In silico error correction improves cfDNA mutation calling.

MOTIVATION: Circulating-free DNA (cfDNA) profiling by sequencing is an important minimally invasive protocol for monitoring the mutation profile of solid tumours in cancer patients. Since the concentration of available cfDNA is limited, sample library generation relies on multiple rounds of PCR amplification, during which the accumulation of errors results in reduced sensitivity and lower accuracy. RESULTS: We present PCR Error Correction (PEC), an algorithm to identify and correct errors in short read sequencing data. It exploits the redundancy that arises from multiple rounds of PCR amplification. PEC is particularly well suited to applications such as single-cell sequencing and circulating tumour DNA (ctDNA) analysis, in which many cycles of PCR are used to generate sufficient DNA for sequencing from small amounts of starting material. When applied to ctDNA analysis, PEC significantly improves mutation calling accuracy, achieving similar levels of performance to more complex strategies that require additional protocol steps and access to calibration DNA datasets. AVAILABILITY AND IMPLEMENTATION: PEC is available under the GPL-v3 Open Source licence, and is freely available from: https://github.com/CRUKMI-ComputationalBiology/PCR_Error_Correction.git. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Effect of combined goniotomy and phacoemulsification on intraocular pressure in open-angle glaucoma patients.

IMPORTANCE: Although goniotomy is known to be successful in treating congenital glaucoma, its effect in adult glaucoma patients remains unclear. BACKGROUND: To evaluate the efficacy and safety of goniotomy performed simultaneously with cataract surgery in treatment of open-angle glaucoma (OAG). DESIGN: Retrospective comparative study. PARTICIPANTS: A total of 76 patients with moderately controlled OAG (intraocular pressure [IOP] ≤ 21 mmHg using medications) undergoing cataract surgery. METHODS: Comparison of patients who underwent the conventional goniotomy during cataract surgery (combined goniotomy group) with those who underwent cataract surgery alone (phaco group). MAIN OUTCOME MEASURES: Changes in IOP and medications, and complications through 12 months. RESULTS: Baseline IOP was 18.2 ± 2.4 mmHg in the combined goniotomy group and 17.4 ± 1.9 mmHg in the phaco group; number of medications was 2.6 ± 1.1 and 2.4 ± 0.9, respectively (P > 0.05). The reduction in IOP and medication use from baseline in the combined goniotomy group was significantly greater at 12 months compared to the phaco group (-3.1 ± 2.9 mmHg vs -1.3 ± 2.4 mmHg and -1.2 ± 0.9 vs -0.7 ± 0.9, respectively, both P < 0.05). The success rate was 76.7% in the combined goniotomy group and 50.0% in the phaco group at 12 months (P = 0.021). No significant complication was observed in either group. CONCLUSIONS AND RELEVANCE: Combined goniotomy and cataract surgery showed a significantly greater reduction in IOP and number of medications compared to cataract surgery alone at 1 year after surgery, with similarly favourable safety profiles.

K-mer clustering algorithm using a MapReduce framework: application to the parallelization of the Inchworm module of Trinity.

BACKGROUND: De novo transcriptome assembly is an important technique for understanding gene expression in non-model organisms. Many de novo assemblers using the de Bruijn graph of a set of the RNA sequences rely on in-memory representation of this graph. However, current methods analyse the complete set of read-derived k-mer sequence at once, resulting in the need for computer hardware with large shared memory. RESULTS: We introduce a novel approach that clusters k-mers as the first step. The clusters correspond to small sets of gene products, which can be processed quickly to give candidate transcripts. We implement the clustering step using the MapReduce approach for parallelising the analysis of large datasets, which enables the use of compute clusters. The computational task is distributed across the compute system using the industry-standard MPI protocol, and no specialised hardware is required. Using this approach, we have re-implemented the Inchworm module from the widely used Trinity pipeline, and tested the method in the context of the full Trinity pipeline. Validation tests on a range of real datasets show large reductions in the runtime and per-node memory requirements, when making use of a compute cluster. CONCLUSIONS: Our study shows that MapReduce-based clustering has great potential for distributing challenging sequencing problems, without loss of accuracy. Although we have focussed on the Trinity package, we propose that such clustering is a useful initial step for other assembly pipelines.

