Systematic benchmarking of imaging spatial transcriptomics platforms in FFPE tissues.

Emerging imaging spatial transcriptomics (iST) platforms and coupled analytical methods can recover cell-to-cell interactions, groups of spatially covarying genes, and gene signatures associated with pathological features, and are thus particularly well-suited for applications in formalin fixed paraffin embedded (FFPE) tissues. Here, we benchmarked the performance of three commercial iST platforms on serial sections from tissue microarrays (TMAs) containing 23 tumor and normal tissue types for both relative technical and biological performance. On matched genes, we found that 10x Xenium shows higher transcript counts per gene without sacrificing specificity, but that all three platforms concord to orthogonal RNA-seq datasets and can perform spatially resolved cell typing, albeit with different false discovery rates, cell segmentation error frequencies, and with varying degrees of sub-clustering for downstream biological analyses. Taken together, our analyses provide a comprehensive benchmark to guide the choice of iST method as researchers design studies with precious samples in this rapidly evolving field.

Virtual Versus Light Microscopy Usage among Students: A Systematic Review and Meta-Analytic Evidence in Medical Education.

BACKGROUND: The usage of whole-slide images has recently been gaining a foothold in medical education, training, and diagnosis. OBJECTIVES: The first objective of the current study was to compare academic performance on virtual microscopy (VM) and light microscopy (LM) for learning pathology, anatomy, and histology in medical and dental students during the COVID-19 period. The second objective was to gather insight into various applications and usage of such technology for medical education. MATERIALS AND METHODS: Using the keywords "virtual microscopy" or "light microscopy" or "digital microscopy" and "medical" and "dental" students, databases (PubMed, Embase, Scopus, Cochrane, CINAHL, and Google Scholar) were searched. Hand searching and snowballing were also employed for article searching. After extracting the relevant data based on inclusion and execution criteria, the qualitative data were used for the systematic review and quantitative data were used for meta-analysis. The Newcastle Ottawa Scale (NOS) scale was used to assess the quality of the included studies. Additionally, we registered our systematic review protocol in the prospective register of systematic reviews (PROSPERO) with registration number CRD42020205583. RESULTS: A total of 39 studies met the criteria to be included in the systematic review. Overall, results indicated a preference for this technology and better academic scores. Qualitative analyses reported improved academic scores, ease of use, and enhanced collaboration amongst students as the top advantages, whereas technical issues were a disadvantage. The performance comparison of virtual versus light microscopy meta-analysis included 19 studies. Most (10/39) studies were from medical universities in the USA. VM was mainly used for teaching pathology courses (25/39) at medical schools (30/39). Dental schools (10/39) have also reported using VM for teaching microscopy. The COVID-19 pandemic was responsible for the transition to VM use in 17/39 studies. The pooled effect size of 19 studies significantly demonstrated higher exam performance (SMD: 1.36 [95% CI: 0.75, 1.96], p < 0.001) among the students who used VM for their learning. Students in the VM group demonstrated significantly higher exam performance than LM in pathology (SMD: 0.85 [95% CI: 0.26, 1.44], p < 0.01) and histopathology (SMD: 1.25 [95% CI: 0.71, 1.78], p < 0.001). For histology (SMD: 1.67 [95% CI: -0.05, 3.40], p = 0.06), the result was insignificant. The overall analysis of 15 studies assessing exam performance showed significantly higher performance for both medical (SMD: 1.42 [95% CI: 0.59, 2.25], p < 0.001) and dental students (SMD: 0.58 [95% CI: 0.58, 0.79], p < 0.001). CONCLUSIONS: The results of qualitative and quantitative analyses show that VM technology and digitization of glass slides enhance the teaching and learning of microscopic aspects of disease. Additionally, the COVID-19 global health crisis has produced many challenges to overcome from a macroscopic to microscopic scale, for which modern virtual technology is the solution. Therefore, medical educators worldwide should incorporate newer teaching technologies in the curriculum for the success of the coming generation of health-care professionals.

Formation of Coelomic Cavities during Abbreviated Development of the Brittle Star Ophioplocus esmarki.

