Aims To propose diagnostic criteria for a presumed incipient choroidal melanoma based on tumour growth rate and tumour doubling time (TDT) and to describe management of such tumours with transpupillary thermotherapy (TTT). Methods Retrospective interventional case series of nine consecutive presumed incipient uveal melanomas diagnosed and treated with TTT in 2010–2017. Growth rate in mm/year and per cent/year in largest basal diameter (LBD) and TDT were compared with published data for uveal melanomas and growing naevi that did not transform to melanoma under long-­term follow-­up. Results The median LBD and thickness were 1.6 mm (range 0.9–2.3) and 0.20 mm (range 0.15–0.29), respectively. The median age was 57 years (range 47–78). Seven tumours were classified as de novo m elanomas and two as transformed naevi. The median time from first observation to diagnosis was 3.3 years (range 2.2–7.3), LBD growth rate 0.25 mm/year (range 0.11–0.72) and 34 per cent/year (range 10–1437), and TDT 609 days (range 97–1612). The estimates matched those reported for uveal melanoma (median TDT 521 days, 90th percentile 2192) and exceeded those for growing naevi (median growth rate 0.04 mm/year, 90th percentile 0.12; 1.1 per cent/year, 90th percentile 2.6). The predicted median age at de novo appearance was 51 years (range 32–63). No tumour grew after TTT during a median follow-­up of 2.1 years (range 0.6–8.7). Conclusions In this series, relative growth rate and

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Key message ZmHSFA2d enhances maize heat and drought tolerance by safeguarding photosynthesis homeostasis, and its expression is directly activated by ZmbHLH124. Abstract Heat stress significantly influences plant growth, development, and productivity. Nevertheless, many maize (Zea mays) heat shock factors (HSFs) remain uncharacterized. Here, we explored the role of ZmHSFA2d in thermotolerance. ZmHSFA2d transcript levels were notably elevated under heat shock. ZmHSFA2d localized to the nucleus and displayed transactivation in yeast. Under heat shock, ZmHSFA2d-overexpressing maize seedlings exhibited greater thermotolerance, increased antioxidant enzyme activities, and reduced reactive oxygen species (ROS) and malondialdehyde (MDA) contents compared to control lines ; however, these effects were reversed following the CRISPR/Cas9-mediated knockout (KO) of ZmHSFA2d. RNA-Seq analysis revealed that the expression of genes encoding ribosomal proteins, including those associated with ribosome assembly and translation progress, was significantly decreased in ZmHSFA2d-KO plants. Quantitative proteomic analysis further indicated that compared to control, the expression of key proteins [chlorophyll a/b binding proteins and NAD(P)H dehydrogenase (NDH) complex subunits] in photosystem was significantly decreased in ZmHSFA2d-KO lines. Furthermore, using Y1H, EMSA, Dual-Luciferin assays, and maize mesophyll protoplast expression, we found that ZmbHLH124, which is responsive to both heat and drought stress, directly upregulated the transcript levels of ZmHSFA2d. Additionally, ZmHSFA2d positively modulating maize drought tolerance, and compare to WT, ribosomal protein genes in ZmHSFA2d-KO plants also notably decreased under drought stress. Overall, our result s indicated that the ZmHSFA2d positively regulates maize heat and drought tolerance by modulating the protein synthesis. This study contributes to the understanding of the role of HSFs in maize thermotolerance and offers useful genetic resources for the breeding of multiple stress-tolerant maize varieties.

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and titles to filter out irrelevant articles, and a third reviewer settled any conflicts. The complete search methodology and results are given in Supplemental Digital Content 1 (see Table S1, http://links.lww.com/AJT/ A224). Inclusion criteria required studies to (1) RCTs evaluating obinutuzumab plus standard therapy versus placebo plus standard therapy, (2) included adults aged 18–75 years with biopsy confirming active lupus nephritis (class III or IV, with or without Class V disease), (3) assessed at least 1 outcome related to complete kidney response, defined by a urinary protein-tocreatinine ratio ,0.5, an eGFR of at least 85% of baseline, and absence of treatment failure, rescue therapy, death or early withdrawal. Exclusion criteria included nonrandomized studies, single-arm trials, case reports, observational stu dies, and abstracts. The quality of study was assessed using the Cochrane Risk of Bias Tool (RoB 2.0). 6 Statistical analyses were performed using Revman 5.4, using mean difference (MD) and 95% confidence intervals (CI). We analyzed dichotomous outcomes, using both risk ratios (RR) and odds ratios (OR) with 95% CI to provide a comprehensive assessment of treatment effects. Two RCTs meeting the predefined inclusion criteria were included in qualitative and quantitative analyses. 3,4 These RCTs reported data from 396 patients with active proliferative lupus nephritis (obinutuzumab =198 patients, placebo = 198 patients).

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