Highly Sensitive HBsAg, Anti-HBc and Anti HBsAg Titres in Early Diagnosis of HBV Reactivation in Anti-HBc-Positive Onco-Haematological Patients

The role of novel HBV markers in predicting Hepatitis B virus reactivation (HBV-R) in HBsAg-negative/anti-HBc-positive oncohaematological patients was examined. One hundred and seven HBsAg-negative/anti-HBc-positive oncohaematological patients, receiving anti-HBV prophylaxis for >18 months, were included. At baseline, all patients had undetectable HBV DNA, and 67.3% were anti-HBs positive. HBV-R occurred in 17 (15.9%) patients: 6 during and 11 after the prophylaxis period. At HBV-R, the median (IQR) HBV-DNA was 44 (27-40509) IU/mL, and the alanine aminotransferase upper limit of normal (ULN) was 44% (median (IQR): 81 (49-541) U/L). An anti-HBc > 3 cut-off index (COI) plus anti-HBs persistently/declining to <50 mIU/mL was predictive for HBV-R (OR (95% CI): 9.1 (2.7-30.2); 63% of patients with vs. 15% without this combination experienced HBV-R (p < 0.001)). The detection of highly sensitive (HS) HBsAg and/or HBV-DNA confirmed at >2 time points, also predicts HBV-R (OR (95% CI): 13.8 (3.6-52.6); 50% of positive vs. 7% of negative patients to these markers experienced HBV-R (p = 0.001)). HS-HBs and anti-HBc titration proved to be useful early markers of HBV-R. The use of these markers demonstrated that HBV-R frequently occurs in oncohaematological patients with signs of resolved HBV infection, raising issues of proper HBV-R monitoring

Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19

: Pediatric Coronavirus Disease 2019 (pCOVID-19) is rarely severe; however, a minority of children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might develop multisystem inflammatory syndrome in children (MIS-C), with substantial morbidity. In this longitudinal multi-institutional study, we applied multi-omics (analysis of soluble biomarkers, proteomics, single-cell gene expression and immune repertoire analysis) to profile children with COVID-19 (n = 110) and MIS-C (n = 76), along with pediatric healthy controls (pHCs; n = 76). pCOVID-19 was characterized by robust type I interferon (IFN) responses, whereas prominent type II IFN-dependent and NF-κB-dependent signatures, matrisome activation and increased levels of circulating spike protein were detected in MIS-C, with no correlation with SARS-CoV-2 PCR status around the time of admission. Transient expansion of TRBV11-2 T cell clonotypes in MIS-C was associated with signatures of inflammation and T cell activation. The association of MIS-C with the combination of HLA A*02, B*35 and C*04 alleles suggests genetic susceptibility. MIS-C B cells showed higher mutation load than pCOVID-19 and pHC. These results identify distinct immunopathological signatures in pCOVID-19 and MIS-C that might help better define the pathophysiology of these disorders and guide therapy

Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels.

Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy. Enrichment analysis, fine-mapping of urate-associated loci and colocalization with gene expression in 47 tissues implicated the kidney and liver as the main target organs and prioritized potentially causal genes and variants, including the transcriptional master regulators in the liver and kidney, HNF1A and HNF4A. Experimental validation showed that HNF4A transactivated the promoter of ABCG2, encoding a major urate transporter, in kidney cells, and that HNF4A p.Thr139Ile is a functional variant. Transcriptional coregulation within and across organs may be a general mechanism underlying the observed pleiotropy between urate and cardiometabolic traits.The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. Variant annotation was supported by software resources provided via the Caché Campus program of the InterSystems GmbH to Alexander Teumer

Natural Resources Research Institute Technical Report

The South Filson Creek Cu-Ni-PGE-Au-Ag mineral occurrence is located on the western margin of the Duluth Complex in Lake County, northeastern Minnesota. The occurrence of primary magmatic and late-stage, structurally controlled mineralization is located in the South Kawishiwi intrusion of the Duluth Complex, approximately 2200 feet above the basal contact. The primary host rock for the mineralization is a medium-grained augite troctolite. Petrographic studies indicate that there were at least two episodes of mineralization. Deposition of primary, coarse-grained, interstitial pyrrhotite, pentlandite, and chalcopyrite occurred in "cloud zones". Primary mineralization was followed by the introduction of hydrothermal fluids along fracture zones, as evidenced by the formation of hydrous minerals, sulfide replacement textures and geochemical signatures suggestive of remobilization. These late-stage fluids deposited secondary sulfides at redox boundaries created by the primary sulfides. The secondary assemblage includes chalcopyrite, bornite, chalcocite, digenite, covellite, violarite, sphalerite, mackinawite, valleriite, and the platinum group minerals, all which occur in extremely fine, discontinuous veinlets that are rarely recognizable in hand specimen. The veinlets were created by hydrofracturing of silicate minerals due to a volume increase initiated by serpentinization of olivine. These veinlets are always proximal to highly serpentinized fractures and are possibly associated with a proposed NE-trending fault zone along the south branch of Filson Creek. The copper-nickel ratio for the deposit is about 3:1. Platinum + palladium correlates with high copper and sulfur. Also, high inter-element correlation between Cu, Ni, Pd, Pt and Au suggests that secondary enrichment of these elements is local in extent and related to faulting and redox boundaries. Statistical analysis suggests, given the available data, that infill drilling could discover a significant quantity of mineralization. The alteration assemblage associated with the secondary mineralization is serpentine, biotite, stilpnomelane, iddingsite, chlorite, sericite, and clay minerals. The alteration is very subtle and is best recognized in thin section. Both alteration and mineralized zones range in thickness from less than one foot to 90 feet.Natural Resources Research Institute, University of Minnesota, Duluth, 5013 Miller Trunk Highway, Duluth, Minnesota 55811; Dept. Civil and Min. Engineering, University of Minnesota, 500 Pillsbury Drive S.E., Minneapolis, Minnesota 55455; Funded by the Greater Minnesota Corporatio