A gene-signature progression approach to identifying candidate small-molecule cancer therapeutics with connectivity mapping.

BACKGROUND: Gene expression connectivity mapping has gained much popularity recently with a number of successful applications in biomedical research testifying its utility and promise. Previously methodological research in connectivity mapping mainly focused on two of the key components in the framework, namely, the reference gene expression profiles and the connectivity mapping algorithms. The other key component in this framework, the query gene signature, has been left to users to construct without much consensus on how this should be done, albeit it has been an issue most relevant to end users. As a key input to the connectivity mapping process, gene signature is crucially important in returning biologically meaningful and relevant results. This paper intends to formulate a standardized procedure for constructing high quality gene signatures from a user's perspective. RESULTS: We describe a two-stage process for making quality gene signatures using gene expression data as initial inputs. First, a differential gene expression analysis comparing two distinct biological states; only the genes that have passed stringent statistical criteria are considered in the second stage of the process, which involves ranking genes based on statistical as well as biological significance. We introduce a "gene signature progression" method as a standard procedure in connectivity mapping. Starting from the highest ranked gene, we progressively determine the minimum length of the gene signature that allows connections to the reference profiles (drugs) being established with a preset target false discovery rate. We use a lung cancer dataset and a breast cancer dataset as two case studies to demonstrate how this standardized procedure works, and we show that highly relevant and interesting biological connections are returned. Of particular note is gefitinib, identified as among the candidate therapeutics in our lung cancer case study. Our gene signature was based on gene expression data from Taiwan female non-smoker lung cancer patients, while there is evidence from independent studies that gefitinib is highly effective in treating women, non-smoker or former light smoker, advanced non-small cell lung cancer patients of Asian origin. CONCLUSIONS: In summary, we introduced a gene signature progression method into connectivity mapping, which enables a standardized procedure for constructing high quality gene signatures. This progression method is particularly useful when the number of differentially expressed genes identified is large, and when there is a need to prioritize them to be included in the query signature. The results from two case studies demonstrate that the approach we have developed is capable of obtaining pertinent candidate drugs with high precision.

Expression-associated polymorphisms of CAV1-CAV2 affect intraocular pressure and high-tension glaucoma risk.

PURPOSE: The human CAV1-CAV2 locus has been associated with susceptibility to primary open-angle glaucoma in four studies of Caucasian, Chinese, and Pakistani populations, although not in several other studies of non-Korean populations. In this study with Korean participants, the CAV1-CAV2 locus was investigated for associations with susceptibility to primary open-angle glaucoma accompanied by elevated intraocular pressure (IOP), namely, high-tension glaucoma (HTG), as well as with IOP elevation, which is a strong risk factor for glaucoma. METHODS: Two single nucleotide polymorphisms (SNPs) were genotyped in 1,161 Korean participants including 229 patients with HTG and 932 healthy controls and statistically examined for association with HTG susceptibility and IOP. One SNP was rs4236601 G>A, which had been reported in the original study, and the other SNP was rs17588172 T>G, which was perfectly correlated (r2=1) with another reported SNP rs1052990. Expression quantitative trait loci (eQTL) analysis was performed using GENe Expression VARiation (Genevar) data. RESULTS: Both SNPs were associated with HTG susceptibility, but the rs4236601 association disappeared when adjusted for the rs17588172 genotype and not vice versa. The minor allele G of rs17588172 was associated significantly with 1.5-fold increased susceptibility to HTG (p=0.0069) and marginally with IOP elevation (p=0.043) versus the major allele T. This minor allele was also associated with decreased CAV1 and CAV2 mRNA in skin and adipose according to the Genevar eQTL analysis. CONCLUSIONS: The minor allele G of rs17588172 in the CAV1-CAV2 locus is associated with decreased expression of CAV1 and CAV2 in some tissues, marginally with IOP elevation, and consequently with increased susceptibility to HTG.

