Single-Chain Nanobody Inhibition of Notch and Avidity Enhancement Utilizing the β-Pore-Forming Toxin Aerolysin.

Notch plays critical roles in developmental processes and disease pathogenesis, which have led to numerous efforts to modulate its function with small molecules and antibodies. Here we present a nanobody inhibitor of Notch signaling derived from a synthetic phage-display library targeting the Notch negative regulatory region (NRR). The nanobody inhibits Notch signaling in a luciferase reporter assay with an IC of about 5 μM and in a Notch-dependent hematopoietic progenitor cell differentiation assay, despite a modest 19 μM affinity for the Notch NRR.

Cancers Detected on Supplemental Breast Ultrasound in Women With Dense Breasts: Update From a Canadian Centre.

Breast ultrasound is one of several tools proposed for supplemental screening of women with dense breasts but is not widely available in Canada. An IRB-approved, evaluation of ultrasound-guided breast biopsies prompted by screening breast ultrasound performed from August 1, 2021, to December 31, 2022, offered to asymptomatic women with category C and D breast tissue density after normal screening mammography (2D) in the provincial organized screening program, or surveillance diagnostic mammography after breast cancer. Risk factors, stage (AJCC 8th ed), incremental cancer detection rate (ICDR), biopsy rates, and positive predictive values for biopsy (PPV3) were evaluated.

, the Cause of Extensive Wood Decay of Almond Trees in California Orchards.

Ganoderma adspersum, previously unreported in North America, was identified as the primary causal agent of root and butt rot-related failure in almond trees in California's Central Valley. This disease has been observed over approximately 340 km in California and in orchards spanning 5 to 20+ years old. The most common sign is reddish-brown basidiomata that develop at the base of the trees in the later stages of the disease.

Association of race and ethnicity with mortality in adults with SLE: a systematic literature review and meta-analysis.

Objectives: Ethnicity and health outcomes are intrinsically interrelated, although mechanisms are complex. SLE is a disease with higher incidence in Asian, Black, Hispanic and Indigenous populations than in White populations. SLE is associated with premature mortality, but it is unclear if ethnicity impacts on health outcomes as studies are frequently underpowered.