Tyrosine kinases are implicated in tumorigenesis and progression, and have emerged as major targets for drug discovery. Tyrosine kinase inhibitors (TKIs) inhibit corresponding kinases from ...phosphorylating tyrosine residues of their substrates and then block the activation of downstream signaling pathways. Over the past 20 years, multiple robust and well-tolerated TKIs with single or multiple targets including EGFR, ALK, ROS1, HER2, NTRK, VEGFR, RET, MET, MEK, FGFR, PDGFR, and KIT have been developed, contributing to the realization of precision cancer medicine based on individual patient's genetic alteration features. TKIs have dramatically improved patients' survival and quality of life, and shifted treatment paradigm of various solid tumors. In this article, we summarized the developing history of TKIs for treatment of solid tumors, aiming to provide up-to-date evidence for clinical decision-making and insight for future studies.
To optimize the performance of the soft actuator, numerical experiments and regression analysis of the multi-structure parameter are presented based on the numerical calculation method. Firstly, ...numerical experiments and regression analysis were performed on the parameters of different driving channel shapes, including equilateral triangle, square, regular pentagon, regular hexagon, and circle, to determine the driving performance under different channel cross-sections. Secondly, numerical experiments and regression analysis were conducted on the parameters of fiber winding diameter and winding angle of the soft actuator, and qualitative analysis was performed on the failure states of the numerical calculations. Lastly, numerical experiments and regression analysis were carried out on the parameters of wall thickness and driving channel length of the soft actuator to determine the influence of these parameters on the driving performance. Through the numerical experiments and regression analysis, this study provides a necessary theoretical foundation for the optimization design of soft actuator, effectively improving the development efficiency and dynamic performance of soft actuators.
Extensive-stage small cell lung cancer (ES-SCLC) is an aggressive disease with poor survival, and platinum-etoposide chemotherapy is indicated as the mainstay of treatment. In this study, we compared ...the efficacy and safety between the cisplatin plus etoposide (EP) and carboplatin plus etoposide (EC) regimens.
A total of 1305 patients with previously untreated ES-SCLC were included in this study. Data from five trials were collected from the public database Project Data Sphere. Survival analysis and adverse events (AEs) analysis were conducted.
Of the 1305 patients, 800 received the EC regimen whereas 505 received the EP regimen as their front-line treatment. Overall, the median progression-free survival (PFS) and the median overall survival (OS) were 172 and 289 days, respectively. The EP and EC treatment groups did not have significantly different PFS or OS. After adjusting for age, sex, body mass index (BMI) and Eastern Cooperative Oncology Group (ECOG) performance status (PS), the EP regimen was independently associated with better PFS (hazard ratio HR = 0.76, 95% CI = 0.63-0.92, p = 0.0041) and OS (HR = 0.79, 95% CI = 0.64-0.97, p = 0.0220) among patients who were overweight and obese (BMI ≥ 25 kg/m
). In the safety analysis, patients who received the EC treatment experienced significantly more grade ≥ 3 AEs (n = 599, 74.9%) than those who received the EP treatment (n = 337, 66.7%; p = 0.002). Furthermore, the EC regimen was associated with a higher risk of grade 3-4 neutropaenia (p = 0.001), thrombocytopaenia (p < 0.001) and hyponatraemia (p = 0.036), whereas the EP regimen was associated with a higher risk of grade 3-4 vomiting (p = 0.021).
In summary, this study presented the efficacy and safety of the EC and EP regimens in patients with ES-SCLC in the first-line setting. Patients who are overweight and obese benefit more from the EP regimen than EC regimen. Approaches to define the optimal chemotherapy regimen in different BMI subgroups are needed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•We assessed the performance of low energy dwellings focusing on the post-construction phase of the building process.•The results of the systems and fabric performance tests showed that the dwellings ...perform closely to expectations.•The evaluation of the construction and monitoring processes suggested that the achievement of the targets was not an easy task.•The findings from this study helped to identify issues that could potentially cause problems in the construction process.