Sectoral retinal nerve fiber layer thinning in branch retinal vein occlusion.

PURPOSE: To analyze longitudinal changes in the retinal nerve fiber layer (RNFL) thickness in branch retinal vein occlusion (BRVO) using optical coherence tomography. METHODS: The authors prospectively analyzed 20 eyes in 20 patients diagnosed with branch retinal vein occlusion (BRVO) and followed for more than 1 year. The RNFL thickness of the normal and occluded eyes was measured at the time of diagnosis and at 1, 3, 6, and 12 months. The authors compared the changes in the occluded eye over the follow-up and the differences between two eyes at each time. They also analyzed the area opposite the occluded area. RESULTS: The thickness of the RNFL in BRVO was significantly reduced at 1, 3, 6, and 12 months (P = 0.005 at 1 month and P = 0.001 at 3, 6, and 12 months) compared with initial thickness. The RNFL thickness at 3 months did not differ significantly between 2 eyes, whereas at 6 months and 12 months, significant (P = 0.032, P = 0.002, respectively.) thinning was observed in the occluded eye. Analysis of the area opposite that of BRVO revealed no significant (P > 0.05) change during the follow-up and no difference between the 2 eyes. CONCLUSION: There was a significant decrease in RNFL thickness over time in BRVO and significant thinning at 6 months compared with the normal eye. Retinal nerve fiber layer thinning needs to be differentiated from glaucoma or systemic disease, but it should be considered the natural course after BRVO.

Variation in the ICAM1-ICAM4-ICAM5 locus is associated with systemic lupus erythematosus susceptibility in multiple ancestries.

OBJECTIVE: Systemic lupus erythematosus (SLE; OMIM 152700) is a chronic autoimmune disease for which the aetiology includes genetic and environmental factors. ITGAM, integrin α(M) (complement component 3 receptor 3 subunit) encoding a ligand for intracellular adhesion molecule (ICAM) proteins, is an established SLE susceptibility locus. This study aimed to evaluate the independent and joint effects of genetic variations in the genes that encode ITGAM and ICAM. METHODS: The authors examined several markers in the ICAM1-ICAM4-ICAM5 locus on chromosome 19p13 and the single ITGAM polymorphism (rs1143679) using a large-scale case-control study of 17 481 unrelated participants from four ancestry populations. The single-marker association and gene-gene interaction were analysed for each ancestry, and a meta-analysis across the four ancestries was performed. RESULTS: The A-allele of ICAM1-ICAM4-ICAM5 rs3093030, associated with elevated plasma levels of soluble ICAM1, and the A-allele of ITGAM rs1143679 showed the strongest association with increased SLE susceptibility in each of the ancestry populations and the trans-ancestry meta-analysis (OR(meta)=1.16, 95% CI 1.11 to 1.22; p=4.88×10(-10) and OR(meta)=1.67, 95% CI 1.55 to 1.79; p=3.32×10(-46), respectively). The effect of the ICAM single-nucleotide polymorphisms (SNPs) was independent of the effect of the ITGAM SNP rs1143679, and carriers of both ICAM rs3093030-AA and ITGAM rs1143679-AA had an OR of 4.08 compared with those with no risk allele in either SNP (95% CI 2.09 to 7.98; p=3.91×10(-5)). CONCLUSION: These findings are the first to suggest that an ICAM-integrin-mediated pathway contributes to susceptibility to SLE.

Comparison of experimental porous silicone implants and porous silicone implants.

BACKGROUND: To investigate the extent and pattern of fibrovascular ingrowth of porous silicone sphere implants compared to porous polyethylene implants. METHODS: Experimental porous silicone sphere implants and porous polyethylene implants were implanted in the left socket of 20 New Zealand white rabbits after enucleation. Fibrovascular ingrowth and maturation was evaluated at 4 weeks and 8 weeks after implantation by histopathologic examination and scanning electron microscope. RESULTS: At 4 weeks after surgery, porous polyethylene implants showed deeper fibrovascular ingrowth than porous silicone sphere implants; 42.4% versus 34.2% of radius of the implants respectively (p = 0.047). However there was no significant difference in the depth of fibrovascular ingrowth between the two groups at 8 weeks after implantation, although porous polyethylene implants showed deeper fibrovascular ingrowth than porous silicone sphere implants; 71.6% versus 63.6% (p = 0.102). CONCLUSIONS: Porous silicone orbital implants demonstrated a comparable extent of fibrovascular ingrowth to that for porous polyethylene implants. Therefore, this new porous silicone sphere implant may be a good candidate to substitute for current porous implants at a lower cost.

