Diffuse large B-cell lymphoma (DLBCL) is a commonly diagnosed, aggressive non-Hodgkin's lymphoma. While R-CHOP chemoimmunotherapy is potentially curative, about 40% of DLBCL patients will fail, highlighting the need to identify biomarkers to optimize management. SAMHD1 has a dNTPase-independent role in promoting resection to facilitate DNA double-strand break (DSB) repair by homologous recombination.
View Article and Find Full Text PDFis a motile, gram negative bacillus in the Enterobacteriaceae family that is a rarely isolated cause of disease, despite being ubiquitous in nature. A 2019 review article identified only 74 reported cases, most often in immunocompromised patients [1]. The organism is generally susceptible to most antibiotics although multiantibiotic resistant strains have been reported.
View Article and Find Full Text PDFStudy Objectives: This study investigated risk factors and estimated rates of acute insomnia disorder in health care workers at the onset of the coronavirus disease 2019 (COVID-19) pandemic.
Methods: A Qualtrics survey of more than 2,300 health care providers was conducted in a single academic health system on May 15, 2020, including practicing attending physicians, residents and fellows in training, advanced practice providers, and nurses. Six hundred and sixty-eight responded (29% response rate).
Failure to achieve pathologic complete response is associated with poor prognosis in breast cancer patients following neoadjuvant chemotherapy (NACT). However, prognostic biomarkers for clinical outcome are unclear in this patient population. Cyclin-dependent kinase 9 (CDK9) is often dysregulated in breast cancer, and its deficiency results in genomic instability.
View Article and Find Full Text PDFDNA double-strand break (DSB) repair by homologous recombination (HR) is initiated by CtIP/MRN-mediated DNA end resection to maintain genome integrity. SAMHD1 is a dNTP triphosphohydrolase, which restricts HIV-1 infection, and mutations are associated with Aicardi-Goutières syndrome and cancer. We show that SAMHD1 has a dNTPase-independent function in promoting DNA end resection to facilitate DSB repair by HR.
View Article and Find Full Text PDFSirtuin 2 (SIRT2) is a sirtuin family deacetylase, which maintains genome integrity and prevents tumorigenesis. Although deficiency in mice leads to tumorigenesis, the functional significance of somatic mutations in human tumors is unclear. Using structural insight combined with bioinformatics and functional analyses, we show that naturally occurring cancer-associated mutations at evolutionarily conserved sites disrupt its deacetylation of DNA-damage response proteins by impairing SIRT2 catalytic activity or protein levels but not its localization or binding with substrate.
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