Begumanker8932

PURPOSE To develop an automated pipeline based on convolutional neural networks to segment lumbar intervertebral discs and characterize their biochemical composition using voxel-based relaxometry, and establish local associations with clinical measures of disability, muscle changes, and other symptoms of lower back pain. METHODS This work proposes a new methodology using MRI (n = 31, across the spectrum of disc degeneration) that combines deep learning-based segmentation, atlas-based registration, and statistical parametric mapping for voxel-based analysis of T1ρ and T2 relaxation time maps to characterize disc degeneration and its associated disability. RESULTS Across degenerative grades, the segmentation algorithm produced accurate, high-confidence segmentations of the lumbar discs in two independent data sets. Manually and automatically extracted mean disc T1ρ and T2 relaxation times were in high agreement for all discs with minimal bias. On a voxel-by-voxel basis, imaging-based degenerative grades were strongly negatively correlated with T1ρ and T2 , particularly in the nucleus. Stratifying patients by disability grades revealed significant differences in the relaxation maps between minimal/moderate versus severe disability The average T1ρ relaxation maps from the minimal/moderate disability group showed clear annulus nucleus distinction with a visible midline, whereas the severe disability group had lower average T1ρ values with a homogeneous distribution. CONCLUSION This work presented a scalable pipeline for fast, automated assessment of disc relaxation times, and voxel-based relaxometry that overcomes limitations of current region of interest-based analysis methods and may enable greater insights and associations between disc degeneration, disability, and lower back pain. © 2020 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.BACKGROUND Perinatal conditions may be associated with future allergic disease; however, data are conflicting and incomplete for childhood allergic rhinitis (AR). The aim of this study was to examine pregnancy outcome (cesarean delivery, preterm birth, low birthweight) and offspring AR as defined by national registers. METHODS Nationwide longitudinal cohort study using prospectively recorded register data from 1 059 600 singleton livebirths born in Sweden in 2001-2012. Cox regression adjusted for infant sex and maternal factors (age at delivery, country of birth, parity, smoking, body mass index, and asthma/pulmonary disease) estimated hazard ratios (HRs) for AR during childhood. RESULTS During the study period 2001-2013, 22 386 (2.11%) children were diagnosed with AR. AR was more common in infants born through cesarean delivery (2.34%) than in those born vaginally (2.10%) (HR = 1.12; 95% confidence interval [95% CI] = 1.08-1.16). This was equivalent to one extra case of AR in 383 children followed up in our study. AR was also associated with moderately preterm birth (≥32-36 weeks of gestation HR = 1.12, 95% CI = 1.04-1.20), large for gestational age (HR = 1.05, 95% CI = 1.01-1.10), and low ( less then 7) 5-minute Apgar score (HR = 1.15, 95% CI = 1.02-1.30). Similar risk estimates were obtained when we restricted the outcome to ≥2 hospital-based records of AR. No association was observed between very preterm birth, post-term birth, low birthweight, or small for gestational age and AR. CONCLUSION Our study indicates an association between pregnancy outcomes and childhood AR, although observed effect sizes were generally modest. © 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.The gut microbiome is an integral part of a species' ecology, but we know little about how host characteristics impact its development in wild populations. Here, we explored the role of such intrinsic factors in shaping the gut microbiome of northern elephant seals (Mirounga angustirostris) during a critical developmental window of 6 weeks after weaning, when the pups stay ashore without feeding. We found substantial sex differences in the early-life gut microbiome, even though males and females could not yet be distinguished morphologically. Sex and age both explained around 15% of the variation in gut microbial beta diversity, while microbial communities sampled from the same individual showed high levels of similarity across time, explaining another 40% of the variation. Only a small proportion of the variation in beta diversity was explained by health status, assessed by full blood counts, but clinically healthy individuals had a greater microbial alpha diversity than their clinically abnormal peers. Across the post-weaning period, the northern elephant seal gut microbiome was highly dynamic. We found evidence for several colonization and extinction events as well as a decline in Bacteroides and an increase in Prevotella, a pattern that has previously been associated with the transition from nursing to solid food. Lastly, we show that genetic relatedness was correlated with gut microbiome similarity in males but not females, again reflecting early sex differences. Our study represents a naturally diet-controlled and longitudinal investigation of how intrinsic factors shape the early gut microbiome in a species with extreme sex differences in morphology and life history. © 2020 The Authors. Molecular Ecology published by John Wiley & Sons Ltd.In domestic goats, the polled intersex syndrome (PIS) refers to XX female-to-male sex reversal associated with the absence of horn growth (polled). The causal variant was previously reported as a 11.7 kb deletion at approximately 129 Mb on chromosome 1 that affects the