Comparison of Vision-related Quality of Life Between Normal Tension Glaucoma and Primary Open-angle Glaucoma.

PRCIS: Although there was little difference in overall vision-related quality of life (VRQOL) between patients with normal tension glaucoma (NTG) and primary open-angle glaucoma (POAG) after controlling for confounding factors, POAG tended to have poorer VRQOL, especially in social functioning and dependency, than NTG. PURPOSE: The fundamental goal of treatment of patients with glaucoma is to preserve their VRQOL. The aim of this study was to compare VRQOL between patients with NTG and those with POAG. MATERIALS AND METHODS: The self-reported National Eye Institute Visual Function Questionnaire (NEI VFQ-25) survey was performed, including clinical, demographic, and socioeconomic data from 506 Korean patients with NTG and 287 with POAG. The mean deviation of the integrated binocular visual field was calculated using the best location method. The NEI VFQ-25 results were evaluated by Rasch analysis to control item difficulty and variation in individual response ability. Propensity score matching was used to control for various confounding factors affecting VRQOL. RESULTS: Although patients with POAG tended to have worse VRQOL than those with NTG, there was no statistically significant between-group difference in ocular pain, near and distance activities, mental health, role difficulties, ability to drive, and the overall composite score. However, the social functioning (P=0.016) and dependency (P=0.026) were significantly poorer in POAG patients. CONCLUSIONS: Overall VRQOL in patients with NTG and POAG was found to be similar. However, social functioning and dependency were significantly worse in those with POAG. These findings are relevant to supporting glaucoma patients.

Analysis of an extended chromosome locus 2p14-21 for replication of the 2p16.3 association with glaucoma susceptibility.

PURPOSE: Susceptibility to primary open-angle glaucoma (POAG) has recently associated with three intergenic single-nucleotide polymorphisms (SNPs) on human chromosome 2p16.3, just outside of the POAG-linkage locus GLC1H (2p15-16.2), in an Afro-Caribbean population. Especially, association of one SNP (rs12994401) was very strong (odds ratio 35) and later replicated in Afro-Americans but not in Ghanaians or Japanese. An extended region was examined in this study to look for SNPs of cross-population association. METHODS: The three reported SNPs and all 63 SNPs considerably correlating with rs12994401 (r(2)≥0.3) in the African-descendent Yoruba were examined for POAG susceptibility association in a Korean population of 1,159 unrelated participants including 226 cases with glaucoma. As these 66 SNPs were spread from 2p14 to 2p21, all SNPs in this extended region were imputed for susceptibility association tests. RESULTS: No susceptibility association was detected with rs12994401 in comparisons between 933 controls and 188 POAG (or 175 high-tension glaucoma) cases (statistical power of 100%), as well as with all 19 other typed SNPs, using logistic regression with adjustment for age and gender. The other 46 SNPs were deemed non-polymorphic in Koreans. Among 21,201 SNPs located in 2p14-21, only 4,260 were imputed to be non-monomorphic, but none of them passed a significance level of multiple testing. No association was observed when the samples were stratified by age or gender. CONCLUSIONS: No typed or imputed SNPs within 2p14-21 showed association with susceptibility to POAG, suggesting that the population inconsistency in 2p16.3 association was unlikely due to linkage disequilibrium differences.

Mutation spectrum of CYP1B1 and MYOC genes in Korean patients with primary congenital glaucoma.

