BOOST: A fast approach to detecting gene-gene interactions in genome-wide case-control studies

Gene-gene interactions have long been recognized to be fundamentally important to understand genetic causes of complex disease traits. At present, identifying gene-gene interactions from genome-wide case-control studies is computationally and methodologically challenging. In this paper, we introduce a simple but powerful method, named `BOolean Operation based Screening and Testing'(BOOST). To discover unknown gene-gene interactions that underlie complex diseases, BOOST allows examining all pairwise interactions in genome-wide case-control studies in a remarkably fast manner. We have carried out interaction analyses on seven data sets from the Wellcome Trust Case Control Consortium (WTCCC). Each analysis took less than 60 hours on a standard 3.0 GHz desktop with 4G memory running Windows XP system. The interaction patterns identified from the type 1 diabetes data set display significant difference from those identified from the rheumatoid arthritis data set, while both data sets share a very similar hit region in the WTCCC report. BOOST has also identified many undiscovered interactions between genes in the major histocompatibility complex (MHC) region in the type 1 diabetes data set. In the coming era of large-scale interaction mapping in genome-wide case-control studies, our method can serve as a computationally and statistically useful tool.Comment: Submitte

Diversified pattern of the human colorectal cancer microbiome

BACKGROUND: The aim of this study is to expand existing knowledge about the CRC-associated microbiome among Han Chinese, and to further discover the variation pattern of the human CRC microbiome across all population. FINDINGS: Using pyrosequencing-based molecular monitoring of bacterial 16S rRNA gene from eight tumor/normal tissue pairs of eight Chinese CRC patients, we analyzed and characterized the basic features of the CRC-associated microbiome. Firstly, we discovered an increasing diversity among tumor-associated bacterial communities. Secondly, in 50% of Chinese CRC patients, we found a significant increase of Roseburia (P = 0.017), and a concurrent decrease of both Microbacterium (P = 0.009) and Anoxybacillus (P = 0.009) in tumor tissue. CONCLUSIONS: We discovered a novel CRC microbiome pattern in Chinese. Both the over-represented Roseburia bacteria at tumor sites and the over-represented Microbacterium and Anoxybacillus bacteria away from tumor sites were both closely related in Chinese CRC patients. Across several populations reported in this study and previously, we observed both common and distinctive patterns of human CRC microbiome’s association with a high-risk of CRC

Micro-patterned TiO2 films for photocatalysis

Titanium dioxide film as a stable material plays an important role in photocatalytic degradation of pollutants. One of the ways to improve photocatalytic efficiency is to increase the active sites on the semiconductor surface. Photolithography is a manufacturing technique for controlling precisely micrographics on surface. Here grating-structured, square-structured and hexagon-structured TiO2 films were prepared by photolithography and the effects of various surface structures on photocatalysis were studied. It was demonstrated that the photocatalytic activity of TiO2 film was not always improved as the surface area increased. The micro-patterned surface would also impede the mass transfer in the process of photocatalysis. (C) 2019 Elsevier B.V. All rights reserved

Protective Effect of Edaravone against Carbon Monoxide Induced Apoptosis in Rat Primary Cultured Astrocytes

Objective. To observe the protective effect of edaravone (Eda) on astrocytes after prolonged exposure to carbon monoxide (CO) and further to investigate the potential mechanisms of Eda against CO-induced apoptosis. Methods. The rat primary cultured astrocytes were cultured in vitro and exposed to 1% CO for 24 h after being cultured with different concentrations of Eda. MTT assay was used to detect the cytotoxicity of CO. Flow cytometry was used to detect the apoptosis rate, membrane potential of mitochondria, and ROS level. The mRNA and protein expressions of Bcl-2, Bax, and caspase-3 were assessed by real-time PCR and Western blotting analysis, respectively. Results. Eda can significantly suppress cytotoxicity of CO, and it can significantly increase membrane potential of mitochondria and Bcl-2 expressions and significantly suppress the apoptosis rate, ROS level, Bax, and caspase-3 expressions. Conclusion. Eda protects against CO-induced apoptosis in rat primary cultured astrocytes through decreasing ROS production and subsequently inhibiting mitochondrial apoptosis pathway

Neural correlates of quantity processing of numeral classifiers.