Recent studies show a mismatch between expected and actual performance in low energy buildings. The differences have been attributed to occupant behaviour and poor quality of the construction. Monitoring building performance during and after construction can ensure that systems and fabric perform as designed. This study sought to evaluate the delivery process of low energy dwellings including the energy and environmental monitoring processes and the performance of the building itself. The study focused on the post-construction phase of the building process and consists of a construction review, as well as fabric and system performance tests. The results of the tests show that the dwellings perform close to design expectations. However, the performance monitoring highlighted issues that could have undermined their performance. The results of the study stress the utility of monitoring activities in low energy buildings, and specifically the need for monitoring low carbon technologies. Recommendations are given to improve the efficiency of monitoring processes in low energy dwellings.
Chlorophyll is an important indicator for monitoring crop growth and is vital for agricultural management. Therefore, rapid and accurate estimation of chlorophyll content is important for decision ...support in precision agriculture to accurately monitor the SPAD (Soil and Plant Analyzer Development) values of winter wheat. This study used winter wheat to obtain canopy reflectance based on UAV hyperspectral data and to calculate different vegetation indices and red-edge parameters. The best-performing vegetation indices and red-edge parameters were selected by Pearson correlation analysis and multiple stepwise regression (MSR). SPAD values were estimated using a combination of vegetation indices, vegetation indices and red-edge parameters as model factors, two types of machine learning (ML), a support vector machine (SVM), and a backward propagation neural network (BPNN), and partial least squares regression (PLSR) for four growth stages of winter wheat, and validated using independent samples. The results show that for the same data source, the best vegetation indices or red-edge parameters for estimating SPAD values differed at different growth stages and that combining vegetation indices with red-edge parameters gave better estimates than using only vegetation indices as an input factor for estimating SPAD values. There is no significant difference between PLSR, SVM, and BPNN methods in estimating SPAD values, with better stability of the estimated models using machine learning methods. Different growth stages have a large impact on winter wheat SPAD values estimates, with the accuracy of the four growth stage models increasing in the following order: booting < heading < filling < flowering. This study shows that using a combination of vegetation indices and red-edge parameters can improve SPAD values estimates compared to using vegetation indices alone. In the future, the choice of appropriate factors and methods will need to be considered when constructing models to estimate crop SPAD values.
The estimation of anthocyanin (Anth) content is very important for observing the physiological state of plants under environmental stress. The objective of this study was to estimate the Anth of ...maize leaves at different growth stages based on remote sensing methods. In this study, the hyperspectral reflectance and the corresponding Anth of maize leaves were measured at the critical growth stages of nodulation, tasseling, lactation, and finishing of maize. First-order differential spectra (FD) were derived from the original spectra (OS). First, the spectral parameters highly correlated with Anth were selected. A total of two sensitive bands (Rλ), five classical vegetation indices (VIS), and six optimized vegetation indices (VIC) were selected from the original and first-order spectra. Then, univariate regression models for Anth estimation (Anth-UR models) and multivariate regression models for estimating anthocyanins (Anth-MR models) were constructed based on these parameters at different growth stages of maize. It was shown that the first-order spectral conversion could effectively improve the correlation between Rλ, VIC, and Anth, and VIC are usually more sensitive to Anth than VIS. In addition, the overall performance of Anth-MR models was better than that of Anth-UR models. Among them, Anth-MR models with the combination of three types of spectral parameters (FD(Rλ) + OS_VIC + FD_VIC/VIS) as inputs had the best overall performance. Moreover, different growth stages had an impact on the Anth estimation models, with tasseling and lactation stages showing better results. The best-performing Anth-MR models for these two growth stages were as follows. For the tasseling stage, the best model was the FD(Rλ) + OS_VIC + VIS-based SVM model, with an R2 of 0.868, RMSE of 0.007, and RPD of 2.19. For the lactation stage, the best-performing model was the FD(Rλ) + OS_VIC + FD_VIC-based RF model, with an R2 of 0.797, RMSE of 0.007, and RPD of 2.24. These results will provide a scientific basis for better monitoring of Anth using remote sensing hyperspectral techniques.
