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Changes in phenology are a conspicuous fingerprint of climate change, leading to fears that phenological mismatches among interacting species will be a leading cause of population declines and extinction. We used quantile regression to analyze museum collection data and estimate changes in the phenological overlap of Baltimore checkerspot butterflies and 12 common nectar plant species over several decades in two geographic regions. We combined these museum data with field estimates of each species flower density and nectar sugar production to estimate changes in resource availability caused by shifts in phenological overlap. Phenological overlap (measured as the proportion of plant flowering during the flight period of an average butterfly) decreased through time, primarily because the flowering period of nectar plants was longer, but the flight period of butterflies was shorter in recent years. Our study was also motivated by the hypothesis that phenological mismatches may be more severe in the southern region due to a midsummer dearth in floral resources, but this hypothesis was not supported by our data. Although phenological overlap was somewhat smaller in the southern region, changes in overlap through time were similar in both regions. When phenological overlap was weighted by nectar sugar production of different species, the overlap increased in the southern region but decreased in the northern region (the opposite of our prediction). Overall, nectar resources were much more abundant at study sites in our northern region than in our southern region, possibly due to differences in land management. Our study demonstrates the complexities of phenological mismatch of interacting species and highlights that phenological changes may have small impacts on population viability.

Abstract Radiation-induced morphea (RIM) is a rare complication of radiotherapy presenting as inflammatory fibrosis, most commonly reported in breast cancer patients. As underlying disease mechanisms are not well understood, targeted therapies are lacking. Since fibroblasts are the key mediators of all fibroproliferative diseases, this study aimed to characterize patient-derived fibroblasts to identify therapeutic targets. We studied primary human control and RIM-fibroblasts on a functional and molecular basis, analyzed peripheral blood and tissue samples and conducted, based on our findings, a treatment attempt in one patient. In RIM, we identified a distinct myofibroblast phenotype reflected by increased alpha-smooth-muscle-actin (αSMA) expression, reduced proliferation and migration rates, and overexpression of osteopontin (OPN). Our RNA sequencing identified aberrant Myc activation as a potential disease driver in RIM fibroblasts, similar to previous findings in systemic sclerosis. Treatment with the anti-inflammatory drug mesalazine reversed the myofibroblast phenotype by targeting Myc. Based on these findings, a patient with RIM was successfully treated with mesalazine, resulting in reduced inflammation and pain and tissue softening, while serum OPN was halved. The present study provides a comprehensive characterization of RIM fibroblasts, suggests a disease-driving role for Myc, demonstrates promising antifibrotic effects of mesalazine and proposes OPN as a biomarker for RIM.

Neutrophil dysregulation, particularly of a low-density subset, is associated with systemic lupus erythematosus (SLE); however, the exact role of normal-density neutrophils in SLE remains unknown. This study compares activation and functional phenotypes of neutrophils from SLE patients and healthy controls to determine potential contributions to SLE pathogenesis. Surface activation markers and release of neutrophil extracellular traps (NETs), granule proteins, and cytokines/chemokines were measured in resting and stimulated neutrophils from SLE patients (n=19) and healthy controls (n=10). Select miRNA and mRNA involved in neutrophil development and function were also measured. Resting SLE neutrophils exhibited fewer activation markers compared to control neutrophils, and activation markers were associated with different plasma cytokines/chemokines in SLE patients compared to healthy controls. However, activation markers increased similarly in SLE and control neutrophils following stimulation with a TLR7/8 agonist, neutrophil growth factors, and bacterial mimic. At the resting state, SLE neutrophils produced significantly more CXCL10 (IP-10), with trends toward other increased cytokines/chemokines. Following stimulation, SLE neutrophils produced fewer NETs and proinflammatory cytokines compared to control neutrophils but more MMP-8. In addition, SLE neutrophils expressed less miR130a, miR132, miR27a, and miR223. In conclusion, SLE neutrophils exhibit distinct functional responses compared to control neutrophils. These functional differences may result from differential gene expression via miRNAs. Furthermore, the differences in functional phenotype of SLE neutrophils suggest that they may contribute to SLE differently dependent on the inflammatory milieu.

The article focuses on the urgent need for enhanced leadership in the water sector to achieve SDG6. Topics include the perceived stagnation in water sector capacity development over the past decade, the critical role of leadership skills in implementing visionary plans, and the evolving landscape of leadership development influenced by inclusivity and generational diversity.

Objective: AURORA 2 evaluated the long‐term safety, tolerability, and efficacy of voclosporin compared to placebo in patients with lupus nephritis (LN) receiving an additional two years of treatment following completion of the one‐year AURORA 1 study. Methods: Enrolled patients continued their double‐blinded treatment of voclosporin or placebo randomly assigned in AURORA 1, in combination with mycophenolate mofetil and low‐dose glucocorticoids. The primary objective was safety assessed with adverse events (AEs) and biochemical and hematological assessments. Efficacy was measured by renal response. Results: A total of 216 patients enrolled in AURORA 2. Treatment was well tolerated with 86.1% completing the study and no unexpected safety signals. AEs occurred in 86% and 80% of patients in the voclosporin and control groups, respectively, with an AE profile similar to that seen in AURORA 1, albeit with reduced frequency. Investigator reported AEs of both glomerular filtration rate (GFR) decrease and hypertension occurred more frequently in the voclosporin than the control group (10.3% vs 5.0%, and 8.6% vs 7.0%, respectively). Mean corrected estimated GFR (eGFR) was within the normal range and stable in both treatment groups. eGFR slope over the two‐year period was −0.2 mL/min/1.73 m2 (95% confidence interval [CI] −3.0 to 2.7) in the voclosporin group and −5.4 mL/min/1.73 m2 (95% CI −8.4 to −2.3) in the control group. Improved proteinuria persisted across three years of treatment, leading to more frequent complete renal responses in patients treated with voclosporin (50.9% vs 39.0%; odds ratio 1.74; 95% CI 1.00–3.03). Conclusion: Data demonstrate the safety and efficacy of long‐term voclosporin treatment over three years of follow‐up in patients with LN. [ABSTRACT FROM AUTHOR]