المؤلفون: Lin Fang, Jingwen Zou, Jie Mei, Wei Wei, Shao-Hua Li, Min Deng, Rong Ping Guo, Rong-Ce Zhao

المصدر: Mutagenesis

مصطلحات موضوعية: AcademicSubjects/SCI01140, Oncology, medicine.medical_specialty, Adenosine, Carcinoma, Hepatocellular, RNA methylation, Health, Toxicology and Mutagenesis, Toxicology, Methylation, chemistry.chemical_compound, Internal medicine, Databases, Genetic, Protein Interaction Mapping, Biomarkers, Tumor, Genetics, medicine, Cluster Analysis, Humans, Protein Interaction Maps, Gene, Genetics (clinical), AcademicSubjects/MED00305, business.industry, Gene Expression Profiling, Liver Neoplasms, Computational Biology, RNA, Cancer, Nomogram, Prognosis, medicine.disease, digestive system diseases, Gene Expression Regulation, Neoplastic, ROC Curve, chemistry, Hepatocellular carcinoma, Original Manuscripts, N6-Methyladenosine, Transcriptome, business

الوصف: Hepatocellular carcinoma (HCC) is still one of the most common malignancies worldwide. The accuracy of biomarkers for predicting the prognosis of HCC and the therapeutic effect is not satisfactory. N6-methyladenosine (m6A) methylation regulators play a crucial role in various tumours. Our research aims further to determine the predictive value of m6A methylation regulators and establish a prognostic model for HCC. In this study, the data of HCC from The Cancer Genome Atlas (TCGA) database was obtained, and the expression level of 15 genes and survival was examined. Then we identified two clusters of HCC with different clinical factors, constructed prognostic markers and analysed gene set enrichment, proteins’ interaction and gene co-expression. Three subgroups by consensus clustering according to the expression of the 13 genes were identified. The risk score generated by five genes divided HCC patients into high-risk and low-risk groups. In addition, we developed a prognostic marker that can identify high-risk HCC. Finally, a novel prognostic nomogram was developed to accurately predict HCC patients’ prognosis. The expression levels of 13 m6A RNA methylation regulators were significantly upregulated in HCC samples. The prognosis of cluster 1 and cluster 3 was worse. Patients in the high-risk group show a poor prognosis. Moreover, the risk score was an independent prognostic factor for HCC patients. In conclusion, we reveal the critical role of m6A RNA methylation modification in HCC and develop a predictive model based on the m6A RNA methylation regulators, which can accurately predict HCC patients’ prognosis and provide meaningful guidance for clinical treatment.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a585bdb267f42da73f435d4b6e2e1d51Test
https://doi.org/10.1093/mutage/geab032Test

المؤلفون: Sunir J. Garg, Mirataollah Salabati, Carl D. Regillo, Jason Hsu, Allen C. Ho, Denis Huang, Raziyeh Mahmoudzadeh, Katherine Awh

المصدر: J Vitreoretin Dis

مصطلحات موضوعية: medicine.medical_specialty, genetic structures, business.industry, Treatment method, Retinal, eye diseases, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, chemistry, Ophthalmology, 030221 ophthalmology & optometry, medicine, Original Manuscripts, sense organs, business, 030217 neurology & neurosurgery, Retinal dialysis

الوصف: Purpose: This work assesses the clinical characteristics and outcomes of various treatment methods in managing rhegmatogenous retinal detachments secondary to retinal dialysis. Methods: In this retrospective, consecutive case series, patients presenting to a tertiary referral vitreoretinal service from 2015 to 2020 were chosen. The primary outcome measure was the single-surgery anatomic success (SSAS) rate in the first 90 days after surgery and overall SSAS rate until the last visit. Results: Eighty-six eyes of 84 patients were included. Mean (SD) age was 30 (14.8) years (range, 7-71 years). Fifty-nine (70%) patients were men and 55 eyes (64%) had a history of trauma. Dialysis occurred in the inferotemporal quadrant in 50 eyes (58%) of the entire cohort and 25 of 55 eyes (45%) with prior trauma. Fifty-one eyes (59.3%) were managed by scleral buckle (SB), 25 eyes (29.2%) with laser retinopexy, and 10 eyes (11.6%) with pars plana vitrectomy (PPV). The SSAS rate in the first 90 days after surgery was 94.1% (81 of 86 eyes), including 90.1% of eyes with SB, 100% of eyes with laser retinopexy, and 100% of eyes with PPV ( P = .07). The overall SSAS rate, however, was 89.5% (77 of 86) eyes, including 90.1% of eyes with SB, 84% of eyes with laser retinopexy, and 100% of eyes with PPV ( P = .4). Final attachment rate was 100% in the entire cohort. Conclusions: With careful consideration of underlying pathology, all 3 treatment modalities can provide high rates of anatomic and functional success.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::48c154e91acdacf11338b710ebe0ce3fTest
https://doi.org/10.1177/24741264211024127Test

