Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Appreciative Mentoring: Applying the Appreciative Framework to a Writing Fellows Program

In this essay, an academic advisor and a writing fellow describe how the framework of appreciative advising highlights aspects of mentoring, and explore how mentoring programs could benefit by adding elements of appreciating advising

The natural history and osteodystrophy of mucolipidosis types II and III

Aim: To assess the natural history and impact of the secondary bone disease observed in patients with mucolipidosis (ML) II and III. Methods: Affected children and adults were ascertained from clinical genetics units around Australia and New Zealand. Diagnoses were confirmed by the National Referral Laboratory in Adelaide. The study encompassed all patients ascertained between 1975 and 2005. Data focussing on biochemical parameters at diagnosis, and longitudinal radiographic findings were sought for each patient. Where feasible, patients underwent clinical review and examination. Examinations included skeletal survey, bone densitometry, and measurement of serum and urine markers of bone metabolism. In a subset of patients, functional assessment using the Pediatric Evaluation and Disability Inventory (PEDI) and molecular analysis of GNPTAB were performed. Results: Twenty-five patients with mucolipidosis were ascertained over a 30-year period. Morbidity and functional outcomes on living patients were described. Serum calcium and phosphate were normal. All, but one patient, had normal alkaline phosphatase. Serum osteocalcin and urine deoxypyridinoline/creatinine were elevated. Two radiological patterns were observed (i) transient neonatal hyperparathyroidism in infants with ML II and (ii) progressive osteodystrophy in patients with ML intermediate and ML III. Molecular analyses of GNPTAB in nine subjects are reported. Conclusion: ML is characterised by a progressive bone and mineral disorder which we describe as the 'osteodystrophy of mucolipidosis'. The clinical and radiographic features of this osteodystrophy are consistent with a syndrome of 'pseudohyperparathyroidism'. Much of the progressive skeletal and joint pathology is attributable to this bone disorder

astropy/astroquery: v0.4.5

What's Changed Update Spectra URLs by @weaverba137 in https://github.com/astropy/astroquery/pull/2214ALMA integration tests fix by @andamian in https://github.com/astropy/astroquery/pull/2224Fix doc build issues by @bsipocz in https://github.com/astropy/astroquery/pull/2226Allow retrieval from a previous ESO archive request by @gbrammer in https://github.com/astropy/astroquery/pull/1614Turn off default verbosity for TapPlus by @bsipocz in https://github.com/astropy/astroquery/pull/2228Refreshing content of RTD config by @bsipocz in https://github.com/astropy/astroquery/pull/2229NED: String has to remain raw by @bsipocz in https://github.com/astropy/astroquery/pull/2230eJWST prelaunch by @jespinosaar in https://github.com/astropy/astroquery/pull/2140MNT: Cleanup of old unused code and configs by @bsipocz in https://github.com/astropy/astroquery/pull/2231Adding changelog rendering to narrative docs by @bsipocz in https://github.com/astropy/astroquery/pull/2233Mast cloudaccess docs update by @jaymedina in https://github.com/astropy/astroquery/pull/2235eJWST release by @jespinosaar in https://github.com/astropy/astroquery/pull/2238eJWST: remove disclaimer for release by @jespinosaar in https://github.com/astropy/astroquery/pull/2243Fix to allow html downloads with alma package by @andamian in https://github.com/astropy/astroquery/pull/2246Deprecate astroquery/utils/download_file_list.py by @eerovaher in https://github.com/astropy/astroquery/pull/2247Expand contribution guidelines by @keflavich in https://github.com/astropy/astroquery/pull/2248Fix for issue #2237: do not cache results that cannot be parsed. by @mkelley in https://github.com/astropy/astroquery/pull/2253Adding python 3.10 to CI by @bsipocz in https://github.com/astropy/astroquery/pull/2186 New Contributors @gbrammer made their first contribution in https://github.com/astropy/astroquery/pull/1614 Full Changelog: https://github.com/astropy/astroquery/compare/v0.4.4...v0.4.