MEF2A restrains cisplatin resistance in gastric cancer cells by modulating NFKBIA/NF-κB signaling pathway.

Cisplatin (DDP) resistance represents a pivotal contributing factor to chemotherapy failure and adverse patient outcomes in gastric cancer (GC). The objective of the present study was to investigate the roles and underlying mechanisms of myocyte enhancer factor 2A (MEF2A) in DDP resistance in GC. GC cell line AGS and MKN-45 cells were applied to construct DDP-resistant cells.

Identification and development of TP53 mutation-associated Long non-coding RNAs signature for optimized prognosis assessment and treatment selection in hepatocellular carcinoma.

Background: The TP53 gene is estimated to be mutated in over 50% of tumors, with the majority of tumors exhibiting abnormal TP53 signaling pathways. However, the exploration of TP53 mutation-related LncRNAs in Hepatocellular carcinoma (HCC) remains incomplete. This study aims to identify such LncRNAs and enhance the prognostic accuracy for Hepatoma patients.

Elexacaftor/Tezacaftor/Ivacaftor Treatment and Depression-related Events.

Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) has been shown to be safe and efficacious in people with cystic fibrosis (pwCF) aged 2 years and older with at least one allele or more. After U.S.

Long-Term Safety and Efficacy of Elexacaftor/Tezacaftor/Ivacaftor in Children Aged ⩾6 Years with Cystic Fibrosis and at Least One Allele: A Phase 3, Open-Label Clinical Trial.

A 24-week, phase 3, open-label study showed elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was safe and efficacious in children aged 6-11 years with cystic fibrosis (CF) and one or more alleles. To assess long-term safety and efficacy of ELX/TEZ/IVA in children who completed the pivotal 24-week phase 3 trial. In this phase 3, two-part (part A and part B), open-label extension study, children aged ⩾6 years with CF heterozygous for and a minimal function mutation (/MF genotypes) or homozygous for ( genotype) who completed the 24-week parent study received ELX/TEZ/IVA based on weight.

A confirmatory basket design considering non-inferiority and superiority testing.

For multiple rare diseases as defined by a common biomarker signature, or a disease with multiple disease subtypes of low frequency, it is often possible to provide confirmatory evidence for these disease or subtypes (baskets) as a combined group. A novel drug, as a second generation, may have marginal improvement in efficacy overall but superior efficacy in some baskets. In this situation, it is appealing to test hypotheses of both non-inferiority overall and superiority on certain baskets.

Phase 3 Open-Label Clinical Trial of Elexacaftor/Tezacaftor/Ivacaftor in Children Aged 2-5 Years with Cystic Fibrosis and at Least One Allele.

Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) has been shown to be safe and effective in people with cystic fibrosis (CF) aged ⩾6 years with at least one allele but has not been studied in younger children. To evaluate the safety, pharmacokinetics, pharmacodynamics, and efficacy of ELX/TEZ/IVA in children with CF aged 2-5 years. In this phase 3, open-label, two-part study (parts A and B), children weighing <14 kg (on Day 1) received ELX 80 mg once daily (qd), TEZ 40 mg qd, and IVA 60 mg each morning and 59.

Safety and efficacy of vanzacaftor-tezacaftor-deutivacaftor in adults with cystic fibrosis: randomised, double-blind, controlled, phase 2 trials.

Background: Elexacaftor-tezacaftor-ivacaftor has been shown to be safe and efficacious in people with cystic fibrosis and at least one F508del allele. Our aim was to identify a novel cystic fibrosis transmembrane conductance regulator (CFTR) modulator combination capable of further increasing CFTR-mediated chloride transport, with the potential for once-daily dosing.

Methods: We conducted two phase 2 clinical trials to assess the safety and efficacy of a once-daily combination of vanzacaftor-tezacaftor-deutivacaftor in participants with cystic fibrosis who were aged 18 years or older.

Minority carrier decay length extraction from scanning photocurrent profiles in two-dimensional carrier transport structures.