المؤلفون: Layan Kaddoura, Thomas W. Hejkal, Lauren Maloley

المصدر: J Vitreoretin Dis

مصطلحات موضوعية: Hypochlorous acid, business.industry, medicine.drug_class, chemistry.chemical_element, Pharmacology, medicine.disease, Iodine, 030207 dermatology & venereal diseases, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endophthalmitis, chemistry, Antiseptic, Antimicrobial effect, 030221 ophthalmology & optometry, medicine, Original Manuscripts, business

الوصف: Purpose: An alternative ocular antiseptic is needed for patients who do not tolerate povidone-iodine (PI). The purpose of this study is to compare the antimicrobial effect of hypochlorous acid (HA) 0.01% with PI 5% applied topically to the ocular surface. Methods: Swabs of the inferior conjunctiva and posterior lower eyelid margin of 40 patients were taken from both eyes and plated onto blood agar plates. One eye was treated with HA and the other with PI, and swabs were taken after 1-minute exposure. The eye treated with PI was rinsed with sterile saline and another swab was taken. Colony-forming units (CFUs) were recorded after 2 days. Patients rated the level of irritation after treatment in each eye. Results: HA and PI both gave significant reduction in CFUs from baseline ( P < .001 for HA and P = .002 for PI). The mean reduction in logCFU ± 95% CI was 0.850 ± 0.387 or greater for HA and 0.749 ± 0.385 or greater for PI; this was equivalent to a mean reduction of 7.1-fold or greater or 86% or greater (95% CI, 66%-94%) for HA and 5.6-fold or greater or 82% or greater (95% CI, 57%-93%) for PI. CFUs increased in 17 eyes after saline rinse. PI caused substantial irritation in 31 of the 40 participants, whereas no individuals had any irritation from topical HA. Conclusions: Both HA and PI were effective in reducing ocular bacterial load. Unlike PI, HA was not irritating to the eye. Saline rinse after topical PI may increase bacterial counts in some individuals.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1bb9fbbcbc2755b99af698f75b59a8c4Test
https://doi.org/10.1177/24741264211013622Test

المؤلفون: Steven M. Bryce, Stephen D. Dertinger, Jeffrey C. Bemis

المصدر: Mutagenesis

مصطلحات موضوعية: 0301 basic medicine, DNA damage, Health, Toxicology and Mutagenesis, Toxicology, medicine.disease_cause, Cell Line, Flow cytometry, Histones, 03 medical and health sciences, chemistry.chemical_compound, Clastogen, 0302 clinical medicine, Genetics, medicine, Humans, Mode of action, Genetics (clinical), medicine.diagnostic_test, Chemistry, Lymphoblast, Flow Cytometry, In vitro, 030104 developmental biology, Biochemistry, 030220 oncology & carcinogenesis, Original Manuscripts, DNA, Oxidative stress, DNA Damage, Mutagens

الوصف: The desire for in vitro genotoxicity assays to provide higher information content, especially regarding chemicals’ predominant genotoxic mode of action, has led to the development of a novel multiplexed assay available under the trade name MultiFlow®. We report here on an experimental design variation that provides further insight into clastogens’ genotoxic activity. First, the standard MultiFlow DNA Damage Assay—p53, γ H2AX, phospho-histone H3 was used with human TK6 lymphoblastoid cells that were exposed for 24 continuous hours to each of 50 reference clastogens. This initial analysis correctly identified 48/50 compounds as clastogenic. These 48 compounds were then evaluated using a short-term, ‘pulse’ treatment protocol whereby cells were exposed to test chemical for 4 h, a centrifugation/washout step was performed, and cells were allowed to recover for 20 h. MultiFlow analyses were accomplished at 4 and 24 h. The γ H2AX and phospho-histone H3 biomarkers were found to exhibit distinct differences in terms of their persistence across chemical classes. Unsupervised hierarchical clustering analysis identified three groups. Examination of the compounds within these groups showed one cluster primarily consisting of alkylators that directly target DNA. The other two groups were dominated by non-DNA alkylators and included anti-metabolites, oxidative stress inducers and chemicals that inhibit DNA-processing enzymes. These results are encouraging, as they suggest that a simple follow-up test for in vitro clastogens provides mechanistic insights into their genotoxic activity. This type of information will contribute to improve decision-making and help guide further testing.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a19e3b9eae7e1fc866b47b48792ff84dTest
https://doi.org/10.1093/mutage/geab014Test