AbstractIn brittle stars, the coelomic cavities that form during embryogenesis contribute to most of the internal organ systems of the juvenile. In the ancestral mode of development, the coelomic cavities begin with bilateral symmetry and play a minor role in the function of the ophiopluteus larva. However, the coelomic cavities undergo extensive changes during metamorphosis to set up the body systems of the juvenile brittle star. Many lineages of brittle stars have evolved life histories without the ophiopluteus larva. The non-feeding vitellaria larva has rapid development of juvenile structures. This work demonstrates the modifications to the origin and early development of the coelomic cavities in a vitellaria larva. Much of the archenteron forms an unpaired axocoel, hydrocoel, and somatocoel. The posterior-most portion of the archenteron forms the rudiment of the juvenile stomach. The right somatocoel and a portion of the left somatocoel form as invaginations of the lateral ectoderm. Later morphogenesis of the axocoel, the hydrocoel, and the two somatocoels is similar to what has been shown for brittle stars with an ophiopluteus larva. Confocal microscopy and three-dimensional modeling were used to show new details for the later morphogenesis of the coelomic cavities. The stone canal originates as an outgrowth of the hydrocoel between lobes 4 and 5. The hydrocoel lobes have minimal migration after they meet to complete the ring canal. The right somatocoel contributes to a component of the axial complex and perihemal system. A detailed description is given for how the left somatocoel contributes to multiple organ systems.

A Study of the Effects of Al, Cr, Hf, and Ti Additions on the Microstructure and Oxidation of Nb-24Ti-18Si Silicide Based Alloys.

In Nb-silicide based alloys Al, Cr, Hf, and Ti additions are crucial for achieving balance of properties. It is not known how the simultaneous addition of Hf with Al and Ti, or Hf with Al, Cr, and Ti affects macrosegregation, and how the alloying affects hardness, Young's modulus and bulk alloy oxidation, and contamination of the solid solution Nbss and the Nb5Si3 compound by oxygen. Two alloys with nominal compositions (at.%) Nb-24Ti-18Si-5Al-5Hf (alloy NbSiTiHf-5Al) and Nb-24Ti-18Si-5Al-5Cr-5Hf (alloy NbSiTiHf-5Al-5Cr) were studied in the as-cast and heat-treated conditions and after isothermal oxidation at 800 and 1200 °C and were compared with similar alloys without Hf. In both alloys there was macrosegregation of Si and Ti, which was more severe in NbSiTiHf-5Al. Both alloys formed Nbss+ßNb5Si3 eutectic. The Nbss was stable and its Al and Cr concentrations increased with increasing Ti concentration. In both conditions the ßNb5Si3 was observed in the alloys NbSiTiHf-5Al and NbSiTiHf-5Al-5Cr, and the γNb5Si3 only in the alloy NbSiTiHf-5Al. In both heat-treated alloys, separate Hf-rich Nb5Si3 grains were formed. The Si and Al concentrations in Nb5Si3 respectively decreased and increased with increasing Ti concentration. Al and Cr had a stronger hardening effect in the Nbss than Al, Cr, and Hf. Al, Cr, and Ti had a stronger negative effect on the Young's modulus of the Nbss compared with Al, Cr, Hf, and Ti. When Nb was substituted by Ti, Cr, and Hf, and Si by Al in the ßNb5Si3, the Young's modulus was reduced compared with the unalloyed silicide. At 800 °C both alloys did not exhibit catastrophic pest-oxidation after 100 h. The Nbss and Nb5Si3 were contaminated by oxygen in both alloys, the former more severely. At 1200 °C the scales spalled-off, more severely in the alloy NbSiTiHf-5Al, where substrate that was heavily contaminated by oxygen below the scale also spalled-off. In both alloys the contamination of Nb5Si3 and Nbss by oxygen was more severe compared with 800 °C, but the silicides were not contaminated by oxygen in their bulk. The Nbss was not contaminated by oxygen only in the bulk of the alloy NbSiTiHf-5Al-5Cr.