Prognostic importance of direct assignment of parent-of-origin via long-read genome and epigenome sequencing in retinoblastoma.

Background: Current clinical sequencing methods cannot effectively detect DNA methylation and allele-specific variation to provide parent-of-origin information from the proband alone. Parent-of-origin effects can lead to differential disease and the inability to assign this in de novo cases limits prognostication in the majority of affected individuals with retinoblastoma, a hereditary cancer with suspected parent-of-origin effects.

Methods: To directly assign parent-of-origin in retinoblastoma patients, genomic DNA was extracted from blood samples for sequencing using a programmable, targeted single-molecule long-read DNA genomic and epigenomic approach.

Interleukin-2-mediated NF-κB-dependent mRNA splicing modulates interferon gamma protein production.

Interferon-gamma (IFNγ) is a pleiotropic cytokine produced by natural killer (NK) cells during the early infection response. IFNγ expression is tightly regulated to mount sterilizing immunity while preventing tissue pathology. Several post-transcriptional effectors dampen IFNγ expression through IFNG mRNA degradation.

Light-sensitive Ca signaling in the mammalian choroid.

The choroid is the thin, vasculature-filled layer of the eye situated between the sclera and the retina, where it serves the metabolic needs of the light-sensing photoreceptors in the retina. Illumination of the interior surface of the back of the eye (fundus) is a critical regulator of subretinal fluid homeostasis, which determines the overall shape of the eye, but it is also important for choroidal perfusion. Noted for having some of the highest blood flow rates in the body, the choroidal vasculature has been reported to lack intrinsic, intravascular pressure-induced (myogenic) autoregulatory mechanisms.

Combined strategy of upfront CTCA and optimal treatment for stable chest pain: rationale and design of the CLEAR-CAD trial.

Background: Patients with stable chest pain suspected of coronary artery disease (CAD) usually undergo multiple diagnostic tests to confirm or rule out obstructive CAD. Some tests may not effectively assess the presence of CAD, precluding optimal treatment. A diagnostic strategy of upfront computed tomography coronary angiography (CTCA) combined with optimal medical therapy (OMT) tailored to the extent of CAD may be superior to standard care in preventing major adverse cardiac events.