المؤلفون: George A. Williams, Jeremy D. Wolfe, Meghan M. Brown, Mariam Aoun, Antonio Capone, Kimberly A. Drenser, Naveen Karthik, Ryan A Shields

المصدر: J Vitreoretin Dis

مصطلحات موضوعية: Retina, 020205 medical informatics, business.industry, education, Retinal, 02 engineering and technology, Telehealth, Patient preference, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine.anatomical_structure, chemistry, 030221 ophthalmology & optometry, 0202 electrical engineering, electronic engineering, information engineering, Optometry, Medicine, Original Manuscripts, business, health care economics and organizations

الوصف: Purpose: This work investigated interest in telehealth services for patients with chronic retinal conditions. Methods: A single-center, multi-office study was conducted of patients with chronic retinal conditions who were seen by 1 of 4 physicians during June 2020. Patients whose next appointment was 6 months or later were telephoned. Patients completed a phone interest survey about their interest in a hybrid telehealth evaluation instead of a complete office evaluation with their provider. Results: Of 2136 patients reviewed, 453 met eligibility to participate in the survey. A total of 159 patients (35.1%) participated, of whom 91 (57.2%) indicated an interest in telehealth at their next follow-up visit. Of the 68 (42.8%) patients without a current interest in telehealth, 13 (19.1%) expressed interest in pursuing telehealth in the future. Age ( P = .19), sex ( P = .22), race ( P = .79), office location ( P = .19), number of prior visits ( P = .58), and median household income by patient’s zip code ( P = .14) were not predictors of telehealth interest. Among diagnoses, dry age-related macular degeneration was associated ( P = .04) with increased interest in telehealth. An increased number of ocular diagnoses were also found to predict a decreased ( P = .04) interest in telehealth. multivariable analysis revealed healthcare provider as the only significant predictor for interest in telehealth ( P = .03). Conclusions: Most patients with chronic retinal conditions may be interested in incorporating telehealth into routine care. Considerations should be made to evaluate interest in telehealth to guide patients to clinical experiences that best suit their needs.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a416bcce14bcf4c003269d4330df7830Test
https://doi.org/10.1177/24741264211003427Test

المؤلفون: Yuki Otsubo, Naohiro Ikeda, Shoji Matsumura, Osamu Morita

المصدر: Mutagenesis

مصطلحات موضوعية: AcademicSubjects/SCI01140, DNA, Bacterial, Salmonella typhimurium, endocrine system, Health, Toxicology and Mutagenesis, DNA Mutational Analysis, Nitro compound, Mutagen, Toxicology, medicine.disease_cause, Sensitivity and Specificity, Genome, DNA sequencing, Ames test, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Genetics, medicine, Genetics (clinical), Carcinogen, 030304 developmental biology, chemistry.chemical_classification, Principal Component Analysis, 0303 health sciences, Mutation, AcademicSubjects/MED00305, Whole Genome Sequencing, Mutagenicity Tests, fungi, food and beverages, Biochemistry, chemistry, 030220 oncology & carcinogenesis, Original Manuscripts, Genome, Bacterial, DNA, Mutagens

الوصف: A precise understanding of differences in genomic mutations according to the mutagenic mechanisms detected in mutagenicity data is required to evaluate the carcinogenicity of environmental mutagens. Recently, we developed a highly accurate genome sequencing method, ‘Hawk-Seq™’, that enables the detection of mutagen-induced genome-wide mutations. However, its applicability to detect various mutagens and identify differences in mutational profiles is not well understood. Thus, we evaluated DNA samples from Salmonella typhimurium TA100 exposed to 11 mutagens, including alkylating agents, aldehydes, an aromatic nitro compound, epoxides, aromatic amines and polycyclic aromatic hydrocarbons (PAHs). We extensively analysed mutagen-induced mutational profiles and studied their association with the mechanisms of mutagens. Hawk-Seq™ sensitively detected mutations induced by all 11 mutagens, including one that increased the number of revertants by approximately 2-fold in the Ames test. Although the sensitivity for less water-soluble mutagens was relatively low, we increased the sensitivity to obtain high-resolution spectra by modifying the exposure protocol. Moreover, two epoxides indicated similar 6- or 96-dimensional mutational patterns; likewise, three SN1-type alkylating agents indicated similar mutational patterns, suggesting that the mutational patterns are compound category specific. Meanwhile, an SN2 type alkylating agent exhibited unique mutational patterns compared to those of the SN1 type alkylating agents. Although the mutational patterns induced by aldehydes, the aromatic nitro compound, aromatic amines and PAHs did not differ substantially from each other, the maximum total base substitution frequencies (MTSFs) were similar among mutagens in the same structural groups. Furthermore, the MTSF was found to be associated with the carcinogenic potency of some direct-acting mutagens. These results indicate that our method can generate high-resolution mutational profiles to identify characteristic features of each mutagen. The detailed mutational data obtained by Hawk-Seq™ can provide useful information regarding mutagenic mechanisms and help identify its association with the carcinogenicity of mutagens without requiring carcinogenicity data.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::aa4ec20521ab57f8adcac6616f5bf017Test
https://doi.org/10.1093/mutage/geab006Test

