PARP Inhibitors for Cancer Therapy.

Rucaparib is an inhibitor of nuclear poly (ADP-ribose) polymerases (inhibition of PARP-1 > PARP-2 > PARP-3), following a similar drug, Olaparib. It disrupts DNA repair and replication pathways (and possibly transcription), leading to selective killing of cancer cells with BRCA1/2 mutations. Rucaparib is approved for recurrent ovarian cancers with germline or somatic mutations in BRCA1/2.

Genetic screening of a Chinese cohort of children with hearing loss using a next-generation sequencing panel.

BACKGROUND: At present, the hereditary hearing loss homepage, ( https://hereditaryhearingloss.org/ ), includes 258 deafness genes and more than 500 genes that have been reported to cause deafness. With few exceptions, the region-specific distributions are unclear for many of the identified variants and genes. METHODS: Here, we used a custom capture panel to perform targeted sequencing of 518 genes in a cohort of 879 deaf Chinese probands who lived in Yunnan. Mutation sites of the parents were performed by high-throughput sequencing and validated by Sanger sequencing. RESULTS: The ratio of male to female patients was close to 1:1 (441:438) and the age of onset was mainly under six. Most patients (93.5%) were diagnosed with moderate to severe deafness. Four hundred and twenty-eight patients had variants in a deafness gene, with a detection rate of 48.7%. Pathogenic variants were detected in 98 genes and a number of these were recurrent within the cohort. However, many of the variants were rarely observed in the cohort. In accordance with the American College of Medical Genetics and Genomics, pathogenic, likely pathogenic and variants of uncertain significance accounted for 34.3%, 19.3% and 46.4% of all detected variants, respectively. The most common genes included GJB2, SLC26A4, MYO15A, MYO7A, TMC1, CDH23, USH2A and WFS1, which contained variants in more than ten cases. The two genes with the highest mutation frequency were GJB2 and SLC26A4, which accounted for 28.5% (122/428) of positive patients. We showed that more than 60.3% of coding variants were rare and novel. Of the variants that we detected, 80.0% were in coding regions, 17.9% were in introns and 2.1% were copy number variants. CONCLUSION: The common mutation genes and loci detected in this study were different from those detected in other regions or ethnic groups, which suggested that genetic screening or testing programs for deafness should be formulated in accordance with the genetic characteristics of the region.

Reduced healthcare access contributes to delay of care in endometrial cancer.

OBJECTIVE: We aimed to characterize delays to care in patients with endometrioid endometrial cancer and the role healthcare access plays in these delays. METHODS: A chart review was performed of patients with endometrioid endometrial cancer who presented with postmenopausal bleeding at a diverse, urban medical center between 2006 and 2018. The time from symptom onset to treatment was abstracted from the medical record. This interval was subdivided to assess for delay to presentation, delay to diagnosis, and delay to treatment. RESULTS: We identified 484 patients who met the inclusion criteria. The median time from symptom onset to treatment was 4 months with an interquartile range of 2 to 8 months. Most patients had stage I disease at diagnosis (88.6%). There was no significant difference in race/ethnicity or disease stage at time of diagnosis between different groups. Patients who had not seen a primary care physician or general obstetrician-gynecologist in the year before symptom onset were more likely to have significantly delayed care (27.7% vs 14.3%, p = 0.02) and extrauterine disease (20.2% vs 4.9%, p < 0.01) compared to those with established care. Black and Hispanic patients were more likely to experience significant delays from initial biopsy to diagnosis. CONCLUSIONS: Delays exist in the evaluation of endometrial cancer. This delay is most pronounced in patients without an established outpatient primary care provider or obstetrician-gynecologist.

Preoperative and pre-chemotherapy CA-125 levels in high-risk early-stage ovarian cancer - An NRG/GOG study.

