Dynamic treatment regimes (DTRs) formalize medical decision-making as a sequence of rules for different stages, mapping patient-level information to recommended treatments. In practice, estimating an optimal DTR using observational data from electronic medical record (EMR) databases can be complicated by nonignorable missing covariates resulting from informative monitoring of patients. Since complete case analysis can provide consistent estimation of outcome model parameters under the assumption of outcome-independent missingness, Q-learning is a natural approach to accommodating nonignorable missing covariates.
View Article and Find Full Text PDFNucleotide availability is crucial for DNA replication and repair; however, the coordinating mechanisms in vivo remain unclear. Here, we show that the circadian clock in the liver controls the activity of the pentose phosphate pathway (PPP) to support de novo nucleotide biosynthesis for DNA synthesis demands. We demonstrate that disrupting the hepatic clock by genetic manipulation or mistimed feeding impairs PPP activity in male mice, leading to nucleotide imbalance.
View Article and Find Full Text PDFFunctional brain changes such as altered cerebral blood flow occur long before the onset of clinical symptoms in Alzheimer's disease (AD) and other neurodegenerative disorders. While cerebral hypoperfusion occurs in established AD, middle-aged carriers of genetic risk factors for AD, including APOE ε4, display regional hyperperfusion due to hypothesised pleiotropic or compensatory effects, representing a possible early biomarker of AD and facilitating earlier AD diagnosis. However, it is not clear whether hyperperfusion already exists even earlier in life.
View Article and Find Full Text PDFTIMP-1 (Tissue Inhibitor of Metalloproteinases-1) is a protein involved in regulating extracellular matrix (ECM) degradation. It is recognized as a significant biomarker for cancer diagnosis. This study aimed to develop and characterize a single-stranded DNA (ssDNA) aptamer targeting human TIMP-1 protein with high affinity and specificity.
View Article and Find Full Text PDFObjective: This study is aimed at identifying key risk factors associated with the onset of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and developing and validating a novel risk prediction model for RA-ILD.
Methods: This is a hospital-based retrospective cohort study. A total of 459 RA patients were selected from Longhua Hospital Affiliated with Shanghai University of Traditional Chinese Medicine between 2015 and 2020 as observation subjects.
Ferroptosis is a novel type of programmed cell death dependent on iron and is characterized by the accumulation of lipid peroxides, which is involved in acute lung injury (ALI). Brazilin, an organic compound known for its potent antioxidant and anti-inflammatory properties, has not been thoroughly studied for its potential impact on lipopolysaccharide (LPS)-induced ALI. Here, we found that pretreatment of brazilin mitigated LPS-induced lung injury and inflammation by inhibiting mitochondrial oxidative stress and ferroptosis, both in vivo and in vitro.
View Article and Find Full Text PDFGrowing evidence suggests inflammatory bowel disease (IBD) is linked to ischemic stroke (IS); however, the results are inconclusive. Therefore, it remains uncertain whether the association between IBD and IS is causal. Herein, we performed a bidirectional Mendelian randomization (MR) study to examine the causal association of IBD with IS.
View Article and Find Full Text PDFPOEMS syndrome is a complex and rare hematological disease involving multiple physiological systems. According to the currently accepted diagnostic criteria for POEMS syndrome, polyneuropathy is one of the primary mandatory criteria. A patient presented with M protein, Castleman disease (CD), elevated vascular endothelial growth factor (VEGF), extravascular volume overload, and endocrinopathy.
View Article and Find Full Text PDFEfforts to prevent dementia can benefit from precision interventions delivered to the right population at the right time; that is, when the potential to reduce risk is the highest. Young adults (aged 18-39 years) are a neglected population in dementia research and policy making despite being highly exposed to several known modifiable risk factors. The risk and protective factors that have the biggest effect on dementia outcomes in young adulthood, and how these associations differ across regions and groups, still remain unclear.
View Article and Find Full Text PDFUnlabelled: African swine fever (ASF) is a highly contagious and often lethal disease caused by African swine fever virus (ASFV) in pigs. Protein palmitoylation is a prevalent posttranslational lipid modification that can modulate viral replication. In this study, we investigated the palmitoylation of ASFV proteins.
