An in vitro CRISPR screen of cell-free DNA identifies apoptosis as the primary mediator of cell-free DNA release.

ABTRACT: Clinical circulating cell-free DNA (cfDNA) testing is now routine, however test accuracy remains limited. By understanding the life-cycle of cfDNA, we might identify opportunities to increase test performance. Here, we profile cfDNA release across a 24-cell line panel and utilize a cell-free CRISPR screen (cfCRISPR) to identify mediators of cfDNA release. Our panel outlines two distinct groups of cell lines: one which releases cfDNA fragmented similarly to clinical samples and purported as characteristic of apoptosis, and another which releases larger fragments associated with vesicular or necrotic DNA. Our cfCRISPR screens reveal that genes mediating cfDNA release are primarily involved with apoptosis, but also identify other subsets of genes such as RNA binding proteins as potential regulators of cfDNA release. We observe that both groups of cells lines identified primarily produce cfDNA through apoptosis. These results establish the utility of cfCRISPR, genetically validate apoptosis as a major mediator of DNA release in vitro, and implicate ways to improve cfDNA assays.

The Readability of Ophthalmological Patient Education Materials Provided by Major Academic Hospitals.

INTRODUCTION: The internet is an increasingly important resource for patients seeking health-related information. Because of this trend, the American Medical Association (AMA) and National Institutes of Health (NIH) recommend that online patient education materials (PEMs) be written between a third and seventh grade level. The present study evaluates the readability levels of ophthalmological PEMs provided by five major academic hospitals, quantifies the availability of accompanying videos and graphics, and examines the extent to which readability may be increased. METHODS: In March 2021, 397 PEMs from five major academic hospitals were extracted for subsequent analysis by seven validated readability assessments. The presence of an accompanying video or graphic was noted. Statistical significance was assessed using the Kruskal-Wallis test with Dunn's multiple comparisons test and the chi-square test. RESULTS: Nearly all articles were written above the recommended reading level of 7th grade. After averaging the scales for each article, the median grade level was 11.7 (interquartile range [IQR], 10.7-12.7). The PEMs with the highest median reading level were provided by the Johns Hopkins University Wilmer Institute (12.6, IQR, 11.3 - 13.6). Only 13.6% and 13.1% of articles had an accompanying video and graphic, respectively. Reduction of sentence length beneath 15 words resulted in an improvement of readability by 2.7 grade levels. CONCLUSIONS: The readability of online patient resources provided by major academic hospitals were above the literacy guidelines recommended by the NIH and AMA. Furthermore, most articles did not include a video or graphic, both of which could potentially improve patient understandability of educational materials. By altering these PEMs, as demonstrated here, institutions could increase the value these articles provide for patients and therefore the quality of the patient-physician relationship.

Trends in Soccer-Related Ocular Injuries within the United States from 2010 through 2019.

PURPOSE: Soccer participation within the United States continues to increase, necessitating consideration of the various injuries that may occur. The present study analyzes trends in the incidence of ocular injuries secondary to soccer trauma, the associated mechanism, and related visual sequelae, and quantifies age- and sex-specific differences in the distributions of these variables. METHODS: The Consumer Product Safety Commission's National Electronic Injury Surveillance System (NEISS) was queried for soccer-related ocular injuries from 2010 through 2019. Data exclusively focused on the globe were selected, and information regarding age, sex, specific diagnosis, mechanism of injury, and visual sequelae were acquired. Significance was calculated using the chi-squared test. RESULTS: 628 NEISS entries were evaluated, extrapolating to a national average incidence of approximately 1580 soccer-related ocular injuries per year. There were a relatively static number of events during the ten-year time period of study. The most common diagnoses were contusions or abrasions (36.1%); among records with a reported mechanism of injury, the most common was contact with the soccer ball (80.9%). Visual sequelae were noted in a significant minority of patients (15.4%). Patients ≤18 and males comprised the majority of visits (68.2% and 70.2%, respectively). Significant sex- and age-specific differences were observed in the distributions of diagnoses. CONCLUSIONS: There are serious visual consequences associated with soccer-related ocular injury. Despite the existence of eye protection, there remain no regulations requiring its consistent use. Therefore, among all parties involved (e.g., players, families, and physicians), there remains a need to increase education regarding the potential ocular dangers associated with the sport.

