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Motivation Several computational and statistical methods have been developed to analyze data generated through the 3C-based methods, especially the Hi-C. Most of the existing methods do not account for dependency in Hi-C data. Results Here, we present ZipHiC, a novel statistical method to explore Hi-C data focusing on the detection of enriched contacts. ZipHiC implements a Bayesian method based on a hidden Markov random field (HMRF) model and the Approximate Bayesian Computation (ABC) to detect interactions in two-dimensional space based on a Hi-C contact frequency matrix. ZipHiC uses data on the sources of biases related to the contact frequency matrix, allows borrowing information from neighbours using the Potts model and improves computation speed using the ABC model. In addition to outperforming existing tools on both simulated and real data, our model also provides insights into different sources of biases that affects Hi-C data. We show that some datasets display higher biases from DNA accessibility or Transposable Elements content. Furthermore, our analysis in Drosophila melanogaster showed that approximately half of the detected significant interactions connect promoters with other parts of the genome indicating a functional biological role. Finally, we found that the micro-C datasets display higher biases from DNA accessibility compared to a similar Hi-C experiment, but this can be corrected by ZipHiC. Availability and implementation The R scripts are available at https://github.com/igosungithub/HMRFHiC.git. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Context: Oxidative stress plays an indispensable role in pathogenesis of Graves' orbitopathy (GO). Ferroptosis is a newly discovered form of cell death resulting from lipid peroxidation. Little is known about the role of ferroptosis in GO. Objective: We aimed to identify the divergent role of ferroptosis in the GO and control orbital fibroblasts (OFs). Methods: Orbital fat/connective tissues and serum immunoglobulins (Igs) were collected from GO and control subjects. Cell viability and lipid peroxidation were measured to evaluate ferroptosis sensitivity. Pyruvate dehydrogenase kinase 2 (PDK2) level and oxygen consumption rate were quantified to assess glycolysis status. Results: Primary OFs were cultured from orbital tissues. Ferroptosis was induced by cystine deprivation and/or erastin treatment. The GO OFs possessed stronger resistance to ferroptosis than the control OFs. Selenium, a potential ferroptosis inhibitor, protected the control OFs from ferroptosis. Both transcriptomic and proteomic analyses indicated glycolytic shift in the GO OFs. Metabolic profiling, PDK2 quantification, and oxygen consumption assay confirmed enhanced glycolysis in the GO OFs. Inhibition of glycolysis by PDK2 knockdown and dichloroacetic acid (DCA) promoted ferroptosis sensitivity in the GO OFs. The ferroptosis-sensitizing effects of DCA were also observed when the GO OFs were treated with GO-Igs. IGF1R overexpression in the GO OFs contributed to glycolysis shift. IGF1R inhibitory antibodies facilitated ferroptosis induction in the GO OFs, but the effects were less remarkable under GO-Igs treatment. Conclusion: These study findings establish that glycolysis facilitates ferroptosis resistance in the GO OFs, providing insights into the therapeutic role of glycolysis for GO treatment. [ABSTRACT FROM AUTHOR]

Motivation Protein–protein interaction (PPI), as a relative property, is determined by two binding proteins, which brings a great challenge to design an expert model with an unbiased learning architecture and a superior generalization performance. Additionally, few efforts have been made to allow PPI predictors to discriminate between relative properties and intrinsic properties. Results We present a sequence-based approach, DeepTrio, for PPI prediction using mask multiple parallel convolutional neural networks. Experimental evaluations show that DeepTrio achieves a better performance over several state-of-the-art methods in terms of various quality metrics. Besides, DeepTrio is extended to provide additional insights into the contribution of each input neuron to the prediction results. Availability and implementation We provide an online application at http://bis.zju.edu.cn/deeptrio. The DeepTrio models and training data are deposited at https://github.com/huxiaoti/deeptrio.git. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

The stimulator of interferon gene (STING) pathway controls both DNA and RNA virus infection. STING is essential for induction of innate immune responses during DNA virus infection, while its mechanism against RNA virus remains largely elusive. We show that STING signaling is crucial for restricting chikungunya virus infection and arthritis pathogenesis. Sting-deficient mice (Stinggt/gt) had elevated viremia throughout the viremic stage and viral burden in feet transiently, with a normal type I IFN response. Stinggt/gt mice presented much greater foot swelling, joint damage, and immune cell infiltration than wild-type mice. Intriguingly, expression of interferon-γ and Cxcl10 was continuously upregulated by approximately 7 to 10-fold and further elevated in Stinggt/gt mice synchronously with arthritis progression. However, expression of chemoattractants for and activators of neutrophils, Cxcl5, Cxcl7, and Cxcr2 was suppressed in Stinggt/gt joints. These results demonstrate that STING deficiency leads to an aberrant chemokine response that promotes pathogenesis of CHIKV arthritis. [ABSTRACT FROM AUTHOR]