المؤلفون: Joseph R Abraham, Sunil K. Srivastava, Amy Babiuch, Joseph Boss, Justis P. Ehlers, Rishi P Singh, Jamie Reese

المصدر: J Vitreoretin Dis

مصطلحات موضوعية: medicine.medical_specialty, Retinal Vein, medicine.diagnostic_test, business.industry, Occlusive disease, Retinal, medicine.disease, Ellipsoid, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, chemistry, Optical coherence tomography, Ophthalmology, Occlusion, 030221 ophthalmology & optometry, Medicine, Original Manuscripts, business, Macular edema, 030217 neurology & neurosurgery

الوصف: Purpose: This work evaluated the longitudinal dynamics of ellipsoid zone (EZ) integrity in retinal vein occlusion (RVO) with macular edema and their relation to outcomes. Methods: Clinical characteristics and optical coherence tomography data of patients with RVO and associated macular edema were collected at baseline and at 3 and 12 months. Macular cube scans were exported into EZ and retinal-layer analysis software. Longitudinal EZ parameters and visual acuity (VA) outcomes were regressed and correlated. Results: The study included 108 eyes of 108 patients; all eyes were treated with antivascular endothelial growth factor therapy at the baseline visit. VA improved from 20/97 at baseline to 20/52 at 3 months and 12 months ( P Conclusions: EZ and outer retinal integrity are correlated with functional outcomes in RVO. Following treatment, EZ integrity improves and is associated with functional improvement. In RVO baseline, EZ features were not associated with 1-year VA outcomes, but evaluation of EZ integrity at 3 months was linked to 1-year outcomes.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c67a457ccd85552a737c24fd8370bf2dTest
https://doi.org/10.1177/2474126420943418Test

المؤلفون: Charles C. Barr, Efrat Fleissig, Omar Abu Saleh

المصدر: J Vitreoretin Dis

مصطلحات موضوعية: medicine.medical_specialty, Visual acuity, genetic structures, business.industry, Retinal detachment repair, Retinal detachment, Vitreoretinal surgery, medicine.disease, eye diseases, Silicone oil, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, chemistry, Ophthalmology, 030221 ophthalmology & optometry, medicine, Original Manuscripts, medicine.symptom, business, 030217 neurology & neurosurgery

الوصف: Purpose: This study compares visual acuity (VA), anatomic outcomes, and complications in eyes that underwent complex retinal detachment (RD) repair in which silicone oil (SO) was retained vs removed. Methods: A retrospective chart review of patients undergoing vitrectomy with SO tamponade. The eyes were divided into 2 groups based upon SO removal or retention. Main outcome measures were corrected VA, anatomic outcomes, and the presence of SO-related complications. Results: Fifty-seven eyes with removed SO and 53 eyes with retained SO were identified. In both groups, the mean best-corrected VA (BCVA) at the final visit was significantly better than at baseline. In the retained-SO group, vision improved from 1.79 ± 0.6 to 1.2 ± 0.7 logarithm of the minimum angle of resolution (logMAR) (Snellen, 20/1200 to 20/350) at the final visit ( P < .001). In the removed-SO group, mean BCVA improved from 1.84 ± 0.5 at baseline to 1.55 ± 0.6 logMAR units (Snellen, 20/1400 to 20/700) at the visit preceding SO removal ( P < .002) and to 1.43 ± 0.6 logMAR units (Snellen, 20/500) at the final visit ( P < .001). Complication rates were similar in both groups, apart from RD, which occurred more frequently in the removed-SO group ( P = .03). Conclusions: There was similarity in VA and complications among patients with removed or retained SO. Removal of SO may benefit eyes with SO-related complications, but SO retention may decrease the chance of RD and may be indicated in selected cases.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::22f020e0792ed9821ca09ddd70b1028fTest
https://doi.org/10.1177/2474126419896658Test