PURPOSE: To elucidate the incidence of cytochrome P450 1B1 (CYP1B1) and myocillin (MYOC) mutations in Korean patients with primary congenital glaucoma (PCG). METHODS: Genomic DNA was collected from peripheral blood of 85 unrelated Korean patients who were diagnosed as having PCG by standard ophthalmological examinations and screened for mutations in the CYP1B1 and MYOC genes by using bi-directional sequencing. RESULTS: Among 85 patients with PCG, 22 patients (22/85; 25.9%) had either one (n=11) or two (n=11) mutant alleles of the CYP1B1 gene. Among 11 different CYP1B1 mutations identified, a frameshift mutation (c.970_971dupAT; p.T325SfsX104) was the most frequent mutant allele (6/33; 18.2%) while p.G329S and p.V419Gfs11X were novel. In the MYOC gene, two variants of unknown significance (p.L228S and p.E240G) were identified in two PCG patients (2/85; 2.4%), respectively. No patient had mutations in both genes. CONCLUSIONS: Although CYP1B1 mutations are major causes of PCG in Korea, ~70% of PCG patients have neither CYP1B1 nor MYOC mutations suggesting a high degree of genetic heterogeneity. Furthermore, the fact that 11 out of 22 patients had only one mutant allele in the CYP1B1 gene necessitates further investigation for other genetic backgrounds underlying PCG.

Prevalence of primary open-angle glaucoma in central South Korea the Namil study.

PURPOSE: To assess the prevalence of primary open-angle glaucoma (POAG) in the Namil-myon area in central South Korea. DESIGN: A cross-sectional, epidemiologic study in a defined population. PARTICIPANTS: Residents aged ≥ 40 years in Namil-myon, a rural agricultural area in central South Korea. METHODS: Each subject underwent a screening that consisted of an interview and ophthalmic examinations, including visual acuity measurement, autorefraction, anterior segment evaluation by optical biometry, slit-lamp examination, Goldmann applanation tonometry, binocular optic disc evaluation, fundus photography, pachymetry, gonioscopy, and screening visual field test using frequency doubling technology. Subjects with suspected glaucoma were referred for definitive examinations. Standard automated field tests and retinal nerve fiber layer analysis using optical coherence tomography (Stratus OCT) or scanning laser polarimetry (GDx VCC) were performed. A diagnosis of glaucoma was made based on the optic disc shape, retinal nerve fiber layer appearance, perimetric results, and other ocular findings. MAIN OUTCOME MEASURES: Prevalence of POAG, mean intraocular pressure (IOP), and mean central corneal thickness (CCT). RESULTS: Of 1928 eligible residents in the area, 1532 (79.5%) participated in this study. The estimated prevalence of POAG in the population aged ≥ 40 years was 3.5% (95% confidence interval [CI], 2.7%-4.3%). The prevalence of POAG with an IOP of ≤ 21 mmHg was 2.7% (95% CI, 2.1%-3.3%), and the prevalence of POAG with an IOP of ≥ 22 mmHg was 0.8% (95% CI, 0.4%-1.2%). The mean IOP for POAG eyes (16.3 ± 4.6 mmHg) was significantly higher than nonglaucomatous eyes (13.3 ± 2.7 mmHg; P = .001). The mean CCT of POAG eyes with an IOP of ≤ 21 mmHg was 528 ± 26 µm, and that of POAG eyes with an IOP ≥ 22 mmHg was 531 ± 37 µm; these values were not significantly different from that of nonglaucomatous eyes (530 ± 31 µm; P = .943 and .996, respectively). CONCLUSIONS: The prevalences of POAG and POAG with an IOP ≤ 21 mmHg in the Namil-myon region of central South Korea were higher than that in most previous reports worldwide, but were similar to the reported rates in black and Japanese populations. The mean IOP of POAG eyes was higher than nonglaucomatous eyes, but the mean CCTs were not different. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Effect of prophylactic topical brimonidine (0.15%) administration on the development of subconjunctival hemorrhage after intravitreal injection.

