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Supplementary Figure S1. CONSORT flow diagram for patient selection

Patient characteristics

Ipilimumab is effective for patients with melanoma, but not for those with less immunogenic tumors. We report a phase II trial of ipilimumab with concurrent or sequential stereotactic ablative radiotherapy to metastatic lesions in the liver or lung (NCT02239900). Ipilimumab (every 3 weeks for 4 doses) was given with radiotherapy begun during the first dose (concurrent) or 1 week after the second dose (sequential) and delivered as 50 Gy in 4 fractions or 60 Gy in 10 fractions to metastatic liver or lung lesions. In total, 106 patients received ≥1 cycle of ipilimumab with radiation. Median follow-up was 10.5 months. Median progression-free survival time was 2.9 months (95% confidence interval, 2.45–3.40), and median overall survival time was not reached. Rates of clinical benefit of nonirradiated tumor volume were 26% overall, 28% for sequential versus 20% for concurrent therapy (P = 0.250), and 31% for lung versus 14% for liver metastases (P = 0.061). The sequential lung group had the highest rate of clinical benefit at 42%. There were no differences in treatment-related adverse events between groups. Exploratory analysis of nontargeted lesions revealed that lesions receiving low-dose radiation were more likely to respond than those that received no radiation (31% vs. 5%, P = 0.0091). This phase II trial of ipilimumab with stereotactic radiotherapy describes satisfactory outcomes and low toxicities, lending support to further investigation of combined-modality therapy for metastatic cancers.

Avocado by-products present a waste issue for cold-pressed avocado oil processors in New Zealand. The avocado seed contains many extractable compounds that are beneficial to health. This work aims to evaluate the effects of roasting fermented avocado seed to produce a food ingredient with beneficial antioxidant and anticancer properties. Avocado seeds were subjected to natural fermentation and inoculated fermentation with either Lactobacillus plantarum or kefir. The fermented samples were evaluated in terms of total plate count values of lactic acid bacteria acetic acid bacteria and yeasts. The number of microorganisms increased significantly (p < 0.001) over the 7 days of fermentation for all samples. Fermentation with L. plantarum resulted in significantly (p < 0.05) higher total phenolic content (TPC) and antioxidant activities compared to kefir and naturally fermented samples. The fermented avocado seeds were further subjected to roasting to yield a shelf-stable dried powder. Roasted samples fermented by L. plantarum had significantly (p < 0.001) higher total polyphenolic content and antioxidant capacity (CUPRAC and Ferric Reducing Antioxidant Power assays) compared to kefir and naturally fermented samples. The avocado seed powder showed the best inhibition effect on Hep G2 followed by the MDA-MB-231 and MCF-7 cancer cell lines. The roasting conditions for optimal antioxidant and anticancer activities were determined to be at 127°C for 24.7 min. This study demonstrated that fermentation of avocado seeds in combination with roasting yielded a powder with good antioxidant and anticancer activities, which can potentially be incorporated into food for added health benefits.

Due to the risk of postoperative hypotension (PH), invasive monitoring is recommended for patients who undergo adrenalectomy for phaeochromocytoma. Due to high costs and limited availability of intensive care, our aim was to identify patients at low risk of PH who may not require invasive monitoring.Data for patients who underwent adrenalectomy for phaeochromocytoma between 2012 and 2020 were retrospectively collected by nine UK centres, including patient demographics, intraoperative and postoperative haemodynamic parameters. Independent risk factors for PH were analysed and used to develop a clinical risk score.PH developed in 118 of 430 (27.4%) patients. On univariable analysis, female sex (p = 0.007), tumour size (p 0.001), preoperative catecholamine level (p 0.001), open surgery (p 0.001) and epidural analgesia (p = 0.006) were identified as risk factors for PH. On multivariable analysis, female sex (OR 1.85, CIThe derived risk score allows stratification of patients at risk of postoperative hypotension after adrenalectomy for phaeochromocytoma. Postoperatively, low risk patients may be managed on a surgical ward, whilst high risk patients should undergo invasive monitoring.

Token acts of online support, also known as clicktivism, have received much criticism in recent years for suppressing subsequent prosocial behavior. However, whether, when, and why individuals perform less prosocial behavior following these acts remains relatively unknown. To address these questions, we designed a lab experiment in which participants ( N = 193) were randomly assigned to engage in public, private, or no act of clicktivism. Consistent with moral self-licensing theory, those who signed an online petition were less likely to donate than those who did not sign any petition. Public clicktivism (compared to private clicktivism) increased donation intentions among those with high impression management tendencies (i.e. high self-monitors). Concerns about one’s moral self-image partially mediated these effects. Theoretical and practical implications of these findings are discussed.