View Article and Find Full Text PDFBackground: Anticipatory grief has been shown to be highly prevalent among family caregivers of patients with advanced illness. However, there is less research on the anticipatory grief of family caregivers with chronic heart failure. Therefore, the purpose of this study was to explore the profile of anticipatory grief among family caregivers of patients with chronic heart failure and to analyze the influencing factors of different profiles.
View Article and Find Full Text PDFPostoperative cognitive dysfunction (POCD) is common in the aged population and associated with poor clinical outcomes. Irisin, an endogenous molecule that mediates the beneficial effects of exercise, has shown neuroprotective potential in several models of neurological diseases. Here we show that preoperative serum level of irisin is reduced in dementia patients over the age of 70.
View Article and Find Full Text PDFThe human brain exhibits high degree of individual variability in both its structure and function, which underlies inter-subject differences in cognition and behavior. It was previously shown that functional connectivity is more variable in the hetero-modal association cortex but less variable in the unimodal cortices. Structural connectivity is the anatomical substrate of functional connectivity, but the spatial and temporal patterns of individual variability in structural connectivity (IVSC) remain largely unknown.
View Article and Find Full Text PDFNeural Regen Res
December 2024
Stroke remains a leading cause of long-term disability worldwide. There is an unmet need for neuromodulatory therapies that can mitigate against neurovascular injury and potentially promote neurological recovery. Transcutaneous vagus nerve stimulation has been demonstrated to show potential therapeutic effects in both acute and chronic stroke.
View Article and Find Full Text PDFTo investigate the protective effects and underlying mechanisms of Qin-Zhu-Liang-Xue decoction (QZLX) in atopic dermatitis (AD) and glucocorticoid resistance, we conducted a single-blinded, randomized controlled clinical trial to evaluate the efficacy and safety of this concoction. Network pharmacology analysis was performed and validated through clinical studies. The efficacy, safety, and mechanism of action of QZLX and glucocorticoid receptor (GR) α recombinant protein were assessed in AD mice induced by 2,4-dinitrofluorobenzene (DNFB).
View Article and Find Full Text PDFSoft actuators hold great promise for applications in biomimetic robots, artificial muscles, and drug delivery systems due to their adaptability in diverse environments. A critical aspect of designing thermally responsive soft actuators is to achieve spatially programmable actuation under a global thermal stimulus. Different local actuation behaviors can be encoded in one actuator to enable complex morphing structures for different tasks.
View Article and Find Full Text PDFBackground: Genetic risk factors start to affect the brain and behavior in Alzheimer's disease (AD) before clinical symptoms occur. Although AD is mainly associated with memory deficits, attention and executive dysfunctions can present at the early presymptomatic stages in middle age for those with non-modifiable risks.
Objective: Here, we investigated whether known risk genes for AD already affected attention in young adulthood.
Homojunction engineering holds promise for creating high-performance photocatalysts, yet significant challenges persist in establishing and modulating an effective junction interface. To tackle this, we designed and constructed a novel Janus homojunction photocatalyst by integrating two different forms of triazole-based carbon nitride (CN). In this design, super-sized, ultrathin nanosheets of carbon-rich CN grow epitaxially on a nitrogen-rich honeycomb network of CN, creating a tightly bound and extensive interfacial contact area.
View Article and Find Full Text PDFNumerous viruses that propagate through the respiratory tract may be initially engulfed by macrophages (Ms) within the alveoli, where they complete their first replication cycle and subsequently infect the adjacent epithelial cells. This process can lead to significant pathological damage to tissues and organs, leading to various diseases. As essential components in host antiviral immune systems, Ms can be polarized into pro-inflammatory M1 Ms or anti-inflammatory M2 Ms, a process involving multiple signaling pathways and molecular mechanisms that yield diverse phenotypic and functional features in response to various stimuli.
View Article and Find Full Text PDFPurpose: China has experienced a heavy public health burden due to the increasing incidence of ischemic stroke (IS). Few studies have evaluated the relationship between particulate matter (PM) exposure and acute ischemic stroke (AIS) in relatively less-polluted areas, and the results have been inconsistent. As a result, this study aimed to investigate and evaluate the association between PM exposure and hospitalizations for AIS in an area with less air pollution.
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