Causal Mediation Analysis with a Three-Dimensional Image Mediator

Causal mediation analysis is increasingly abundant in biology, psychology, and epidemiology studies, etc. In particular, with the advent of the big data era, the issue of high-dimensional mediators is becoming more prevalent. In neuroscience, with the widespread application of magnetic resonance technology in the field of brain imaging, studies on image being a mediator emerged. In this study, a novel causal mediation analysis method with a three-dimensional image mediator is proposed. We define the average casual effects under the potential outcome framework, explore several sufficient conditions for the valid identification, and develop techniques for estimation and inference. To verify the effectiveness of the proposed method, a series of simulations under various scenarios is performed. Finally, the proposed method is applied to a study on the causal effect of mother$^{\prime}$s delivery mode on child$^{\prime}$s IQ development. It is found that the white matter in certain regions of the frontal-temporal areas has mediating effects.Comment: 35 pages, 9 figure

Supervised Sparsity Preserving Projections for Face Recognition

Recently feature extraction methods have commonly been used as a principled approach to understand the intrinsic structure hidden in high-dimensional data. In this paper, a novel supervised learning method, called Supervised Sparsity Preserving Projections (SSPP), is proposed. SSPP attempts to preserve the sparse representation structure of the data when identifying an efficient discriminant subspace. First, SSPP creates a concatenated dictionary by class-wise PCA decompositions and learns the sparse representation structure of each sample under the constructed dictionary using the least squares method. Second, by maximizing the ratio of non-local scatter to local scatter, a Laplacian discriminant function is defined to characterize the separability of the samples in the different sub-manifolds. Then, to achieve improved recognition results, SSPP integrates the learned sparse representation structure as a regular term into the Laplacian discriminant function. Finally, the proposed method is converted into a generalized eigenvalue problem. The extensive and promising experimental results on several popular face databases validate the feasibility and effectiveness of the proposed approach

An integrated dynamic design system for aerostatic spindle development

In this paper an integrated dynamic design and modeling system is developed for aerostatic spindle development. This system integrates initial structural design, bearing stiffness computation and the spindle dynamic performance prediction. Modal fitting is used to transform the finite element model into a two-degree-of-freedom system model, which will make it easier to control the system and calculate the dynamic response. The design system is implemented by using commercial software, such as Pro/E, Matlab and Ansys. Consequently, the integrated dynamic design system enables the designers to cost-effectively complete structural design of an aerostatic spindle. A case study has been presented in this paper for design of an aerostatic spindle used for flycutting. The machining results demonstrate the effectiveness of the developed integrated dynamic design system for aerostatic spindles design

Chronic disease knowledge and its determinants among chronically ill adults in rural areas of Shanxi Province in China: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Chronic disease knowledge is an important prerequisite for an individual to implement behavioural changes towards the prevention and control of chronic diseases (CDs). Limited information is available about the relationship between different levels of health services and CD knowledge among rural residents with CDs. This research explores the distribution characteristics of CD knowledge and its determinants among chronically ill adults in rural China according to the aspects of patients and health service providers.</p> <p>Methods</p> <p>A cross-sectional study was undertaken to estimate distribution characteristics of CD knowledge and collect data of socio-demographic characteristics, healthcare institutions attendances, duration of illness, and family history of CDs. Participants were 1060 rural adults with hypertension or type II diabetes. Correct responses to 12 questions were summed into a total knowledge score, and participants were divided into an adequate health knowledge group (score ≥ 6) or an inadequate health knowledge group (score < 5). Logistic regression was used determine the predictors of adequate CD health knowledge.</p> <p>Results</p> <p>The mean age of participants was 61.34 years (SD = 10 years). Out of a possible 12, the median score on the CD knowledge questionnaire was 3.0. About 25% of participants were classified as having adequate CD knowledge. Those who had a family history and/or long duration of CDs were more likely to have adequate health knowledge. Participants who received CD health information and self-care instructions from their physicians had 2.67 and 13.34 times greater odds of possessing adequate health knowledge than those who received no information, respectively. Adequate CD knowledge was strongly associated with regular check-ups, especially for those who attended township hospitals (OR = 40.17).</p> <p>Conclusions</p> <p>Having regular check-ups at a fixed healthcare institution and receiving health information from physicians are important measures for increasing CD knowledge among rural adults with CDs. Township hospitals are the most effective settings for health education. It is important to develop an effective community-based prevention and control mechanism for CDs. This requires township hospitals to take a leading role in improving CD knowledge among chronically ill patients, and enhancing implementation of health education in rural China.</p

