Background
Muscle wasting is prevalent in cancer patients, and early recognition of this phenomenon is important for risk stratification. Recent studies have suggested that the creatinine–cystatin C ...ratio may correlate with muscle mass in several patient populations. The association between creatinine–cystatin C ratio and survival was assessed in cancer patients.
Methods
A total of 3060 patients who were evaluated for serum creatinine and cystatin C levels at the time of cancer diagnosis were included. The primary outcome was 6‐month mortality. The 1‐year mortality, and length of intensive care unit (ICU) and hospital stay were also evaluated.
Results
The mean age was 61.6 ± 13.5 years, and 1409 patients (46.0%) were female. The median creatinine and cystatin C levels were 0.9 (interquartile range IQR, 0.6–1.3) mg/dL and 1.0 (IQR, 0.8–1.5) mg/L, respectively, with a creatinine–cystatin C ratio range of 0.12–12.54. In the Cox proportional hazards analysis, an increase in the creatinine–cystatin C ratio was associated with a significant decrease in the 6‐month mortality (per 1 creatinine–cystatin C ratio, hazard ratio HR 0.35; 95% confidence interval CI, 0.28–0.44). When stratified into quartiles, the risk of 6‐month mortality was significantly lower in the highest quartile (HR 0.30; 95% CI, 0.24–0.37) than in the lowest quartile. Analysis of 1‐year mortality outcomes revealed similar findings. These associations were independent of confounding factors. The highest quartile was also associated with shorter lengths of ICU and hospital stay (both P < 0.001).
Conclusions
The creatinine–cystatin C ratio at the time of cancer diagnosis significantly associates with survival and hospitalization in cancer patients.
Highly transparent and nanostructured nickel oxide (NiO) films through pulsed laser deposition are introduced for efficient CH3NH3PbI3 perovskite solar cells. The (111)‐oriented nanostructured NiO ...film plays a key role in extracting holes and preventing electron leakage as hole transporting material. The champion device exhibits a power conversion efficiency of 17.3% with a very high fill factor of 0.813.
The formation of a dense and uniform thin layer on the substrates is crucial for the fabrication of high-performance perovskite solar cells (PSCs) containing formamidinium with multiple cations and ...mixed halide anions. The concentration of defect states, which reduce a cell’s performance by decreasing the open-circuit voltage and short-circuit current density, needs to be as low as possible. We show that the introduction of additional iodide ions into the organic cation solution, which are used to form the perovskite layers through an intramolecular exchanging process, decreases the concentration of deep-level defects. The defect-engineered thin perovskite layers enable the fabrication of PSCs with a certified power conversion efficiency of 22.1% in small cells and 19.7% in 1-square-centimeter cells.
To fabricate efficient formamidinium tin iodide (FASnI3) perovskite solar cells (PSCs), it is essential to deposit uniform and dense perovskite layers and reduce Sn4+ content. Here we used ...solvent-engineering and nonsolvent dripping process with SnF2 as an inhibitor of Sn4+. However, excess SnF2 induces phase separation on the surface of the perovskite film. In this work, we report the homogeneous dispersion of SnF2 via the formation of the SnF2–pyrazine complex. Consequently, we fabricated FASnI3 PSCs with high reproducibility, achieving a high power conversion efficiency of 4.8%. Furthermore, the encapsulated device showed a stable performance for over 100 days, maintaining 98% of its initial efficiency.
While immunotherapy combined with chemotherapy (Chemo-IO) is generally recognized for providing superior outcomes compared to monotherapy (mono-IO), it is associated with a higher incidence of ...treatment-related adverse events (TRAEs), which may lead to treatment discontinuation. In this study, we compared the rates of treatment discontinuation between mono-IO and Chemo-IO as first-line treatments for various solid tumors.
We systematically reviewed clinical trials from databases (PubMed, Embase, Cochrane Library, and an additional source) published from January 1, 2018, to July 10, 2023. We included phase III randomized controlled trials (RCTs) that utilized immunotherapy agents in at least one arm as first-line treatments for a variety of solid tumors. Data extraction followed the Preferred Reporting Items for Systematic Reviews (PRISMA) extension statement for network meta-analysis. A random effects model was used for the network meta-analysis, with the risk of bias assessed using the Cochrane risk-of-bias tool II. The primary outcomes encompassed treatment discontinuation rates due to TRAEs among patients who underwent immunotherapy, either alone or combined with chemotherapy, for various solid tumors. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated to compare between treatment groups.
From 29 RCTs, a total of 21,677 patients and 5 types of treatment were analyzed. Compared to mono-IO, Chemo-IO showed a significantly higher rate of discontinuation due to TRAEs (RR 2.68, 95% CI 1.98-3.63). Subgroup analysis for non-small cell lung cancer (NSCLC) patients also exhibited a greater risk of discontinuation due to TRAEs with Chemo-IO compared to mono-IO (RR 2.93, 95% CI 1.67-5.14). Additional analyses evaluating discontinuation rates due to either treatment emergent adverse events (TEAEs) or AEs regardless of causality (any AEs) consistently revealed an elevated risk associated with Chemo-IO.