Carrier transport was studied both numerically and experimentally using scanning photocurrent microscopy (SPCM) in two-dimensional (2D) transport structures, where the structure size in the third dimension is much smaller than the diffusion length and electrodes cover the whole terminal on both sides. Originally, one would expect that with increasing width in 2D transport structures, scanning photocurrent profiles will gradually deviate from those of the ideal one-dimensional (1D) transport structure. However, the scanning photocurrent simulation results surprisingly showed almost identical profiles from structures with different widths.

Stochastic Functional Estimates in Longitudinal Models with Interval-Censored Anchoring Events.

Timelines of longitudinal studies are often anchored by specific events. In the absence of fully observed the anchoring event times, the study timeline becomes undefined, and the traditional longitudinal analysis loses its temporal reference. In this paper, we considered an analytical situation where the anchoring events are interval-censored.

High-Yield Two-Dimensional Metal-Organic Framework Derivatives for Wideband Electromagnetic Wave Absorption.

Two-dimensional metal-organic frameworks (2D-MOFs) and their derivatives are promising for catalysis, energy storage, gas separation, etc. due to their unique microstructure and physicochemical properties. Many efforts have been devoted to fabricating 2D-MOFs with challenges remaining in yield and fine control of their thickness and lateral size.

A Phase 3 Open-Label Study of Elexacaftor/Tezacaftor/Ivacaftor in Children 6 through 11 Years of Age with Cystic Fibrosis and at Least One Allele.

Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was shown to be efficacious and safe in patients ≥12 years of age with cystic fibrosis and at least one (cystic fibrosis transmembrane conductance regulator) allele, but it has not been evaluated in children <12 years of age. To assess the safety, pharmacokinetics, and efficacy of ELX/TEZ/IVA in children 6 through 11 years of age with -minimal function or - genotypes. In this 24-week open-label phase 3 study, children ( = 66) weighing <30 kg received 50% of the ELX/TEZ/IVA adult daily dose (ELX 100 mg once daily, TEZ 50 mg once daily, and IVA 75 mg every 12 h) whereas children weighing ⩾30 kg received the full adult daily dose (ELX 200 mg once daily, TEZ 100 mg once daily, and IVA 150 mg every 12 h).

A New Fitting Method for Ambipolar Diffusion Length Extraction in Thin Film Structures Using Photoluminescence Measurement with Scanning Excitation.

A new simple method is proposed to extract the ambipolar diffusion length for two-dimensional (2D) electronic transport in thin film structures using a scanning photoluminescence microscopy (SPLM) setup. No spatially-resolved photoluminescence detection methods are required. By measuring the excitation-position-dependent PL intensity across the edge of a semiconductor, ambipolar diffusion length can be extracted from the SPLM profile through a simple analytic fitting function.

Study design of single-arm phase II immunotherapy trials with long-term survivors and random delayed treatment effect.

In the traditional study design of a single-arm phase II cancer clinical trial, the one-sample log-rank test has been frequently used. A common practice in sample size calculation is to assume that the event time in the new treatment follows exponential distribution. Such a study design may not be suitable for immunotherapy cancer trials, when both long-term survivors (or even cured patients from the disease) and delayed treatment effect are present, because exponential distribution is not appropriate to describe such data and consequently could lead to severely underpowered trial.

A randomized controlled trial testing a virtual perspective-taking intervention to reduce race and socioeconomic status disparities in pain care.

We conducted a randomized controlled trial of an individually tailored, virtual perspective-taking intervention to reduce race and socioeconomic status (SES) disparities in providers' pain treatment decisions. Physician residents and fellows (n = 436) were recruited from across the United States for this two-part online study. Providers first completed a bias assessment task in which they made treatment decisions for virtual patients with chronic pain who varied by race (black/white) and SES (low/high).

A New Analytic Formula for Minority Carrier Decay Length Extraction from Scanning Photocurrent Profiles in Ohmic-Contact Nanowire Devices.