OBJECTIVES: To determine clinical significance of preoperative and pre-chemotherapy CA-125 in high-risk early-stage epithelial ovarian cancer patients. METHODS: All patients with stage IA/IB and grade 3, stage IC, clear cell, or completed resected stage II cancer were enrolled in a phase III trial and treated with chemotherapy. Kaplan-Meier method and Cox proportional hazards model were used for statistical analyses. RESULTS: 427 patients with high-risk early-stage ovarian cancer were enrolled. Of 213 patients with preoperative CA-125 data, 79% had elevated CA-125. Median preoperative CA-125 level was 103 U/mL. Patients with ≤10, 11-15, and > 15 cm tumors had median preoperative CA-125 levels of 62, 131 and 158 U/mL, respectively (p = 0.002). For the 350 patients with data for pre-chemotherapy CA-125 level, 69% had elevated pre-chemotherapy CA-125 above 35 U/mL with median value of 65 U/mL. However, age, race, stage, cell type and grade of disease were not correlated with CA-125 levels before and after surgery. On multivariate analysis, elevated pre-chemotherapy CA-125 independently predicted worse recurrence-free survival (HR = 2.13, 95% CI: 1.23-3.69; p = 0.007) and overall survival (HR = 1.99, 95% CI: 1.10-3.59; p = 0.022) after adjusting for age, stage, cell type and grade of disease. Compared to those with normal CA-125, patients with elevated pre-chemotherapy CA-125 had lower recurrence-free survival (RFS, 87% vs. 75%; p = 0.007) and overall survival (OS, 88% vs. 82%; p = 0.02). However, preoperative CA-125 was not prognostic of RFS (p = 0.699) or OS (p = 0.701). CONCLUSIONS: Preoperative CA-125 was elevated in nearly 80% of high-risk early-stage ovarian cancer patients. Pre-chemotherapy CA-125 was associated with recurrence-free and overall survival; however, preoperative CA-125 was not prognostic.

Co-existing TP53 and ARID1A mutations promote aggressive endometrial tumorigenesis.

TP53 and ARID1A are frequently mutated across cancer but rarely in the same primary tumor. Endometrial cancer has the highest TP53-ARID1A mutual exclusivity rate. However, the functional relationship between TP53 and ARID1A mutations in the endometrium has not been elucidated. We used genetically engineered mice and in vivo genomic approaches to discern both unique and overlapping roles of TP53 and ARID1A in the endometrium. TP53 loss with oncogenic PIK3CAH1047R in the endometrial epithelium results in features of endometrial hyperplasia, adenocarcinoma, and intraepithelial carcinoma. Mutant endometrial epithelial cells were transcriptome profiled and compared to control cells and ARID1A/PIK3CA mutant endometrium. In the context of either TP53 or ARID1A loss, PIK3CA mutant endometrium exhibited inflammatory pathway activation, but other gene expression programs differed based on TP53 or ARID1A status, such as epithelial-to-mesenchymal transition. Gene expression patterns observed in the genetic mouse models are reflective of human tumors with each respective genetic alteration. Consistent with TP53-ARID1A mutual exclusivity, the p53 pathway is activated following ARID1A loss in the endometrial epithelium, where ARID1A normally directly represses p53 pathway genes in vivo, including the stress-inducible transcription factor, ATF3. However, co-existing TP53-ARID1A mutations led to invasive adenocarcinoma associated with mutant ARID1A-driven ATF3 induction, reduced apoptosis, TP63+ squamous differentiation and invasion. These data suggest TP53 and ARID1A mutations drive shared and distinct tumorigenic programs in the endometrium and promote invasive endometrial cancer when existing simultaneously. Hence, TP53 and ARID1A mutations may co-occur in a subset of aggressive or metastatic endometrial cancers, with ARID1A loss promoting squamous differentiation and the acquisition of invasive properties.

The Rising Importance of Stock-Linked Assets in the Black-White Wealth Gap.

