While immune checkpoint inhibitors are increasingly used for various cancers, unpredictable immune-related adverse events (irAEs) such as autoimmune encephalitis is life-threatening. Here, we report an association between human leukocyte antigen (HLA) and atezolizumab-induced encephalitis.
From an institutional prospective cohort for encephalitis, we identified patients with autoimmune encephalitis after the use of atezolizumab, a PD-L1 (programmed death-ligand 1) inhibitor, from August 2016 to September 2019 and analyzed their HLA genotypes.
A total of 290 patients received atezolizumab, and seven patients developed autoimmune encephalitis, and five of whom were enrolled for the analysis. The patients presented altered mentality, seizures, or myelitis. Three patients had the HLA-B*2705 genotype in common (60%), which is significantly frequent given its low frequency in the general population (2.5%). After Bonferroni correction, HLA-B*2705 was significantly associated with autoimmune encephalitis by atezolizumab (corrected P<0.001, odds ratio 59, 95% CI=9.0~386.9).
Here we found that three in five patients with autoimmune encephalitis associated with atezolizumab had the rare HLA-B*2705 genotype. Further systematic analyses in larger cohorts are necessary to investigate the value of HLA screening to prevent the life-threatening adverse events.
Here we found that three in five patients with autoimmune encephalitis associated with atezolizumab had the rare HLA-B*2705 genotype. Further systematic analyses in larger cohorts are necessary to investigate the value of HLA screening to prevent the life-threatening adverse events.We read with considerable interest the study by Gusenbauer and Haddaway (Gusenbauer and Haddaway, 2020, Research Synthesis Methods, doi10.1002/jrsm.1378) comparing the systematic search qualities of 28 search systems, including Google Scholar (GS) and PubMed. Google Scholar and PubMed are the two most popular free academic search tools in biology and chemistry, with GS being the number one search tool in the world. Those academics using GS as their principal system for literature searches may be unaware of research which enumerates five critical features for scientific literature tools that greatly influenced Gusenbauer's 2020 study. Using this list as the framework for a targeted comparison between just GS and PubMed, we found stark differences which overwhelmingly favored PubMed. In this comment, we show that by comparing the characteristics of the two search tools, features that are particularly useful in one search tool, but are missing in the other, are strikingly spotlighted. One especially popular feature that ubiquitously appears in GS, but not in PubMed, is the forward citation search found under every citation as a clickable Cited by N link. We seek to improve the PubMed search experience using two approaches. First, we request that PubMed add Cited by N links, making them as omnipresent as the GS links. Second, we created an open-source command-line tool, pmidcite, which is used alongside PubMed to give information to researchers to help with the choice of the next paper to examine, analogous to how GS's Cited by N links help to guide users. Ipatasertib datasheet Find pmidcite at https//github.com/dvklopfenstein/pmidcite.Ten new xanthone derivatives have been designed and synthesized for their potential antibacterial activity. All compounds have been screened against Staphylococcus epidermidis strains ATCC 12228 and clinical K/12/8915. The highest antibacterial activity was observed for compound 3 5-chloro-2-((4-(2-hydroxyethyl)piperazin-1-yl)methyl)-9H-xanthen-9-one dihydrochloride, exhibiting MIC of 0.8 µg/ml against ATCC 12228 strain, compared to linezolid (0.8 µg/ml), ciprofloxacin (0.2 µg/ml) or trimethoprim and sulfamethoxazole (0.8 µg/ml). For the most active compound 3, genotoxicity assay with use of Salmonella enterica serovar Typhimurium revealed safety in terms of genotoxicity at concentration 75 µg/ml and antibacterial activity against Salmonella at all higher concentrations. A final in silico prediction of skin metabolism of compound 3 seems promising, indicating stability of the xanthone moiety in the metabolism process.An electroactive room-temperature phosphorescence (RTP) polymer has been demonstrated based on a characteristic donor-oxygen-acceptor geometry. Compared with the donor-acceptor reference, the inserted oxygen atom between donor and acceptor can not only decrease hole-electron orbital overlap to suppress the charge transfer fluorescence, but also strengthen spin-orbital coupling effect to facilitate the intersystem crossing and subsequent phosphorescence channels. As a result, a significant RTP is observed in solid states under photo excitation. Most noticeably, the corresponding polymer light-emitting diodes (PLEDs) reveal a dominant electrophosphorescence with a record-high external quantum efficiency of 9.7 %. The performance goes well beyond the 5 % theoretical limit for typical fluors, opening a new door to the development of pure organic RTP polymers towards efficient PLEDs.Bovine respiratory disease (BRD) has a complex pathogenesis and aetiology, being the costliest disease affecting the cattle industry in North America. In this study, we applied Nanopore-based viral metagenomic sequencing to explore the nasal virome of cattle upon arrival at feedlot and related the findings to the development of BRD. Deep nasal swabs (DNS) from 310 cattle for which BRD outcomes were known (155 cattle developed BRD within 40 days and 155 remained healthy) were included. The most prevalent virus in on-arrival samples was bovine coronavirus (BCV) (45.2%, 140/310), followed by bovine rhinitis virus B (BRBV) (21.9%, 68/310), enterovirus E (EVE) (19.6%, 60/310), bovine parainfluenza virus 3 (BPIV3) (10.3%, 32/310), ungulate tetraparvovirus 1 (UTPV1) (9.7%, 30/310) and influenza D virus (7.1%, 22/310). No relationship was found between BRD development and the number of viruses detected, the presence of any specific individual virus or combination of viruses. Bovine kobuvirus (BKV) was detected in 2.6% of animals (8/310), being the first report of this virus in Canada.Ipatasertib datasheet
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