PURPOSE: Brimonidine (0.15%), which is used to lower intraocular pressure, is an α-2-adrenergic agonist that has vasoconstrictive effects. This study examined whether the administration of brimonidine (0.15%) before intravitreal injection prevents subconjunctival hemorrhage. METHODS: A prospective, randomized, double-masked single-center study. Two hundred and forty-four patients (244 eyes) who underwent intravitreal injection were prospectively examined. The control group (118 eyes) was given normal saline, while the experimental group received 0.15% brimonidine (126 eyes) 30 minutes before the intravitreal injection. On Days 1 and 7, the treatment outcome was assessed using slit-lamp microscopy. The severity of subconjunctival hemorrhage was scored on a scale of 1 (mild) to 3 (severe). To determine the size of the affected area, the lengths of the short and long axes of the subconjunctival hemorrhage were measured in millimeters and then multiplied. To consider both the severity and the size of subconjunctival hemorrhage, the severity score was multiplied by the size of the subconjunctival hemorrhage. RESULTS: Subconjunctival hemorrhage occurred as a result of intravitreal injection in 13.5% (17 eyes) of the brimonidine group and in 29.7% (35 eyes) of the control group (P = 0.003). On Days 1 and 7, the severity and size of the subconjunctival hemorrhage and the product of these 2 parameters were significantly lower in the brimonidine group. CONCLUSION: The administration of 0.15% brimonidine before an intravitreal injection decreased the incidence, severity, and size of subconjunctival hemorrhage.

Intraoperative endolaser retinopexy around the sclerotomy site for prevention of retinal detachment after pars plana vitrectomy.

PURPOSE: To investigate whether intraoperative endolaser retinopexy around the sclerotomy site during pars plana vitrectomy can prevent the postoperative complication of retinal detachment (RD). METHODS: Two hundred and seventy-eight patients who had undergone 20-gauge pars plana vitrectomy for various vitreoretinal disorders were investigated retrospectively. Patients who had rhegmatogenous RD and who underwent panretinal photocoagulation for diabetic retinopathy were excluded. In Group 1, 152 patients had not undergone laser retinopexy around the sclerotomy site, and in Group 2, 126 patients had undergone laser retinopexy around the sclerotomy site. The incidence rates of postoperative RD were compared. RESULTS: In Group 1, 7 cases (4.6%) of RD developed: 6 cases (3.9%) of sclerotomy-related retinal breaks, and 1 of a sclerotomy-unrelated retinal break. In Group 2, superior RD developed in 1 case (0.8%), but no sclerotomy-related retinal break was observed. CONCLUSION: Endolaser retinopexy around the sclerotomy site is relatively simple to perform, without inducing particular complications. It is expected to reduce the development of postoperative RD (4.6% vs. 0.8%; P = 0.08) and especially sclerotomy-related RD (3.9% vs. 0%; P = 0.03).

Major concerns regarding food services based on news media reports during the COVID-19 outbreak using the topic modeling approach.

BACKGROUND/OBJECTIVES: Coronavirus disease 2019 (COVID-19) cases were first reported in December 2019, in China, and an increasing number of cases have since been detected all over the world. The purpose of this study was to collect significant news media reports on food services during the COVID-19 crisis and identify public communication and significant concerns regarding COVID-19 for suggesting future directions for the food industry and services. SUBJECTS/METHODS: News articles pertaining to food services were extracted from the home pages of major news media websites such as BBC, CNN, and Fox News between March 2020 and February 2021. The retrieved data was sorted and analyzed using Python software. RESULTS: The results of text analytics were presented in the format of the topic label and category for individual topics. The food and health category presented the effects of the COVID-19 pandemic on food and health, such as an increase in delivery services. The policy category was indicative of a change in government policy. The lifestyle change category addressed topics such as an increase in social media usage. CONCLUSIONS: This study is the first to analyze major news media (i.e., BBC, CNN, and Fox News) data related to food services in the context of the COVID-19 pandemic. Text analytics research on the food services domain revealed different categories such as food and health, policy, and lifestyle change. Therefore, this study contributes to the body of knowledge on food services research, through the use of text analytics to elicit findings from media sources.