Studies have examined the racial disparities in household characteristics, homeownership, and familial transfer as primary drivers of the Black-White wealth gap in the United States. This study assesses the importance of stock-linked assets in generating wealth inequality. As financial assets become a growing component of household portfolios, the Black-White wealth gap is increasingly associated with the racial disparity in stock-linked assets. Using data from the Survey of Consumer Finances and the Panel Study of Income Dynamics, this study shows that the contribution of stock-linked assets to the Black-White wealth gap has expanded in both absolute and relative terms, surpassing those of homeownership and business equity. Furthermore, a substantial disparity in financial wealth exists even for otherwise similar Black and White households. Although the disparity is larger among those with more economic resources, a gap remains among those with less. Lastly, our analysis shows that the combination of lower ownership levels and lower returns on financial wealth among Black households could account for a quarter of the Black-White wealth accumulation gap, net of differences in current net worth and household characteristics. Our findings suggest that considering financial assets is critical for understanding contemporary racial wealth inequality.

Risk and dose-response relationship of diabetes mellitus for endophthalmitis after cataract surgery in a nationwide cohort study in Taiwan.

BACKGROUND: To investigate the risk of endophthalmitis after cataract surgery in patients with diabetes mellitus (DM) and evaluate the dose-response relationship. METHODS: This retrospective cohort study enrolled patients who underwent bilateral cataract surgeries from 2000 to 2017 in Taiwan National Health Insurance Research Database. The endophthalmitis rates within 3 months after cataract surgery were compared between DM and non-DM cohorts using a generalised estimating equation. The diabetes complications severity index (DSCI) score was adopted to assess the dose-response effect on the endophthalmitis rate. RESULTS: A total of 883 398 patients (1 766 796 eyes) were included. Patients with DM had an increased risk of endophthalmitis after cataract surgery than patients without DM (0.261% vs. 0.242%, adjusted odds ratio = 1.09, 95% confidence interval = 1.03-1.16). The higher endophthalmitis rate in the DM group than in the non-DM group remains after excluding those with prior vitrectomy or intravitreal injection (IVI), and took IVI between the cataract surgery and endophthalmitis (p = 0.0156, 0.0048, and 0.0139). There was a significant dose-response relationship on the likelihood of endophthalmitis in DM patients when DCSI score >10. The endophthalmitis rate is highest among DM complications in patients with metabolic disorders (0.342%). CONCLUSION: DM was a risk factor for endophthalmitis after cataract surgery after adjusting for age, sex, common systemic disorders, and excluding those with prior vitrectomy or IVI and having IVI between cataract surgery and endophthalmitis. A dose-response relationship was noted in DM patients with a DCSI score >10.

Substantial Decline in Invasive Pneumococcal Disease During Coronavirus Disease 2019 Pandemic in Hong Kong.

Compared with other countries, a more substantial decrease in the incidence of invasive pneumococcal disease was observed in Hong Kong, which is most likely attributable to the proactive mass adoption of face masks by the public. Human behavioral changes, particularly mask wearing, should be considered as an additional preventive strategy against invasive pneumococcal disease.

The clinical and prognostic significance of pre-chemotherapy serum CA-125 in high-risk early stage ovarian cancer: An NRG/GOG ancillary study.

OBJECTIVES: To determine the clinical and prognostic significance of CA-125 trends prior to, during, and after chemotherapy in high-risk early-stage epithelial ovarian cancer patients. METHODS: All patients were enrolled in a phase III randomized trial (GOG 157) following upfront surgery for grade 3 stage IA/IB, stage IC, or stage II disease, and had been treated with either three or six cycles of carboplatin/paclitaxel. Kaplan-Meier method and Cox proportional hazards model were used to evaluate recurrence-free survival (RFS) and overall survival (OS). RESULTS: Of 350 patients, the median pre-chemotherapy CA-125 was 65 (IQR: 31-129). 71% of Whites had an elevated CA-125 compared to 47% of non-Whites (p = 0.006). Following the first cycle of chemotherapy, 74% of those with elevated CA-125 had normalization. Those who had normalization of CA-125 after 1 cycle had significantly better 5-year RFS (81% vs. 65%, p = 0.003) and OS (87% vs. 75%, p = 0.009) compared to those who did not normalize (defined as ≤35 U/mL). The pattern of CA-125 change following chemotherapy cycle 1, from normal to normal vs. elevated to normal vs. elevated to elevated had corresponding RFS of 87% vs. 80% vs. 68% (p = 0.013), and OS of 92% vs. 88% vs. 77% (p = 0.009). However, the percent decline (p = 0.993) and absolute nadir normal value of CA-125 (0-10 vs. 11-35 U/mL) were not predictive of outcome (p = 0.4). CONCLUSIONS: Normal baseline CA125 and normalization of this biomarker after the first cycle of chemotherapy were associated with better survival in high-risk early-stage epithelial ovarian cancer patients.

