PURPOSE In contrast to the predominant chronic UV-exposure-induced cutaneous melanoma in Caucasians, acral and mucosal comprise the majority of melanomas in Asia and respond less effectively to established treatments. The clinical application of PD-1 blockade is yet to be explored in metastatic melanoma in China. EXPERIMENTAL DESIGN This phase II study was to evaluate safety and efficacy of toripalimab in advanced Chinese melanoma patients who had failed in systemic treatments. Toripalimab was given at 3 mg/kg IV Q2W until disease progression or unacceptable toxicity. The primary objective was safety and objective response rate. RESULTS 128 melanoma patients were enrolled, including 50 acral and 22 mucosal. As of August 15, 2019, 23-month after the last enrollment, 116 (90.6%) experienced treatment-related adverse events. ≥Grade 3 TRAEs occurred in 25 (19.5%) patients. Among 127 patients assessed, 1 CR, 21 PR and 51 SD were observed for objective response rate of 17.3% and disease control rate of 57.5%. Median duration of response was not reached. Median progression-free survival was 3.6m (95%CI 2.7 to 5.3) and median overall survival was 22.2m (95%CI 15.3 to NE). Patients with positive PD-L1 staining in tumor biopsies had significant better ORR (38.5% versus 11.9%, p=0.0065), PFS (7.7m versus 2.7m, p=0.013) and OS (not reached versus 14.4m, p=0.0005) than PD-L1 negative patients. CONCLUSIONS This is the largest prospective anti-PD-1 clinical study in advanced melanoma with predominantly acral and mucosal subtypes. Toripalimab demonstrated a manageable safety profile and durable clinical response in Chinese patients with metastatic melanoma refractory to standard therapy. Copyright ©2020, American Association for Cancer Research.BACKGROUND Pancreatic cancer is the third leading cause of cancer death in the United States, and 80% of patients present with advanced, incurable disease. Risk markers for pancreatic cancer have been characterized, but combined models are not used clinically to identify individuals at high risk for the disease. METHODS Within a nested case-control study of 500 pancreatic cancer cases diagnosed after blood collection and 1,091 matched controls enrolled in four U.S. prospective cohorts, we characterized absolute risk models that included clinical factors (e.g., body mass index, history of diabetes), germline genetic polymorphisms, and circulating biomarkers. RESULTS Model discrimination showed an area under ROC curve of 0.62 via cross-validation. Our final integrated model identified 3.7% of men and 2.6% of women who had at least 3 times greater than average risk in the ensuing 10 years. Individuals within the top risk percentile had a 4% risk of developing pancreatic cancer by age 80 years and 2% 10-year risk at age 70 years. CONCLUSIONS Risk models that include established clinical, genetic, and circulating factors improved disease discrimination over models using clinical factors alone. IMPACT Absolute risk models for pancreatic cancer may help identify individuals in the general population appropriate for disease interception. ©2020 American Association for Cancer Research.Cortex development is controlled by temporal patterning of neural progenitor (NP) competence with sequential generation of deep and superficial layer neurons, but underlying mechanisms remain elusive. Here, we report a role of heterogeneous nuclear ribonucleoprotein A3 (HNRNPA3) in regulating the division of early cortical NPs that mainly give rise to deep-layer neurons via direct neurogenesis. HNRNPA3 is highly expressed in NPs of mouse and human cortex at early stages with a unique peri-chromosome pattern. Intriguingly, down-regulation of HNRNPA3 caused chromosome disarrangement, which hindered normal separation of chromosomes during NP division, leading to mitotic delay. Furthermore, HNRNPA3 is associated with the cohesin-core subunit SMC1A and controls its association with chromosomes, implicating a mechanism for the role of HNRNPA3 in regulating chromosome segregation in dividing NPs. Hnrnpa3 deficient mice exhibited reduced cortical thickness, especially of deep layers. Moreover, down-regulation of HNRNPA3 in cultured human cerebral organoids led to marked reduction in NPs and deep-layer neurons. Thus, this study has identified a critical role of HNRNPA3 in NP division and highlighted the relationship between mitosis progression and early neurogenesis. © 2020. Published by The Company of Biologists Ltd.OBJECTIVES The Burns and Scalds Assessment Template (BaSAT) is an evidence-based proforma coproduced by researchers and ED staff with the aim of (1) standardising the assessment of children attending ED with a burn, (2) improving documentation and (3) screening for child maltreatment. This study aimed to test whether the BaSAT improved documentation of clinical, contributory and causal factors of children’s burns. METHODS A retrospective before-and-after study compared the extent to which information was recorded for 37 data fields after the BaSAT was introduced in one paediatric ED. Pre-BaSAT, a convenience sample of 50 patient records of children who had a burn was obtained from the hospital electronic database of 2007. The post-BaSAT sample included 50 randomly selected case notes from 2016/2017 that were part of another research project. Fisher’s exact test and Mann-Whitney U tests were conducted to test for statistical significance. RESULTS Pre-BaSAT, documentation of key data fields was poor. Post-BaSAT, this varied less between patients, and median completeness significantly (p less then 0.001) increased from 44% (IQR 4%-94%) to 96% (IQR 94%-100%). Information on ‘screening for maltreatment, referrals to social care and outcome’ was poorly recorded pre-BaSAT (median of 4% completed fields) and showed the greatest overall improvement (to 95%, p less then 0.001). Documentation of domestic violence at home and child’s ethnicity improved significantly (p less then 0.001) post-BaSAT; however, these were still not recorded in 36% and 56% of cases, respectively. CONCLUSION Introduction of the BaSAT significantly improved and standardised the key clinical data routinely recorded for children attending ED with a burn. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. learn more Published by BMJ.