Simpsonasmussen6159

50 x 10-8 for rs62053992. In the replication stage, among 4 significant and independent genetic variants, rs2049604 in the FOXP2 gene and rs62053992 in the LINC01572 gene were weakly replicated in GSSFHS (P = 0.0240 and P = 0.0202, respectively). CONCLUSIONS We have identified 3 loci associated with neck or shoulder pain in the UK Biobank cohort, two of which were weakly supported in a replication cohort. Further evidence is needed to confirm their roles in neck or shoulder pain. Hexadimethrine Bromide © The Author(s) 2020. Published by Oxford University Press.BACKGROUND As part of the Household Influenza Vaccine Evaluation (HIVE) study, acute respiratory infections (ARI) have been identified in children and adults over 8 years. METHODS Annually, 890 to 1441 individuals were followed and contacted weekly to report ARIs. Specimens collected during illness were tested for human coronaviruses (HCoV) types OC43, 229E, HKU1, and NL63. RESULTS In total, 993 HCoV infections were identified over 8 years, with OC43 most commonly seen and 229E the least. HCoVs were detected in a limited time period, between December and April/May, and peaked in January/February. Highest infection frequency was in children less then 5 years (18 per 100 person-years), with little variation in older age groups (range 7 to 11 per 100 person-years). Overall, 9% of adult cases and 20% of cases in children were associated with medical consultation. Of the 993 infections, 260 were acquired from an infected household contact. The serial interval between index and household-acquired cases ranged from 3.2 to 3.6 days and the secondary infection risk ranged from 7.2% to 12.6% by type. CONCLUSIONS Coronaviruses are sharply seasonal. They appear, based on serial interval and secondary infection risk, to have similar transmission potential to influenza A(H3N2) in the same population. © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.Circular DNA is ubiquitous in nature in the form of plasmids, circular DNA viruses, and extrachromosomal circular DNA (eccDNA) in eukaryotes. Sequencing of such molecules is essential to profiling virus distributions, discovering new viruses and understanding the roles of eccDNAs in eukaryotic cells. Circular DNA enrichment sequencing (CIDER-Seq) is a technique to enrich and accurately sequence circular DNA without the need for polymerase chain reaction amplification, cloning, and computational sequence assembly. The approach is based on randomly primed circular DNA amplification, which is followed by several enzymatic DNA repair steps and then by long-read sequencing. CIDER-Seq includes a custom data analysis package (CIDER-Seq Data Analysis Software 2) that implements the DeConcat algorithm to deconcatenate the long sequencing products of random circular DNA amplification into the intact sequences of the input circular DNA. The CIDER-Seq data analysis package can generate full-length annotated virus genomes, as well as circular DNA sequences of novel viruses. Applications of CIDER-Seq also include profiling of eccDNA molecules such as transposable elements (TEs) from biological samples. The method takes ~2 weeks to complete, depending on the computational resources available. Owing to the present constraints of long-read single-molecule sequencing, the accuracy of circular virus and eccDNA sequences generated by the CIDER-Seq method scales with sequence length, and the greatest accuracy is obtained for molecules less then 10 kb long.Precision oncology relies on accurate discovery and interpretation of genomic variants, enabling individualized diagnosis, prognosis and therapy selection. We found that six prominent somatic cancer variant knowledgebases were highly disparate in content, structure and supporting primary literature, impeding consensus when evaluating variants and their relevance in a clinical setting. We developed a framework for harmonizing variant interpretations to produce a meta-knowledgebase of 12,856 aggregate interpretations. We demonstrated large gains in overlap between resources across variants, diseases and drugs as a result of this harmonization. We subsequently demonstrated improved matching between a patient cohort and harmonized interpretations of potential clinical significance, observing an increase from an average of 33% per individual knowledgebase to 57% in aggregate. Our analyses illuminate the need for open, interoperable sharing of variant interpretation data. We also provide a freely available web interface (search.cancervariants.org) for exploring the harmonized interpretations from these six knowledgebases.An amendment to this paper has been published and can be accessed via a link at the top of the paper.The enhancement of immune responses upon treatment with immune checkpoint inhibitors can have the desired outcome of reinvigorating antitumour immune surveillance, but often at the expense of immune-related adverse events (irAEs). This novel disease entity often prompts comparisons with, and extrapolation of treatment approaches from, primary autoimmune disorders. Accordingly, current treatment guidelines for irAEs make generic recommendations adapted from the literature describing primary autoimmune diseases, without taking into consideration the substantial disparity of the immunohistopathological findings within each organ affected by an irAE. The treatment modalities themselves are complex and have many potential drawbacks, such as serious and rarely fatal infections, drug toxicities overlapping with irAEs and the risk of compromising cancer immune surveillance. Herein, we provide an overview of key cellular and soluble immunological factors mediating irAEs and propose a model integrating this knowledge with the immunohistopathological findings of the affected organs for a personalized decision-making process for each patient.Multiplicity of infection (MOI) and genetic diversity of P. falciparum infections are important surrogate indicators for assessing malaria transmission intensity in different regions of endemicity. Determination of MOI and diversity of P. falciparum among asymptomatic carriers will enhance our understanding of parasite biology and transmission to mosquito vectors. This study examined the MOI and genetic diversity of P. falciparum parasite populations circulating in Mbita, a region characterized as one of the malaria hotspots in Kenya. The genetic diversity and multiplicity of P. falciparum infections in 95 asymptomatic school children (age 5-15 yrs.) residing in Mbita, western Kenya were assessed using 10 polymorphic microsatellite markers. An average of 79.69% (Range 54.84-95.74%) of the isolates analysed in this study were polyclonal infections as detected in at least one locus. A high mean MOI of 3.39 (Range 2.24-4.72) and expected heterozygosity (He) of 0.81 (Range 0.57-0.95) was reported in the study population.