Activated fibroblasts induce immune escape of TSCC through CCL25/AKT pathway.

OBJECTIVES: Accumulating evidence suggests that activated fibroblasts are the key cells in the T-cell response to tumor immunosuppression. We attempted to investigate the effect of activated fibroblasts on PD-L1 expression and the related immune escape mechanism in tongue squamous cell carcinoma. METHODS: Western blotting, qPCR, and other techniques were used to study the expression of PD-L1 in tongue squamous cell carcinoma cells and the nude mouse model of transplanted tumors in vivo; clinical tissue samples were verified. In addition, we established a direct coculture model of T cells and tongue squamous cell carcinoma cells explore the mechanisms of immune escape. RESULTS: We found that PDGF-BB induces fibroblast activation by facilitating the oversecretion of chemokine CCL25. Further analysis showed that CCL25 derived from activated fibroblasts activated the Akt signaling pathway to promote PD-L1 expression. The activated fibroblasts inhibited T-cell IFN-γ secretion through the CCL25/Akt/PD-L1 pathway, which indirectly inhibited T-cell proliferation. CONCLUSION: Activated fibroblasts can induce the high expression of PD-L1 in the oral and tongue squamous cell carcinoma cell line Cal-27 via the CCL25/CCR9/p-Akt axis, to significantly inhibit the proliferation and IFN-γ secretion of T cells and promote the immune escape of tongue squamous cell carcinoma cells.

Ultrasound-assisted ocular drug delivery: A review of current evidence.

Efficient ocular drug delivery is a challenging clinical problem with various therapeutic options but no clearly preferred methodology. Given the ubiquity of ultrasound as a diagnostic technique, the safety profile of ultrasound in an ocular context, and the prospect of custom-made ultrasound-sensitive contrast agents, ultrasound presents an attractive ocular drug delivery modality. In this review, we evaluate our present understanding of ultrasound as it relates to ocular drug delivery and significant knowledge gaps in the field. In doing so, we hope to call attention to a potentially novel drug delivery pathway that could be manipulated to treat or cure ocular diseases.

A Contrastive Learning Pre-Training Method for Motif Occupancy Identification.

Motif occupancy identification is a binary classification task predicting the binding of DNA motif instances to transcription factors, for which several sequence-based methods have been proposed. However, through direct training, these end-to-end methods are lack of biological interpretability within their sequence representations. In this work, we propose a contrastive learning method to pre-train interpretable and robust DNA encoding for motif occupancy identification. We construct two alternative models to pre-train DNA sequential encoder, respectively: a self-supervised model and a supervised model. We augment the original sequences for contrastive learning with edit operations defined in edit distance. Specifically, we propose a sequence similarity criterion based on the Needleman-Wunsch algorithm to discriminate positive and negative sample pairs in self-supervised learning. Finally, a DNN classifier is fine-tuned along with the pre-trained encoder to predict the results of motif occupancy identification. Both proposed contrastive learning models outperform the baseline end-to-end CNN model and SimCLR method, reaching AUC of 0.811 and 0.823, respectively. Compared with the baseline method, our models show better robustness for small samples. Specifically, the self-supervised model is proved to be practicable in transfer learning.