Objective: Access to palliative care (PC) is important for many patients with uncontrolled symptom burden from serious or complex illness. However, many patients who could benefit from PC do not receive it early enough or at all. We sought to address this problem by building a predictive model into a comprehensive clinical framework with the aims to (i) identify in-hospital patients likely to benefit from a PC consult, and (ii) intervene on such patients by contacting their care team.Materials and Methods: Electronic health record data for 68 349 inpatient encounters in 2017 at a large hospital were used to train a model to predict the need for PC consult. This model was published as a web service, connected to institutional data pipelines, and consumed by a downstream display application monitored by the PC team. For those patients that the PC team deems appropriate, a team member then contacts the patient's corresponding care team.Results: Training performance AUC based on a 20% holdout validation set was 0.90. The most influential variables were previous palliative care, hospital unit, Albumin, Troponin, and metastatic cancer. The model has been successfully integrated into the clinical workflow making real-time predictions on hundreds of patients per day. The model had an "in-production" AUC of 0.91. A clinical trial is currently underway to assess the effect on clinical outcomes.Conclusions: A machine learning model can effectively predict the need for an inpatient PC consult and has been successfully integrated into practice to refer new patients to PC. [ABSTRACT FROM AUTHOR]

Objective: Despite increased use of electronic health records (EHRs), the clinical impact of system downtime is unknown.Materials and Methods: This retrospective matched cohort study evaluated the impact of EHR downtime episodes lasting more than 60 minutes over a 6-year study period. Patients age 18 years or older who underwent surgical procedures at least 60 minutes in duration with an inpatient stay exceeding 24 hours within the study period were eligible for inclusion. Out of 4115 patients exposed to 1 of 176 EHR downtime episodes, 4103 patients were matched to an unexposed cohort in a 1:1 ratio. Multivariable regression analysis, as well as trend analysis for effect of duration of downtime on outcomes, was performed.Results: Downtime-exposed patients had operating room duration 1.1 times longer (p < .001) and postoperative length of stay 1.04 times longer (p = .007) compared to unexposed patients. The 30-day mortality rates were similar between these groups (odds ratio 1.26, p > .05). In trend analysis, there was no association between duration of downtime with respect to evaluated outcomes, postoperative length of stay, and 30-day mortality.Conclusion: EHR downtime had no impact on 30-day mortality. Potential associations for increased postoperative length of stay and duration of time spent in the operating room were observed among downtime-exposed patients. No trend effect was observed with respect to duration of downtime and postoperative length of stay and 30-day mortality rates. [ABSTRACT FROM AUTHOR]

Rice blast disease caused by the fungus Magnaporthe grisea (M. grisea) is one of the most serious diseases for the cultivated rice Oryza sativa (O. sativa). A key factor causing rice blast disease and defense might be protein–protein interactions (PPIs) between rice and fungus. In this research, we have developed a computational pipeline to predict PPIs between blast fungus and rice. After cross-prediction by interolog-based and domain-based method, we achieved 532 potential PPIs between 27 fungus proteins and 236 rice proteins. Accuracy of jackknife test, 10-fold cross-validation test and independent test for these PPIs were 90.43, 93.85 and 84.67%, respectively, by using support vector machine classification method. Meanwhile, the pathogenic genes of blast fungus were enriched in the predicted PPIs network when compared with 1000 random interaction networks. The rice regulatory network was downloaded and divided into 228 subnetworks with over six nodes, and the top seven subnetworks affected by blast fungus through PPIs were investigated. The results indicated that 34 upregulated and 12 downregulated master regulators in rice interacting with the fungus proteins in response to the infection of blast fungus. The common master regulators in rice in response to the infection of M. grisea , Xanthomonas oryzae pv.oryzae and rice stripe virus were analyzed. The ubiquitin proteasome pathway was the common pathway in rice regulated by these three pathogens, while apoptosis signaling pathway was induced by fungus and bacteria. In summary, the results in this article provide insight into the process of blast fungus infection. [ABSTRACT FROM AUTHOR]