National Institutes of Health Funding Trends to Ophthalmology Departments at U.S. Medical Schools.

PURPOSE: To analyze trends in National Institutes of Health (NIH) funding in ophthalmology and characterize its distribution to departments and principal investigators (PIs) affiliated with U.S. medical schools. DESIGN: Longitudinal descriptive analysis. METHODS: We queried publically accessible data from the Blue Ridge Institute for Medical Research and NIH RePORTER to determine annual funding trends in ophthalmology from 2009 to 2020. To characterize the distribution of funding, we further ranked the top departments and principal investigators (PIs). Department websites (among other online resources) were utilized to extract characteristics of the latter cohort. RESULTS: After adjusting for inflation, we observed a modest 9% increase in median NIH funding to academic ophthalmology departments between 2009 and 2020. In the same time period, among individual PIs, this translated to a 9% decline in median funding. Our results among both departments and PIs indicated a persistent inequality in NIH funding. In 2020, 10 ophthalmology departments received 44% of total funding, which is consistent with findings from prior years. Our ranking of PIs by average annual NIH funding indicated a disproportionate representation of males (76%) and PhDs (58%) in the top 50. CONCLUSIONS: Overall, the results of this investigation suggest NIH funding remains limited for individual investigators, reflecting the increasingly competitive nature of the grant application process. Systemic alterations will be required to reverse these trends. If not accomplished, nascent and established researchers alike will continue to endure challenges in obtaining and maintaining funding.

Characteristics of the least-cited and most-cited articles in ophthalmology journals: A pilot study.

BACKGROUND: Limited research has examined differences between uncited papers and their most-cited counterparts. By comparing characteristics of each cohort, it is possible to better determine factors associated with increased citation count in the ophthalmology literature. METHODS: We initially identified all research articles published in six popular general ophthalmology journals (Ophthalmology, JAMA Ophthalmology, Investigative Ophthalmology and Visual Sciences, American Journal of Ophthalmology, British Journal of Ophthalmology, and Graefe's Archive for Clinical and Experimental Ophthalmology) between 2001 and 2011. Forty-nine articles were identified as having accrued zero citations as of March 2021 and were compared with an equivalent number of articles with the highest number of citations published in the same journals and time period. Significance (p < 0.05) for comparisons was determined using the Mann-Whitney U test and Fisher's exact test. RESULTS: Compared to the least-cited articles, the most-cited articles were significantly more likely to be clinical, multi-institutional, and multi-national in scope, report a statistically significant result, have a conflict of interest, state a funding source, and have higher sample sizes. These publications had significantly more words in the abstract and manuscript and more references. Overall, the first authors of the most-cited articles were significantly more likely to be female and report greater prior research productivity, as assessed by the relative citation ratio (RCR). CONCLUSION: Considering a small number of articles were uncited at least a decade after publication, it appears most research is useful for future investigations. However, there remain distinct differences between uncited articles and their most-cited equivalents in ophthalmology.

The Relative Citation Ratio: Examining a Novel Measure of Research Productivity among Southern Academic Ophthalmologists.