TLCrys: Transfer Learning Based Method for Protein Crystallization Prediction.

X-ray diffraction technique is one of the most common methods of ascertaining protein structures, yet only 2-10% of proteins can produce diffraction-quality crystals. Several computational methods have been proposed so far to predict protein crystallization. Nevertheless, the current state-of-the-art computational methods are limited by the scarcity of experimental data. Thus, the prediction accuracy of existing models hasn't reached the ideal level. To address the problems above, we propose a novel transfer-learning-based framework for protein crystallization prediction, named TLCrys. The framework proceeds in two steps: pre-training and fine-tuning. The pre-training step adopts attention mechanism to extract both global and local information of the protein sequences. The representation learned from the pre-training step is regarded as knowledge to be transferred and fine-tuned to enhance the performance of crystalization prediction. During pre-training, TLCrys adopts a multi-task learning method, which not only improves the learning ability of protein encoding, but also enhances the robustness and generalization of protein representation. The multi-head self-attention layer guarantees that different levels of the protein representation can be extracted by the fine-tuned step. During transfer learning, the fine-tuning strategy used by TLCrys improves the task-specialized learning ability of the network. Our method outperforms all previous predictors significantly in five crystallization stages of prediction. Furthermore, the proposed methodology can be well generalized to other protein sequence classification tasks.

Chinese Version of the Vision-Related Quality of Life (NEI-VFQ-25) among Patients with Various Ocular Disorders: A Pilot Study.

Background and Objectives: Subjective visual function is currently becoming an increasing appreciation in assessing the health-related quality of life. This study aimed to assess the vision-related quality of life (VRQOL) among patients with refractive errors, keratoconus, senile cataract, and age-related macular degeneration (AMD) using the Chinese version of the National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ-25). Materials and Methods: The questionnaire of NEI-VFQ-25 was filled out in a clinical setting or by telephone/mail. Univariate and multivariate analyses were used to determine which factors are associated with the NEI-VFQ-25. Results: From June 2018 to January 2019, 28 patients with refractive error, 20 patients with keratoconus, 61 with senile cataracts, and 17 with AMD completed the questionnaire NEI-VFQ-25. There were significant differences in the NEI-VFQ-25 subscale of general vision (p = 0.0017), ocular pain (p = 0.0156), near activities (p = 0.0002), vision-specific social functioning (p = 0.007), vision-specific mental health (p = 0.0083), vision-specific dependency (p = 0.0049), color vision (p < 0.0001), peripheral vision (p = 0.0065), and total score (p < 0.0001) among four disease groups, respectively. The multiple linear regression revealed that the best-corrected visual acuity (BCVA) and disease group were important factors of the total NEI-VFQ-25. After adjusting for BCVA, patients with AMD had a worse total NEI-VFQ-25 score than patients with refractive error, keratoconus, or senile cataracts. Conclusions: Among the patients with four ocular disorders and a broad vision spectrum from normal, partial sight, low vision to legal blindness, the BCVA of their better eye was the most important factor in the VRQOL.

Effect of the time interval between cataract surgery for both eyes on mental health outcome: a cohort study of 585,422 patients.

BACKGROUND: Cataract surgeries can improve mental health outcomes. However, previous studies have not investigated whether the time interval between cataract surgeries for 2 eyes affects mental health outcomes. METHODS: We used the whole-population National Health Insurance (NHI) claims data from Taiwan to conduct a cohort study. Patients who received cataract surgeries for both eyes were identified (n = 585,422). The mental health inpatient and outpatient consultations received by these patients were analyzed, with different time intervals (< 3, 3 to 6, 6 to 12, and > 12 months) between the surgeries. Negative binominal regression was performed to estimate the interaction of the first eye surgery with the time interval. RESULTS: The number of mental health consultations was lowest among patients with a time interval of < 3 months (1.783-1.743, P < .001), and a negative dose response effect was observed, such that a longer time interval corresponded to a lower reduction in the number of mental health consultations. For patients with a time interval of > 12 months, the predicted number of mental health consultations increased from 1.674 to 1.796 (P < .001). CONCLUSIONS: Given a patient expected to receive surgeries for both eyes within 1 year, scheduling both surgeries within a short time interval may be beneficial for maximizing the effects of cataract surgery in reducing the number of mental health consultations.

