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Major anti-vaccine groups were sowing seeds of doubt on Facebook weeks before the US government launched its vaccine development program 'Operation Warp Speed'. Early anti-vaccine misinformation campaigns outpaced public health messaging and hampered the rollout of COVID-19 vaccines. Major anti-vaccine groups were sowing seeds of doubt on Facebook weeks before the US government launched its vaccine development program 'Operation Warp Speed'. Early anti-vaccine misinformation campaigns outpaced public health messaging and hampered the rollout of COVID-19 vaccines. We aimed to detect influenza variants with reduced susceptibility to baloxavir marboxil (baloxavir) and oseltamivir and identify differences in the clinical course between children with and without these variants after anti-viral treatment. During the 2019-2020 influenza season, we enrolled children with confirmed influenza A (20 treated with baloxavir and 16 with oseltamivir). We analyzed patients' sequential viral RNA loads and infectious virus titers, the drug susceptibilities of clinical isolates, and amino acid substitutions in the viral polymerase acidic protein subunits or neuraminidase. We assessed patients' clinical information using questionnaires. All viral RNA loads and virus titers were significantly decreased after treatment, but we detected baloxavir-resistant and the oseltamivir-resistant variants in 5 of 20 and 3 of 16 patients, respectively. The duration of fever was similar between patients with and without the variants, but infectious viral shedding lasted 3 days longer in patients with baloxavir-resistant variants. In addition, the duration to improvement of clinical symptoms was longer in these patients (75.0h vs. 29.5h; p = 0.106). After anti-viral treatment, the emergence of baloxavir-resistant variants may affect the patients' clinical course, but oseltamivir-resistant variants had no clinical impact. After anti-viral treatment, the emergence of baloxavir-resistant variants may affect the patients' clinical course, but oseltamivir-resistant variants had no clinical impact.A new safety testing paradigm that relies on gene expression biomarker panels was developed to easily and quickly identify drug-induced injuries across tissues in rats prior to drug candidate selection. Here, we describe the development, qualification, and implementation of gene expression signatures that diagnose tissue degeneration/necrosis for use in early rat safety studies. Approximately 400 differentially expressed genes were first identified that were consistently regulated across 4 prioritized tissues (liver, kidney, heart, and skeletal muscle), following injuries induced by known toxicants. Hundred of these "universal" genes were chosen for quantitative PCR, and the most consistent and robustly responding transcripts selected, resulting in a final 22-gene set from which unique sets of 12 genes were chosen as optimal for each tissue. The approach was extended across 4 additional tissues (pancreas, gastrointestinal tract, bladder, and testes) where toxicities are less common. Mathematical algorithms were generated to convert each tissue's 12-gene expression values to a single metric, scaled between 0 and 1, and a positive threshold set. For liver, kidney, heart, and skeletal muscle, this was established using a training set of 22 compounds and performance determined by testing a set of approximately 100 additional compounds, resulting in 74%-94% sensitivity and 94%-100% specificity for liver, kidney, and skeletal muscle, and 54%-62% sensitivity and 95%-98% specificity for heart. Similar performance was observed across a set of 15 studies for pancreas, gastrointestinal tract, bladder, and testes. Bundled together, we have incorporated these tissue signatures into a 4-day rat study, providing a rapid assessment of commonly seen compound liabilities to guide selection of lead candidates without the necessity to perform time-consuming histopathologic analyses. Cesarean section (CS), breastfeeding, and geographic location can influence the infant microbiota. In this systematic review, evidence of the association between mode of delivery and infant gut microbiota up to 6 months of age was evaluated, as was the role of breastfeeding in this association, according to PRISMA guidelines. The Pubmed, Web of Science, Scopus, Embase, Medical Database, and Open Grey databases were searched. A total of 31 observational studies with ≥2 infant stool collections up to the sixth month of age and a comparison of gut microbiota between CS and vaginal delivery (VD) were included. Infants born by CS had a lower abundance of Bifidobacterium and Bacteroides spp. at almost all points up to age 6 months. Populations of Lactobacillus, Bifidobacterium longum, Bifidobacterium catenulatum, and Escherichia coli were reduced in infants delivered by CS. Infants born by CS and exclusively breastfed had greater similarity with the microbiota of infants born by VD. Species of Bifidobacterium and Bacteroides are potentially reduced in infants born by CS. Geographic location influenced bacterial colonization. PROSPERO registration no. 42017071285. PROSPERO registration no. 42017071285.Transfer-RNAs (tRNAs) help ribosomes decode mRNAs and synthesize proteins; however, tRNA fragments produced under certain conditions, known as tRNA-derived small RNAs (tsRNAs), have been found to play important roles in pathophysiological processes. In the reproductive system, tsRNAs are abundant in gametes and embryos and at the maternal-fetal interface, as well as in microvesicles like epididymosomes, seminal plasma exosomes, and syncytiotrophoblast-derived extracellular vesicles. tsRNAs can affect gamete cell maturation, zygote activation, and early embryonic development. https://www.selleckchem.com/products/msa-2.html tsRNAs can transmit epigenetic information to later generations. In particular, exposure to environmental factors such as nutrition, isoproterenol, and poly(IC) may allow tsRNAs to transfer information to the gametes or placenta to alter offspring phenotype. The underlying mechanisms of tsRNAs action include transposon silencing, translation regulation, and target mRNA degradation. Herein, we review the currently reported tsRNAs in the reproductive system, their validated functions, and potential roles.
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