COVID-19 biomarkers,drug targets and bioinformatics approaches for drug repurposing The identification of COVID-19 biomarkers, the discovery of therapeutictargetsfordrugsandthebioinformaticsapproaches fordrugrepurposingarekeyresearchtopicstoaddressforfacing the COVID-19 disease. Bioinformatics tools and resources for SARS-CoV-2 and COVID-19 research Next-generationsequencingisthecentraltechnologyfordetecting genomes of SARS-CoV-2 that provides the basic data about the virus. Bioinformatics helping to mitigate the impact of COVID-19 - Editorial. [Extracted from the article]

Biographers and critics of D. H. Lawrence have long recognized the significance of his various schemes to establish small utopian communities in locations such as Florida, the Andes, Palestine, Connecticut, and New Mexico. Recent accounts have, however, sought to distinguish the so-called 'Rananim' fantasy which Lawrence created with his wife and a select group of friends over Christmas and New Year 1914–1915 from his later schemes for communitarian living. This essay offers a detailed and revisionary reassessment of the contexts of the Rananim fantasy, drawing on little-known evidence and a previously overlooked textual source to suggest that the largely forgotten playwright, author and critic Gilbert Cannan shared Lawrence's anti-war views in this period and actively participated in the formulation of Rananim and the associated plan to inhabit an island in the South Seas. [ABSTRACT FROM AUTHOR]

Objective. Gout is associated with dyslipidaemia. Association of the apolipoprotein A1-C3-A4 gene cluster with gout has previously been reported in a small study. To investigate a possible causal role for this locus in gout, we tested the association of genetic variants from APOA1 (rs670) and APOC3 (rs5128) with gout. Methods. We studied data for 2452 controls and 2690 clinically ascertained gout cases of European and New Zealand Polynesian (Maōri and Pacific) ancestry. Data were also used from the publicly available Atherosclerosis Risk in Communities study (n = 5367) and the Framingham Heart Study (n = 2984). Multivariate adjusted logistic and linear regression was used to test the association of single-nucleotide polymorphisms with gout risk, serum urate, triglyceride and high-density lipoprotein cholesterol (HDL-C). Results. In Polynesians, the T-allele of rs670 (APOA1) increased (odds ratio, OR= 1.53, P= 4.9-10-6) and the G-allele of rs5128 (APOC3) decreased the risk of gout (OR= 0.86, P = 0.026). In Europeans, there was a strong trend to a risk effect of the T-allele for rs670 (OR= 1.1, P= 0.055), with a significant protective effect of the G-allele for rs5128 being observed after adjustment for triglycerides and HDL-C (OR= 0.8, P= 0.039). The effect at rs5128 was specific to males in both Europeans and Polynesians. Association in Polynesians was independent of any effect of rs670 and rs5128 on triglyceride and HDL-C levels. There was no evidence for association of either single-nucleotide polymorphism with serum urate levels (P≥0.10). Conclusion. Our data, replicating a previous study, supports the hypothesis that the apolipoprotein A1-C3-A4 gene cluster plays a causal role in gout. [ABSTRACT FROM AUTHOR]

The epigenetic mechanisms, including histone modifications, DNA cytosine methylation, histone variants and noncoding RNAs (ncRNAs), play a key role in determining transcriptional outcomes. Recently, many studies have demonstrated that the different epigenetic mechanisms interplay with each other rather than work independently. In this article, we outline a framework for how different epigenetic mechanisms work with each other in Arabidopsis thaliana. We build a network of cross-talk between chromatin marks based on six classes of cross-talk interactions. The first pattern details coordinated modifications that act together to enhance or repress gene expression. The second pattern details bivalent modifications that act antagonistically toward gene expression. The third pattern is for unilateral promotion of one modification by the existence of another modification. The fourth pattern is for unilateral inhibition of one modification by another modification. The fifth pattern is for mutual inhibitory patterns. The sixth pattern is for epigenetic modifications that appear independent. We also explore the mutual regulation between chromatin marks and ncRNAs in various ways. These regulations can be divided into six parts: how ncRNA affects the binding of chromatin mark, such as miR2Epi, siR2Epi and lncR2Epi; how chromatin mark regulates ncRNA, such as Epi2miR, Epi2siR and Epi2lncR. A comprehensive network of cross-talk between different epigenetic mechanisms will help in fully understanding the functional roles and biological impacts of epigenetic regulation. [ABSTRACT FROM AUTHOR]