Identification of cancer hallmark-associated gene and lncRNA cooperative regulation pairs and dictate lncRNA roles in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common malignant tumour in the oral and maxillofacial region. Numerous cancers share ten common traits ("hallmarks") that govern the transformation of normal cells into cancer cells. Long non-coding RNAs (lncRNAs) are important factors that contribute to tumorigenesis. However, very little is known about the cooperative relationships between lncRNAs and cancer hallmark-associated genes in OSCC. Through integrative analysis of cancer hallmarks, somatic mutations, copy number variants (CNVs) and expression, some OSCC-specific cancer hallmark-associated genes and lncRNAs are identified. A computational framework to identify gene and lncRNA cooperative regulation pairs (GLCRPs) associated with different cancer hallmarks is developed based on the co-expression and co-occurrence of mutations. The distinct and common features of ten cancer hallmarks based on GLCRPs are characterized in OSCC. Cancer hallmark insensitivity to antigrowth signals and self-sufficiency in growth signals are shared by most GLCRPs in OSCC. Some key GLCRPs participate in many cancer hallmarks in OSCC. Cancer hallmark-associated GLCRP networks have complex patterns and specific functions in OSCC. Specially, some key GLCRPs are associated with the prognosis of OSCC patients. In summary, we generate a comprehensive landscape of cancer hallmark-associated GLCRPs that can act as a starting point for future functional explorations, the identification of biomarkers and lncRNA-based targeted therapy in OSCC.

Immigration and the Wage Distribution in the United States.

This article assesses the connection between immigration and wage inequality in the United States. Departing from the focus on how the average wages of different native groups respond to immigration, we examine how immigrants shape the overall wage distribution. Despite evidence indicating that an increased presence of low-skilled immigrants is associated with losses at the lower end of wage distribution, we do not observe a similar result between high-skilled immigrants and natives at the upper end. Instead, the presence of foreign-born workers, whether high- or low-skilled, is associated with substantial gains for high-wage natives, particularly those at the very top. Consequently, increased immigration is associated with greater wage dispersion.

[Effect of Nifuroxazide on Proliferation, Migration, and Invasion of Thyroid Papillary Carcinoma Cells].