Validation of Konsung Compass 2000 Dry Biochemical Analyzer

Dry biochemical analyzers have been increasingly popular in many tests by primary hospitals, field hospitals and other areas subject to economic and medical underdevelopment as well as poor transportation. With the increasing demand for POCT in primary medical care around the world, upgrading of dry biochemical analyzers has been a hot topic in technical research. Against such context, Konsung Compass2000 dry biochemical analyzer, a POCT system with high precision and accuracy, is developed. Furthermore, the upgraded dry biochemical analyzers can, in a more convenient and accurate way, monitor glucose, lipid and other indices affecting the course of chronic diseases

CRISPR-Cas9 mediated cell line engineering of apoptosis pathways increases antibody expression with site-specific modifications for antibody drug conjugation

New generation of antibody drug conjugates (ADCs) have expanded the repertoire of antibody drugs in the clinic and the market for cancer and inflammation indications by using highly stable linkers to attach potent small-molecule drug to various targeting antibodies. The drug and site of drug linkage to the antibody can have profound impact on the physiochemical properties and pharmacological profile of the ADC. Ambrx has developed a technology, Eukaryotic Chemical Orthogonal Directed Engineering (EuCODE), which allows non-natural amino acids with diverse physicochemical and biological properties to be genetically encoded and site-specifically incorporated into proteins/antibodies in mammalian cells. The non-natural amino acid provides a handle for the attachment of a small-molecule drug to generate homogenous ADC with a defined Drug-to-Antibody Ratio (DAR). To establish a CHO expression system for high production of monoclonal antibodies (mAbs) containing non-natural amino acids, we successfully generated a EuCODE platform cell line stably expressing engineered amber suppressor tRNA and its cognate tRNA synthetase specific for non-natural amino acid para-acetyl phenylalanine (pAF). When transfected with antibody of interest engineered with amber nonsense codon (TAG) at selected sites suitable for drug conjugation, this EuCODE platform cell line generates stable cell lines producing pAF containing mAbs for site-specifically conjugated ADC. In order to improve production titers of pAF containing antibody and achieve a robust platform, the platform cell line and stable cell lines were further evolved using CRISPR/Cas9 genome editing technology to sequentially knock out selected genes in glutamine synthesis and apoptosis pathways to improve selection efficiency and prevent loss of viable cell mass in production cultures, respectively. Inhibition of apoptosis pathway leads to dramatic increase in viable cell mass and results in extended production time and increased productivity. Phenotypic and genetic properties of these CRISPR engineered cell lines and product quality of the antibody will be discussed in the context of using the platform to develop a commercial manufacturing cell line

Line bisection performance in patients with generalized anxiety disorder and treatment-resistant depression

Background and Objectives The line bisection error to the left of the true center has been interpreted as a relative right hemisphere activation, which might relate to the subject's emotional state. Considering that patients with generalized anxiety disorder (GAD) or treatment-resistant depression (TRD) often have negative emotions, we hypothesized that these patients would bisect lines significantly leftward. Methods We tried the line bisection task in the right-handed healthy volunteers (n = 56), GAD (n = 47) and TRD outpatients (n = 52). Subjects also completed the Zuckerman - Kuhlman Personality Questionnaire, the Zuckerman Sensation Seeking Scales, and the Plutchik-van Praag Depression Inventory. Results GAD patients scored highest on the Neuroticism-Anxiety trait, TRD patients scored highest on depression, and both patients scored lower on the Sociability trait. Patients with GAD also bisected lines significantly leftward compared to the healthy subjects. The Frequency of the bisection error was negatively correlated with Disinhibition-Seeking in the healthy subjects, and with Total sensation-seeking and Experience-Seeking in GAD patients, while the Magnitude of the line bisection error was negatively correlated with depression in TRD patients. Conclusions The study suggests a stronger right hemispheric activation, a weaker left activation, or both in the GAD, instead of TRD patients

