Search

Idiopathic normal pressure hydrocephalus (iNPH) affects mainly aged populations. The gradual shortening of telomere length (TL) is one of the hallmarks of aging. Whereas the genetic contribution of TL to the iNPH is incompletely understood. We aimed to investigate the causal relationship between TL and iNPH through the Mendelian randomization (MR) analysis. We respectively obtained 186 qualified single nucleotide polymorphisms (SNPs) of TL and 20 eligible SNPs of iNPH for MR analysis. The result of MR analysis showed that genetically predicted longer TL was significantly associated with a reduced odd of iNPH (odds ratio [OR] = 0.634 95% Confidence interval [CI] 0.447–0.899, p = 0.011). The causal association remained consistent in multivariable MR (OR = 0.530 95% CI 0.327–0.860, p = 0.010). However, there was no evidence that the iNPH was causally associated with the TL (OR = 1.000 95% CI 0.996–1.004, p = 0.955). Our study reveals a potential genetic contribution of TL to the etiology of iNPH, that is a genetically predicted increased TL might be associated with a reduced risk of iNPH. [ABSTRACT FROM AUTHOR]

Liquid biopsy techniques based on deep sequencing of plasma cell‐free DNA (cfDNA) could detect the low‐frequency somatic mutations and provide an accurate diagnosis for many cancers. However, for brain gliomas, reliable performance of these techniques currently requires obtaining cfDNA from patients' cerebral spinal fluid, which is cumbersome and risky. Here we report a liquid biopsy method based on sequencing of plasma cfDNA fragments carrying 5‐hydroxymethylcytosine (5hmC) using selective chemical labeling (hMe‐Seal). We first constructed a dataset including 180 glioma patients and 229 non‐glioma controls. We found marked concordance between cfDNA hydroxymethylome and the aberrant transcriptome of the underlying gliomas. Functional analysis also revealed overrepresentation of the differentially hydroxymethylated genes (DhmGs) in oncogenic and neural pathways. After splitting our dataset into training and test cohort, we showed that a penalized logistic model constructed with training set DhmGs could distinguish glioma patients from healthy controls in both our test set (AUC = 0.962) and an independent dataset (AUC = 0.930) consisting of 111 gliomas and 111 controls. Additionally, the DhmGs between gliomas with mutant and wild‐type isocitrate dehydrogenase (IDH) could be used to train a cfDNA predictor of the IDH mutation status of the underlying tumor (AUC = 0.816), and patients with predicted IDH mutant gliomas had significantly better outcome (P =.01). These results indicate that our plasma cfDNA 5hmC sequencing method could obtain glioma‐specific signals, which may be used to noninvasively detect these patients and predict the aggressiveness of their tumors. [ABSTRACT FROM AUTHOR]

Splines are irreplaceable in high-speed aviation fields due to their simplicity, reliability, and high specific power. Aviation splines are not only subjected to severe operating mechanical loads, but also sometimes operate under grease-lubricated and non-lubricated environments. All of this results in aviation splines suffering widespread failures. Since the 1960s, many researchers have carried out much research on aviation splines. The wide range of research topics demonstrates the technical challenges of understanding aviation spline. This paper reviews the research of aviation spline from the aspects of failure form, fatigue strength, surface contact stress, effects of lubrication, and misalignment on wear, as well as experiments. Relevant research shows crowned splines can mitigate the spline wear process induced by angular misalignment, and oil-lubricating splines experience almost no wear. This paper also looks forward to the future development directions of aviation splines. [ABSTRACT FROM AUTHOR]