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Mendelian and early-onset severe psychiatric phenotypes often involve genetic variants having a large effect, offering opportunities for genetic discoveries and early therapeutic interventions. Here, the index case is an 18-year-old boy, who at 14 years of age had a decline in cognitive functioning over the course of a year and subsequently presented with catatonia, auditory and visual hallucinations, paranoia, aggression, mood dysregulation, and disorganized thoughts. Exome sequencing revealed a stop-gain mutation in RCL1 (NM_005772.4:c.370 C > T, p.Gln124Ter), encoding an RNA 3′-terminal phosphate cyclase-like protein that is highly conserved across eukaryotic species. Subsequent investigations across two academic medical centers identified eleven additional cases of RCL1 copy number variations (CNVs) with varying neurodevelopmental or psychiatric phenotypes. These findings suggest that dosage variation of RCL1 contributes to a range of neurological and clinical phenotypes.

OBJECTIVE Machine learning algorithms have shown groundbreaking results in neuroimaging. Herein, the authors evaluate the performance of a newly developed convolutional neural network (CNN) to detect and quantify the thickness, volume, and midline shift (MLS) of subdural hematoma (SDH) from noncontrast head CT (NCHCT). METHODS NCHCT studies performed for the evaluation of head trauma in consecutive patients between July 2018 and April 2021 at a single institution were retrospectively identified. Ground truth determination of SDH, thickness, and MLS was established by the neuroradiology report. The primary outcome was performance of the CNN in detecting SDH in an external validation set, as measured using area under the receiver operating characteristic curve analysis. Secondary outcomes included accuracy for thickness, volume, and MLS. RESULTS Among 263 cases with valid NCHCT according to the study criteria, 135 patients (51%) were male, the mean (± standard deviation) age was 61 ± 23 years, and 70 patients were diagnosed with SDH on neuroradiologist evaluation. The median SDH thickness was 11 mm (IQR 6 mm), and 16 patients had a median MLS of 5 mm (IQR 2.25 mm). In the independent data set, the CNN performed well, with sensitivity of 91.4% (95% CI 82.3%–96.8%), specificity of 96.4% (95% CI 92.7%–98.5%), and accuracy of 95.1% (95% CI 91.7%–97.3%); sensitivity for the subgroup with an SDH thickness above 10 mm was 100%. The maximum thickness mean absolute error was 2.75 mm (95% CI 2.14–3.37 mm), whereas the MLS mean absolute error was 0.93 mm (95% CI 0.55–1.31 mm). The Pearson correlation coefficient computed to determine agreement between automated and manual segmentation measurements was 0.97 (95% CI 0.96–0.98). CONCLUSIONS The described Viz.ai SDH CNN performed exceptionally well at identifying and quantifying key features of SDHs in an independent validation imaging data set.

Aptamers have been the subject of more than 144,000 papers to date. However, there has been a growing concern that errors in reporting aptamer research limit the reliability of these reagents for research and other applications. These observations noting inconsistencies in the use of our RNA anti-lysozyme aptamer served as an impetus for our systematic review of the reporting of aptamer sequences in the literature. Our detailed examination of literature citing the RNA anti-lysozyme aptamer revealed that 93% of the 61 publications reviewed reported unexplained altered sequences with 86% of those using DNA variants. The ten most cited aptamers were examined using a standardized methodology in order to categorize the extent to which the sequences themselves were apparently improperly reproduced, both in the literature and presumably in experiments beyond their discovery. Our review of 800 aptamer publications spanned decades, multiple journals, and research groups, and revealed that 44% of the papers reported unexplained sequence alterations. We identified ten common categories of sequence alterations including deletions, substitutions, additions, among others. The robust data set we have produced elucidates a source of irreproducibility and unreliability in our field and can be used as a starting point for building evidence-based best practices in publication standards to elevate the rigor and reproducibility of aptamer research.