Abstract only
e18144
Background: Many publications report under representation of minorities in certain subgroups, which may limit the generalizability of clinical trial (CT) results. This analysis, ...investigates and reports enrollment trends in CTs submitted between 2006-2017 in support of marketing applications for drugs indicated for the treatment of urothelial (UC) and renal cancer carcinoma (RCC), and compares them to incidence rates of these diseases by Surveillance, Epidemiology, and End Results (SEER) registry and the US census bureau. Methods: We identified all marketing applications for the treatment of UC and RCC that provided the primary evidence of safety and efficacy and aggregated the demographic data across trials and disease. Using these two pooled datasets, we compared the patient proportions enrolled in each of the race, sex and age categories to the corresponding rates in US cancer population estimated based on the corresponding incidence rates reported by SEER and the US census bureau using a Chi-squared test. Results: The pooled seven UC and 14 RCC CTs provided 2035 and 6757 patients respectively. The results are summarized below for the 939 (46%) UC and 1489 (22%) RCC patients enrolled in the US. Conclusions: Our findings indicate that majority of the patients were enrolled outside of the US. There were lower proportion of Black patients (4% vs 8%), older patients, age ≥ 75 years (30% vs 48%) and males (74% vs 80%) enrolled in UC population in the US. Higher proportions were observed in both White (89% vs 85%) and Asian (4% vs 2%) patients in UC and in White (90% vs 79%) patients in RCC.Table: see text
Two stage designs are widely used in clinical trials because of statistical efficiency and ethical considerations. When the second stage design setting is modified at the interim analysis based on ...the first stage data, dependencies between the first and second stage data are induced. These dependencies can lead to a complex asymptotic distribution, rather than a standard normal distribution, which complicates the parametric inference at the end of the study. In this research, random information measures are introduced for parametric inference in a two stage adaptive optimal design. Besides exploring the asymptotic properties with the random information measures theoretically, an extensive simulation study is conducted to compare the performance of different random information measures and the Fisher information measure. In addition, a two-stage adaptive enrichment design is proposed based on the bivariate model. The random information measures are applied in the analysis of the proposed design. This design is assessed in a simulation study, and works well under different scenarios. This study shows that to improve parametric inference following a two stage design, random information measures can be considered. Finally, several directions for future research are discussed.
A two-stage adaptive optimal design is an attractive option for increasing the efficiency of clinical trials. In these designs, based on interim data, the locally optimal dose is chosen for further ...exploration, which induces dependencies between data from the two stages. When the maximum likelihood estimator (MLE) is used under nonlinear regression models with independent normal errors in a pilot study where the first stage sample size is fixed, and the second stage sample size is large, the Fisher information fails to normalize the estimator adequately asymptotically, because of dependencies. In this situation, we present three alternative random information measures and show that they provide better normalization of the MLE asymptotically. The performance of random information measures is investigated in simulation studies, and the results suggest that the observed information performs best when the sample size is small.
Clay minerals can hinder the transport of various contaminants in soil and aquifer, but how clay minerals affect the transport of nanoparticles in aquifers has not been investigated in depth. In this ...paper, the transport of surfactants dispersed multi-walled carbon nanotubes（MWCNTs） in welldefined quartz sand and mixtures of quartz sand and clay minerals（kaolinite and montmorillonite） with varying ionic strengths was studied. Sodium dodecyl benzenesulfonate（SDBS） and octyl-phenolethoxylate（TX100） MWCNT suspensions can migrate through quartz sand easily, but the presence of less than 2% w/w clay minerals in quartz sand can significantly hinder the transport of MWCNT suspensions, especially at high ion strength（0.6 m M CaCl2）. The inhibition mechanism of clay minerals for surfactant-dispersed MWCNTs in porous media is the interception of MWCNTs. Kaolinite has stronger inhibition effect for MWCNTs transport than montmorillonite because more kaolinite can be retained in the quartz sand. Adsorption of surfactants by clay minerals does not affect the transport of MWCNTs significantly. This finding is important for the environmental assessment of MWCNT transport risks in soils and aquifers.
Among the multitudinous methodologies to steer on-surface reactions, less attention has been paid to the effect of externally introduced halogen atoms. Herein, highly selective trans-dehydrogenation ...coupling at the specific meta-C–H site of two poly(p-phenylene) molecules, p-quaterphenyl (Ph4) and p-quinquephenyl (Ph5), is achieved on Cu(111) by externally introduced bromine atoms. Scanning tunneling microscopy/spectroscopy experiments reveal that the formed molecular assembly structure at a stoichiometric ratio of 4:1 for Br to Ph4 or 5:1 for Br to Ph5 can efficiently promote the reactive collision probability to trigger the trans-coupling reaction at the meta-C–H site between two neighboring Ph4 or Ph5 molecules, leading to an increase in the coupling selectivity. Such Br atoms can also affect the electronic structure and adsorption stability of the reacting molecules. It is conceptually demonstrated that externally introduced halogen atoms, which can provide an adjustable halogen-to-precursor stoichiometry, can be employed to efficiently steer on-surface reactions.
