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W-linked genes show evidence of degeneration, including high rates of protein evolution and reduced expression. Most are found in young lineage-specific strata, with only a few high expression ancestral W-genes remaining, consistent with the progressive erosion of non-recombining regions. Among these, the splicing factor U2AF2 stands out as a promising candidate for primary sex determination, opening new avenues for understanding the molecular basis of the reproductive biology of this group.The Puma lineage within the family Felidae consists of three species that last shared a common ancestor around 4.9 million years ago. Whole-genome sequences of two species from the lineage were previously reported the cheetah (Acinonyx jubatus) and the mountain lion (Puma concolor). The present report describes a whole-genome assembly of the remaining species, the jaguarundi (Puma yagouaroundi). We sequenced the genome of a male jaguarundi with 10X Genomics linked reads and assembled the whole-genome sequence. The assembled genome contains a series of scaffolds that reach the length of chromosome arms and is similar in scaffold contiguity to the genome assemblies of cheetah and puma, with a contig N50 = 100.2 kbp and a scaffold N50 = 49.27 Mbp. We assessed the assembled sequence of the jaguarundi genome using BUSCO, aligned reads of the sequenced individual and another published female jaguarundi to the assembled genome, annotated protein-coding genes, repeats, genomic variants and their effects with respect to the protein-coding genes, and analyzed differences of the two jaguarundis from the reference mitochondrial genome. The jaguarundi genome assembly and its annotation were compared in quality, variants and features to the previously reported genome assemblies of puma and cheetah. Computational analyzes used in the study were implemented in transparent and reproducible way to allow their further reuse and modification.

Bacille Calmette-Guérin (BCG) vaccination has beneficial off-target effects that may include protecting against non-mycobacterial infectious diseases. We aimed to determine whether neonatal BCG vaccination reduces lower respiratory tract infections (LRTI) in infants in the MIS BAIR trial.

In this investigator-blinded trial, neonates in Australia were randomised to receive BCG-Denmark vaccination or no BCG at birth. buy PF-04620110 Episodes of LRTI were determined by symptoms reported in parent-completed 3-monthly questionnaires over the first year of life. Data were analysed by intention-to-treat using binary regression. Clinicaltrials.gov (NCT01906853).

From August 2013 to September 2016, 1272 neonates were randomised to the BCG vaccination (n=637) or control (n=635) group. The proportion of participants with an episode of LRTI in the first year of life among BCG-vaccinated infants was 54.8% compared to 58.0% in the control group, resulting in a risk difference of -3.2 (95% CI -9.0 to 2.6) after multiple imputation. There was no interaction observed between the primary outcome and sex, maternal BCG or the other pre-specified effect modifiers.

Based on the findings of this trial, there is insufficient evidence to support the use of neonatal BCG vaccination to prevent LRTI in the first year of life in high-income settings.

Based on the findings of this trial, there is insufficient evidence to support the use of neonatal BCG vaccination to prevent LRTI in the first year of life in high-income settings.In keloid fibroblasts, microRNA-21 (miR-21) enhances activation of the TGF-β-Smad-signaling pathway by downregulating Smad7 expression, thereby promoting keloid fibroblast proliferation and collagen production. However, it is unclear whether miR-21 performs the above-mentioned functions through exosomal transport. Here, we extracted exosomes from the culture supernatants of keloid and normal skin fibroblasts, and observed that exosomes from both cell types secreted exosomes; however, keloid fibroblasts secreted significantly more exosomal miR-21 than normal skin fibroblasts (P less then 0.001). Interestingly, we also observed that exosomal miR-21 could enter target keloid fibroblasts. In addition, inhibiting exosomal miR-21 upregulated Smad7 protein expression and reduced Smad2 and Smad3 protein levels in target keloid fibroblasts. Furthermore, inhibiting exosomal miR-21 downregulated collagen I and collagen III expression in target keloid fibroblasts, increased the proportion of apoptotic cells, and reduced cell proliferation. Taken together, these results show that exosomal miR-21 promoted proliferation and collagen production in keloid fibroblasts by inhibiting Smad7. Thus, we identified regulatory roles for miR-21 in promoting keloid fibroblast proliferation and participating in keloid formation and development. These findings imply that miR-21 may serve as a novel target for controlling the development of keloids.

Low-dose direct oral anticoagulants (DOACs) in adjunct to antiplatelet therapy, known as dual pathway inhibition (DPI), have been tested to prevent ischaemic events in patients with cardiovascular disease (CVD). We conducted a systematic review and meta-analysis to determine the overall safety and efficacy of low-dose DOACs vs. placebo on a background of antiplatelet therapy.

All randomized controlled trials (RCTs) comparing low-dose DOAC (defined as a dosage below the lowest approved for stroke prevention) vs. placebo among patients with CVD receiving single or dual antiplatelet therapy in at least 50% of the population and followed for at least 6 months, were included. Incidence rate ratios (IRRs) with 95% confidence intervals (CIs) were used to overcome different follow-up durations across trials. The primary efficacy endpoint was major adverse cardiovascular events (MACE) and the primary safety endpoint major bleeding. A pre-specified subgroup analysis was performed for different DOAC-dose regimens.

eeding without any trade-off in efficacy compared to other low-dose DOAC regimens.

In patients with CVD, a low-dose DOAC regimen vs. placebo, on a background of antiplatelet therapy, is effective in reducing ischaemic events at the expense of increased major and all bleeding, but without significantly increasing intracranial or fatal bleeds, while the reduction of cardiovascular and total mortality is not statistically significant. A DPI with very low-dose DOAC (i.e. rivaroxaban 2.5 mg twice daily) appears particularly advantageous, especially when combined with a single antiplatelet agent and used among patients at high ischaemic and low bleeding risk.

This study is registered in PROSPERO (CRD42021232744).

This study is registered in PROSPERO (CRD42021232744).