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Klavsen Mueller posted an update 6 months, 3 weeks ago
Positive associations between social jetlag with zBMI, % fat, and fat mass index were seen in univariable and unadjusted multivariable analyses. Following adjustments for known confounders, social jetlag remained significantly associated with zBMI (β=0.12, p=0.013). Simple slopes suggested a positive association in girls (β=0.19, p=0.006) but not in boys (β=0.03, p=0.703).
Obesity prevention efforts, particularly in girls, may benefit from targeted approaches to improving the consistency of sleep timing in youth.
Obesity prevention efforts, particularly in girls, may benefit from targeted approaches to improving the consistency of sleep timing in youth.The Green Revolution of the 1960s boosted cereal crop yields in part through widespread adoption of semi-dwarf plant varieties, many of which were later found to have mutations in either gibberellins (GAs) homeostasis or DELLA proteins. GA is essential for plant growth and developmental regulation and plays an important role in improving crop plant architecture for enhanced grain yield under high nitrogen conditions. A complex regulatory network governs the spatially and temporally controlled genes expression through integrative GA signaling in response to multiple endogenous and environmental cues. In this review, we summarize current advances in understanding the molecular mechanisms of DELLA-dependent and DELLA-independent GA signaling pathways and their contributions to plant developmental and metabolic adaptations to changes in nitrogen availability. The progress in molecular understanding of the plant growth-metabolic coordination will facilitate breeding strategies for future sustainable agriculture and a new Green Revolution.
Immune checkpoint inhibitors (ICIs) have led to a paradigm change in the management of metastatic renal cell carcinoma (mRCC). Prospective trials have focused on ICI treatment in the first or second line. click here The aim of this analysis is to evaluate the benefit of ICI across different treatment lines.
This is a single-center retrospective study that included mRCC patients who received ICIs in various treatment lines. Objective response rates (ORR), progression-free survival (PFS) and overall survival (OS) were evaluated.
Ninety-four patients were eligible for full evaluation. Patients were classified as International mRCC Database Consortium (IMDC) risk group categorization as good, intermediate and poor risk in 26.8%, 61.6% and 14.8% of cases, respectively. They were treated with ICI monotherapy, dual ICI therapy and ICI+ tyrosine kinase inhibitor in 59%, 20% and 21% of cases, respectively. ORR, median PFS and OS for the entire cohort was 39.4%, 9.67 months and 23.6 months (95% CI 13.3-33.9 months), respectively. The ORR by treatment line was 33% in first, 40.4% in the second, 35% in the third and 43.5% in the fourth line and beyond. Median PFS by treatment line was 8.6, 10.3, 7.9 and 7.23 months, respectively. The median OS was not reached in first-line treatment and was 26.2, 18.1 and 20.7 months in the second, third and fourth line and beyond, respectively.
ICIs or ICI combinations are active in all treatment lines and should also be offered in heavily pretreated patients. Patient selection based on tumor and patient factors allows for maximal benefit from ICI-based therapies.
ICIs or ICI combinations are active in all treatment lines and should also be offered in heavily pretreated patients. Patient selection based on tumor and patient factors allows for maximal benefit from ICI-based therapies.The gut-brain axis plays a critical role in the maintenance of the gastrointestinal tract homeostasis. Several enteric pathogens have developed strategies to sense neurochemical molecules to regulate their virulence in the gut. Additionally, there is growing evidence that gut dysbiosis can strongly affect host brain responses. Here we review different mechanisms that have been proposed to mediate gut-brain axis communication using Citrobacter rodentium, a natural murine enteric pathogen and one of the most widely used small animal models for studying host-microbe interactions. We highlight studies that have identified-specific pathways used by C. rodentium to sense host neurochemicals during colonization as well as behavioral responses and brain pathologies affected by pathogen colonization of the gut.
PD-L1 expression on tumor cells (TCs) or immune cells (ICs) may be used as a prognostic marker for survival in patients with NSCLC. We characterized PD-L1 expression on TCs or ICs in a patient cohort with NSCLC to determine associations between PD-L1 expression and overall survival (OS), according to EGFR and KRAS mutation status.
Danish patients aged >18 years diagnosed with NSCLC before 2014 on first- (N = 491), second- (N = 368), or third-line (N = 498) therapy were included. Data were extracted from population-based medical registries. Tumor samples from pathology archives were tested for biomarkers. High PD-L1 expression was defined as expression on ≥25 % of TCs or ICs based on first diagnostic biopsy or surgical resection. KRAS and EGFR mutation status were tested using PCR-based assays. Cox regression analysis was used to compute adjusted HRs and associated 95 % CIs.
PD-L1 TC and IC ≥ 25 % were observed in 24.3 %-31.0 % and 11.7-14.7 % of patients, respectively. EGFR and KRAS mutations were detected in 4.7 %-8.8 % and 26.5 %-30.7 % of patients, respectively. PD-L1 TC ≥ 25 % was not associated with survival advantage in first- (HR = 0.96, 95 % CI 0.75-1.22), second- (1.08, 0.81-1.42), or third-line (0.94, 0.74-1.20) therapy. PD-L1 IC ≥ 25 % was associated with survival advantage in second-line (HR = 0.56, 95 % CI 0.36-0.86) and third-line (0.69, 0.49-0.97) but not first-line (1.00, 0.70-1.41) therapy.
No association was observed between PD-L1 TC ≥ 25 % and OS in any therapy line. PD-L1 IC ≥ 25 % may confer survival benefit among some patients who reach second-line therapy.
No association was observed between PD-L1 TC ≥ 25 % and OS in any therapy line. PD-L1 IC ≥ 25 % may confer survival benefit among some patients who reach second-line therapy.