Carbon nanotubes (CNTs), because of their wide application, will inevitably enter aquatic systems, but the fate and transport of their suspensions in the environment are largely unknown. Clay ...minerals are expected to interact with CNT suspensions, affecting their fate and bioavailability. This study investigated the influence of clay minerals (kaolinite and montmorillonite) on the stability of surfactant (SDBS, CTAB, and TX100) facilitated multiwalled CNT (MWCNT) suspensions. Adsorption of the surfactants by MWCNTs and clay minerals was also examined. This is a first study on the interaction between clay minerals and surfactant-CNT suspensions. Sorption of SDBS by clay minerals and MWCNTs followed the order MWCNTs ≫ montmorillonite ≈ kaolinite; but sorption of CTAB and TX100 followed the order montmorillonite > MWCNTs > kaolinite. For SDBS suspended MWCNTs, introduction of montmorillonite and kaolinite could not change their stability; for CTAB suspended MWCNTs, both montmorillonite and kaolinite greatly deposited the suspended MWCNTs; for TX100 suspended MWCNTs, montmorillonite could partially deposit the suspended MWCNTs, whereas kaolinite showed minimal effect. Two mechanisms of clay minerals affecting MWCNT suspensions are (1) removal of surfactants by clay minerals from solution and MWCNT surface and (2) bridging between clay mineral and MWCNTs by surfactant.
Polymers are essential components of modern-day materials and are widely used in various fields. The dielectric constant, a key physical parameter, plays a fundamental role in the light-, ...electricity-, and magnetism-related applications of polymers, such as dielectric and electrical insulation, battery and photovoltaic fabrication, sensing and electrical contact, and signal transmission and communication. Over the past few decades, numerous efforts have been devoted to engineering the intrinsic dielectric constant of polymers, particularly by tailoring the induced and orientational polarization modes and ferroelectric domain engineering. Investigations into these methods have guided the rational design and on-demand preparation of polymers with desired dielectric constants. This review article exhaustively summarizes the dielectric constant engineering of polymers from molecular to mesoscopic scales, with emphasis on application-driven design and on-demand polymer synthesis rooted in polymer chemistry principles. Additionally, it explores the key polymer applications that can benefit from dielectric constant regulation and outlines the future prospects of this field.
Abstract
Severe peripheral nerve injury leads to the irreparable disruption of nerve fibers. This leads to disruption of synapses with the designated muscle, which consequently go through progressive ...atrophy and damage of muscle function. The molecular mechanism that underlies the re-innervation process has yet to be evaluated using proteomics or transcriptomics. In the present study, multi-dimensional data were therefore integrated with transcriptome and proteome profiles in order to investigate the mechanism of re-innervation in muscles. Two simulated nerve injury muscle models in the rat tibial nerve were compared: the nerve was either cut (denervated, DN group) or crushed but with the nerve sheath intact (re-innervated, RN group). The control group had a preserved and intact tibial nerve. At 4 weeks, the RN group showed better tibial nerve function and recovery of muscle atrophy compared to the DN group. As the high expression of
Myh3, Postn, Col6a1 and Cfi
, the RN group demonstrated superior re-innervation as well. Both differentially expressed genes (DEGs) and proteins (DEPs) were enriched in the peroxisome proliferator-activated receptors (PPARs) signaling pathway, as well as the energy metabolism. This study provides basic information regarding DEGs and DEPs during re-innervation-induced muscle atrophy. Furthermore, the crucial genes and proteins can be detected as possible treatment targets in the future.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Accumulating data have revealed the pivotal function of tripartite motif protein 38 (TRIM38) in tumors. In view of this, this investigation aims to explore the function and potential mechanism of ...TRIM38 in non-small cell lung cancer (NSCLC). A xenotypic tumor model was established in vivo by subcutaneously injecting NSCLC cells (2 × 10
cells) in tail vein of each mouse. Relative expression of TRIM38 mRNA was detected via quantitative real-time polymerase chain reaction (qRT-PCR). For exploring the role of TRIM38 in vivo and in vitro, mice or NSCLC cells were divided into two groups: the vector group and the TRIM38 overexpression group. Also, protein expression levels of TRIM38, Vimentin, E-cadherin, and N-cadherin were determined using western blotting and immunohistochemistry staining. Tumor nodules of mouse lung tissues were assessed via performing H&E staining. Moreover, proliferation of NSCLC cells was evaluated through colony formation and CCK-8 assays. Further, migration and invasion of NSCLC cells were assessed through wound healing and transwell assays. Protein levels of pathway-related proteins including p-p65, p65, IκB, p-IκB, p-AMPK, AMPK, and NLRP3 were examined through western blotting analysis. Tumor lung tissues of mice and NSCLC cells showed low protein and mRNA expression of TRIM38. Functionally, up-regulation of TRIM38 reduced the number of tumor nodules and suppressed epithelial-to-mesenchymal transition (EMT) in lung tissues of mice. Furthermore, up-regulation of TRIM38 in NSCLC cells inhibited migration, invasion, EMT, and proliferation. With respect to the mechanism, in vivo experiments, the inhibitory effects of TRIM38 overexpression on tumor nodules, and EMT were reversed by AMPK inhibitor. In vitro experiments, TRIM38 overexpression caused down-regulation of p-IκB and p-p65 as well as up-regulation of p-AMPK. The inhibitory effects of TRIM38 overexpression on migration, proliferation, invasion, and EMT of NSCLC cells were reversed by overexpression of NLRP3. Concurrently, AMPK inhibitor enhanced the TRIM38-overexpressed NSCLC cell's abilities in migration, clone formation, invasion, and proliferation. TRIM38 regulated the AMPK/NF-κB/NLRP3 pathway to suppress the NSCLC's progression and development.