Effects of Miosis on Anterior Chamber Structure in Glaucoma Implant Surgery.

We investigated changes in anterior chamber (AC) structure after miosis in phakic eyes and pseudophakic eyes with glaucoma. In this prospective study, patients scheduled for glaucoma implant surgery were examined using anterior segment optical coherence tomography before and after miosis. Four AC parameters (AC angle, peripheral anterior chamber (PAC) depth, central anterior chamber (CAC) depth, and AC area) were analyzed before and after miosis, and then compared between phakic and pseudophakic eyes. Twenty-nine phakic eyes and 36 pseudophakic eyes were enrolled. The AC angle widened after miosis in both the phakia and pseudophakia groups (p = 0.019 and p < 0.001, respectively). In the phakia group, CAC depth (p < 0.001) and AC area (p = 0.02) were significantly reduced after miosis, and the reductions in PAC depth, CAC depth, and AC area were significantly greater than in the pseudophakia group (all p < 0.05). Twenty-five patients (86.2%) in the phakia group and 17 (47.2%) in the pseudophakia group had reduced CAC depth (p = 0.004). Although miosis increased the AC angle in both groups, AC depth decreased in most phakic eyes and a substantial number of pseudophakic eyes. Preoperative miosis before glaucoma implant surgery may interfere with implant tube placement distant from the cornea during insertion into the AC.

Validation of the EuroClonality-NGS DNA capture panel as an integrated genomic tool for lymphoproliferative disorders.

Current diagnostic standards for lymphoproliferative disorders include multiple tests for detection of clonal immunoglobulin (IG) and/or T-cell receptor (TCR) rearrangements, translocations, copy-number alterations (CNAs), and somatic mutations. The EuroClonality-NGS DNA Capture (EuroClonality-NDC) assay was designed as an integrated tool to characterize these alterations by capturing IGH switch regions along with variable, diversity, and joining genes of all IG and TCR loci in addition to clinically relevant genes for CNA and mutation analysis. Diagnostic performance against standard-of-care clinical testing was assessed in a cohort of 280 B- and T-cell malignancies from 10 European laboratories, including 88 formalin-fixed paraffin-embedded samples and 21 reactive lesions. DNA samples were subjected to the EuroClonality-NDC protocol in 7 EuroClonality-NGS laboratories and analyzed using a bespoke bioinformatic pipeline. The EuroClonality-NDC assay detected B-cell clonality in 191 (97%) of 197 B-cell malignancies and T-cell clonality in 71 (97%) of 73 T-cell malignancies. Limit of detection (LOD) for IG/TCR rearrangements was established at 5% using cell line blends. Chromosomal translocations were detected in 145 (95%) of 152 cases known to be positive. CNAs were validated for immunogenetic and oncogenetic regions, highlighting their novel role in confirming clonality in somatically hypermutated cases. Single-nucleotide variant LOD was determined as 4% allele frequency, and an orthogonal validation using 32 samples resulted in 98% concordance. The EuroClonality-NDC assay is a robust tool providing a single end-to-end workflow for simultaneous detection of B- and T-cell clonality, translocations, CNAs, and sequence variants.

Profiles and Clinical Characteristics of Newly Diagnosed Glaucoma in Urban Korea: A Multicenter Study.

PURPOSE: To explore the clinical characteristics and profiles of newly diagnosed glaucoma subtypes in urban Korea. METHODS: All newly diagnosed glaucoma patients enrolled in the participating ophthalmology outpatient clinics were included. A review of medical history including family history of glaucoma was conducted. The patients underwent complete ophthalmologic examinations including visual field test. The diagnosis of glaucoma was based on the International Society of Geographical and Epidemiological Ophthalmology criteria developed by glaucoma specialists. RESULTS: A total of 198,671 patients visited the participating ophthalmology outpatient clinics during the study period (from January 1, 2001 to June 30, 2016), of which 5,530 (2.8%) were diagnosed with glaucoma. The mean age of the newly diagnosed glaucoma patients was 52.0 ± 17.3 years (range, 6 to 89) and 2,830 patients were male (51.2%). The mean untreated intraocular pressure and vertical cup-to-disc ratio of the optic nerve head of newly diagnosed glaucoma eyes were 22.1 ± 10.6 mmHg and 0.66 ± 0.22, respectively. The most frequently observed subtypes of glaucoma were: normal tension glaucoma (33.0%) primary open-angle glaucoma (28.4%), ocular hypertension (11.1%), chronic angle-closure glaucoma (6.8%), neovascular glaucoma (5.2%), glaucoma associated with inflammation (3.8%), acute angle-closure glaucoma (3.3%), and glaucoma associated with aphakia or pseudophakia (2.2%). CONCLUSIONS: Normal tension glaucoma was the most frequently observed glaucoma subtype in urban ophthalmology outpatient clinics in Korea.