ObjectiveClassifiers play an important role in describing the quantity information of objects. Few studies have been conducted to investigate the brain organization for quantity processing of classifiers. In the current study, we investigated whether activation of numeral classifiers was specific to the bilateral inferior parietal areas, which are believed to process numerical magnitude.MethodUsing functional MRI, we explored the neural correlates of numeral classifiers, as compared with those of numbers, dot arrays, and nonquantity words (i.e., tool nouns).ResultsOur results showed that numeral classifiers and tool nouns elicited greater activation in the left inferior frontal lobule and left middle temporal gyrus than did numbers and dot arrays, but numbers and dot arrays had greater activation in the middle frontal gyrus, precuneus, and the superior and inferior parietal lobule in the right hemisphere. No differences were found between numeral classifiers and tool nouns.ConclusionThe results suggest that quantity processing of numeral classifiers is independent of that of numbers and dot arrays, supporting the notation-dependent hypothesis of quantity processing

CODA: A Real-World Road Corner Case Dataset for Object Detection in Autonomous Driving

Contemporary deep-learning object detection methods for autonomous driving usually assume prefixed categories of common traffic participants, such as pedestrians and cars. Most existing detectors are unable to detect uncommon objects and corner cases (e.g., a dog crossing a street), which may lead to severe accidents in some situations, making the timeline for the real-world application of reliable autonomous driving uncertain. One main reason that impedes the development of truly reliably self-driving systems is the lack of public datasets for evaluating the performance of object detectors on corner cases. Hence, we introduce a challenging dataset named CODA that exposes this critical problem of vision-based detectors. The dataset consists of 1500 carefully selected real-world driving scenes, each containing four object-level corner cases (on average), spanning more than 30 object categories. On CODA, the performance of standard object detectors trained on large-scale autonomous driving datasets significantly drops to no more than 12.8% in mAR. Moreover, we experiment with the state-of-the-art open-world object detector and find that it also fails to reliably identify the novel objects in CODA, suggesting that a robust perception system for autonomous driving is probably still far from reach. We expect our CODA dataset to facilitate further research in reliable detection for real-world autonomous driving. Our dataset will be released at https://coda-dataset.github.io.Comment: ECCV 202

Post-marketing safety surveillance of dalfampridine for multiple sclerosis using FDA adverse event reporting system

Objective: To investigate and analyze the post-marketing adverse event (AE) data of multiple sclerosis (MS) therapeutic drug dalfampridine using the US Food and Drug Administration Adverse Event Reporting System (FAERS) for its clinical safety application.Methods: Use OpenVigil2.1 platform to obtain AE data of dalfampridine from FAERS from February 2010 to September 2022. Match “adverse drug reaction” with preferred term (PT) and system organ class (SOC) according to the Medical Dictionary for Regulatory Activities (MedDRA), then merge the same PT and delete non-AE PT. Positive signals were identified by the reporting odds ratio (ROR), proportional reporting ratio (PRR), and Bayesian confidence propagation neural network (BCPNN) methods. When AE signals met the criteria of those three methods, they were identified as positive signals.Results: A total of 44,092 dalfampridine-related AE reports were obtained, and 335 AE signals were identified, including 11,889 AE reports. AEs were more common in females and in the 45–65 age group, which is consistent with the epidemiological characteristics of MS. The 335 AE signals involved 21 SOCs, including investigations, infections and infestations, eye disorders, etc. Among the top 20 PTs in signal strength, 10 were associated with abnormal lymphocyte percentage and count, and 5 were associated with abnormal urine tests, some of which were not described in the instruction, such as spinal cord injury cauda equina, haemoglobin urine present, urinary sediment abnormal and so on. The most frequently reported AE signals were urinary tract infection, dizziness, condition aggravated. In addition, 23 AE signals with death outcomes were identified, with an incidence of less than 0.1%.Conclusion: Data mining of FAERS was conducted to analyze the AEs of dalfampridine, and new AE signals were found. This study provides a reference for the safe use of dalfampridine in the treatment of MS

Primary Clinical Evaluation of Photodynamic Therapy With Oral Leukoplakia in Chinese Patients

Background: Photodynamic therapy (PDT) has demonstrated promising results in the treatment of oral leukoplakia. This study evaluated the clinical efficacy and side effects of PDT in the treatment of Chinese patients with oral leukoplakia.Methods: Twenty-nine patients with oral leukoplakia were enrolled in this study, including patients with both homogenous and non-homogenous lesions and various dysplastic tissues. All patients received PDT using a 632 nm laser at 500 mW/cm2 power density at a dosage of 90–180 J/cm2 and with aminolevulinic acid (ALA) used as a photosensitizer. A fixing and restricting complex as well as high laser power density for PDT in oral cavity was applied.Results: An overall response rate of 86.2% was achieved in this study, including 55.2% complete remission and 31.0% partial remission. The only adverse events observed in subjects were transient local ulcer and pain. It is observed the PDT utilizing ALA showed strong effectiveness in patients with moderate to severe dysplasia, as less treatment time per cm2 of lesion is required.Conclusion: Topic ALA-PDT is effective to treat oral leukoplakia, especially for that with the presence of dysplasia. A fixing and restricting complex as well as high laser power density for PDT in oral cavity should be considered as an optimal choice