Spatially resolved current measurements such as scanning photocurrent microscopy (SPCM) have been extensively applied to investigate carrier transport properties in semiconductor nanowires. A traditional simple-exponential-decay formula based on the assumption of carrier diffusion dominance in the scanning photocurrent profiles can be applied for carrier diffusion length extraction using SPCM in Schottky-contact-based or p-n junction-based devices where large built-in electric fields exist. However, it is also important to study the electric-field dependent transport properties in widely used ohmic-contact nanowire devices where the assumption of carrier diffusion dominance is invalid.

Distribution-free estimation of local growth rates around interval censored anchoring events.

Biological processes are usually defined on timelines that are anchored by specific events. For example, cancer growth is typically measured by the change in tumor size from the time of oncogenesis. In the absence of such anchoring events, longitudinal assessments of the outcome lose their temporal reference.

Weighted log-rank test for time-to-event data in immunotherapy trials with random delayed treatment effect and cure rate.

A cancer clinical trial with an immunotherapy often has 2 special features, which are patients being potentially cured from the cancer and the immunotherapy starting to take clinical effect after a certain delay time. Existing testing methods may be inadequate for immunotherapy clinical trials, because they do not appropriately take the 2 features into consideration at the same time, hence have low power to detect the true treatment effect. In this paper, we proposed a piece-wise proportional hazards cure rate model with a random delay time to fit data, and a new weighted log-rank test to detect the treatment effect of an immunotherapy over a chemotherapy control.

Transgelin induces dysfunction of fetal endothelial colony-forming cells from gestational diabetic pregnancies.

Fetal exposure to gestational diabetes mellitus (GDM) predisposes children to future health complications including hypertension and cardiovascular disease. A key mechanism by which these complications occur is through the functional impairment of vascular progenitor cells, including endothelial colony-forming cells (ECFCs). Previously, we showed that fetal ECFCs exposed to GDM have decreased vasculogenic potential and altered gene expression.

Folate metabolism genetic polymorphisms and meningioma and glioma susceptibility in adults.

Polymorphic variants of genes involved in folate metabolism are implicated in the susceptibility to meningioma and glioma, but the results from published articles are controversial and inconclusive. Therefore, we performed this meta-analysis including all studies available to evaluate the relationship between folate metabolism genetic polymorphisms and the susceptibility to meningioma and glioma in adults. We searched the literature in PubMed, EMBASE and Cochrane Central Library for relevant articles published up to August 2016.

Kinetic analyses of vasculogenesis inform mechanistic studies.

Vasculogenesis is a complex process by which endothelial stem and progenitor cells undergo de novo vessel formation. Quantitative assessment of vasculogenesis is a central readout of endothelial progenitor cell functionality. However, current assays lack kinetic measurements.

Development and validation of a composite score for excessive alcohol use screening.

This study was undertaken to develop a composite measure that combines the discriminant values of individual laboratory markers routinely used for excessive alcohol use (EAU) for an improved screening performance. The training sample consisted of 272 individuals with known history of EAU and 210 non-alcoholic individuals. The validation sample included 100 EAU and 75 controls.

Resveratrol improved the spatial learning and memory in subclinical hypothyroidism rat induced by hemi-thyroid electrocauterization.

The major purpose of this study was to investigate the effect of resveratrol (RES) on the spatial learning and memory ability in subclinical hypothyroidism (SCH) rat model and the potential mechanism. A SCH rat model was induced by hemi-thyroid electrocauterization and the activity of hypothalamus-pituitary-thyroid (HPT) axis was detected. The spatial learning and memory ability was tested using Morris water maze (MWM) and Y-maze.

Optical double-sideband modulation to single-sideband modulation conversion using period-one nonlinear dynamics of semiconductor lasers for radio-over-fiber links.

To distribute microwaves over fibers, optical single-sideband (SSB) modulation signals are preferred to optical double-sideband (DSB) modulation signals. This study investigates an optically injected semiconductor laser at period-one nonlinear dynamics for optical DSB-to-SSB conversion. For the operating microwave frequencies up to 40 GHz investigated in this study, the proposed system regenerates or even enhances the microwave features of an optical DSB input while converting its optical feature into SSB with an intensity difference of at least 20 dB.