Comparison of college students' behavior toward nutrition information communication between Korea and the US.

BACKGROUND/OBJECTIVES: The expansion of menu labeling to restaurants has created a need to study customers' behavior toward nutrition information. Therefore, the purpose of this research was to compare college students' behavior toward nutrition information communication between Korea and the US. This study consisted of three objectives: 1) to compare the frequency of usage as well as degree of trust regarding smartphone-based communication channels in the acquisition of nutrition information among college students between Korea and the US, 2) to compare knowledge-sharing behavior related to nutrition information among college students between Korea and the US, and 3) to identify the role of country in the process of knowledge-sharing behavior. SUBJECTS/METHODS: A survey was distributed via the web to college students in Korea and the US. Data were collected in the 2nd week of March 2017. Completed responses were collected from 423 Koreans and 280 Americans. Differences between Koreans and Americans were evaluated for statistical significance using a t-test. In order to verify the effects of knowledge self-efficacy and transactive memory capability on knowledge-sharing behavior related to nutrition information, a regression analysis was performed. RESULTS: Significant differences were found in the frequency of usage as well as degree of trust in communication channels related to nutrition information between Korean and American college students. While knowledge self-efficacy and tractive memory capability had positive effects on knowledge-sharing behavior related to nutrition information, country had a significant effect on the process. CONCLUSIONS: This study is the first to compare customer behavior toward nutrition information acquisition and sharing between Korea and the US. Comparative research on nutrition information revealed differences among the different countries. Therefore, this study contributes to the body of knowledge on the nutrition information research, in particular, by providing a comparison study between countries.

Effects of Topical Prostaglandin Analog on Macular Thickness Following Cataract Surgery with Postoperative Topical Bromfenac Treatment.

PURPOSE: To evaluate changes in macular thickness in patients continuing prostaglandin analog (PGA) treatment during the perioperative period involving bromfenac treatment. METHODS: Patients with glaucoma who were using a topical PGA were randomly assigned to two groups in this randomized controlled trial: PGA continuing study group and PGA discontinued glaucoma control group. Patients without ocular diseases other than cataract were enrolled into the non-glaucomatous group. After the cataract surgery, the patients used bromfenac twice per day for 4 weeks. Optical coherence tomography was performed in all patients preoperatively and at 1 month postoperatively. Changes in macular thickness were compared among the three groups. RESULTS: There were 32 eyes in the study group, 33 eyes in the glaucoma control group, and 58 eyes in the non-glaucomatous group. We found statistically significant postoperative changes in central macular thickness in all groups (4.30 ± 8.01 µm in the PGA continuing group, 9.20 ± 13.88 µm in the PGA discontinued group, and 7.06 ± 7.02 µm in the non-glaucomatous group, all p < 0.008), but no significant difference among the three groups (p = 0.161). Cystoid macular edema occurred in only one patient in the non-glaucomatous group (p = 0.568). CONCLUSIONS: Continuous use of PGAs during the perioperative period was not significantly associated with increased macular thickness after uncomplicated cataract surgery. In the absence of other risk factors (e.g., capsular rupture, uveitis, or diabetic retinopathy), discontinuing PGAs for the prevention of macular edema after cataract surgery with postoperative bromfenac treatment is unnecessary in patients with glaucoma.