المؤلفون: Obuli Ramachandran, Piyush Kohli, Naresh Babu Kannan, Kim Ramasamy, Sagnik Sen

المصدر: J Vitreoretin Dis

مصطلحات موضوعية: Pars plana, medicine.medical_specialty, Coloboma, genetic structures, business.industry, medicine.medical_treatment, Retinal detachment, Vitrectomy, Retinal, Vitreoretinal surgery, medicine.disease, eye diseases, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine.anatomical_structure, chemistry, Ophthalmology, 030221 ophthalmology & optometry, medicine, Original Manuscripts, sense organs, business, 030217 neurology & neurosurgery, Small gauge vitrectomy

الوصف: Purpose: Choroidal coloboma (CC) eyes are associated with a high risk of retinal detachment (RD), which are challenging to repair. Methods: We retrospectively evaluated medical records of 30 patients with CC associated with RD who underwent pars plana vitrectomy at our tertiary care center. Data recorded were age, CC and RD morphology, breaks, resurgeries performed, and final outcome. Results: Patients’ ages ranged from 2 to 49 years. CC was present in 53 of 60 eyes (88%), with 41 of 60 eyes (68.3%) associated with iris coloboma. RD was present in 36 of 53 CC eyes (67.9%), with 10 of 53 (18.9%) having bilateral RD. Thirty-one eyes with RD underwent 23-gauge pars plana vitrectomy. Colobomatous region breaks were detected in 5 of 31 eyes (16.1%), peripheral breaks only in 12 of 31 (38.7%), and both types in 3 of 31 eyes (9.7%). Silicone oil endotamponade was used in 29 of 31 eyes (93.5%) and perfluoropropane (C3F8) in 2 of 31 eyes (6.45%). Median postoperative follow-up duration was 31.5 months. Fourteen of 31 eyes (45.2%) developed redetachment requiring resurgery, with 50% developing within 6 months. Eighteen of 31 eyes (58.1%) maintained retinal attachment at last follow-up without endotamponade, whereas the rest were oil filled. Final visual outcome between macula-involved and macula-spared CC eyes was not significantly different; however, best visual acuity achieved any time during follow-up was significantly better in macula-spared eyes. Conclusions: RD surgery in CC eyes has a risk of frequent redetachments and subnormal gain of vision over the long term, especially in colobomas involving the macula. Endolaser in 360° peripheries in addition to barrage of the margin of the coloboma may be considered to help maintain the attached retina.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d03c473d465471a532b21845d2422699Test
https://doi.org/10.1177/2474126419893542Test

المؤلفون: Parker J. Williams, Ellie Westfall, Jiong Yan, Nieraj Jain, J.D. Wilgucki

المصدر: J Vitreoretin Dis

مصطلحات موضوعية: 0301 basic medicine, Pediatrics, medicine.medical_specialty, medicine.diagnostic_test, Pathogenic mutation, Practice patterns, business.industry, Yield (finance), Retinal, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, chemistry, 030221 ophthalmology & optometry, Medicine, Original Manuscripts, business, Genetic testing

الوصف: Purpose: This article analyzes 2 practice patterns our institution uses for genetic testing of patients with inherited retinal diseases (IRDs) and compares testing completion and diagnostic yield rates. Methods: A retrospective, consecutive chart review series was conducted of patients with a clinically diagnosed rod-mediated IRD. All IRDs were diagnosed between 2 intervals: November 1, 2015, through November 30, 2016 (referral to a medical genetics clinic for testing) or December 1, 2016, through December 30, 2017 (same-day, in-office genetic testing). Results: A total of 189 patients were included in the study. Of patients who received an out-of-office referral for genetic testing, 10 of 84 (12%) patients proceeded with testing, whereas 74 of 84 (88%) patients did not complete testing. For patients who received in-office genetic testing, 104 of 105 (99%) completed testing. The difference in test completion was statistically significant ( P < .001). In addition, genetic testing for out-of-office referrals identified a causative mutation in 5 of 10 (50%) patients, whereas in-office genetic testing identified a causative mutation in 42 of 104 (40.4%) patients. The difference in causative mutation discovery was not statistically significant ( P = .18) between the 2 groups. Conclusions: In-office genetic testing is a novel practice pattern that provides a more consistent and accessible method for IRD genetic diagnosis. Compared with an out-of-office referral for genetic testing, in-office genetic testing offers a similar rate of causative gene mutation identification but a greatly higher rate of test completion, therefore potentially offering a much higher yield for genetic diagnosis of IRDs.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f70019a7fbed5ce7fe8521616c02ce0cTest
https://doi.org/10.1177/2474126419878145Test