Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data.

Telomere length is a risk factor in disease and the dynamics of telomere length are crucial to our understanding of cell replication and vitality. The proliferation of whole genome sequencing represents an unprecedented opportunity to glean new insights into telomere biology on a previously unimaginable scale. To this end, a number of approaches for estimating telomere length from whole-genome sequencing data have been proposed. Here we present Telomerecat, a novel approach to the estimation of telomere length. Previous methods have been dependent on the number of telomeres present in a cell being known, which may be problematic when analysing aneuploid cancer data and non-human samples. Telomerecat is designed to be agnostic to the number of telomeres present, making it suited for the purpose of estimating telomere length in cancer studies. Telomerecat also accounts for interstitial telomeric reads and presents a novel approach to dealing with sequencing errors. We show that Telomerecat performs well at telomere length estimation when compared to leading experimental and computational methods. Furthermore, we show that it detects expected patterns in longitudinal data, repeated measurements, and cross-species comparisons. We also apply the method to a cancer cell data, uncovering an interesting relationship with the underlying telomerase genotype

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GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility

Brain Abnormalities in Congenital Fibrosis of the Extraocular Muscles Type 1: A Multimodal MRI Imaging Study.

To explore the possible brain structural and functional alterations in congenital fibrosis of extraocular muscles type 1 (CFEOM1) patients using multimodal MRI imaging.T1-weighted, diffusion tensor images and functional MRI data were obtained from 9 KIF21A positive patients and 19 age- and gender-matched healthy controls. Voxel based morphometry and tract based spatial statistics were applied to the T1-weighted and diffusion tensor images, respectively. Amplitude of low frequency fluctuations and regional homogeneity were used to process the functional MRI data. We then compared these multimodal characteristics between CFEOM1 patients and healthy controls.Compared with healthy controls, CFEOM1 patients demonstrated increased grey matter volume in bilateral frontal orbital cortex and in the right temporal pole. No diffusion indices changes were detected, indicating unaffected white matter microstructure. In addition, from resting state functional MRI data, trend of amplitude of low-frequency fluctuations increases were noted in the right inferior parietal lobe and in the right frontal cortex, and a trend of ReHo increase (p<0.001 uncorrected) in the left precentral gyrus, left orbital frontal cortex, temporal pole and cingulate gyrus.CFEOM1 patients had structural and functional changes in grey matter, but the white matter was unaffected. These alterations in the brain may be due to the abnormality of extraocular muscles and their innervating nerves. Future studies should consider the possible correlations between brain morphological/functional findings and clinical data, especially pertaining to eye movements, to obtain more precise answers about the role of brain area changes and their functional consequence in CFEOM1

Delay-sensitive and delay-insensitive deconvolution perfusion-CT: similar ischemic core and penumbra volumes if appropriate threshold selected for each

Introduction: Perfusion-CT (PCT) processing involves deconvolution, a mathematical operation that computes the perfusion parameters from the PCT time density curves and an arterial curve. Delay-sensitive deconvolution does not correct for arrival delay of contrast, whereas delay-insensitive deconvolution does. The goal of this study was to compare delay-sensitive and delay-insensitive deconvolution PCT in terms of delineation of the ischemic core and penumbra. Methods: We retrospectively identified 100 patients with acute ischemic stroke who underwent admission PCT and CT angiography (CTA), a follow-up vascular study to determine recanalization status, and a follow-up noncontrast head CT (NCT) or MRI to calculate final infarct volume. PCT datasets were processed twice, once using delay-sensitive deconvolution and once using delay-insensitive deconvolution. Regions of interest (ROIs) were drawn, and cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) in these ROIs were recorded and compared. Volume and geographic distribution of ischemic core and penumbra using both deconvolution methods were also recorded and compared. Results: MTT and CBF values are affected by the deconvolution method used (p < 0.05), while CBV values remain unchanged. Optimal thresholds to delineate ischemic core and penumbra are different for delay-sensitive (145% MTT, CBV 2ml × 100g−1 × min−1) and delay-insensitive deconvolution (135% MTT, CBV 2ml × 100g−1 × min−1 for delay-insensitive deconvolution). When applying these different thresholds, however, the predicted ischemic core (p = 0.366) and penumbra (p = 0.405) were similar with both methods. Conclusion: Both delay-sensitive and delay-insensitive deconvolution methods are appropriate for PCT processing in acute ischemic stroke patients. The predicted ischemic core and penumbra are similar with both methods when using different sets of thresholds, specific for each deconvolution method

Directional emissions from perovskite nanocrystals thin film enabled by metasurface integration through one step spin-coating process

Advances in thin film light-emitting devices have fueled the rapid growth of a new class of solid-state lighting devices, featuring low fabrication cost, high quantum efficiency, and broadband spectrum coverage, etc. In contrast to the conventional inorganic semiconductors that rely on lattice matched high crystalline quality substrate, solution processable thin films eliminate the dependence on the substrate, which is highly desired for the ease and versatility of integrations with foreign medium. By taking this advantage, this work developed an ultracompact solution to control the directionality of thin film emitters using integrated dielectric metasurface through one step spin-coating process. As a proof of concept, directional emissions from perovskite nanocrystal thin film, including collimated light emissions and two-dimensional beam steering, are experimentally demonstrated. Notably, our approach, where light emitters were integrated on the back side of substrate after the fabrication of metasurface, judiciously avoids any potential degradation of material optical quality caused by the multi-step nanofabrication. Therefore, it can serve as a generalized scheme to engage the advantageous properties of dielectric metasurface, including the compactness, high efficiency, and beam controllability with the emerging thin film light-emitting diodes (LEDs), which is applicable to a wide range of solution processable materials, including organic light-emitting diodes, quantum-dot light emitting diodes, polymer LEDs, and perovskite LEDs, opening up new pathways to develop low-cost and ultra-compact solid state light sources with versatile beams characteristics. [Figure not available: see fulltext.]

Directional emissions from perovskite nanocrystals thin film enabled by metasurface integration through one step spin-coating process

Advances in thin film light-emitting devices have fueled the rapid growth of a new class of solid-state lighting devices, featuring low fabrication cost, high quantum efficiency, and broadband spectrum coverage, etc. In contrast to the conventional inorganic semiconductors that rely on lattice matched high crystalline quality substrate, solution processable thin films eliminate the dependence on the substrate, which is highly desired for the ease and versatility of integrations with foreign medium. By taking this advantage, this work develops an ultracompact solution to control the directionality of thin film emitters using integrated dielectric metasurface through one step spin-coating process. As a proof of concept, directional emissions from perovskite nanocrystal thin film, including collimated light emissions, two-dimensional beam steering, are experimentally demonstrated. Notably, our approach, where light emitters were integrated on the back side of substrate after the fabrication of metasurface, judiciously avoids any potential degradation of material optical quality caused by the multi-step nanofabrication. Therefore, it can serve as a generalized scheme to engage the advantageous properties of dielectric metasurface, including the compactness, high efficiency, and beam controllability with the emerging thin film LEDs, which is applicable to a wide range of solution processable materials, including organic light-emitting diodes, quantum-dot light emitting diodes, polymer LEDs, and perovskite LEDs, opening up new pathways to develop low-cost, ultra-compact solid state light sources with versatile beams characteristics

fMRI data results.

<p>ALFF increase (p< 0.001, uncorrected) in right inferior parietal lobe and right frontal cortex and ReHo increase (p<0.001 uncorrected) in left precentral gyrus, left orbital frontal cortex, temporal pole and Cingulate gyrus.</p