BACKGROUND
Epidemiologic evidence reporting the role of frailty in survival among older adults with a prior cancer diagnosis is limited.
METHODS
A total of 2050 older adults (≥60 years old) surviving ...for at least 1 year after a cancer diagnosis and 9474 older adults without a cancer history from the National Health and Nutrition Examination Survey (1999‐2014) were included for analysis. The exposure variable, a 45‐item frailty index (FI), was categorized on the basis of validated cutoffs (FI ≤ 0.10 fit, 0.10 < FI ≤ 0.21 prefrail, and FI > 0.21 frail). All‐cause mortality was ascertained via the National Death Index. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) and 95% confidence interval (CIs) for the FI, and this was followed by restricted cubic splines depicting dose‐response curves.
RESULTS
For older cancer survivors, the mean age at the baseline was 72.6 years (SD, 7.1 years); 5.9% were fit, 38.2% were prefrail, and 55.9% were frail. Older adults without a cancer history were slightly younger (mean age, 70.0 years) and less frail (47.9% were frail). At each level of the FI, cancer survivors (1.9 per 100 person‐years for FI ≤ 0.10, 3.4 per 100 person‐years for 0.10 < FI ≤ 0.21, and 7.5 per 100 person‐years for FI > 0.21) had higher mortality than their cancer‐free counterparts (1.4 per 100 person‐years for FI ≤ 0.10, 2.4 per 100 person‐years for 0.10 < FI ≤ 0.21, and 5.4 per 100 person‐years for FI > 0.21). The multivariable model suggested a positive association between the FI and all‐cause mortality for survivors (aHR for FI > 0.21 vs FI ≤ 0.10, 2.80; 95% CI, 1.73‐4.53) and participants without a cancer history (aHR for FI > 0.21 vs FI ≤ 0.10, 2.75; 95% CI, 2.29‐3.32). Restricted cubic splines indicated that all‐cause mortality risk increased with the FI in a monotonic pattern.
CONCLUSIONS
Frailty is associated with a higher risk of death in older cancer survivors and the elderly without a cancer history.;
Older cancer survivors will be at higher risk for mortality if they are living with substantial burdens of frailty. Understanding the frailty status is informative for developing long‐term interventions for promoting the health of older cancer survivors.
Although geological parameters are known to affect the penetration rate (PR) of a tunnel boring machine (TBM), their relation to the probability of TBM PR has been rarely considered. In this article, ...a probabilistic evaluation model of TBM PR was proposed. Firstly, the marginal distributions of five geological parameters were confirmed by mathematical statistics. Then Copula theory was used to construct a five-dimensional joint probability distribution of the geological parameters in line with the marginal distributions. Next, the collected geological parameters were utilized to train a three-layer backpropagation neural network (BPNN) model for predicting the TBM PR. Finally, A Copula—BPNN coupled model was built for estimating the probability of TBM PR, and a Weibull distribution function of the predicted TBM PR was obtained through Monte Carlo simulation. Considering the uncertainty, correlation, and multi-factor influence, this paper realized the probabilistic evaluation of TBM PR. Discussion on the parameter uncertainty and independence shows that the variability of the geological parameters is necessary in TBM PR prediction. Quantitative probability estimation of the TBM PR can help with optimizing the driving parameters under different geological conditions to improve construction efficiency.
Carbon nanotube (CNT) films, as two-dimensional assemblies of CNT, have attracted much interest and are widely used in many fields due to their unique structures and excellent performance. However, ...the preparation of high-strength and multiply recyclable CNT films remains a challenge in the sustainable development of traditional disposable CNT materials with permanent cross-links. Here, we prepare end-thiol hyperbranched polymers (BTHP-n, n = 6, 12, 24) to modify CNT film via thiol–ene click reaction. BTHP not only increases simultaneously the tensile strength, electrical conductivity, modulus, toughness by 1690, 257, 1867, and 2316%, respectively, but also remarkably improves the wettability and recyclability of CNT film. The enhancement mechanism is the combined effect of cross-linking structure between CNTs, rigid benzene and hexahydro-s-triazine rings, hyperbranched topological structure, and hydrogen bond interactions between polymer molecules. The detailed analysis of the degradation of the polymer in the modified CNT film (BTCNT) is attributed to the cleavage of the C–N and amide bonds. The close-loop recycled CNT film (100%) and monomer (72.15%) are reused to realize the cycles of BTCNT, which has good cycle performance with above 90 and 87% maintenance rate in tensile strength and electrical conductivity, respectively. This paper is hopeful to bring an applicable approach to solve the difficulty of recycling CNT films in traditional materials with permanent cross-links, while promoting the widespread application and sustainable development of CNT films in the field of flexible wearable devices.
