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Introduction Myelofibrosis (MF) is one of the classic myeloproliferative neoplasms and can occur de novo or following transformation from polycythemia vera (PPV MF) or essential thrombocythemia (PET MF). It can be associated with constitutional symptoms and splenomegaly, both of which can negatively impact quality of life. The only curative option for MF is allogeneic stem cell transplantation. Studies have shown that JAK2 inhibitors such as ruxolitinib are effective in reducing both splenomegaly and symptom burden. Although there is no approved treatment for patients who progress on ruxolitinib, anecdotal evidence suggests patients may respond to a re-challenge of ruxolitinib after drug cessation. Patients and Methods We conducted a multi-institutional, retrospective case series to study patients who were re-challenged with ruxolitinib after inadequate response to or loss of response with an initial treatment course. Thirteen patients were identified. Six patients had primary MF, 3 patients had PPV MF, and 4 patients had PET MF. Ten patients were JAK2-positive, 2 were CALR-positive, and 1 patient had neither mutation. Nine patients received 1 ruxolitinib re-challenge, and 4 received 2 re-challenges. Response was defined as improvement in constitutional symptoms and/or reduction in spleen size. Results During the primary treatment course with ruxolitinib, there was improvement in constitutional symptoms and reduction in spleen size in 92% and 85% of patients, respectively. Following cessation of ruxolitinib, all patients received a first re-challenge course with improvement in symptoms and splenomegaly in 92% and 69%, respectively. Of the 4 patients who received a second re-challenge course of ruxolitinib, all had improvements in spleen size and constitutional symptoms. Six patients have continued on a first or second ruxolitinib re-challenge course with good response. Conclusion Our study demonstrates that re-exposure to ruxolitinib following a period of treatment cessation in patients with MF can lead to durable responses with regards to both splenomegaly and symptom burden.

Even though over half of the world's soil organic carbon (SOC) is stored in subsoils (> 20 cm deep), and the old ages of subsoil OC indicate its cycling differs from surface SOC, there are few studies examining in situ decomposition processes in deep soils. Here, we added 13C-labeled fine roots to 15, 55, and 95 cm depths of a well characterized coniferous forest Alfisol and monitored the amount of root-derived C remaining over 6, 12, and 30 months. We recovered the root-derived C in microbial phospholipid fatty acids (PLFAs) after 6 months and in coarse (> 2 mm) particulate, fine (< 2 mm) particulate, and dense, mineral-associated pools after 6, 12, and 30 months. Overall, root decomposition in the first 6 months was similar among all depths but significantly diverged at 30 months with faster decomposition at 15 cm than at 95 cm. There were more fungal and Gram negative-associated PLFAs at 15 cm than at 95 cm, and 13C analysis revealed those microbial groups preferred the added root carbon to native SOC. Mineral-associations were not the cause of slower decomposition at depth because similar amounts of applied root C was recovered in the dense fraction at all depths. The largest difference among depths was in the amount of root C recovered in the coarse particulate fraction, which was greater at 95 cm (50%) than at 15 cm (15%). Slower decomposition of the particulate pool at depth likely contributed to the increase in C:N ratios and depletion of δ13C values below 60 cm depth in our soil profiles. Simulations of these soils using the CORPSE model, which incorporates microbial priming effects and mineral stabilization of SOC, reproduced patterns of particulate and mineral-associated SOC over both time and depth and suggested that a lack of priming by root exudates at depth could account for the slower decomposition rate of particulate root material. Decomposition of deep particulate SOC may increase if root exudation or dissolved OC transport to depth increases.

Passive acoustic recorders were deployed over two years (February 2018–March 2020) in the Salish Sea to monitor the underwater soundscape. Seasonal cycles and differences between the open Strait of Juan de Fuca and protected inner waterways were pervasive during this period. A comparison between natural and human-derived noise demonstrated the impact of anthropogenic activities on the sound field. Elevated ambient noise levels during winter resulted predominantly from greater sea states and storm events. Abiotic additions were defined through correlations to wind speed, wave and precipitation measures. Vessel noise was a pervasive anthropogenic addition; commercial vessel noise was consistently present, whereas smaller vessels showed weekly and diurnal patterns, especially during the summer when their presence increased. A better understanding of the different soundscape constituents, and when each dominates, is crucial to understanding the human impact on underwater ecosystems and the organisms within them, leading to more effective mitigation measures.

BACKGROUND Health benefits associated with diets rich in vegetables and fruit (VF) are often attributed to the antioxidant activity of their constituent phytochemicals. However, in vivo evidence that VF actually reduce markers of oxidative stress is limited. OBJECTIVE An 8-wk dietary intervention was conducted to test the hypothesis that increased VF consumption decreases oxidative stress. Urinary excretion of 8-isoprostane F2alpha (8-iso-PGF2alpha) was used as an index of whole-body lipid peroxidation. DESIGN The diets evaluated had comparable amounts of all macronutrients but varied in their content of VF. After a 2-wk low-VF (3.0 servings/d) run-in diet, 246 women were randomly assigned to receive either 3.6 (low) or 9.2 (high) servings VF/d. The low-VF group was switched to the high-VF diet during the final 2 wk of the study. Blood and first-void urine specimens were obtained at baseline and at 2-wk intervals thereafter. RESULTS The run-in diet reduced 8-iso-PGF2alpha concentrations by 33% (P < 0.0001). The excretion of 8-iso-PGF2alpha with the low-VF diet remained the same as that with the run-in diet, whereas urinary concentrations of 8-iso-PGF2alpha were further reduced (P < 0.01) by the high-VF diet, either fed throughout the study or when the diet was switched from low to high VF (P = 0.05). The greatest reductions in 8-iso-PGF2alpha were observed in subjects in the highest quartile of baseline concentrations of 8-iso-PGF2alpha. CONCLUSIONS A significant reduction in the excretion of 8-iso-PGF2alpha was induced by the run-in diet and the high-VF diet. The degree of reduction was related to the subject's baseline urinary concentration of 8-iso-PGF2alpha.