Background: The association between elevated admission serum uric acid (SUA) and risk of in-hospital acute kidney injury (AKI) is limited. The aim of this studywas to assess the risk of developing AKI in all hospitalized patients with various admission SUA levels. Methods: This is a single-center retrospective study conducted at a tertiary referral hospital. All hospitalized adult patientswho had admission SUA available from January 2011 through December 2013 were analyzed in this study. Admission SUA was categorized based on its distribution into six groups (<3.4, 3.4-4.5, 4.5-5.8, 5.8-7.6, 7.6-9.4 and >9.4 mg/dL). The primary outcome was in-hospital AKI occurring after hospital admission. Logistic regression analysiswas performed to obtain the odds ratio (OR) of AKI of various admission SUA levels using the most common SUA level range (5.8-7.6 mg/dL) as the reference group. Results: Of 1435 patients enrolled, AKI occurred in 263 patients (18%). The incidence of AKI and need for dialysis was increased in patients with higher admission SUA levels. After adjusting for potential confounders, SUA >9.4 mg/dL was associated with an increased risk of developing AKI, with ORs of 1.79 [95% confidence interval (CI) 1.13-2.82]. Conversely, admission SUA <3.4 and 3.4-4.5 mg/dL were associated with a decreased risk of developing AKI, with ORs of 0.38 (95% CI 0.17-0.75) and 0.50 (95% CI 0.28-0.87), respectively. Conclusions: Elevated admission SUA was associated with an increased risk for in-hospital AKI. [ABSTRACT FROM AUTHOR]

Natural antisense transcripts (NATs) are endogenous transcripts that can form double-stranded RNA structures. Many protein-coding genes (PCs) and non-protein-coding genes (NPCs) tend to form cis-NATs and trans-NATs, respectively. In this work, we identified 4,080 cis-NATs and 2,491 trans-NATs genome-widely in Arabidopsis. Of these, 5,385 NAT-siRNAs were detected from the small RNA sequencing data. NAT-siRNAs are typically 21nt, and are processed by Dicer-like 1 (DCL1)/DCL2 and RDR6 and function in epigenetically activated situations, or 24nt, suggesting these are processed by DCL3 and RDR2 and function in environment stress. NAT-siRNAs are significantly derived from PC/PC pairs of trans-NATs and NPC/NPC pairs of cis-NATs. Furthermore, NAT pair genes typically have similar pattern of epigenetic status. Cis-NATs tend to be marked by euchromatic modifications, whereas trans-NATs tend to be marked by heterochromatic modifications. [ABSTRACT FROM AUTHOR]

A recent highlight of genomics research has been the discovery of many families of transcripts which have function but do not code for proteins. An important group is long noncoding RNAs (IncRNAs), which are typically longer than 200 nt, and whose members originate from thousands of loci across genomes. We review progress in understanding the biogenesis and regulatory mechanisms of lncRNAs. We describe diverse computational and high throughput technologies for identifying and studying lncRNAs. We discuss the current knowledge of functional elements embedded in lncRNAs as well as insights into the IncRNA-based regulatory network in animals. We also describe genome-wide studies of large amount of IncRNAs in plants, as well as knowledge of selected plant IncRNAs with a focus on biotic/abiotic stress-responsive IncRNAs. [ABSTRACT FROM AUTHOR]

During cell division, a bipolar array of microtubules forms the spindle through which the forces required for chromosome segregation are transmitted. Interestingly, the spindle as a whole is stable enough to support these forces even though it is composed of dynamic microtubules, which are constantly undergoing periods of growth and shrinkage. Indeed, the regulation of microtubule dynamics is essential to the integrity and function of the spindle. We show here that a member of an important class of microtubuledepolymerizing kinesins, KLP10A, is required for the proper organization of the acentrosomal meiotic spindle in Drosophila melanogaster oocytes. In the absence of KLP10A, microtubule length is not controlled, resulting in extraordinarily long and disorganized spindles. In addition, the interactions between chromosomes and spindle microtubules are disturbed and can result in the loss of contact. These results indicate that the regulation of microtubule dynamics through KLP10A plays a critical role in restricting the length and maintaining bipolarity of the acentrosomal meiotic spindle and in promoting the contacts that the chromosomes make with microtubules required for meiosis I segregation. [ABSTRACT FROM AUTHOR]

This chapter has six sections 1. Pre-1945 Fiction; 2. Post-1945 Fiction; 3. Pre-1950 Drama; 4. Post-1950 Drama; 5. Pre-1950 Poetry. 6. Irish Poetry. Section 1(a) is by Andrew Radford; section 1(b) is by Sam Slote; section 1(c) is by Andrew Harrison; section 1(d) is by Eric Sandberg; section 2 is by Nick Bentley; section 3 is by Rebecca D’Monté; section 4 is by Graham Saunders; section 5 is by Matthew Creasy; section 6 is by Maria Johnston. [ABSTRACT FROM PUBLISHER]

