Search

Background: The APOE gene is the strongest genetic risk factor for late-onset Alzheimer's Disease (LOAD). However, the gene regulatory mechanisms at this locus remain incompletely characterized. Methods: To identify novel AD-linked functional elements within the APOE locus, we integrated SNP variants with multi-omics data from human postmortem brains including 2,179 RNA-seq samples from 3 brain regions and two ancestries (European and African), 667 DNA methylation samples, and ChIP-seq samples. Additionally, we plotted the expression trajectory of APOE transcripts in human brains during development. Results: We identified an AD-linked APOE transcript (jxn1.2.2) particularly observed in the dorsolateral prefrontal cortex (DLPFC). The APOE jxn1.2.2 transcript is associated with brain neuropathological features, cognitive impairment, and the presence of the APOE4 allele in DLPFC. We prioritized two independent functional SNPs (rs157580 and rs439401) significantly associated with jxn1.2.2 transcript abundance and DNA methylation levels. These SNPs are located within active chromatin regions and affect brain-related transcription factor-binding affinities. The two SNPs shared effects on the jxn1.2.2 transcript between European and African ethnic groups. Conclusion: The novel APOE functional elements provide potential therapeutic targets with mechanistic insight into the disease etiology. [ABSTRACT FROM AUTHOR]

Large Language Models (LLMs) such as ChatGPT possess advanced capabilities in understanding and generating text. These capabilities enable ChatGPT to create text based on specific instructions, which can serve as augmented data for text classification tasks. Previous studies have approached data augmentation (DA) by either rewriting the existing dataset with ChatGPT or generating entirely new data from scratch. However, it is unclear which method is better without comparing their effectiveness. This study investigates the application of both methods to two datasets: a general-topic dataset (Reuters news data) and a domain-specific dataset (Mitigation dataset). Our findings indicate that: 1. ChatGPT generated new data consistently enhanced model's classification results for both datasets. 2. Generating new data generally outperforms rewriting existing data, though crafting the prompts carefully is crucial to extract the most valuable information from ChatGPT, particularly for domain-specific data. 3. The augmentation data size affects the effectiveness of DA; however, we observed a plateau after incorporating 10 samples. 4. Combining the rewritten sample with new generated sample can potentially further improve the model's performance. [ABSTRACT FROM AUTHOR]

Background: Connective tissue diseases (CTD), including systemic lupus erythematosus and rheumatoid arthritis (RA), have long been treated with hydroxychloroquine (HCQ). However, prolonged HCQ use poses a risk of adverse effects, particularly retinopathy., Objective: To detect early retinal changes assessed by optical coherence tomography angiography (OCTA) in CTD patients with long-term HCQ treatment and to explore the relationship between OCTA parameters and the concentrations of HCQ and its metabolites., Design: A cross-sectional study conducted from March 2020 to October 2021 at the First Affiliated Hospital of Anhui Medical University., Methods: The area and perimeter of the foveal avascular zone (FAZ), the thickness of the fovea and parafovea, and the vascular density of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) in each area of the macula were measured by OCTA in 43 CTD patients treated with HCQ for over 6 months. Meantime, blood concentrations of HCQ and its metabolites were determined by high-performance liquid chromatography-tandem mass spectrometry, and the clinical documents of all 43 involved patients were collected., Results: There is no significant correlation between OCTA outcomes and the patient's age, disease duration, and weight-dependent dose. HCQ cumulative duration positively correlated with FAZ area and perimeter ( r  = 0.419, p  = 0.005 and r  = 0.407, p  = 0.007, respectively) and negatively correlated with the foveal vessel density in DCP ( r  = -0.378, p  = 0.012). HCQ cumulative dose had a positive correlation with FAZ area and perimeter ( r  = 0.445, p  = 0.003 and r  = 0.434, p  = 0.004, respectively) and had a negative correlation with foveal vessel density in SCP and DCP ( r  = -0.383, p  = 0.011 and r  = -0.424, p  = 0.005, respectively). OCTA outcomes did not correlate with HCQ and its metabolite concentrations., Conclusion: OCTA could be used to detect microvascular changes in the macula of CTD patients with long-term HCQ therapy. It was not found the concentrations of HCQ and its metabolites were associated with retinal vascular changes., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)