Chemo-IO was associated with an elevated risk of treatment discontinuation not only due to TRAEs but also any AEs or TEAEs. Given that the treatment duration can impact clinical outcomes, a subset of patients might benefit more from mono-IO than combination therapy. Further research is imperative to identify and characterize this subset.
Accumulating evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes various neurological symptoms in patients with coronavirus disease 2019 (COVID-19). ...The most dominant immune cells in the brain are microglia. Yet, the relationship between neurological manifestations, neuroinflammation, and host immune response of microglia to SARS-CoV-2 has not been well characterized. Here, we reported that SARS-CoV-2 can directly infect human microglia, eliciting M1-like proinflammatory responses, followed by cytopathic effects. Specifically, SARS-CoV-2 infected human microglial clone 3 (HMC3), leading to inflammatory activation and cell death. RNA sequencing (RNA-seq) analysis also revealed that endoplasmic reticulum (ER) stress and immune responses were induced in the early, and apoptotic processes in the late phases of viral infection. SARS-CoV-2-infected HMC3 showed the M1 phenotype and produced proinflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor α (TNF-α), but not the anti-inflammatory cytokine IL-10. After this proinflammatory activation, SARS-CoV-2 infection promoted both intrinsic and extrinsic death receptor-mediated apoptosis in HMC3. Using K18-hACE2 transgenic mice, murine microglia were also infected by intranasal inoculation of SARS-CoV-2. This infection induced the acute production of proinflammatory microglial IL-6 and TNF-α and provoked a chronic loss of microglia. Our findings suggest that microglia are potential mediators of SARS-CoV-2-induced neurological problems and, consequently, can be targets of therapeutic strategies against neurological diseases in patients with COVID-19.
Recent studies reported neurological and cognitive sequelae in patients with COVID-19 months after the viral infection with several symptoms, including ageusia, anosmia, asthenia, headache, and brain fog. Our conclusions raise awareness of COVID-19-related microglia-mediated neurological disorders to develop treatment strategies for the affected patients. We also indicated that HMC3 was a novel human cell line susceptible to SARS-CoV-2 infection that exhibited cytopathic effects, which could be further used to investigate cellular and molecular mechanisms of neurological manifestations of patients with COVID-19.
Accurate estimation of sodium intake is a key requirement for evaluating the efficacy of interventional strategies to reduce salt intake. The effectiveness of a smartphone application in measuring ...dietary sodium intake was assessed. This study included 46 participants who consented to register in Noom’s food-logging program. All participants were followed up for six months from the day of enrollment. The mean age of the participants was 40.2 ± 12.3 years, and 22 (48%) participants were male. The average number of times/weeks the meals were logged was 16.2 ± 10.3. At baseline, the mean 24-h urine sodium was 124.3 mmol/24 h. The mean sodium intake measured by the smartphone application and calculated using the 24-h urine sodium was 2020.9 mg/24 h and 2857.6 mg/24 h, respectively. During the second visit, the mean 24-h urine sodium was 117.4 mmol/24 h. The mean sodium intake measured by the smartphone application and calculated using the 24-h urine sodium was 1456.0 mg/24 h and 2698.3 mg/24 h, respectively. Sodium intake measured using the smartphone application positively correlated with that calculated using the 24-h urine sodium at baseline (r = 0.464; p < 0.001) and follow-up (r = 0.334; p= 0.023). Dietary sodium intake measured using a smartphone application correlated well with that estimated using 24-h urine sodium level.
J. Neurochem. (2010) 115, 1668-1680. ABSTRACT: Microglia activation plays a pivotal role in neurodegenerative diseases, and thus controlling microglial activation has been suggested as a promising ...therapeutic strategy for neurodegenerative diseases. In the present study, we showed that ginsenoside Rh1 inhibited inducible nitric oxide synthase, cyclooxygenase-2, and pro-inflammatory cytokine expression in lipopolysaccharide (LPS)-stimulated microglia, while Rh1 increased anti-inflammatory IL-10 and hemeoxygenase-1 (HO-1) expression. Suppression of microglial activation by Rh1 was also observed in the mouse brain following treatment with LPS. Subsequent mechanistic studies revealed that Rh1 inhibited LPS-induced MAPK phosphorylation and nuclear factor-κB (NF-κB)-mediated transcription without affecting NF-κB DNA binding. As the increase of pCREB (cAMP responsive element-binding protein) is known to result in suppression of NF-κB-mediated transcription, we examined whether Rh1 increased pCREB levels. As expected, Rh1 increased pCREB, which was shown to be related to the anti-inflammatory effect of Rh1 because pre-treatment with protein kinase A inhibitors attenuated the Rh1-mediated inhibition of nitric oxide production and the up-regulation of IL-10 and HO-1. Furthermore, treatment of HO-1 shRNA attenuated Rh1-mediated inhibition of nitric oxide and reactive oxygen species production. Through this study, we have demonstrated that protein kinase A and its downstream effector, HO-1, play a critical role in the anti-inflammatory mechanism of Rh1 by modulating pro- and anti-inflammatory molecules in activated microglia.