The article presents a narrative bibliography that records and evaluates scholarly writing on modern English literature. It is divided into seven sections including general writing, pre-1945 fiction, post-1945 fiction, pre-1950 drama, post-1950 drama, pre-1950 poetry, and Irish poetry. Cited works include "Transatlantic Literary Studies: A Reader," edited by Susan Manning and Andrew Taylor, Pericles Lewis' "Cambridge Introduction to Modernism," Susan Brook's "Literature and Cultural Criticism in the 1950s: The Feeling Male Body," Elizabeth Schafer's "Lilian Baylis," and Daniel Tobin's "The Book of Irish American Poetry."

The reliable interpretation of Affymetrix GeneChip data is a multi-faceted problem. The interplay between biophysics, bioinformatics and mining of GeneChip surveys is leading to new insights into how best to analyse the data. Many of the molecular processes occurring on the surfaces of GeneChips result from the high surface density of probes. Interactions between neighbouring adjacent probes affect their rate and strength of hybridization to targets. Competing targets may hybridize to the same probe, and targets may partially bind to more than one probe. The formation of these partial hybrids results in a number of probes not reaching thermodynamic equilibrium during hybridization. Moreover, some targets fold up, or cross-hybridize to other targets. Furthermore, probes may fold and can undergo chemical satifration. There are also sequence-dependent differences in the rates of target desorption during the washing stage. Improvements in the mappings between probe sequence and biological data- bases are leading to more accurate gene expression profiles. Moreover, algorithms that combine the intensities of multiple probes into single measures of expression are increasingly dependent upon models of the hybridization processes occurring on GeneChips. The large repositories of GeneChip data can be searched for systematic effects across many experiments. This data mining has led to the discovery of a family of thousands of probes, which show correlated expression across thousands of GeneChip experiments. These probes contain runs of guanines, suggesting that G-quadruplexes are able to form on GeneChips. We discuss the impact of these structures on the inter- pretation of data from GeneChip experiments. [ABSTRACT FROM AUTHOR]

We describe various types of outliers seen in Affymetrix GeneChip data. We have been able to utilise the data in the Gene Expression Omnibus to screen GeneChips across a range of scales, from single probes, to spatially adjacent fractions of arrays, to whole arrays, to whole experiments. In this review we describe a number of causes for why some reported intensities might be misleading on GeneChips. [ABSTRACT FROM AUTHOR]

Chapter XIV of the book "The Year's Work in English Studies," Volume 87, edited by William Baker and Kenneth Womack is presented. It offers a discussion of several studies of modern literature. It states that in "Touch and Intimacy in First World War Literature," by Santanu Das, the intense reaction of novelist Ford Madox Ford to the Great War in his book "Parade's End" is clarified. Meanwhile, it says that the "English Fiction Since 1984: Narrating a Nation," by Brian Finney is another contribution to literary criticism of contemporary fiction.

We present an overview of image-processing methods for Affymetrix GeneChips. All GeneChips are affected to some extent by spatially coherent defects and image processing has a number of potential impacts on the downstream analysis of GeneChip data. Fortunately, there are now a number of robust and accurate algorithms, which identify the most disabling defects. One group of algorithms concentrate on the transformation from the original hybridisation DAT image to the representative CEL file. Another set uses dedicated pattern recognition routines to detect different types of hybridisation defect in replicates. A third type exploits the information provided by public repositories of GeneChips (such as GEO). The use of these algorithms improves the sensitivity of GeneChips, and should be a prerequisite for studies in which there are only few probes per relevant biological signal, such as exon arrays and SNP chips. [ABSTRACT FROM AUTHOR]

Presents a measurement of carbon monoxide (CO) in the starburst of NGC 253. Implications on the lines towards the nucleus of the starburst galaxy NGC 253; Absence of evidence for isotope-selective photodissociation of CO; Existence of barred orbits of NGC 253.

The article discusses the article "Laura Philippine" by D.H. Lawrence, focusing on how the date of composition has never been determined after it was first referenced by Lawrence in a 1928 letter. Information is provided on proposed dates from scholars David Ellis and James T. Boulton before the author goes on to discuss the discovery of a holograph manuscript of the essay which suggests it was composed in April 1927.

A letter to the editor is presented claiming that there is no evidence for association of the systemic lupus erythematosus-associated ITGAM variant, R77H, with rheumatoid arthritis in the Caucasian population.