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It is becoming increasingly clear that the worldwide outbreak of severe acute respiratory syndrome coronavirus 2 will have long-term negative consequences. Some patients report functional complaints long after recovery from coronavirus disease-2019 (COVID-19), which include fatigue, breathlessness, heart palpitations, loss or alteration of taste and smell, and problems with attention, memory, and cognition. However, the long-term complications for those patients who had severe symptoms and prolonged hypoxia during their course of their hospital stay is still unknown. We report 2 patients with confirmed diagnoses of COVID-19 who experienced prolonged infection and developed rapid progressive dementia following COVID-19 pneumonia after a follow-up period of 5 to 10 months. As these cases may become more prevalent over time, we should learn to recognize the early signs of long-term COVID-19 complications in those who are especially vulnerable to neurocognitive decline.

Misregulation of long non-coding RNA (lncRNA) genes has been linked to a wide variety of cancer types. Here we report on Mammary Tumor Associated RNA 25 (MaTAR25), a nuclear enriched and chromatin associated lncRNA that plays a role in mammary tumor cell proliferation, migration, and invasion, both in vitro and in vivo. MaTAR25 functions by interacting with purine rich element binding protein B (PURB), and associating with a major downstream target gene Tensin1 (Tns1) to regulate its expression in trans. The Tns1 protein product is a critical component of focal adhesions linking signaling between the extracellular matrix and the actin cytoskeleton. Knockout of MaTAR25 results in down-regulation of Tns1 leading to a reorganization of the actin cytoskeleton, and a reduction of focal adhesions and microvilli. We identify LINC01271 as the human ortholog of MaTAR25, and importantly, increased expression of LINC01271 is associated with poor patient prognosis and metastasis. Our findings demonstrate that LINC01271 represents a potential therapeutic target to alter breast cancer progression., A group of long non-coding RNAs (lncRNAs), Mammary Tumor Associated RNAs 1-30 (MaTARs 1-30), are differentially expressed between mammary tumor cells and normal mammary epithelial cells. Here the authors report that MaTAR25 plays a role in breast cancer cell proliferation, migration and invasion by regulating the expression of the Tensin1 gene in trans.

Streptococcus lutetiensis has been known to cause sepsis in adults, but only one case regarding neonatal sepsis has been reported internationally, with no sequelae. We report the first case of neonatal bacteremia and meningitis with empyema caused by S. lutetiensis in the United States.

Hepatocellular carcinoma, the most common type of liver malignancy, is one of the most lethal forms of cancer. We identified a long non-coding RNA, Gm19705, that is overexpressed in hepatocellular carcinoma and mouse embryonic stem cells. We named this RNA Pluripotency and Hepatocyte Associated RNA Overexpressed in HCC, or PHAROH. Depletion of PHAROH impacts cell proliferation and migration, which can be rescued by ectopic expression of PHAROH. RNA-seq analysis of PHAROH knockouts revealed that a large number of genes with decreased expression contain a Myc motif in their promoter. MYC is decreased in knockout cells at the protein level, but not the mRNA level. RNA-antisense pulldown identified nucleolysin TIAR, a translational repressor, to bind to a 71-nt hairpin within PHAROH, sequestration of which increases MYC translation. In summary, our data suggest that PHAROH regulates MYC translation by sequestering TIAR and as such represents a potentially exciting diagnostic or therapeutic target in hepatocellular carcinoma.

Long non-coding RNAs (lncRNAs) are an emerging class of regulatory molecules that have been shown to play important roles in tumorigenesis and cancer progression. Here, we studied the recently identified lncRNA Mammary Tumor Associated RNA 20 (MaTAR20) in mammary cancer progression. A CRISPR/Cas9 knockout of MaTAR20 in the metastatic 4T1 cell line led to reduced cancer cell proliferation and increased cell surface adhesion compared to control cells. Consistent with these knockout results antisense oligonucleotide (ASO) mediated knockdown of MaTAR20 resulted in reduced growth and invasion in 4T1 cells, and in primary mammary tumor organoids derived from the MMTV-PyMT mouse model of breast cancer. Injection of MaTAR20-specific ASOs subcutaneously into tumor bearing MMTV-PyMT mice resulted in smaller and highly necrotic tumors in comparison to mice injected with a scrambled control ASO. To investigate the molecular mechanism by which MaTAR20 acts to advance mammary tumor progression, we applied a combination of RNA-sequencing and RNA-pulldown coupled to DNA-sequencing. These analyses demonstrated that the nuclear retained lncRNA is associated with several essential cancer signaling pathways such as VEGF signaling. In particular, MaTAR20 directly binds to and regulates the expression of Tnfsf15. Our results indicate that MaTAR20 is an important driver of mammary tumor progression and represents a promising new therapeutic target.

Hepatocellular carcinoma, the most common type of liver malignancy, is one of the most lethal forms of cancer. We identified a long non-coding RNA, Gm19705, that is overexpressed in hepatocellular carcinoma and mouse embryonic stem cells. We named this RNA Pluripotency and Hepatocyte Associated RNA Overexpressed in HCC, or PHAROH. Depletion of PHAROH impacts cell proliferation and migration, which can be rescued by ectopic expression of PHAROH. RNA-seq analysis of PHAROH knockouts revealed that a large number of genes with decreased expression contain a c-Myc motif in their promoter. C-MYC is decreased at the protein level, but not the mRNA level. RNAantisense pulldown identified nucleolysin TIAR, a translational repressor, to bind to a 71-nt hairpin within PHAROH, sequestration of which increases c-MYC translation. In summary, our data suggest that PHAROH regulates c-MYC translation by sequestering TIAR and as such represents a potentially exciting diagnostic or therapeutic target in hepatocellular carcinoma.

SUMMARYMisregulation of long non-coding RNA genes has been linked to a wide variety of cancer types. Here we report onMammaryTumorAssociatedRNA 25 (MaTAR25), a nuclear enriched and chromatin associated lncRNA that plays a role in mammary tumor cell proliferation, migration, and invasion, bothin vitroandin vivo.MaTAR25functions by interacting with purine rich element binding protein B (PURB), and associating with a major downstream target geneTensin 1(Tns1) to regulate its expression intrans. Knockout ofMaTAR25results in down-regulation ofTns1leading to a reorganization of the actin cytoskeleton, and a reduction of focal adhesions and microvilli. The human ortholog ofMaTAR25,LINC01271, is upregulated with human breast cancer stage and metastasis.SIGNIFICANCELncRNAs have great potential to reveal new regulatory mechanisms of function as well as having exciting therapeutic capacity given their ease of being targeted by nucleic acid drugs. Our study ofMaTAR25,and its human orthologLINC01271,reveal an unexpected function of this lncRNA in breast cancer progression by regulatingTns1gene expression, whose protein product is a critical component of focal adhesions linking signaling between the extracellular matrix and the actin cytoskeleton. We identifiedLINC01271 asthe human ortholog ofMaTAR25, and importantly, increased expression ofLINC01271is associated with poor patient prognosis and cancer metastasis. Our findings demonstrate thatLINC01271represents an exciting therapeutic target to alter breast cancer progression.