential approach to creative problem solving in technology firms, but few studies have considered the information system integration service industry. To address this gap, drawing on the micro-ecology theory, we developed a research model to explore the mediating role of four types of knowledge sharing (i.e., automatic response, rational reflection, ridiculed reflection, and stolen reflection) in the relationship between problem solving self-efficacy (PSSE) and IT workers' job performance. Data were collected from 307 System Integration IT workers by using the snowball sampling method via a Google questionnaire. Structural equation modeling was used to test the hypotheses of the relationships between the variables. The results showed that PSSE can positively predict four knowledge sharing types; except for stolen reflection, the others can positively predict job performance. The implication of this study is that automatic response systems and rational reflection systems in knowledge sharing can enhance job performance, supported by PSSE. It is hoped that managers can generate System Integration workers' rational reflection to effectively evoke knowledge sharing.

Characterizing Medicine Quality by Active Pharmaceutical Ingredient Levels: A Systematic Review and Meta-Analysis across Low- and Middle-Income Countries.

Substandard and falsified medicines are often reported jointly, making it difficult to recognize variations in medicine quality. This study characterized medicine quality based on active pharmaceutical ingredient (API) amounts reported among substandard and falsified essential medicines in low- and middle-income countries (LMICs). A systematic review and meta-analysis was conducted using PubMed, supplemented by results from a previous systematic review, and the Medicine Quality Scientific Literature Surveyor. Study quality was assessed using the Medicine Quality Assessment Reporting Guidelines (MEDQUARG). Random-effects models were used to estimate the prevalence of medicines with < 50% API. Among 95,520 medicine samples from 130 studies, 12.4% (95% confidence interval [CI]: 10.2-14.6%) of essential medicines tested in LMICs were considered substandard or falsified, having failed at least one type of quality analysis. We identified 99 studies that reported API content, where 1.8% (95% CI: 0.8-2.8%) of samples reported containing < 50% of stated API. Among all failed samples (N = 9,724), 25.9% (95% CI: 19.3-32.6%) reported having < 80% API. Nearly one in seven (13.8%, 95% CI: 9.0-18.6%) failed samples were likely to be falsified based on reported API amounts of < 50%, whereas the remaining six of seven samples were likely to be substandard. Furthermore, 12.5% (95% CI: 7.7-17.3%) of failed samples reported finding 0% API. Many studies did not present a breakdown of actual API amount of each tested sample. We offer suggested improved guidelines for reporting poor-quality medicines. Consistent data on substandard and falsified medicines and medicine-specific tailored interventions are needed to ensure medicine quality throughout the supply chain.

Stimuli-responsive hydrogel microcapsules for the amplified detection of microRNAs.

A method for the synthesis of DNA-based acrylamide hydrogel microcapsules loaded with quantum dots as a readout signal is introduced. The shell of DNA-acrylamide hydrogel microcapsules is encoded with microRNA-responsive functionalities, being capable of the detection of cancer-associated microRNA. The microRNA-141 (miR-141), a potential biomarker in prostate cancer, was employed as a model target in the microcapsular biosensor. The sensing principle of the microcapsular biosensor is based on the competitive sequence displacement of target miR-141 with the bridging DNA in the microcapsule's shell, leading to the unlocking of DNA-acrylamide hydrogel microcapsules and the release of the readout signal provided by fluorescent quantum dots. The readout signal is intensified as the concentration of miR-141 increases. While miR-141 was directly measured by DNA-acrylamide hydrogel microcapsules, the linear range for the detection of miR-141 is 2.5 to 50 µM and the limit of detection is 1.69 µM. To improve the sensitivity of the microcapsular biosensor for clinical needs, the isothermal strand displacement polymerization/nicking amplification machinery (SDP/NA) process was coupled to the DNA-acrylamide hydrogel microcapsule sensor for the microRNA detection. The linear range for the detection of miR-141 is improved to the range of 102 to 105 pM and the limit of detection is 44.9 pM. Compared to direct microcapsular biosensing, the detection limit for miR-141 by microcapsules coupled with strand-displacement amplification is enhanced by four orders of magnitude.

MiDSystem: A comprehensive online system for de novo assembly and analysis of microbial genomes.

The substantial reduction in experimental cost of next-generation sequencing techniques makes it feasible to assemble a bacterial genome of unknown species de novo and acquire substantial genetic information from environmental samples. Many bioinformatics tools and algorithms have also been developed for prokaryotes, but complex parameter settings and command line-based user interfaces cause a significant entry barrier for novices. Efficient construction of pipelines that integrate all the available genomic data poses a major challenge to the understanding of unknown pathogens. MiDSystem is a comprehensive online system for analyzing genomic data from microbiomes. With a user-friendly interface, MiDSystem supports both de novo assembly and metagenomic analysis pipelines. It is designed to automatically analyze whole genome shotgun sequencing data of bacteria submitted by users. Multiple analytical steps can be performed directly on the system, and the results generated from the embedded tools are visualized in an online summary report to make it more interpretable. Constructing a genome de novo has gradually become the foundation of bacterial studies. Taking both single species and metagenomic samples into consideration, MiDSystem can greatly reduce the time and effort for analysis of bacterial genomic data. Use of MiDSystem will enable more focus to be placed on understanding the etiology of bacterial infections and microorganism ecologies.