Fibrolamellar hepatocellular carcinoma (FLC) is a rare and often lethal liver cancer with no proven effective systemic therapy. Inhibition of the antiapoptotic protein BCL-XL was found to synergize ...with a variety of systemic therapies in vitro using cells dissociated from patient-derived xenografts (PDX) of FLC or cells dissociated directly from surgical patient resections. As BCL-XL is physiologically expressed in platelets, prior efforts to leverage this vulnerability in other cancers have been hampered by severe thrombocytopenia. To overcome this toxicity, we treated FLC models with DT2216, a proteolysis targeting chimera (PROTAC) that directs BCL-XL for degradation via the von Hippel-Lindau (VHL) E3 ligase, which is minimally expressed in platelets. The combination of irinotecan and DT2216 in vitro on cells directly acquired from patients or in vivo using several xenografts derived from patients with FLC demonstrated remarkable synergy and at clinically achievable doses not associated with significant thrombocytopenia.
Land subsidence has become a widespread engineering geological problem due to human-induced causes such as the withdrawal of groundwater and the extraction of coal and ores. There is a relative lack ...of research on land subsidence under the coupling effect of groundwater and coal mining. This paper uses numerical and theoretical computational models to study land subsidence under the coupling effect of groundwater and coal mining. The study area is a coal mine in Jining City from 2000 to 2020. Numerical results show that groundwater withdrawal induces substantial land subsidence over a long period and that the rate of land subsidence decreases over time. The maximum land subsidence was 128 mm in 2010. Due to coal extraction (2015), the area induces significant land subsidence in the short term. The maximum land subsidence in 2016 was 305 mm. Based on the stochastic medium theory, this paper establishes a theoretical model for land subsidence under the coupling effect of groundwater and coal mining. And based on the numerical results, the theoretical subsidence equation applicable to the area is calculated. By comparing the theoretical results with the actual measurement results, the analysis proves that the equation can better calculate the land subsidence of the model.
This study investigated the effects of thermal pretreatment and ex-situ grinding on the production of bio-oil and biochar from the pyrolysis of mallee wood cylinders in a fluidised-bed reactor. The ...wood cylinders were firstly pretreated at 150–380°C and were then crushed into small particles before further pyrolysis at 500°C. Thermal pretreatment alone for wood cylinders could not promote the bio-oil yield. Combined thermal pretreatment at low temperatures and subsequent grinding facilitated the formation of bio-oil and minimised the formation of biochar. This is because the thermal pretreatment and grinding partially destroyed the cell wall structure and improved the mass transfer of volatiles exiting from the particles during the subsequent pyrolysis. However, if the pretreatment temperature was above 260°C, the biochar yields increased due to the cross-linking and charring reactions. These charring reactions compromised the beneficial effects of grinding, leading to decreases in the formation of bio-oil. The balance between thermal pretreatment and grinding needed to be delicately managed to maximise the formation of bio-oil. The pretreatment temperature would significantly affect the composition of bio-oil from the ex-situ grinding pyrolysis. The controlled pretreatment temperature could somewhat “activate” lignin or cause cross-linked bonds in biomass which was responsible for the formation of aromatics.
•Effects of thermal treatment and grinding on pyrolysis of wood cylinders were studied.•The bio-oil yield was not promoted by the thermal treatment of wood cylinders.•Low temperature treatment with ex-situ grinding greatly promoted bio-oil formation.•High temperature treatment compromised beneficial effects of grinding on bio-oil yield.•Balance between pretreatment and grinding was responsible for the bio-oil formation.
Beclin 1 is a well-established core mammalian autophagy protein that is embryonically indispensable and has been presumed to suppress oncogenesis via an autophagy-mediated mechanism. Here, we show ...that Beclin 1 is a prenatal primary cytoplasmic protein but rapidly relocated into the nucleus during postnatal development in mice. Surprisingly, deletion of beclin1 in in vitro human cells did not block an autophagy response, but attenuated the expression of several DNA double-strand break (DSB) repair proteins and formation of repair complexes, and reduced an ability to repair DNA in the cells exposed to ionizing radiation (IR). Overexpressing Beclin 1 improved the repair of IR-induced DSB, but did not restore an autophagy response in cells lacking autophagy gene Atg7, suggesting that Beclin 1 may regulate DSB repair independent of autophagy in the cells exposed to IR. Indeed, we found that Beclin 1 could directly interact with DNA topoisomerase IIβ and was recruited to the DSB sites by the interaction. These findings reveal a novel function of Beclin 1 in regulation of DNA damage repair independent of its role in autophagy particularly when the cells are under radiation insult.
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