OBJECTIVE: To explore the effect of nifuroxazide on proliferation, migration, and invasion of thyroid papillary carcinoma cells. METHODS: BCPAP and TPC-1 cell lines treated with different concentration (0, 1.25, 2.5, 5, 10, 20 µmol/L) of nifuroxazide, respectively. Cell viability and proliferation of BCPAP and TPC-1 was evaluated by MTT and colony formation assay. Apoptosis analysis and cell nuclear changes were determined by staining with Hoechst 33258 and visualized by a fluorescence microscope after treatment with nifuroxazide. Western blot analysis was used to evaluate protein expressions of apoptosis and invasion of BCPAP cells treated (48 h) with nifuroxazide. Transwell assay was conducted to evaluate ability of cell migration and invasion. RESULTS: After being treated with nifuroxazide (0, 1.25, 2.5 µmol/L and 0, 1.25 µmol/L) for 24, 48, 72 h respectively, decreased proliferations of BCPAP and TPC-1 cell lines were not obvious ( P>0.05). However, treated BCPAP and TPC-1 cells with higher concentration respectively (5, 10, 20 µmol/L and 5, 10 µmol/L) of nifuroxazide for 24, 48, 72 h, the inhibitory effects were significantly obvious ( P<0.05), and the inhibitory effects were increased in a CM(155mm]concentration- and time-dependent manner. The inhibition in proliferation of TPC-1 cell with nifuroxazide (2.5, CM)]5 µmol/L) took effect from 72 h and 48 h ( P<0.05), respectively. Clone formations of BCPAP and TPC-1 cells were significantly inhibited after being exposed to nifuroxazide (2.5, 5 µmol/L) for 10 d ( P<0.05). Hoechst 33258 staining assay showed that nifuroxazide (10 µmol/L) treatment resulted in cell shrinking, nuclear fragmentation and formation of condensed nuclei with bright-blue fluorescence. After 48 h, the percentage of apoptotic cells of BCPAP and TPC-1 significantly increased respectively as the concentration of nifuroxazide with 10 µmol/L ( P<0.005). Pro-apoptotic protein CC-3 and Bax expression levels increased significantly ( P<0.05), and the expression of anti-apoptotic protein Bcl-2 decreased significantly ( P<0.05) in BCPAP cells after nifuroxazide-treatment (10 µmol/L) for 48 h. The percentage of migrations and invasions of BCPAP and TPC-1 significantly decreased ( P<0.05) in the presence of nifuroxazide (10 µmol/L, 48 h). Nifuroxazide (10 µmol/L) treatment significantly decreased the expressions of matrix metalloproteinase (MMP)-2 and MMP-9 in BCPAP cells ( P<0.05) . Expression of MMPs family inhibitor-tissue inhibitors of metalloproteinase (TIMP)-2 increased ( P<0.05). CONCLUSION: Nifuroxazide inhibits the proliferation of thyroid cancer cells BCPAP and TPC-1, induceds the cell apoptosis by up-regulating the expressions of CC-3 and Bax proteins in vitro, and blocks migration and invasion of cells in vitro by reducing protein expressions of MMP-2 and MMP-9.

Myopia Prevention and Outdoor Light Intensity in a School-Based Cluster Randomized Trial.

PURPOSE: To investigate the effectiveness of a school-based program promoting outdoor activities in Taiwan for myopia prevention and to identify protective light intensities. DESIGN: Multi-area, cluster-randomized intervention controlled trial. PARTICIPANTS: A total 693 grade 1 schoolchildren in 16 schools participated. Two hundred sixty-seven schoolchildren were in the intervention group and 426 were in the control group. METHODS: Initially, 24 schools were randomized into the intervention and control groups, but 5 and 3 schools in the intervention and control groups, respectively, withdrew before enrollment. A school-based Recess Outside Classroom Trial was implemented in the intervention group, in which schoolchildren were encouraged to go outdoors for up to 11 hours weekly. Data collection included eye examinations, cycloplegic refraction, noncontact axial length measurements, light meter recorders, diary logs, and questionnaires. MAIN OUTCOME MEASURES: Change in spherical equivalent and axial length after 1 year and the intensity and duration of outdoor light exposures. RESULTS: The intervention group showed significantly less myopic shift and axial elongation compared with the control group (0.35 diopter [D] vs. 0.47 D; 0.28 vs. 0.33 mm; P = 0.002 and P = 0.003) and a 54% lower risk of rapid myopia progression (odds ratio, 0.46; 95% confidence interval [CI], 0.28-0.77; P = 0.003). The myopic protective effects were significant in both nonmyopic and myopic children compared with controls. Regarding spending outdoor time of at least 11 hours weekly with exposure to 1000 lux or more of light, the intervention group had significantly more participants compared with the control group (49.79% vs. 22.73%; P < 0.001). Schoolchildren with longer outdoor time in school (≥200 minutes) showed significantly less myopic shift (measured by light meters; ≥1000 lux: 0.14 D; 95% CI, 0.02-0.27; P = 0.02; ≥3000 lux: 0.16 D; 95% CI, 0.002-0.32; P = 0.048). CONCLUSIONS: The school-based outdoor promotion program effectively reduced the myopia change in both nonmyopic and myopic children. Outdoor activities with strong sunlight exposure may not be necessary for myopia prevention. Relatively lower outdoor light intensity activity with longer time outdoors, such as in hallways or under trees, also can be considered.