Body habitus vs. hepatic steatosis: Understanding the drivers of non-diagnostic shear wave elastography

Purpose: Shear Wave Elastography (SWE) is frequently non-diagnostic in obese patients, a key cohort at risk for liver disease. Subcutaneous fat and hepatic steatosis are suspected drivers, but their relative contribution is unknown. We compare ultrasound-guided attenuation parameter (UGAP), a marker of steatosis, body mass index (BMI), and skin-to-liver capsule distance (SCD) to predict non-diagnostic SWE. Materials and methods: This IRB approved, single center retrospective study included adults with SWE and diagnostic UGAP exams between June and December 2023. Fasting patients were imaged in supine position with right arm abducted, via an intercostal window during neutral breath hold. The median of 10 measurements in the right lobe was analyzed for SWE and UGAP. SWE measurements were ≥2 cm from the capsule while UGAP depth was fixed at 4 cm from the probe. Exams were considered non-diagnostic for SWE (measured in m/s) if the Interquartile Range/Median Ratio (IQR/M) was >15 % or if diagnostic measurements could not be obtained. UGAP IQR/M > 30 % or complete measurement failure was considered non-diagnostic. Univariate Receiver Operating Characteristic (ROC) curves compared UGAP (dB/cm/MHz), BMI (kg/m2), and SCD (mm) prediction of non-diagnostic SWE by the DeLong test. Results: 87 participants (48 male) with mean age of 54.7 ± 15.7 years were analyzed. UGAP [OR: 1.63 per 0.1 dB/cm/MHz, p = 0.02, AUC = 0.66], BMI [OR: 1.23, p < 0.001, AUC = 0.77], and SCD [OR: 1.27, p < 0.001, AUC = 0.81) were predictors of non-diagnostic SWE. UGAP prediction of non-diagnostic SWE was similar in subgroups with the measurement region at least 1 cm (OR: 1.64, n = 68), and 2 cm (OR: 1.54, n = 16) from the liver capsule. UGAP was a worse predictor than SCD (p = 0.04), while not significantly different than BMI (p = 0.15). BMI and SCD did not differ in predicting non-diagnostic SWE (p = 0.44). Conclusion: Our small preliminary study demonstrated that body habitus and hepatic attenuation, a marker of steatosis, both contribute to non-diagnostic SWE exams, however body wall thickness is the key driver. This informs patient selection for SWE exams and guides future research to mitigate these technical shortcomings. Clinical relevance/application: Patients with hepatic steatosis and large body habitus are at increased risk of non-diagnostic ultrasound shear wave elastography (SWE) exams. These patients, particularly those with increased body wall thickness, may benefit from liver fibrosis evaluation with alternative approaches following an initial non-diagnostic SWE exam. Researchers working to improve SWE technique should pay particular attention to mitigating attenuation and phase aberration from the body wall as this is the key driver of non-diagnostic exams

Spatially resolved transcriptome profiling in model plant species

Understanding complex biological systems requires functional characterization of specialized tissue domains. However, existing strategies for generating and analysing high-throughput spatial expression profiles were developed for a limited range of organisms, primarily mammals. Here we present the first available approach to generate and study highresolution, spatially resolved functional profiles in a broad range of model plant systems. Our process includes highthroughput spatial transcriptome profiling followed by spatial gene and pathway analyses. We first demonstrate the feasibility of the technique by generating spatial transcriptome profiles from model angiosperms and gymnosperms microsections. In Arabidopsis thaliana we use the spatial data to identify differences in expression levels of 141 genes and 189 pathways in eight inflorescence tissue domains. Our combined approach of spatial transcriptomics and functional profiling offers a powerful new strategy that can be applied to a broad range of plant species, and is an approach that will be pivotal to answering fundamental questions in developmental and evolutionary biology.</p

miR-CLIP capture of a miRNA targetome uncovers a lincRNA H19-miR-106a interaction

Identifying the interaction partners of noncoding RNAs is essential for elucidating their functions. We have developed an approach, termed microRNA crosslinking and immunoprecipitation (miR-CLIP), using pre-miRNAs modified with psoralen and biotin to capture their targets in cells. Photo-crosslinking and Argonaute 2 immunopurification followed by streptavidin affinity purification of probe-linked RNAs provided selectivity in the capture of targets, which were identified by deep sequencing. miR-CLIP with pre-miR-106a, a miR-17-5p family member, identified hundreds of putative targets in HeLa cells, many carrying conserved sequences complementary to the miRNA seed but also many that were not predicted computationally. miR-106a overexpression experiments confirmed that miR-CLIP captured functional targets, including H19, a long noncoding RNA that is expressed during skeletal muscle cell differentiation. We showed that miR-17-5p family members bind H19 in HeLa cells and myoblasts. During myoblast differentiation, levels of H19, miR-17-5p family members and mRNA targets changed in a manner suggesting that H19 acts as a 'sponge' for these miRNAs