Trigeminal neuralgia (TN) is a complex orofacial pain syndrome characterized by the paroxysmal onset of pain attacks in the trigeminal distribution. The underlying mechanism for this debilitating ...condition is still not clearly understood. Decades of basic and clinical evidence support the demyelination hypothesis, where demyelination along the trigeminal afferent pathway is a major driver for TN pathogenesis and pathophysiology. Such pathological demyelination can be triggered by physical compression of the trigeminal ganglion or another primary demyelinating disease, such as multiple sclerosis. Further examination of TN patients and animal models has revealed significant molecular changes, channelopathies, and electrophysiological abnormalities in the affected trigeminal nerve. Interestingly, recent electrophysiological recordings and advanced functional neuroimaging data have shed new light on the global structural changes and the altered connectivity in the central pain-related circuits in TN patients. The current article aims to review the latest findings on the pathophysiology of TN and cross-examining them with the current surgical and pharmacologic management for TN patients. Understanding the underlying biology of TN could help scientists and clinicians to identify novel targets and improve treatments for this complex, debilitating disease.
The focus of the paper is to use a single weibo from a user to predict whether the user account is verified, referred to as verified account prediction, on Sina Weibo. To the best of our knowledge, ...verified account prediction on Sina Weibo has not been studied. For better understanding of the prediction problem, a comprehensive data analysis of weibos related to verified accounts is conducted first. Then, verified account prediction is formulated as a sequence learning problem. Specifically, a weibo from a user is represented as a sequence of feature values by feature hashing and whether the user account is verified is the corresponding label to predict. A deep learning approach is proposed for solving verified account prediction in this formulation. The proposed approach significantly outperforms the shallow learning methods in the comparisons in terms of accuracy and F1 by large margins in the experiments.
Active DNA demethylation via ten-eleven translocation (TET) family enzymes is essential for epigenetic reprogramming in cell state transitions. TET enzymes catalyze up to three successive oxidations ...of 5-methylcytosine (5mC), generating 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), or 5-carboxycytosine (5caC). Although these bases are known to contribute to distinct demethylation pathways, the lack of tools to uncouple these sequential oxidative events has constrained our mechanistic understanding of the role of TETs in chromatin reprogramming. Here, we describe the first application of biochemically engineered TET mutants that unlink 5mC oxidation steps, examining their effects on somatic cell reprogramming. We show that only TET enzymes proficient for oxidation to 5fC/5caC can rescue the reprogramming potential of Tet2-deficient mouse embryonic fibroblasts. This effect correlated with rapid DNA demethylation at reprogramming enhancers and increased chromatin accessibility later in reprogramming. These experiments demonstrate that DNA demethylation through 5fC/5caC has roles distinct from 5hmC in somatic reprogramming to pluripotency.
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•TET mutants that stall oxidation at 5hmC uncouple active DNA demethylation pathways•TET-mediated oxidation to 5fC/5caC, but not 5hmC, promotes iPSC reprogramming efficiency•Novel base resolution-sequencing methods reveal distinctive roles for 5hmC from 5fC/5caC•5fC/5caC is the major driver of DNA demethylation during iPSC reprogramming
Caldwell et al. use novel TET catalytic mutants that uncouple two distinct mechanisms of active DNA demethylation: passive loss of 5hmC and direct excision of 5fC/5caC. They identify the 5fC/5caC pathway as the major driver of DNA demethylation during iPSC reprogramming, with important roles in gene regulation and chromatin reorganization.
Objective
Injuries are a major burden on the Australian healthcare system. Power tool usage is a common cause of accidental injury. A better understanding of the trends of power tool injuries will ...inform prevention strategies and potentially mitigate costs.
Methods
The ED databases from two level 1 hospitals were reviewed for presentations between 2005 and 2015 resulting from accidental injury with power tools. A subgroup of patients presenting to one hospital between 2016 and 2017 were interviewed about the activities and circumstances that led to their injuries, and followed up 3 months later to assess outcomes.
Results
A total of 4057 cases of accidental injury from power tool use were identified. Power saws and grinders contributed to 54% of injuries. Most injuries were located on an upper limb (48%) or the head and neck (30%). Over half (54%) of all head injuries were associated with metal and wood fragments to the eye from grinders, drills and saws. Hospital admission rates were highest for patients aged >60 years. Injuries to females were <5% of all presentations, but 40% of those caused by lawnmowers. Among the 200 patients interviewed, lapses in concentration during use, and modification and inappropriate use of a power tool were the main contributors to injury. Recovery periods >3 months were common.
Conclusions
Accidental injuries from power tool use have a considerable impact on ED resources and can affect the long‐term quality of life of those injured. Effective education about safe usage and protection may prevent many injuries.
Discussions of cross-border marriages between women from developing countries and men from economically advanced countries often focus on the objectification of women, while the process through which ...men are presented as “marriageable entities” is rarely examined. In this article, I explore the case of China, where middle-aged, divorced women are seeking second-chance marriages with Western men via international cyber-dating agencies. Contrary to the stereotypical portrayal of Western men as rich and powerful in the Chinese media, many of the Western men enrolled at the cyber-dating agencies I am studying earn a modest income. I analyze the agencies’ portrayal of their Western male clients as caring, family oriented, and worthy of marrying despite their lack of wealth. Results from this article show that masculinity is fluid, malleable, and continuously being reconstructed in accordance with the changing demographic and socioeconomic patterns of the globalizing world.
Modification of cytosine-guanine dinucleotides (CpGs) is a key part of mammalian epigenetic regulation and helps shape cellular identity. Tet enzymes catalyze stepwise oxidation of 5-methylcytosine ...(mC) in CpGs to 5-hydroxymethylcytosine (hmC), or onward to 5-formylcytosine (fC) or 5-carboxylcytosine (caC). The multiple mC oxidation products, while intricately linked, are postulated to play independent epigenetic roles, making it critical to understand how the products of stepwise oxidation are established and maintained. Using highly sensitive isotope-based studies, we newly show that Tet2 can yield fC and caC by iteratively acting in a single encounter with mC-containing DNA, without release of the hmC intermediate, and that the modification state of the complementary CpG has little impact on Tet2 activity. By revealing Tet2 as an iterative, de novo mC oxygenase, our study provides insight into how features intrinsic to Tet2 shape the epigenetic landscape.
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