The Diagnostic Yield and Implications of Targeted Founder Pathogenic Variant Testing in an Israeli Cohort.

Founder pathogenic variants (PVs) are prevalent in Israel. This study investigated the current practice of offering cancer patients two-step genetic testing, starting with targeted testing for recurring founder PVs, followed, if negative, by next-generation sequencing. A total of 2128 subjects with cancer or a positive family history underwent oncogenetic testing with a panel of 51 recurring PVs at a tertiary medical center in March 2020-January 2023.

Bi-allelic variants in INTS11 are associated with a complex neurological disorder.

The Integrator complex is a multi-subunit protein complex that regulates the processing of nascent RNAs transcribed by RNA polymerase II (RNAPII), including small nuclear RNAs, enhancer RNAs, telomeric RNAs, viral RNAs, and protein-coding mRNAs. Integrator subunit 11 (INTS11) is the catalytic subunit that cleaves nascent RNAs, but, to date, mutations in this subunit have not been linked to human disease. Here, we describe 15 individuals from 10 unrelated families with bi-allelic variants in INTS11 who present with global developmental and language delay, intellectual disability, impaired motor development, and brain atrophy.

Toward multimode-fiber shape sensing.

We demonstrate machine-learning assisted dynamic tracking of the shape of a multimode fiber whose spatial configuration is manipulated by the movement of three linear stages. The data source used for the analysis is the coherent speckle pattern of light that has made a round trip in the fiber.

Resting-state heart rate variability (HRV) mediates the association between perceived chronic stress and ambiguity avoidance.

Chronic stress is associated with profound behavioral and physiological alterations, including intolerance to uncertainty and reduced resting-state heart-rate-variability (HRV). Critically, uncertainty may arise in situations with known probabilities (risk) or unknown probabilities (ambiguity). Whether associations between chronic stress and decision-making under uncertainty are dependent on the specific type of uncertain decisions, and whether physiological alterations play a role in these putative associations is not yet clear.