Klebsiella pneumoniae is an opportunistic pathogen that frequently causes nosocomial urinary tract infection (UTI). The aim of this study was to investigate the prevalence of extended-spectrum ...β-lactamases (ESBL), plasmid-mediated quinolone resistance (PMQR) genes, in acquired AmpC (ac-AmpC) β‑lactamase‑producing K. pneumoniae isolates from patients with nosocomial UTI and to characterize the transmissibility of plasmids harbouring multiple resistance genes. From January 2017 to June 2018, we collected 46 ac-AmpC-producing K. pneumoniae isolates causing UTI from a tertiary care hospital in China. Antimicrobial susceptibility assays showed that non-susceptibility of all isolates to third-generation cephalosporin and fluoroquinolone was very high (>80%). Diverse types of ESBLs and PMQR genes, including bla
(n = 23), bla
(n = 1)
bla
(n = 2)
bla
(n = 4), bla
(n = 24)
bla
(n = 6)
bla
(n = 6)
bla
(n = 1) and bla
(n = 26)
as well as qnrA (n = 2), qnrB (n = 39) and qnrS (n = 2) genes were identified amongst AmpC-producing K. pneumoniae isolates. The bla
qnrB and several ESBLs genes from six strains harbouring multiple AmpC (at least two ampC) were co-transferrable to recipients via conjugation or electroporation, with IncFIA, IncFIB and IncA/C being the dominant replicons. Conserved genetic context associated with the mobilization of bla
genes was detected. Forty-six isolates were categorized into 25 enterobacterial repetitive intergenic consensus (ERIC) types, and the 6 isolates harbouring multiple AmpC genes belonged to ST1 lineage. This work reports that the emergence of plasmids co-harbouring multiple resistance determinants and mediating the local prevalence in K. pneumoniae causing UTI in China.
The different life paths of the generation following immigration have become a matter of public discussion and scholarly research in the past decades in many migrant-receiving countries. These ...differences would be key points for the immigration decision made by first-generation immigrants. This paper adopts a new perspective to study the differences in task supplies and economic status between natives and two generations of immigrants to see their different life paths. This paper estimates differences in task supply and earnings between natives and immigrants in 1970 and 2015, which are the beginning and end of the fifth (and current) wave of immigration to Canada. Furthermore, using a three-fold Blinder-Oaxaca decomposition, I link the average weekly wage of workers to their task productivity, and try to find the effects of the returns to tasks as well as different task supplies on the average wage gap between natives and immigrants. Finally, I use ordered probit and logit models to demonstrate and measure the significant effects of immigrant status on an employee's labour market segment.
We aimed to explore the potential role of omega-3 (ω-3) fatty acids on acne vulgaris by modulating gut microbiota.
We randomly divided the untreated acne patients into two groups with or without ω-3 ...fatty acids intervention for 12 weeks. The Sprague Dawley (SD) rats with acne model were given isotretinoin, ω-3 fatty acids or their combination respectively. Then the colonic contents samples of the drug intervention SD rats were transferred to the pseudo sterile rats with acne model. The severity of the disease was assessed by the Global Acne Grading System (GAGS) score of the patients, and the swelling rate of auricle and the pathological section of the rat with acne model. The 16S rDNA gene sequencing was performed to detect the alteration of the gut microbiota.
ω-3 fatty acids could increase the diversity of the gut microbiota and regulate the flora structure positively both in the patients and rats, increase the abundance of butyric acid producing bacteria and GAGS score in the patients, and alleviate the inflammation and comedones of rats.
Supplementation of ω-3 fatty acids could alleviate the inflammation of acne vulgaris by increasing the abundance of butyric acid producing bacteria.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Increasing knowledge on the hallmark characteristics of cancer and tumor pharmacology has promoted the introduction of phytochemicals, such as traditional Chinese medicine (TCM) in cancer therapy, ...which modulate numerous molecular targets and exert anticancer activities. β-elemene, an active and non-toxic compound isolated from the Chinese medicinal herb Rhizoma Zedoariae, has been explored as a potent anti-cancer agent against multiple cancers in extensive clinical trials and experimental research in vivo and in vitro. β-elemene exerts therapeutic potential via modulation of core hallmark capabilities of cancer by suppressing proliferative signaling, such as MAPK and PI3K/Akt/mTOR pathway, inducing cell death, up-regulating growth suppressors, deactivating invasion and metastasis and interacting replicative immortality and attenuating angiogenesis. Recent studies have significantly improved our understanding of anti-cancer activities and underlying molecular mechanisms of this Chinese medicine. This review presents these novel findings regarding the unique properties of β-elemene as an agent for cancer treatment, with an emphasis on multi-targeting biological and molecular regulation.
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