EWS-FLI1 increases transcription to cause R-loops and block BRCA1 repair in Ewing sarcoma.

Ewing sarcoma is an aggressive paediatric cancer of the bone and soft tissue. It results from a chromosomal translocation, predominantly t(11;22)(q24:q12), that fuses the N-terminal transactivation domain of the constitutively expressed EWSR1 protein with the C-terminal DNA binding domain of the rarely expressed FLI1 protein. Ewing sarcoma is highly sensitive to genotoxic agents such as etoposide, but the underlying molecular basis of this sensitivity is unclear. Here we show that Ewing sarcoma cells display alterations in regulation of damage-induced transcription, accumulation of R-loops and increased replication stress. In addition, homologous recombination is impaired in Ewing sarcoma owing to an enriched interaction between BRCA1 and the elongating transcription machinery. Finally, we uncover a role for EWSR1 in the transcriptional response to damage, suppressing R-loops and promoting homologous recombination. Our findings improve the current understanding of EWSR1 function, elucidate the mechanistic basis of the sensitivity of Ewing sarcoma to chemotherapy (including PARP1 inhibitors) and highlight a class of BRCA-deficient-like tumours.

Author Correction: EWS-FLI1 increases transcription to cause R-loops and block BRCA1 repair in Ewing sarcoma.

In this Letter, the sentence beginning "This work was funded…." in the Acknowledgements should have read "CPRIT (RP140105) to J.C.R." rather than "CPRIT (RP150445) to J.C.R." This error has been corrected online.

Incident Ocular Inflammation After COVID-19 Infection in a US Veteran Population.

PURPOSE: To investigate whether COVID-19 infection is a risk factor for incident ocular inflammatory disease. DESIGN: Retrospective case-crossover study. METHODS: The US Veterans Health Administration Corporate Data Warehouse was used to identify patients with positive COVID-19 testing and incident ocular inflammatory disease between March 2020 and May 2022. The timing of incident ocular inflammation and COVID-19 testing was assessed for each participant to determine whether positive COVID-19 testing occurred 0-60 days prior to incident ocular inflammation diagnosis (risk period) or 15-75 days after incident ocular inflammation diagnosis (control period). The main outcome measure was the odds of positive COVID-19 testing in the risk period versus control period. RESULTS: Of the 1006 patients with incident ocular inflammation and a positive COVID-19 test in the study period, the age mean ± standard deviation was 62.6 ± 9.8 years and 840 (83%) were male. The odds of COVID-19 exposure was higher in the risk than control period (odds ratio [OR], 1.56; 95% confidence interval [CI], 1.04-2.36; P = 0.03). Ocular inflammation was more likely to be bilateral in the risk period (OR, 3.97; 95% CI, 1.01-23.01; P = 0.03). Other ocular features and demographic characteristics were similar in the risk and control periods. Most cases of ocular inflammation were quiescent at the most recent eye examination. CONCLUSIONS: Incident ocular inflammation is associated with COVID-19 infection, but the increased risk is small, and the ocular inflammation is typically acute.

Rare Thelazia californiensis infant ocular infestation.

Purpose: A rare case of Thelazia californiensis ocular infestation was diagnosed and treated in an 11-month-old patient. Observations: The patient presented with a visual acuity of 20/130 OU by Teller cards. Exam demonstrated a white, mobile worm in the inferomedial fornix of the right eye. The remainder of the exam was otherwise normal. The worm was removed under anesthesia and identified as Thelazia californiensis by the Division of Parasitic Diseases and Malaria, at the Centers for Disease Control and Prevention. Conclusions and importance: This case demonstrates a rare but important cause of follicular conjunctivitis and mobile foreign bodies, especially in patients with a supportive history of exposure to the intermediate and definitive hosts of Thelazia species.

Identification of clinical factors associated with timing and duration of spontaneous regression of retinopathy of prematurity not requiring treatment.

OBJECTIVE: Identify clinical factors that delay or prolong spontaneous regression of retinopathy of prematurity (ROP). STUDY DESIGN: Secondary analysis of three prospective studies with 76 infants with ROP not requiring treatment, born ≤30 weeks postmenstrual age (PMA) and ≤1500 grams. Outcomes were PMA at greatest severity of ROP (PMA MSROP), at which regression began, at time of complete vascularization (PMA CV), and regression duration. Pearson's correlation coefficients, t-tests, or analyses of variance were calculated. RESULTS: Increased positive bacterial cultures, hyperglycemia, transfusion volume of platelets and red blood cells and severity of ROP were associated with later PMA MSROP. Positive bacterial cultures, maternal chorioamnionitis, and less iron deficiency were associated with later PMA CV and prolonged regression duration. Slower length gain was associated with later PMA CV. P < 0.05 for all. CONCLUSIONS: Preterm infants with inflammatory exposures or linear growth impairment may require longer surveillance for ROP resolution and complete vascularization.