HIV infection drives interferon signaling within intestinal SARS-CoV-2 target cells

SARS-CoV-2 infects epithelial cells of the human gastrointestinal (GI) tract and causes related symptoms. HIV infection impairs gut homeostasis and is associated with an increased risk of COVID-19 fatality. To investigate the potential link between these observations, we analyzed singlecell transcriptional profiles and SARS-CoV-2 entry receptor expression across lymphoid and mucosal human tissue from chronically HIV-infected individuals and uninfected controls. Absorptive gut enterocytes displayed the highest coexpression of SARS-CoV-2 receptors ACE2, TMPRSS2, and TMPRSS4, of which ACE2 expression was associated with canonical interferon response and antiviral genes. Chronic treated HIV infection was associated with a clear antiviral response in gut enterocytes and, unexpectedly, with a substantial reduction of ACE2 and TMPRSS2 target cells. Gut tissue from SARS-CoV-2-infected individuals, however, showed abundant SARS-CoV-2 nucleocapsid protein in both the large and small intestine, including an HIV-coinfected individual. Thus, upregulation of antiviral response genes and downregulation of ACE2 and TMPRSS2 in the GI tract of HIV-infected individuals does not prevent SARS-CoV-2 infection in this compartment. The impact of these HIVassociated intestinal mucosal changes on SARS-CoV-2 infection dynamics, disease severity, and vaccine responses remains unclear and requires further investigation

ICAR: endoscopic skull‐base surgery

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Improved haplotype inference by exploiting long-range linking and allelic imbalance in RNA-seq datasets

© 2020, The Author(s). Haplotype reconstruction of distant genetic variants remains an unsolved problem due to the short-read length of common sequencing data. Here, we introduce HapTree-X, a probabilistic framework that utilizes latent long-range information to reconstruct unspecified haplotypes in diploid and polyploid organisms. It introduces the observation that differential allele-specific expression can link genetic variants from the same physical chromosome, thus even enabling using reads that cover only individual variants. We demonstrate HapTree-X’s feasibility on in-house sequenced Genome in a Bottle RNA-seq and various whole exome, genome, and 10X Genomics datasets. HapTree-X produces more complete phases (up to 25%), even in clinically important genes, and phases more variants than other methods while maintaining similar or higher accuracy and being up to 10× faster than other tools. The advantage of HapTree-X’s ability to use multiple lines of evidence, as well as to phase polyploid genomes in a single integrative framework, substantially grows as the amount of diverse data increases

A systematic review of the endoscopic repair of cerebrospinal fluid leaks

Objectives: To provide an up-to-date review of the literature on the safety and efficacy of the endoscopic technique for cerebrospinal (CSF) leak repairs. Data Sources: PubMed, Medline/Old Medline, and Cochrane Central databases. Review Methods: Using the above outlined data sources, studies involving the endoscopic repair of CSF leaks were reviewed independently by 2 researchers. Studies included met the following criteria: full-text article written in the English language, at least 5 human patients undergoing purely endoscopic surgical repair of a CSF leak, and documented follow-up. Data extracted included leak etiology, presentation and location, the use of imaging, intrathecal fluorescein, and adjunctive measures as well as the success rate of the repair. Results: Fifty-five studies, involving 1778 fistulae repairs, were included for analysis. Spontaneous leaks were most prevalent, with the ethmoid roof and sphenoid the most common sites involved. The overall success rate of repair was high at 90% for primary and 97% for secondary repairs. A low complication rate of less than 0.03% was reported. Conclusion: The endoscopic repair of CSF fistula is both safe and effective and should be considered the standard of care for most cases. Evidence supporting adjunctive measures such as lumbar drains and antibiotics remains limited despite their common use.Alkis J. Psaltis, Rodney J. Schlosser, Caroline A. Banks, James Yawn, and Zachary M. Sole