Spatial transcriptomics of healthy and fibrotic human liver at single-cell resolution.

Single-cell RNA sequencing (scRNA-seq) has advanced our understanding of cell types and their heterogeneity within the human liver, but the spatial organization at single-cell resolution has not yet been described. Here we apply multiplexed error robust fluorescent in situ hybridization (MERFISH) to map the zonal distribution of hepatocytes, spatially resolve subsets of macrophage and mesenchymal populations, and investigate the relationship between hepatocyte ploidy and gene expression within the healthy human liver. Integrating spatial information from MERFISH with the more complete transcriptome produced by single-nucleus RNA sequencing (snRNA-seq), also reveals zonally enriched receptor-ligand interactions.

Power and sample size calculation for non-inferiority trials with treatment switching in intention-to-treat analysis comparing RMSTs.

Background: Difference in Restricted Mean Survival Time (DRMST) has attracted attention and is increasingly used in non-inferiority (NI) trials because of its superior power in detecting treatment effects compared to hazard ratio. However, when treatment switching (also known as crossover) occurs, the widely used intention-to-treat (ITT) analysis can underpower or overpower NI trials.

Methods: We propose a simulation-based approach, named , to calculate powers and determine the necessary sample size to achieve a desired power for non-inferiority trials that allow treatment switching, in ITT analysis using DRMST.

Psychometric evaluation of the Autism Symptom Dimensions Questionnaire.

Aim: To replicate and extend previous psychometric findings for the Autism Symptom Dimensions Questionnaire (ASDQ).

Method: Using a cross-sectional design in two samples, including a total of 3366 children and adolescents (aged 2-17 years; 1399 with autism spectrum disorder) and a small case series, factor structure, measurement invariance, reliability, construct validity, screening and diagnostic efficiency, and detection of reliable change were examined for the ASDQ.

Results: Strong psychometric properties were observed, including replicable factor structure, strong measurement invariance, adequate-to-excellent scale and conditional reliability, strong convergent and discriminant validity, and good screening efficiency.

Noninvasive Assessment of Liver Fibrosis in Patients With Iron Overload.

Objective: We assessed the diagnostic performance of ultrasound two-dimensional shear wave elastography (US 2D-SWE) to predict clinically significant fibrosis (CSF) in patients with serologic iron overload (SIO) and the subgroup with histologic liver iron overload (LIO).

Methods: A single-center retrospective cross-sectional study of adults with SIO (serum ferritin ≥ 200 ng/mL in females and ≥ 300 ng/mL in males) and suspected chronic liver disease with nonfocal liver biopsy results and US 2D-SWE exams within 1 year was performed. Histopathological fibrosis stage ≥2 and liver iron ≥2+ was considered CSF and LIO, respectively.

Development of a fibrin-targeted theranostic for gastric cancer.

Patients with advanced gastric cancer (GCa) have limited treatment options, and alternative treatment approaches are necessary to improve their clinical outcomes. Because fibrin is abundant in gastric tumors but not in healthy tissues, we hypothesized that fibrin could be used as a high-concentration depot for a high-energy beta-emitting cytotoxic radiopharmaceutical delivered to tumor cells. We showed that fibrin is present in 64 to 75% of primary gastric tumors and 50 to 100% of metastatic gastric adenocarcinoma cores.