RNASeqR: An R Package for Automated Two-Group RNA-Seq Analysis Workflow.

RNA-Seq analysis has revolutionized researchers' understanding of the transcriptome in biological research. Assessing the differences in transcriptomic profiles between tissue samples or patient groups enables researchers to explore the underlying biological impact of transcription. RNA-Seq analysis requires multiple processing steps and huge computational capabilities. There are many well-developed R packages for individual steps; however, there are few R/Bioconductor packages that integrate existing software tools into a comprehensive RNA-Seq analysis and provide fundamental end-to-end results in pure R environment so that researchers can quickly and easily get fundamental information in big sequencing data. To address this need, we have developed the open source R/Bioconductor package, RNASeqR. It allows users to run an automated RNA-Seq analysis with only six steps, producing essential tabular and graphical results for further biological interpretation. The features of RNASeqR include: six-step analysis, comprehensive visualization, background execution version, and the integration of both R and command-line software. RNASeqR provides fast, light-weight, and easy-to-run RNA-Seq analysis pipeline in pure R environment. It allows users to efficiently utilize popular software tools, including both R/Bioconductor and command-line tools, without predefining the resources or environments. RNASeqR is freely available for Linux and macOS operating systems from Bioconductor (https://bioconductor.org/packages/release/bioc/html/RNASeqR.html).

Proposal and validation of a new grading system for pterygium (SLIT2).

BACKGROUND/AIMS: To propose and validate a new pterygium grading system based on slit-lamp evaluation. METHODS: This prospective cross-sectional study included 217 patients with pterygium. All patients underwent slit-lamp examination, and slit-lamp photographs were independently graded by two graders twice. A total of eight parameters were evaluated and all parameters were assigned with a score of 1-4 (normal-severe). Intra-rater and inter-rater reliability as determined by weighted Cohen's kappa analysis. RESULTS: A total of 868 independent assessment, based on 217 slit-lamp images, were performed by two graders. For conjunctival assessment, the intra-rater reliability was excellent for body thickness (κ=0.81-0.89) and size at limbus (κ=0.87-0.92), substantial-to-excellent for body vascularity (κ=0.72-0.86), and moderate-to-excellent for body length (κ=0.57-0.81), whereas the inter-rater reliability was excellent for size at limbus (κ=0.86), substantial for body thickness (κ=0.72-0.73) and body vascularity (κ=0.66-0.75), and moderate for body length (κ=0.54-0.57). For corneal assessment, the intra-rater reliability was excellent for all four parameters (κ=0.84-0.90) whereas the inter-rater reliability was excellent for head length (κ=0.86-0.87), substantial-to-excellent for head vascularity (κ=0.78-0.82), substantial for Stocker's line (κ=0.79-0.80) and head thickness (κ=0.67-0.69). The grading system was named SLIT2, which included S tocker's line, S ize at limbus, L ength of head/body, I njection/vascularity of body/head, and T hickness of body/head. CONCLUSION: The proposed SLIT2 grading system, consisting of eight components, may serve as a reliable tool to standardise the reporting of pterygium severity and disease recurrence for clinical and research applications.

Cosmetic outcome of femtosecond laser-assisted pterygium surgery.

BACKGROUND: To examine the cosmetic outcome of femtosecond laser-assisted pterygium surgery (FLAPS) with conjunctival autograft (CAG) and its potential predictive factors. METHODS: This was a prospective interventional case series (NCT02866968). We included 29 patients (29 eyes) with primary pterygium who underwent FLAPS. Cosmetic outcome was graded by two graders (an ophthalmology resident and an experienced ophthalmologist) using Hirst classification system (1-4 = excellent-poor). Weighted Cohen's kappa analysis was performed to examine the intra- and inter-rater reliability. The relationship between cosmetic outcome and various factors were determined by Spearman's correlation coefficients (r). RESULTS: The preoperative severity of pterygium (Tan grading system) was mild/atrophic (7%), moderate/intermediate (62%), and severe/fleshy (31%). An ultrathin CAG (mean thickness of 74.5 ± 9.8 µm) was fashioned intraoperatively. An excellent cosmetic outcome of FLAPS (median ± IQR) was observed at 3 months (1.0 ± 1.0) and remained similar at 6 months (1.0 ± 0.0) and 12 months (1.0 ± 0.0) postoperatively. At final follow-up, 27 (93%) patients achieved good-to-excellent cosmetic outcome, with 1 (3%) patient having a poor outcome due to incomplete pterygium removal. Weighted kappa analysis of Hirst grading system showed excellent intra-rater (κ = 0.86-0.95) and inter-rater reliability (κ = 0.84-0.88). There was a weak and borderline significant correlation between good cosmetic outcome and reduced postoperative CAG thickness (r = 0.38, P = 0.06) but not with age, gender, preoperative pterygium severity, or intraoperative CAG thickness. CONCLUSIONS: FLAPS can result in an excellent cosmetic outcome, which may be attributed to the beneficial effect of an ultrathin CAG. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02866968 . Registered in July 2016.

Erratum: Iyer, A., et al. Integrative Analysis and Machine Learning Based Characterization of Single Circulating Tumor Cells. J. Clin. Med. 2020, 9, 1206.

In the published manuscript [...].