Molecular and serological characterization of hepatitis B vaccine breakthrough infections in serial samples from two plasma donors

Abstract Background Although vaccines for hepatitis B virus (HBV) are highly effective, HBV infections in vaccinees occur. Index samples of breakthrough infections are typically anti-HBc negative but HBV DNA positive with protective anti-HBs levels while HBsAg detection may be delayed or absent. HBsAg mutations have been associated with some vaccine breakthrough cases. Methods This research characterizes the serological and molecular profiles of vaccine breakthrough infections in serial samples from two commercially available plasma donor panels. Samples were tested with commercially available assays for HBV antigens and antibodies: HBsAg, HBeAg, anti-HBc, anti-HBc IgM, anti-HBe, and anti-HBs. Different immunoassay approaches for earlier detection of breakthrough infection were explored including hepatitis B core-related antigen (HBcrAg), a research assay for preS2 antigen, and a new prototype ARCHITECT HBsAg assay with improved sensitivity. The prototype HBsAg assay is fully automated and involves no sample pre-treatment. Molecular testing included HBV DNA quantitation and sequencing of preS1, preS2, surface, and basal core promoter/core promoter genes. Results Although the research preS2 antigen assay allowed earlier detection of the breakthrough infections than current HBsAg assays and HBcrAg, the new prototype ARCHITECT HBsAg assay provided the earliest serologic detection. The ability of the new prototype HBsAg assay to detect HBsAg in the presence of anti-HBs was investigated using known concentrations of native HBsAg mixed with anti-HBs from a vaccinee. The results demonstrated that the prototype ARCHITECT assay is more sensitive in detecting HBsAg in the presence of anti-HBs than current HBsAg assays. Sequencing revealed multiple substitutions in preS1, preS2, and S regions for one panel including a rare D144N substitution associated with vaccine breakthrough that emerged with increasing frequency as the breakthrough infection developed. Conclusions When compared with other immunoassay approaches, the new prototype ARCHITECT HBsAg assay allows earlier detection of vaccine breakthrough infections and more sensitive detection of HBsAg in the presence of anti-HBs. Molecular characterization of longitudinal samples demonstrated the progressive appearance of a rare HBsAg mutation associated with vaccine breakthrough

Quaking Aspen at the Residential-Wildland Interface: Ungulate Herbivory and Forest Conservation

Quaking aspen (Populus tremuloides Michx.) forests are experiencing numerous impediments across North America. In the West, recent drought, fire suppression, insects, diseases, climate trends, inappropriate management, and ungulate herbivory are impacting these high biodiversity forests. Additionally, ecological tension zones are sometimes created where the above factors intermingle with jurisdictional boundaries. The public-private land interface may result in stress to natural areas where game species nd refuge and plentiful forage at the expense of ecosystem function. We examined putative herbivore impacts to aspen forests at Wolf Creek Ranch (WCR), a large residential landscape in northern Utah. Forty-three ha-1 monitoring plots were established to measure a range of attributes summarizing location description, tree and vegetation condition, and herbivore presence. Additionally, we tested the ability of a stand-level visual rating system to represent more detailed field measures along with aspen forest understory surveys. Elk (Cervus elaphus L.) herbivory is currently having a strong effect on aspen in the study area, reducing many locations to single-layer aspen forests dominated by aging canopy trees. Regeneration (\u3c 2 m stems) is experiencing moderate-to-high browse and recruitment (2 - 6 m stems) are below replacement levels on approximately half of WCR\u27s aspen forests. The condition rating system represented significant trends in forest cover, canopy height, stand aspect, regeneration, recruitment, and tree mortality. Ordination of all plot and forest data found a strong negative relationship between elk presence and recruitment success. We make recommendations for addressing di cult herbivore- aspen interactions where publicly managed wildlife present barriers to conservation of privately owned forest reserves