Enhanced Oxidative Stress Is Responsible for TRPV4-Induced Neurotoxicity

Transient receptor potential vanilloid 4 (TRPV4) has been reported to be responsible for neuronal injury in pathological conditions. Excessive oxidative stress can lead to neuronal damage, and activation of TRPV4 increases the production of reactive oxygen species and nitric oxide (NO) in many types of cells. The present study explored whether TRPV4-induced neuronal injury is mediated through enhancing oxidative stress. We found that intracerebroventricular injection of the TRPV4 agonist GSK1016790A increased the content of methane dicarboxylic aldehyde (MDA) and NO in the hippocampus, which was blocked by administration of the TRPV4 specific antagonist HC-067047. The activities of catalase (CAT) and glutathione peroxidase (GSH-Px) were decreased by GSK1016790A, whereas the activity of superoxide dismutase remained unchanged. Moreover, the protein level and activity of neuronal nitric oxide synthase (nNOS) were increased by GSK1016790A, and the GSK1016790A-induced increase in NO content was blocked by an nNOS specific antagonist ARL-17477. The GSK1016790A-induced modulations of CAT, GSH-Px and nNOS activities and the protein level of nNOS were significantly inhibited by HC-067047. Finally, GSK1016790A-induced neuronal death and apoptosis in the hippocampal CA1 area were markedly attenuated by administration of a reactive oxygen species scavenger Trolox or ARL-17477. We conclude that activation of TRPV4 enhances oxidative stress by inhibiting CAT and GSH-Px and increasing nNOS, which is responsible, at least in part, for TRPV4-induced neurotoxicity

Optimal dose of fenfluramine in adjuvant treatment of drug-resistant epilepsy: evidence from randomized controlled trials

ObjectiveSeveral clinical trials have suggested that fenfluramine (FFA) is effective for the treatment of epilepsy in Dravet syndrome (DS) and Lennox–Gastaut syndrome (LGS). However, the exploration of its optimal target dose is ongoing. This study aimed to summarize the best evidence to inform this clinical issue.Materials and methodsWe searched PubMed, Embase (via Ovid), and Web of Science for relevant literature published before December 1st, 2023. Randomized, double-blind, placebo-controlled studies that evaluated the efficacy, safety, and tolerability of FFA in DS and LGS were identified and meta-analysis was performed according to doses. The study was registered with PROSPERO (CRD42023392454).ResultsSix hundred and twelve patients from four randomized controlled trials were enrolled. The results demonstrated that FFA at 0.2, 0.4, or 0.7 mg/kg/d showed significantly greater efficacy compared to placebo in terms of at least 50% reduction (p &lt; 0.001, p &lt; 0.001, p &lt; 0.001) and at least 75% reduction (p &lt; 0.001, p = 0.007, p &lt; 0.001) in monthly seizure frequency from baseline. Moreover, significantly more patients receiving FFA than placebo were rated as much improved or very much improved in CGI-I by both caregivers/parents and investigators (p &lt; 0.001). The most common treatment-emergent adverse events were decreased appetite, diarrhea, fatigue, and weight loss, with no valvular heart disease or pulmonary hypertension observed in any participant. For dose comparison, 0.7 mg/kg/d group presented higher efficacy on at least 75% reduction in seizure (p = 0.006) but not on at least 50% reduction. Weight loss (p = 0.002), decreased appetite (p = 0.04), and all-cause withdrawal (p = 0.036) were more common in 0.7 mg/kg/d group than 0.2 mg/kg/d. There was no statistical difference in other safety parameters between these two groups.ConclusionThe higher range of the licensed dose achieves the optimal balance between efficacy, safety, and tolerability in patients with DS and LGS.Clinical trial registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023392454