transcription of both FOXL2 and several long non-coding RNAs. In the meantime the presence of different versions of the PIS deletion was postulated and trials to establish genetic testing with the existing molecular genetic information failed. Therefore, we revisited this variant by long-read whole-genome sequencing of two genetically female (XX) goats, a PIS-affected and a horned control. This revealed the presence of a more complex structural variant consisting of a deletion with a total length of 10 159 bp and an inversely inserted approximately 480 kb-sized duplicated segment of a region located approximately 21 Mb further downstream on chromosome 1 containing two genes, KCNJ15 and ERG. Publicly available short-read whole-genome sequencing data, Sanger sequencing of the breakpoints and FISH using BAC clones corresponding to both involved genome regions confirmed this structural variant. A diagnostic PCR was developed for simultaneous genotyping of carriers for this variant and determination of their genetic sex. We showed that the variant allele was present in all 334 genotyped polled goats of diverse breeds and that all analyzed 15 PIS-affected XX goats were homozygous. Our findings enable for the first time a precise genetic diagnosis for polledness and PIS in goats and add a further genomic feature to the complexity of the PIS phenomenon. © 2020 Stichting International Foundation for Animal Genetics.BACKGROUND Behçet's disease (BD) is a rare, multisystem vasculitis disease characterized by recurrent orogenital ulcerations with its etiology remained unclear. The transcription factor p53 has been reported to be upregulated in some autoimmune diseases, such as lupus erythematosus, dermatomyositis, and psoriasis. However, little is known about its alteration in BD. METHODS Keratinocyte cultures of both skin and oral origins were treated sera of 18 Behcet patients for 24 hours and analyzed by indirect immunofluorescence for p53 expression. The specificity of p53 expression was confirmed by siRNA-mediated p53 knockdown and the serum IgG removal studies. The expression of p53 levels was quantitatively analyzed with ImageJ. RESULTS It was shown that the expression of p53 is increased in skin and oral keratinocyte cell lines, in both the nucleus and cytoplasm of cells treated with patient sera compared to controls. Either p53 knockdown or IgG removal results in a reduction of p53 levels relative to cells treated with patient sera without p53 knockdown or IgG depletion. CONCLUSIONS This in vitro study provides the first evidence that BD sera can induce the p53 expression in keratinocytes that may have implications in Behcet pathogenesis. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.BACKGROUND In 2015, a previously unrecognized intracytoplasmic erythrocytic inclusion was discovered in anemic wild-caught adult gopher tortoises (Gopherus polyphemus). Subsequently, molecular diagnostics revealed this inclusion to be a novel Anaplasma sp. OBJECTIVES The goal of this study was to morphologically characterize these erythrocytic inclusions by light and transmission electron microscopy (TEM). METHODS Blood samples were taken from two car-injured wild-caught gopher tortoises for the preparation of Wright-Giemsa stained smears and TEM specimens. CBC data were serially performed and morphologically examined during treatment periods. RESULTS Studies revealed a moderate to severe anemia with moderate regeneration as indicated by polychromasia and the presence of immature erythroid precursors. In addition, on light microscopy, one to two variably-sized round basophilic stippled paracentral erythrocytic inclusions were present per cell in both animals and involved 10%-25% of erythrocytes. Selleckchem Guggulsterone E&Z TEM identified the intraerythrocytic inclusions as discrete membrane-bound cytoplasmic vacuoles (morulae) containing membrane-bound bacterial subunits that were of variable size, shape, and electron density. Serial hematologic data indicated complete remission of the infection in response to a single long-term course of doxycycline. CONCLUSIONS The presence of a regenerative anemia in gopher tortoises from Florida revealed a newly recognized bacterial species that has morphologic characteristics similar to members of the genus Anaplasma. © 2020 American Society for Veterinary Clinical Pathology.Direct-acting antiviral agents (DAAs) represent a class of drugs targeting viral proteins and have been demonstrated to be very successful in combating viral infections in clinic. However, DAAs suffer from several inherent limitations, including narrow-spectrum antiviral profiles and liability to drug resistance, and hence there are still unmet needs in the treatment of viral infections. In comparison, host targeting antivirals (HTAs) target host factors for antiviral treatment. Since host proteins are probably broadly required for various viral infections, HTAs are not only perceived, but also demonstrated to exhibit broad-spectrum antiviral activities. In addition, host proteins are not under the genetic control of viral genome, and hence HTAs possess much higher genetic barrier to drug resistance as compared with DAAs. In recent years, much progress has been made to the development of HTAs with the approval of chemokine receptor type 5 antagonist maraviroc for human immunodeficiency virus treatment and more in the pipeline for other viral infections. In this review, we summarize various host proteins as antiviral targets from a medicinal chemistry prospective. Challenges and issues associated with HTAs are also discussed. © 2020 Wiley Periodicals, Inc.