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1.
Cao  Jie  Xie  Chengyu  Hou  Zhiru 《Ecotoxicology (London, England)》2022,31(2):259-270
Ecotoxicology - Soil heavy metal pollution evaluations are a necessary measure for mine ecological control projects. In this study, the heavy metals Pb, Zn and Cd were studied in mining areas,...  相似文献   
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Neoadjuvant programmed cell death protein 1 (PD-1) blockade exhibits promising efficacy in patients with mismatch repair deficient (dMMR) colorectal cancer (CRC). However, discrepancies between radiological and histological findings have been reported in the PICC phase II trial (NCT 03926338). Therefore, we strived to discern radiological features associated with pathological complete response (pCR) based on computed tomography (CT) images. Data were obtained from the PICC trial that included 36 tumors from 34 locally advanced dMMR CRC patients, who received neoadjuvant PD-1 blockade for 3 months. Among the 36 tumors, 28 (77.8%) tumors achieved pCR. There were no statistically significant differences in tumor longitudinal diameter, the percentage change in tumor longitudinal diameter from baseline, primary tumor sidedness, clinical stage, extramural venous invasion status, intratumoral calcification, peritumoral fat infiltration, intestinal fistula and tumor necrosis between the pCR and non-pCR tumors. Otherwise, tumors with pCR had smaller posttreatment tumor maximum thickness (median: 10 mm vs 13 mm, P = .004) and higher percentage decrease in tumor maximum thickness from baseline (52.9% vs 21.6%, P = .005) compared to non-pCR tumors. Additionally, a higher proportion of the absence of vascular sign (P = .003, odds ratio [OR] = 25.870 [95% CI, 1.357-493.110]), nodular sign (P < .001, OR = 189.000 [95% CI, 10.464-3413.803]) and extramural enhancement sign (P = .003, OR = 21.667 [2.848-164.830]) was observed in tumors with pCR. In conclusion, these CT-defined radiological features may have the potential to serve as valuable tools for clinicians in identifying patients who have achieved pCR after neoadjuvant PD-1 blockade, particularly in individuals who are willing to adopt a watch-and-wait strategy.  相似文献   
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Two Janus-associated kinase inhibitors (JAKi) (initially ruxolitinib and, more recently, fedratinib) have been approved as treatment options for patients who have intermediate-risk and high-risk myelofibrosis (MF), with pivotal trials demonstrating improvements in spleen volume, disease symptoms, and quality of life. At the same time, however, clinical trial experiences with JAKi agents in MF have demonstrated a high frequency of discontinuations because of adverse events or progressive disease. In addition, overall survival benefits and clinical and molecular predictors of response have not been established in this population, for which the disease burden is high and treatment options are limited. Consistently poor outcomes have been documented after JAKi discontinuation, with survival durations after ruxolitinib ranging from 11 to 16 months across several studies. To address such a high unmet therapeutic need, various non-JAKi agents are being actively explored (in combination with ruxolitinib in first-line or salvage settings and/or as monotherapy in JAKi-pretreated patients) in phase 3 clinical trials, including pelabresib (a bromodomain and extraterminal domain inhibitor), navitoclax (a B-cell lymphoma 2/B-cell lymphoma 2-xL inhibitor), parsaclisib (a phosphoinositide 3-kinase inhibitor), navtemadlin (formerly KRT-232; a murine double-minute chromosome 2 inhibitor), and imetelstat (a telomerase inhibitor). The breadth of data expected from these trials will provide insight into the ability of non-JAKi treatments to modify the natural history of MF.  相似文献   
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Analyzing functional species’ characteristics (species traits) that represent physiological, life history and morphological characteristics of species help understanding the impacts of various stressors on aquatic communities at field conditions. This research aimed to study the combined effects of pesticides and other environmental factors (temperature, dissolved oxygen, dissolved organic carbon, floating macrophytes cover, phosphate, nitrite, and nitrate) on the trait modality distribution of aquatic macrofauna communities. To this purpose, a field inventory was performed in a flower bulb growing area of the Netherlands with significant variation in pesticides pressures. Macrofauna community composition, water chemistry parameters and pesticide concentrations in ditches next to flower bulb fields were determined. Trait modalities of nine traits (feeding mode, respiration mode, locomotion type, resistance form, reproduction mode, life stage, voltinism, saprobity, maximum body size) likely to indicate pesticides impacts were analyzed. According to a redundancy analysis, phosphate -and not pesticides- constituted the main factor structuring the trait modality distribution of aquatic macrofauna. The functional composition could be ascribed for 2–4 % to pesticides, and for 3–11 % to phosphate. The lack of trait responses to pesticides may indicate that species may have used alternative strategies to adapt to ambient pesticides stress. Biomass of animals exhibiting trait modalities related to feeding by predation and grazing, presence of diapause form or dormancy, reproduction by free clutches and ovoviviparity, life stage of larvae and pupa, was negatively correlated to the concentration of phosphate. Hence, despite the high pesticide pollution in the area, variation in nutrient-related stressors seems to be the dominant driver of the functional composition of aquatic macrofauna assembly in agricultural ditches.  相似文献   
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