Concurrent chemoradiotherapy with cisplatin + S-1 versus cisplatin + other third-generation agents for locally advanced non-small-cell lung cancer: a meta-analysis of individual participant data

Background For decades, concurrent chemo-radiotherapy with cisplatin-based regimen has been a standard therapy for locally advanced stage III non-small-cell lung cancer (NSCLC). We conducted individual-participant-data (IPD) meta-analyses to compare S-1/cisplatin versus other third-generation anti-cancer medications plus cisplatin regimens with the goal of determining whether or not S-1/cisplatin was the ideal choice for treatment accompanied by radiotherapy (RT). Methods A thorough search was performed using multiple electronic databases. We integrated the IPD of each trial and analyzed the resulting meta-database. The primary endpoint was the overall survival (OS), and the secondary endpoints included the progression-free survival (PFS), objective response rate (ORR), toxicities, and treatment delivery. Subgroup analyses were conducted based on baseline characteristics. Statistical analyses were stratified by trials. Results Three randomized control trials (WJOG5008L study, SPECTRA study, and TORG1018 study) were found. Of the 316 patients enrolled in those studies, 159 received S-1/cisplatin (SP), and 157 were assigned to other combination chemotherapy. The median OS for the SP arm was 48.2 months, and that of the non-SP arm was 42.4 months. The combined hazard ratio (HR) for the OS was 0.895 (95% confidence interval [CI] 0.638–1.256), and no heterogeneity was noted among the trials (test for heterogeneity, p = 0.87; I2 = 0). The median PFS for the SP and non-SP arms was 12.8 and 14.0 months, respectively. The corresponding HR for the PFS was 1.022 (95% CI 0.776–1.347), and there was evidence of moderate heterogeneity among the trials (test for heterogeneity, p = 0.16; I2 = 0.46). The ORRs were 69.7% (95% CI 62.1–76.7%) and 70.9% (95% CI 63.7–78.1%) in the SP and non-SP arms, respectively. The toxicity profile showed that SP caused significantly fewer instances of grade 3–4 leukopenia and neutropenia than non-SP regimens. Conclusion No marked differences were detected in the OS, PFS, or ORR between the SP and non-SP arms. SP had significantly less myelosuppression and better treatment compliance as a chemotherapy regimen for concurrent chemoradiation in locally advanced NSCLC than non-SP regimens.

Cardiovascular disease protein biomarkers are associated with kidney function: the Framingham Heart Study

Background. Biomarkers common to chronic kidney disease (CKD) and cardiovascular disease (CVD) may reflect early impairments underlying both diseases. Methods. We evaluated associations of 71 CVD-related plasma proteins measured in 2,873 Framingham Heart Study (FHS) Offspring cohort participants with cross-sectional continuous eGFR and with longitudinal change in eGFR from baseline to follow-up (ΔeGFR). We also evaluated the associations of the 71 CVD proteins with the following dichotomous secondary outcomes: prevalent CKD stage ≥3(cross-sectional), new-onset CKD stage ≥3 (longitudinal), and rapid decline in eGFR (longitudinal). Proteins significantly associated with eGFR and ΔeGFR were subsequently validated in 3,951 FHS Third Generation cohort participants and were tested using Mendelian randomization (MR) analysis to infer putatively causal relations between plasma protein biomarkers and kidney function. Results. In cross-sectional analysis, 37 protein biomarkers were significantly associated with eGFR at FDR<0.05 in the FHS Offspring cohort and 20 of these validated in the FHS Third Generation cohort at p<0.05/37. In longitudinal analysis, 27 protein biomarkers were significantly associated with ΔeGFR at FDR<0.05 and 12 of these were validated in the FHS Third Generation cohort at p<0.05/27. Additionally, 35 protein biomarkers were significantly associated with prevalent CKD, five were significantly associated with new-onset CKD, and 17 were significantly associated with rapid decline in eGFR. MR suggested putatively causal relations of melanoma cell adhesion molecule (MCAM; -0.011±0.003 mL/min/1.73m2, p=5.11E-5) and epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1; -0.006±0.002 mL/min/1.73m2, p=0.0001) concentration with eGFR. Discussion/Conclusions: Eight protein biomarkers were consistently associated with eGFR in cross-sectional and longitudinal analysis in both cohorts and may capture early kidney impairment; others were implicated in association and causal inference analyses. A subset of CVD protein biomarkers may contribute causally to the pathogenesis of kidney impairment and should be studied as targets for CKD treatment and early prevention.

Size-tunable fluorescent dendrimersomes via aggregation-induced emission

Tetraphenylethylene-functionalized amphiphilic Janus dendrimers of up to third generation are synthesized. Their self-assembly has been studied under kinetic and thermodynamic control. By varying the dendrimer generation number and the self-assembly...

Effects of enrichmemt planting with native tree species on bacterial community structure and potential impact on Eucalyptus plantations in southern China

Multi-generational planting of Eucalyptus species degrades soil quality but the introduction of legumes can improve soil fertility and microbial diversity. However, the effects of introducing non-legume native tree species on soil nutrients and bacterial community structure remain poorly understood. This study investigated the impacts of the conversion of third generation monoculture Eucalyptus plantations to mixed systems including Eucalyptus urograndis with Cinnamomum camphora (EC) and E. urograndis with Castanopsis hystrix (EH), on soil chemical and biochemical properties and bacterial community structure, diversity and functions. First generation E. urophylla plantations were the control. Results show that planting the third generation Eucalyptus led to a significant decrease in pH, organic matter, nutrient content, enzyme activities (invertin, acid phosphataes, and urease), and bacterial α-diversity compare to the controls. However, the mixed planting showed significant improvement in soil chemical and biochemical attributes and bacterial α-diversity, although the E. urograndis and C. hystrix planting had no improvement. Chloroflexi (oligotrophic bacteria) were significantly enriched in third generation Eucalyptus and Eucalyptus + C. hystrix, while proteobacteria increased significantly in the E. urograndis with C. camphora plantings. The relative abundance of multiple metabolic pathways increased significantly in the third generation Eucalyptus plantations whereas membrane transport-related genes were enriched in soils of the mixed systems. The changes in bacterial community structures in the two mixed systems were driven by diversity, organic matter and acid phosphatase, while bacterial functions were affected by invertase, $${\mathrm{NO}}_{3}^{-}$$ NO 3 - -N, diversity and urease. These results suggest that the transformation of successive monoculture Eucalyptus plantations into mixed plantations reduces the depletion of soil nutrients and enhances the ecological function of soil microorganisms.