PurposeTo analyze research productivity, as assessed by the National Institutes of Health-supported relative citation ratio (RCR), for a cohort of Southern academic ophthalmologists.DesignA descriptive and cross-sectional design was used. Data on gender, academic rank (assigned as an assistant professor, associate professor, professor, or degrees, and career duration were collected using online resources. Research yield was quantified using mean and weighted RCR data queried from the iCite database. Significant between-group differences were calculated using the Mann-Whitney U-test and the Kruskal-Wallis test.SettingsPracticing academic ophthalmologists at Accreditation Council for Graduate Medical Education-accredited ophthalmology programs in the Southern United States (n = 1018).ResultsFor all Southern academic ophthalmologists, median mean RCR was 0.90 (IQR 0.18-1.71) and median weighted RCR was 5.12 (IQR 0.34-33.18). Advanced academic rank and PhD acquisition were significantly associated with increased mean and weighted RCR. After exclusion of faculty within the "other" category, median mean RCR was 1.12 (IQR 0.54-1.80) and median weighted RCR was 11.65 (IQR 2.03-45.58). Furthermore, effects of career duration and gender emerged. Ophthalmologists with longer careers had significantly higher mean and weighted RCR than their younger counterparts. Males had significantly higher mean and weighted RCR than females.ConclusionsAcademic rank and attainment of a PhD degree were correlated with increased research productivity. When analyses focused exclusively on faculty not in the "other" subgroup, male gender, and lengthier career were associated with increased mean and weighted RCR, the former of which potentially highlights differences in professional advancement between genders.

The relative citation ratio and the h-index among academic ophthalmologists: A retrospective cross-sectional analysis.

BACKGROUND: Limited research has evaluated the relative citation ratio (RCR), a novel measure of research productivity. Accordingly, there remains a minimal understanding of its practical value relative to established metrics such as the h-index. Here, we examined correlations between the mean and weighted RCR scores and the h-index and explore the influence of academic rank, career duration, PhD acquisition, and fellowship training on these metrics. METHODS: Data regarding the academic rank (e.g. assistant professor, associate professor, professor, or "other"), career duration, degrees, fellowship training, and research yield were collected for 1018 academic ophthalmologists practicing in the southern United States of America. The iCite and Scopus databases were utilized to quantify research yield via calculations of mean and weighted RCR, and h-index, respectively. RESULTS: Significant correlations were observed between the h-index and the mean (ρ = 0.62, P < 0.001) and weighted RCR (ρ = 0.84, P < 0.001). Advanced academic rank was associated with increased indices values. In a subset of ophthalmologists excluding members of the "other" category, career duration was moderately correlated with h-index (ρ = 0.45, P < 0.001), and weakly correlated with mean (ρ = 0.14, P < 0.001) and weighted (ρ = 0.26, P < 0.001) RCR. PhD and fellowship acquisition were associated with increased research yield. CONCLUSION: The findings suggest that the RCR is an effective measure of research yield, while resolving deficiencies present in the h-index. Further research remains to characterize the RCR's value relative to other established markers of research productivity.

Analysis of Factors That Influence Academic Productivity Among Neurological and Orthopedic Spine Surgeons.

BACKGROUND: Academic productivity plays a growing role in professional advancement in academic medicine. This study aimed to assess academic productivity among spine surgeons by investigating differences in h indices between neurological and orthopedic spine surgeons. METHODS: The American Association of Neurological Surgeons (AANS) Neurosurgical Residency Training Program Directory provided names of U.S. and Canadian academic neurological surgeons. The National Institutes of Health (NIH) Research Portfolio Online Reporting Tools database was consulted for NIH funding statuses of the surgeons. Scopus yielded the h indices. Orthopedic spine surgeons were identified at the same institutions as the neurological spine surgeons, and NIH funding statuses and h indices were identified from the same databases. Differences between the disciplines and across the categories of NIH funding receipt, having a Ph.D., and academic rank were analyzed. RESULTS: Inclusion criteria were met by 215 neurological spine surgeons and 513 orthopedic spine surgeons. Neurological spine surgeons had a mean h index of 21.16, and orthopedic spine surgeons had a mean h index of 14.08 (P < 0.0001). Neurological surgeons with NIH funding had higher (P < 0.0001) h indices (34.15) than surgeons without funding (19.29). Likewise, orthopedic surgeons with NIH funding had higher (P < 0.001) h indices (42.83) than surgeons without funding (13.39). Analysis of variance showed that department chairmen and professors had higher h indices than associate or assistant professors among neurological (P < 0.01) and orthopedic (P < 0.001) surgeons. CONCLUSIONS: These results demonstrate the importance of the h index in measuring academic productivity among neurological and orthopedic spine surgeons.